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Mitochondrial Capacity and Thiamine: Notes from a Presentation

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mitochondrial illness

Mid December, I gave a talk on mitochondrial capacity and thiamine’s role therein (included below). My argument was that mitochondrial capacity e.g. their capacity to produce ATP efficiently from the foods we consume, and to meet the demands of living, drives health or illness. I also argued that thiamine drives mitochondrial capacity, and thus, is implicated in modern illness.

It is an argument I have made for years now, and of course, I wrote a book about it, together with the late Dr. Derrick Lonsdale. It is not something readily considered by western medicine, however. Even as our understanding of the molecular mechanisms and pathways connected to mitochondrial functioning has expanded over the last century, the fundamental nature of mitochondrial energetics remains underappreciated. We look to everything else the mitochondria do as somehow more important to health and disease than simple energetic capacity, forgetting that these other processes do not happen without sufficient energy.

Energy is the most basic unit of life. It is the capacity to transform something into something else. Absent this, we are nothing more than rocks.

That said, I did learn a few things when preparing for this talk. Namely, I learned how many discrete disease there are. Did you know that we now have over 26,000 separate disease entities recognized by the medical profession and over 18,000 ‘global’ or ‘systemic’ disease entities? I did not and was shocked. Before I looked this up, I thought we had maybe a few thousand, ten thousand if I were being generous. Never once did I contemplate 26,000. That is absolutely insane. Worse yet, apparently there are over 20,000 pharmaceutical products currently on the market. A pill for every ill – almost.

With all of this knowledge, one might think we have advanced in our capacity for health and healing. One would be wrong. According to the latest research, 76% of the population deals with at least one chronic condition. And quite unironically, despite the endless discrimination of discrete diseases, most symptoms, from 25-75% according to one report, remain medically unexplained. We are drowning in distinctions where perhaps there should be none, or at least far fewer, and we are none the wiser or healthier for it.

From my perspective, I cannot help but wonder how many of these discrete diseases are not simply expressions of poor mitochondrial capacity? Sure, there are potentially millions of combinations of interactions between genetics and the lived environment that are likely to affect disease presentation, but is each set of symptoms really representative of a separate disease? From a mitochondrial perspective, probably not.

Moreover, if mitochondrial capacity is the key to health, then instead of searching for and naming each permutation of disease expression and creating new drugs for each, we could go back to the basics and ask ourselves – what do I need to be healthy and am I getting it? If I am ill, chances are I am missing something, probably lots of somethings and those missing components to health, along with the long list of environmental toxicants and genetic interactions that lessen mitochondrial capacity, are what is driving illness. Perhaps if we support the mitochondria and view health from that perspective, we can reduce the burden of disease while culling the impossible and growing list of supposedly discrete diseases.

Alas, none of that will happen, at least not on a scale that would make a difference. That said, perhaps my lectures and articles might help a few people reclaim their health and their family’s health. For me, that is a win.

Here is the latest.

Mitochondrial Capacity, Thiamine, and Dysautonomia

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Is TTFD Toxic?

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Is TTFD toxic

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.

Therapeutic index of 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.

  1. 267 cases of sudden-onset deafness was treated with 150mg TTFD orally, with most therapeutic effect seen after 2-3 months of treatment
  2. 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.
  3. 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.
  4. Beriberi treated with 150mg IV one week, followed by 100mg oral long-term (2014)
  5. Cardiac failure 100mg IV (1987)
  6. Heart and circulatory failure (2008)
  7. TTFD administered to 15 year old boy to treat beriberi, remained on the therapy long-term
  8. 18 patients with non-diabetic peripheral neuropathy 1-3 months, no serious side effects
  9. Wernicke encephalopathy in hemodialysis – 100mg/iv, later oral continued for 2 months until improvement (2009)
  10. Diabetic lactic acidosis – 100mg/day IV for 7 days resolution in symptoms, followed by 75mg indefinitely (2008)
  11. Beriberi w/ pulmonary hypotension – 50mg long-term (2019)
  12. E/beriberi after intestinal resection – 150mg IV three days, 75mg long-term (2018):
  13. E/Shoshin beriberi – 150mg/IV, 75mg oral long-term (2013)
  14. A case of Wernicke’s encephalopathy with severe cardiac sympathetic dysfunction – 100mg (2012)
  15. 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)
  16. Beriberi neuropathy and shoshin beriberi that developed 6 years after gastrectomy on the cardia side – 100mg TTFD long term (2013)
  17. Chemotherapy induced W.E – IV thiamine HCL followed by TTFD 75mg long-term (2008)
  18. Postoperative W.E treated with 100mg IV TTFD (1998)
  19. Cardiomyopathy associated with mitochondrial disease that developed heart failure, treated with 100mg long-term (2017)
  20. Mitochondria rescue formula recommended for acute encephalopathy: including TTFD 100mg (2019)
  21. Pediatric acute encephalopathy neuroprotection protocol – cocktail including 200mg TTFD in 15 children (2013)
  22. 200mg TTFD x 31 children childhood acute encephalopathy (part of protocol) (2014)
  23. Lactic acidosis caused by low-dose metformin: Thiamine HCL 100mg followed by 75mg TTFD long-term, normalization of all liver values (2014)
  24. Beriberi mimicking Guillain-Barré syndrome – IV TTFD 100mg resolved this
  25. Shoshin beriberi – IV TTFD 150mg for 11 days, indefinite oral dose 150mg TTFD long-term
  26. 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.
  27. 75mg TTFD improved cerebral blood flow in deficiency
  28. 75mg TTFD used in mitochondrial myopathy long-term
  29. 50mg TTFD used to treat edema and weight gain and marginal thiamine deficiency – authors recommend TTFD instead of thiamine HCL (2021)
  30. Biguanide-induced lactic acidosis treated with 100mg, then 300mg TTFD (2017)
  31. 100mg used to treat encephalopathy w/ hyperammonemia (2003)
  32. Subacute spinal degeneration caused by B12 deficiency treated with B12 and 75mg TTFD long-term (2020)
  33. 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.

  1. 194 cases of infantile beriberi cured with IM/IV thiamine and TTFD (1987)
  2. 50 infants treated with TTFD for cardiac beriberi (1997)
  3. 70 children with infantile beriberi cured with intravenous TTFD (1990)
  4. 48 cases of infantile cerebral beriberi (0-3 years old) treated with TTFD (1997)
  5. 35 cases of infantile beriberi cured TTFD (2010)
  6. 10 cases of infantile cerebral beriberi cured with B1 HCL and TTFD
  7. 10 cases of cerebral beriberi and basal ganglia damage treated with TTFD injections (2003)
  8. 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)
  9. 283 out of 285 children with rectal prolapse cured by TTFD injection into “changqiang” acupoint (1988)
  10. 89 cases of rectal prolapse also treated with TTFD acupoint injection (1998)
  11. 50 cases of cerebral hypoplasia improved with acupoint injection of acetyl glutamine and TTFD (1983)
  12. 35 patients treated for hyperthyroidism with TTFD as adjunctive treatment (1999)
  13. 50 cases of costochondritis cured with Analgin + TTFD injection (1993)
  14. 13 children with ocular nerve palsy cured with TTFD (2010)
  15. 50 cases of urinary incontinence treated with acupoint injection of combination of acetyl glutamine, TTFD and/or r-aminobutyric acid (1990)
  16. 26 cases of delayed peripheral neuropathy due to organophosphate poisoning treated with acupuncture and TTFD injection (2001)
  17. 47 cases of lumbar disc protrusion treated with acupoint injection, B12 and TTFD (1994)
  18. 38 cases of facial neuritis treated with acupuncture and vitamins including TTFD injection (1999)
  19. 60 cases of migraine treated with Chinese medicine, flunarizine, and TTFD (2004)
  20. 24 cases of migraine treated with TTFD acupoint injection (1990)
  21. 40 patients with cerebrovascular disease addressed using acetyl glutamine and TTFD scalp acupoint injections (2001)
  22. 30 cases diabetic neuropathy, 75mg TTFD used as a control in– 60% effective (2002)
  23. 69 cases of Bell’s Palsy, TTFD used with acyclovir (1999)
  24. 120 cases of Bell’s Palsy treated with oral TTFD, methylb12, and/or electroacupuncture and facial muscle exercise (2019)
  25. 65 cases of Meniere’s Diseases treated with TCM, vitamins including TTFD injections
  26. 118 cases of herpes zoster treated with TTFD in conjunction with acyclovir and traditional Chinese medicine (2013).
  27. 100 cases of senile deafness treated with cocktail including TTFD (2000)
  28. 36 cases of cervical spondylotic radiculopathy treated with control of TTFD and naproxen – 75% effective (2009)
  29. 60 cases of postherpetic neuralgia treated with cocktail including TTFD
  30. 1 case of polerarteritis nodosa w/peripheral neuritis treated with cocktail including TTFD
  31. 1 case of central paralytic dysphagia (tuberculosis meningitis) unresponsive to conventional treatment cured by injection of TTFD at meridian acupoint (1974)
  32. 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. 

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ASD, Seizures, and Eosinophilic Esophagitis: Could They Be Thiamine Related?

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seizures, EOE, Autism, thiamine

My 18 year old son has ASD and has had a seizure disorder since he was 6 years old. He has tried virtually all anti-epileptic drugs. Either the side effects were unbearable, they made his seizures worse, or had no effect on his seizures. He was diagnosed with Eosinophilic Esophagitis. He is underweight and of short stature, and always has been. Mitochondrial tests show that complex II is working at 26% capacity. He is also autistic. He has tested positive for folate receptor antibody.

Over the years he has done several rounds of antibiotics, including Flagyl, which I have since learned that it significantly depletes the body of thiamine. He has also taken several rounds of Diflucan, Azithromycin, Vancomycin, Augmentin, Amox for various issues including candida, clostridia, gram negative gut bacteria, etc.

He is currently on Lamictal and just started Briviact for seizures. The Briviact causes anger and aggression issues. He currently deals with OCD tendencies. He was recently found to have bone density of 2.8 standard deviations below normal. This falls in the range of osteoporosis, but he has not been diagnosed with it because of his age.

He eats fresh and a lot of dried fruit, meats, raw and cooked greens, white rice, lots of cooked veggies, eggs. He also takes Lipothiamine 100 mg/day, Magnesium 550 mg, a multi-vitamin, calcium, vitamin D, and K, all at the direction of his doctors.

Childbirth and Infancy

M was born on July 9th 2005 7lbs 9oz. He was full-term. I had high blood pressure at 41 weeks and labor was induced. He would not drop into position and he became distressed and so was delivered via cesarean while I was under general anesthesia.

He spent 4 days in the NICU because he aspirated meconium and would not latch to feed. While in the NICU, he was administered antibiotics. He was formula-fed, not breast-fed.

As an infant, the large size of his head was somewhat of a concern for the pediatrician. He was administered vaccinations according to the CDC guidelines for the first 12 months. He had infantile spasms off and on. He spiked a fever for every vaccination. Tylenol was administered. He received 3 doses of flu vaccine, accidentally, within 3 months.

He did not sleep well, and still doesn’t.

Initially, he was very precocious. As an infant, he would put puzzles together that were for much older children. He would complete sorting activities that were well beyond his age range. He did not babble and eye-contact was fleeting.

After his 18 month vaccination, he lost just about everything within 2 weeks. After these vaccinations, he couldn’t do his puzzles, bring food to his mouth, smile, couldn’t stand to be read to when he previously loved to be read to. He also developed a sensitivity to light and sound and cried a lot.

At 24 months, he was diagnosed with profound autism.

PANDAS/PANS and Eosinophilic Esophagitis

At age 10 years, he abruptly lost skills again and it was thought he had PANDAS/PANS as he had several strep infections treated with antibiotics. He did a several month long courses of Augmentin or Azithromycin to treat PANDAS/PANS. He had a severe trauma at age 11. He was horrifically abused by a school employee.

He has always been of short-stature nearing 5th percentile for height, and slightly overweight for his age, until age 14 when he started having symptoms of Eosinophilic Esophagitis. He was diagnosed with EoE at 15 and has struggled to keep his weight high enough as he dealt with the intense pain, fatigue, and esophagus issues with this condition. He is currently taking Dupixent for his Eosinophilic Esophagitis as the PPI and Budesonide slurry were not addressing the issues. So far Dupixent is allowing him to eat. His diet remains very restricted due to having so many trigger foods and he has almost no appetite.

He eats a lot of dried and fresh fruit. He loves greens, raw and cooked. He also eats meat, white rice noodles.  He eats mostly an organic diet. He does occasionally enjoy candy.

Seizures

He developed seizures at age 6. These were controlled for a while on Depakote, but the side effects of Depakote were too much for him and so we had to stop. His seizures are now not controlled. He has 1-2 tonic-clonic seizures per week, plus several staring spells all throughout the day. Recent EEG showed abnormal spikes and discharges in the frontal and temporal lobes. It indicated his seizures involved many places on his brain. Brain surgery was being considered for seizures at this time, but ruled out as an option due to the nature of his seizures.

He has failed several other seizure meds including Vimpat, Zonegran, Aptiom, Topamax, Onfi, and others. He is currently on Lamotrigine and Epidiolex for his seizures. He also takes trazadone and gabapentin for sleep, although these do not consistently help him sleep. He is so consumed by fatigue and can hardly get out of bed even to walk across the room. With tons of encouragement he can do brief periods of school work. The meds cause him to lose focus and become frustrated. He seems to almost always be lost in a fog and unable to participate in basic conversations without losing focus or becoming too exhausted to continue. Each seizure will cause him to be in bed for 2-3 days. He has fallen many times going into a seizure and is now afraid to leave the safety of his bedroom. He will come out, but rarely.

He has intermittent issues with nystagmus. He had a bad case of COVID 2 years ago, which caused clusters of seizures and constant nystagmus.

He has an exaggerated startle response.

Despite It All

M is a sweet young man. He is brilliant. He loves animals. He tells everyone he sees that he is so happy to see them. He is working with a local legislator on how to improve rights for non-speaking people, especially in the court room. He is completing all of his high school courses at home with straight A’s and he is a published poet.

He does not speak, but he communicates by pointing to letters on an alphabet board. This is a skill that took him years to learn. He communicates at an age-appropriate level or higher. He is working, slowly, toward a standard high school diploma.

Postscript

Based upon what I have learned from this website, I discussed thiamine with our physician. It turns out, she heard Dr. Lonsdale speak years ago. She recommended 50mg of Lipothiamine. The entire time he was taking it, he had no seizures. I was not sure that it was thiamine or the meds until we ran out for about a week. The seizures returned, but as soon as we resumed the Lipothiamine, they disappeared again. He has been taking it again and now it has been 2 weeks without seizures. I don’t want to get my hopes up, but it could definitely be a piece of the puzzle. Are there others out there with similar experiences?

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 Gerd Altmann from Pixabay.

This story was published originally on January 2024. 

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Western Medicine: A House Built on Sand

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Western medicine - house built on sand

Let Food Be Medicine

At the risk of repeating myself too much as in former pages of this website, I want to return to discussing in some depth the fallacies incorporated in our present approach to health and disease. You may or may not remember that I have stated a number of times that Hippocrates (400 BCE) uttered the formula “Let food be thy medicine and medicine thy food”. Having been construed as the “father of modern medicine”, it has seemed to me for a long time that he has been ignored as a “parent”.

For centuries, there was no idea about disease. The early Egyptians bored holes in people’s heads “to let out the evil spirits”. Throughout medieval history the only treatment seems to have been “bloodletting”. In our modern world, horns from the rhinoceros are regarded so highly for their medical properties, that this wonderful animal is reaching the point of annihilation. Pharmaceutical drugs, with the exception of antibiotics, only treat symptoms. I ask you, does this make any sense at all in the light of what Hippocrates suggested?

Because humanity tends to follow a collective pattern and only rarely listens to an idea derived from rational deduction, I view medicine as like a traveler on a road without a known destination. In my imagination, he comes to a fork in the road, but the signpost records information on only one fork. It reads “kill the enemy”, reminding me of the story of Semmelweiss, a lone thinker in his time and who “gave thought to the message on the signpost”. Most physicians are familiar with this story but it is worth repeating.

Semmelweiss was a physician who lived at a time before microorganisms had been discovered. He presided over an obstetric ward where there were 10 beds on one side and 10 beds on the other. The physicians would deliver their patients without changing their clothes or washing their hands. As we would expect today, the death rate from infection was extremely high. Semmelweiss said to himself, “they must be bringing [the enemy] in on their hands” and he devised the first known clinical experiment. He made it a rule for the physicians on one side of the ward to wash their hands in chlorinated lime before they delivered their patient. The physicians on the other side of the ward continued to deliver their patients in the same old way. As we would easily recognize today, it did not require a statistician to see the difference between the incidences of infections on the two sides of the ward. Irrespective of the fact that this was a dramatic discovery that later had obvious meaning, Semmelweiss was accused by the medical authorities of the day of being non-scientific because he could not explain what it was that was supposed to be on the hands of the physicians. Of course the medical establishment had no idea that their model for disease was catastrophically wrong, although collectively certain that their philosophy bore all the hallmarks of scientific truth. Semmelweiss had offended the medical establishment and they threw him out of the hospital. He died a pauper in a mental hospital.

The First Medical Paradigm: Kill the Enemy

When microorganisms were discovered to be responsible for infections, it fulfilled the message on the signpost and it became the first paradigm in medicine. Kill the bacteria: kill the virus: kill the cancer cell, but try not to kill the patient. If we look at the history of this time, we find that a lot of patients were killed in the concerted attempts to find ways and means of killing the enemy. We all remember the discovery of penicillin and how it led to the antibiotic era, still the major therapeutic methodology, even though we know that it is running into bacterial resistance and has never been a good idea for viruses or cancer cells.

Although the germ theory had been around for a long time, Louis Pasteur, Ferdinand Cohn and Robert Koch were able to prove it and are regarded as the founders of microbiology. However, Pasteur was said to have uttered the words on his deathbed “I was wrong: the microbe (germ) is nothing. The terrain (the interior of the human body) is everything”. Perhaps he had unknowingly voiced the principles of the next paradigm in medicine.

The Second Medical Paradigm: Genetic Determinism

The monk, Mendel, by his work on the segregation of peas, formulated what came to be known as the genetic mechanisms of Mendelian inheritance and the discovery of DNA modeled the next stage in our collective development. The fact that each of us is built from a complex code that dictates who we are was a remarkable advance. The fact that the construction of the code sometimes contained mistakes (mutations) led us to explaining many diseases and for a long time we believed that the genes were fixed entities, dictating their inexorable commands throughout life. However, the newest science of epigenetics has shown us that the DNA that makes up our genes can sometimes be manipulated by nutrition and lifestyle, as well as by artificial means in the laboratory.

Health: The Ability to Respond Effectively to a Hostile Environment

We are surrounded by germs that exist everywhere, many of which cause disease as we are all too well aware. Nevertheless, whatever evolutionary mystery guides our development, we are all equipped with an extraordinarily complex, genetically determined, defense system. We now know that this is organized and directed by the brain. Assuming that the genetic determinations of the terrain are completely intact, we can be reasonably assured that we can defend ourselves from any germ that Mother Nature can throw at us. Built in mechanisms in the brain require a huge amount of energy when it goes into action directing the traffic of the immune system. It is a crisis and can be likened to a war between the body and the attacking organisms. Thus, if Pasteur may have stated the next paradigm in medicine, what does it mean?

As an example, a typical microbial attack causes a common disease that goes by the name of febrile lymphadenopathy (strep throat). The throat becomes inflamed, perhaps because the increased blood supply brings in white blood cells, acting in defense. An increase in circulating white cells also occurs, bringing a brigade of defensive soldiers. The glands in the neck become swollen because they catch the germs that get into the lymph system.  Lastly, the increased temperature of the body is also part of the defense. Germs are programmed to have their most intense virulence at 37°C, the normal body temperature. If this temperature is increased, the attacking germ does not have its maximum efficiency. In other words, what we are looking at as the illness is really the act of brain/body defensive interaction. Besides attempting to kill the attacking germ as safely as possible, should we not be assisting the defense? The answer calls into question the relationship between genetic intactness and the required energy to drive the complex defensive action. Perhaps a genetic mistake (mutation) can sometimes be manipulated by an epigenetic approach through nutrients, just as advised by Hippocrates.

Disease: The Inability to Adapt to the Environment

If we look at health as the ability to respond effectively and adapt to environmental, mental and physical stressors, it is possible to re-conceptualize illness by the manner in which that response is carried out. A healthy individual will respond to stressors without problem, because of an efficiently effective mobilization of energy dependent mechanisms. In contrast, individuals who are not healthy will respond in one of two ways. Either the defense mechanisms will be incomplete or absent or over-reactive and inconsistent. Listed below are examples of both. Note that this is in line with the ancient philosophy of Yin and Yang or, in modern terms “everything in moderation”. Too much of anything is as bad as too little.

Exhausted Defense Systems

When I was a resident in my English teaching hospital, before the antibiotic era, I admitted a patient with pneumonia who was known to have chronic tuberculosis. He was seen to be “unconsciously picking at thin air with his fingers” and the physician for whom I was resident pointed out that it was a classic example of “a sick brain” and that he would die. He never had any fever, elevation of white blood cells or any other marker of an infection but at autopsy, his body was riddled with small staphylococcal abscesses. He had lived in the east end of London, notorious for poverty and malnutrition at that time. In fact, as an organism, he never showed the slightest sign of a defense. His “sick brain” was completely disabled in any attempt to organize his defense.

Excessive or Aberrant Defense Mechanisms

Many years ago I was confronted with two six-year-old unrelated boys who for several years had each experienced repeated episodes of febrile lymphadenopathy. Both boys had been treated elsewhere as episodes of infection. In each case the swollen glands in the neck were enormous. One of the boys had been admitted to a hospital for a gland to be removed surgically for study. It had been found that the gland was just enlarged but had a perfectly normal anatomy, only contributing to the mystery. One of the curious parts of the history was that each of these boys had been indulged with sweets. Because I was well aware that sweet indulgence could induce vitamin B1 (thiamine) deficiency, I tested them and found that both were indeed deficient in this vitamin. Treatment with large doses of thiamine completely prevented any further attacks. The mothers of the boys were advised to prohibit their sweet indulgence. I needed some evidence and asked one of the mothers to stop giving thiamine to her son. Three weeks later he experienced a nightmare, sleep walking and another episode of lymphadenopathy that quickly resolved with thiamine.  A nightmare and sleep walking supported the contention that the brain was involved in the action. In addition, his recurrent illnesses had been associated with increased concentrations of two B vitamins, folate and B12, both of which decreased into the acceptably normal range with thiamine treatment. Of course, this added complexity to an explanation.

What I had already learned about thiamine deficiency is that it makes the part of the brain that controls automatic mechanisms much more sensitive. One or more reflexes are activated unnecessarily. No reflex activation is as bad as too much. Thus, the “trigger-happy” defense mechanisms were being activated falsely. Thiamine is perhaps the most important chemical compound derived from diet that presides over the intricacies of energy metabolism. All that was required was an improved energy input to the brain. Folate and B12 are vitamins that work in energy consuming mechanisms and I hypothesized that their respective functions were stalled for lack of energy, causing their accumulation in the blood. Whatever the explanation, the facts were as described. It is interesting that the high levels of folate and B12 had been found at the hospital where a lymph node had been removed. The mother had been accused of giving too many vitamins to her child. She had told me that she did not understand this explanation because she had not given any vitamins to him. I had measured them solely to verify this finding.

The Treatment of Disease Should Begin with Host Defenses

We exist in a hostile environment. Each day throughout life we live in anticipation of potential attack. A physical attack may be an injury, an infection or an ingested toxin. A mental attack, divorce, grieving, loneliness, generally referred to as “stress” may be virtually anything that causes the brain to go into increased action. In facing both physical and mental forces, it is the brain that organizes the defense and it demands an increase in energy output that depends solely on the ability to burn fuel. The fuel burning process is governed by a combination of genetically determined ability and the nature of the fuel. Thus, the treatment of all disease is dependent on this combination being effective. It can be seen as obvious that killing the enemy is insufficient. As our culture exists at the present time, trying to get people to understand the necessity of perfect nutrition is a pipe dream. This particularly applies to youth and the artificiality of the food industry. However, our culture is also virtually brainwashed to accept tablets as a means of treating anything.

In our recently published book “Thiamine Deficiency, Dysautonomia and High Calorie Malnutrition“, Dr. Marrs and I have shown that thiamine deficiency is extraordinarily common and that supplementary thiamine and magnesium together balance the ratio of empty calories to the required concentration of cofactors necessary for their oxidation. The question remains, would vitamin supplementation, just as artificial, be a more successful sell as a preventive measure? We have shown that the symptoms derived from prolonged high calorie malnutrition can last for years as an unrecognized polysymptomatic illness that haunts many physicians’ offices. Early recognition represents an easy cure. There is a good deal of evidence that ignoring the symptoms and the persistence of high calorie malnutrition creates a gradual deterioration that then turns up as chronic disease. Some drugs, metronidazole being an example, will precipitate thiamine deficiency, so we have to recognize the precarious nature of the present medical approach in the use of drugs whose action in treating disease is often unknown. Although recognition of the artificiality of thiamine supplementation is implicit in this proposal, it is better than allowing a common example of continued morbidity to exist.

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 Phil Hearing on Unsplash.

This article was published originally on July 19, 2018. 

Rest in peace Derrick Lonsdale, May 2024.

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Lessons Learned About Recovering From Thiamine Deficiency

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lessons learned with thiamine deficiency

It has been a year since I started taking high dose vitamin B1 (thiamine) for a variety of chronic symptoms including: Lyme disease, CFS/ME, endometriosis, histamine intolerance and other food intolerances, SIBO, chronic complicated migraine with aura, chronic insomnia, chronic severe light and exercise intolerance, to name a few. By traditional medicine, each of these conditions was considered unique and thus treated individually. I have learned that they are not separate conditions, but simply different manifestations of disturbed mitochondrial metabolism. In my case, all of this was related to deficiencies in thiamine and other vitamins and minerals. My recovery has been difficult and I have made many mistakes along the way, but hopefully, I learned from them. I am publishing my story here so that you may also learn from my experience. You can read my original story here.

Lesson 1: Magnesium Formulation Is Important

Magnesium is required to change thiamine from its free form to the active form called thiamine pyrophosphate (TPP). Without sufficient magnesium, supplemental or consumed thiamine remains inactive and basically useless. This means that magnesium deficiency can cause a functional thiamine deficiency. I understood this, but what I did not understand, was that there are many different formulations of magnesium supplement, each with pros and cons relative to the individual’s specific needs. I thought they were all interchangeable.

For me, and for individuals with heart related symptoms, magnesium taurate is preferred. One of my first mistakes I made was to ignore Dr. Lonsdale’s comments in which he talked about the importance of taking magnesium taurate. I understood it as meaning that magnesium was important and did not understand that it was a special form of magnesium with cardio protective effects due to the taurine content.

When I initially took magnesium taurate, I noticed an increase in my wellbeing, especially in the fatigue and headache that I would develop after walking around the house or being intellectually active, but I didn’t know that it was the taurine component that was responsible for that change. For a while, I stopped taking magnesium taurate and returned to using other forms of magnesium (magnesium citrate or malate). They did not help as much as the taurate. During this time, I also realized that I do not tolerate magnesium glycinate or bisglycinate. If I take that form, I have a terrible headache on the right side of my head. The glycine activates glutamate via NMDA receptors in the brain causing some excitatory activity. This may be why I could not tolerate it. Others do not have a problem with magnesium glycinate.

Over the last two weeks, I was that taking magnesium malate and taurine separately.  I wanted to avoid spending a lot of money on magnesium taurate, so I tried to buy a cheap form of magnesium – magnesium malate – and combine it with taurine which is inexpensive when purchased in bulk. This did not provide the same benefits as magnesium taurate. I experienced chest pressure and pain and my resting pulse went back to being higher than 65-70 BPM. Once I began taking magnesium taurate again, my heart rate and chest pain/pressure disappeared.

So the lesson here, is that different formulations of magnesium work for different people. It is important to research which form may work better for you and your set of symptoms and not to assume they are interchangeable.

Lessons 2-3: TTFD Degrades with Heat and Light and Interruptions to Thiamine Repletion Cause Setbacks

One other important thing I realized was that thiamine is destroyed by UV light. This meant that in August, when I put my TTFD powder (a form of synthetic thiamine that crosses cell barriers more easily) in a transparent container on the kitchen table, and left it there all day long while sunlight shone directly on it through the big windows in my kitchen, it was being destroyed every day. I experienced a big crash during that month, especially since I was taking all the other vitamins and minerals that were serving as co-factors. I could not explain it and was thinking that even this therapy was losing its effect, that my recovery was over, and that I could no longer hope for a better quality of life.

However, in September, I received my new order of TTFD powder. The very day I received it, I took my regular dosage from this new batch. The difference was incredible in terms of my symptoms. It was night and day. The effects were truly remarkable and unmistakable. I’m very careful now with my TTFD powder and make sure it stays in an opaque container.

Lesson 4: Treating My Carnitine Deficiency. Once Again Formulation Matters.

Another thing that I had not been able to fix was my carnitine deficiency. This was discovered by the neurologist who suspected that I was dealing with a FAOD (fatty acid oxidation disorder) or a mitochondrial disease back in February. Free carnitine levels in blood are supposed to be between 17 and 49, while mine was 6. I tried taking various forms of carnitine (L-carnitine, acetyl-L-carnitine, l-carnitine tartrate, Optimized Carnitine, propionyl-L-carnitine) but they all had a laxative effect which was aggravating my symptoms. I asked my neurologist if there were injections with carnitine that could replace the pills, but was left to figure it out for myself. And I did.

Through much research, I found a form that worked for me. It is called Propionyl-L-Carnitine. This form of carnitine is a known agent that protects against ischemia  – quote from the linked study:

Free CoA and propionyl-CoA cannot enter or leave mitochondria, but propionyl groups are transferred between separate CoA pools by prior conversion to propionyl-L-carnitine. This reaction requires carnitine and carnitine acetyl transferase, an enzyme abundant in heart tissue. Propionyl-L-carnitine traverses both mitochondrial and cell membranes. Within the cell, this mobility helps to maintain the mitochondrial acyl-CoA/CoA ratio. When this ratio is increased, as in carnitine deficiency states, deleterious consequences ensue, which include deficient metabolism of fatty acids and urea synthesis.

This form of carnitine has made a huge difference in my health, especially with one particular symptom – the wet cough that had accompanied my walking around the house since April 2021.

More Energy and Exercise Tolerance with the Correct Supplements

In October, I began taking magnesium taurate and I also added higher doses of potassium to my regimen, just to see if I tolerated them. I had taken rather lower doses of potassium on and off since starting high dose TTFD. One of the things higher potassium solved, was the aftertaste (or after smell) that I used to get with 300 mg TTFD. I know most people dislike it, since it’s a sulphur smell, although I never disliked it.

After about two weeks on magnesium taurate and higher potassium intake with every dose of TTFD, I began propionyl-L-Carnitine HCL and Optimized Carnitine again. I noticed that they no longer had a laxative effect and I doubled my dose of propionyl-L-carnitine HCL so that I was taking about 600 mg three times a day, combined with one capsule of Optimized Carnitine.

After about a week, I noticed that I had more energy. I no longer needed to eat every three or four hours, I no longer had dyspnea or wet cough during the day when I was walking around the house. All those symptoms speak of cardiomyopathy and were resolving with the supplements. I still need to avoid sleeping on my left side and instead sleep on an incline on my back to be able to sleep through the night, but it my sleep is so much better now. My headache, something that has tortured me since I attempted intermittent fasting in 2018, is now gone. This makes me think that the right-sided headache is one of the symptoms of my heart not being able to do its job properly.

One of the things that helps the most with mitochondrial biogenesis is exercise and it is highly recommended for people with mitochondrial disease. However, in many studies it is noted that if cardiomyopathy is present, then this therapeutic cannot really be used. This is important because many people recovered and improved their exercise intolerance, but still develop symptoms after too much physical effort and wonder what they could further do to improve their symptoms.

After finding the right supplements to correct my deficiencies, I’m able to walk around the house without it aggravating or triggering my symptoms. Prior to this, I was largely bedridden and would have flares every time I attempted to do anything. I have a device that measures how many steps I take and it shows that I walk at least 1000 steps per day when I do nothing and spend 95% of the day in bed.
Now I’m able to go out and walk around my apartment building, which is about 150 meters and do not suffer any consequence. I tried walking more than that and if I do, my main symptoms come back (insomnia, heart symptoms and headache). It is progress, but I still have a long way to go.

I am also capable of learning a little bit of German every day. While my memory is still very poor, at least what I learn “stays” in my brain and the knowledge/understanding of the language accumulates slowly day by day. Intellectual activity no longer triggers the terrible, hours-long headache it once did.

Improved Sleep: Correcting the “Histamine Bucket”, Insomnia, and Heart Symptoms

Since becoming ill, I have had insomnia, likely due to my heart struggling to maintain a constant rate and rhythm. One of the very first things I heard that could explain my constant awakenings especially around 2-3am in the morning is the theory of the “histamine bucket”. This theory argues that around 2-3 am, there is some shift in our body’s physiology and histamine is released. Thus, if you already have a lot of histamines in your body, due to mast cell activation or low DAO, your histamine bucket is full and it will make you wake up. While this is plausible, I do not believe it is sufficient to cause these early morning awakenings. It is not a cause in and of itself, but one of the many things that get dysregulated downstream after nutritional deficiencies are ignored for a period of time.

My chronic early morning insomnia began in 2015, when my thiamine levels dropped and the aggravated mitochondrial disease began to unfold. I remember waking up and I would feel my heart beating more strongly (though not pounding), sometimes I would hear a pulsatile “whoosh” sound in my ear. I would also feel weird sensations in my chest, though not pressure. During those months, I would experience on and off dyspnea while walking to my office. I didn’t think anything of it because I approach my health in the exact opposite manner people with real hypochondria do. I just thought it was a subjective “feeling”, thus not worthy of an inquiry into a possible objective cause for it.

The experience I had in the last few weeks with the supplements mentioned above makes me doubt that mast cell activation or histamine “bucket” overflow are the main causes of waking up constantly at 2 or 3 a.m. I believe it’s most likely connected with the impact histamines have on the heart – they are a known factor in developing heart failure and using antihistamines does help in preventing/postponing the onset of heart failure. This also explains why of all medications, antihistamines were the only ones that helped with a lot of my symptoms in 2016/2017.

When I started taking magnesium taurate, potassium in high enough doses and propionyl-L-carnitine, my heart symptoms improved and my sleep improved. Recently, I woke up at 3 a.m. and I immediately took a low dose of magnesium taurate and a little bit of potassium citrate. I fell asleep again in 15 minutes and in the morning I felt ok. In the past, when I would take something like L-theanine. It would force my body to go back to sleep immediately after 2 a.m., but I would feel much worse in the morning, more than if I just had insomnia.

Restoring Normal Heart Rate

One of the most important things has been reducing my resting pulse from 75-80 BPM to my normal, prior to 2016 resting pulse which used to be 60-65 BPM. I remember I used to complain about it and doctors or nurses just brushed me off. They would say that if it is under 90 BPM, then it is not a medical symptom of anything. I knew they were wrong, but how could I argue? Somehow these people in white coats think that heart failure or other cardiac diseases start out of the blue, when in fact these diseases represent years and years of ignored symptoms before the onset of the full-blown disease with typical manifestations is recognized.

Lessons Learned

Everything that helps my heart function better and recover faster improves all of my symptoms, no matter how much they may seem unrelated. This is what I observed about my own body and I encourage everyone to listen to their body and understand that all symptoms are related.

If one version of one supplement does not work, try another form and combine it with different forms and dosages of other supplements. By supplement, I understand all substances that are naturally found in food or produced by the body.

When I saw that simple forms of L-carnitine don’t have an observable effect, I simply started searching for better forms of carnitine and found propionyl-L-carnitine, which is the physiologically active form of carnitine. Why I looked for other forms of carnitine? Because I learned from experience that high dose vitamin B1, as thiamine HCL didn’t help, but that high dose Allithiamine (a formulation with TTFD) helped and still helps my body working again as it should.

I found taurine (again) by searching for supplements that improve heart failure symptoms. When I first heard about it while reading one of Dr. Lonsdale’s comments, I didn’t understand why it was important.

No one should ever quit trying to figure out their own matrix of symptoms. Begin with the vitamins and minerals, while at the same time addressing infections, limiting damaging diets, limiting exposure to toxic substances and so on. I firmly believe that all diseases with chronic fatigue involve some degree of mitochondrial dysfunction – inherited or acquired. The prototype documented, unquestionable illness that causes hundreds of symptoms, i.e. a multi-systemic illness, is inherited mitochondrial disease.

I know personally of two other people who were completely bedridden, suffering from constant light intolerance, having to live in my bed for two years with a sleeping mask all day and all night, unresponsive to any treatment or approach promoted by the online integrative medicine doctors and communities. I did not think I would ever be able to become house bound, not able to tolerate light, to think or cook for myself. The ability to no longer be bedridden and forced to live in total isolation in darkness and to be house bound is nothing short of a miracle. I owe that to thiamine.

Usually people who end up in that state for so long never recover because all known alternative treatments are exhausted and high dose thiamine for chronic illness is virtually unheard of. I will make sure to do everything in my power to change this, no matter the costs, because there’s just too much unnecessary suffering out there.

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 created using Canva AI.

This article was published originally on December 9, 2021. 

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Ondine’s Curse: When Breathing Is No Longer Automatic

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ondine's curse

Ondine is a mythological figure whose tale goes back to the ancient Greeks. She is described as a water nymph who fell in love with a mortal male. He is said to have eventually jilted her, causing her to curse him. She abolished automatic controls in his body so that he had to remember them and control them consciously. This included automatic breathing. Eventually he became so tired that he fell asleep. Automatic breathing ceased and he died. The Ondine character has appeared and reappeared throughout history and must have represented a phenomenon that had been observed many times as a cause of an inexplicable sudden death at night.

Automatic Breathing, Apnea, SIDs, and Ondine’s Curse

The human brain is connected to the spinal cord by means of a part of the brain called the brainstem. It contains nerve centers that deal with the control of automatic breathing. These centers are connected, through the autonomic nervous system, to the muscles and organs that control breathing, explaining why breathing continues without our having to think about it. It is an automatic life-sustaining process. Of course, we can interrupt the automatic mechanisms voluntarily. We can hold the breath, cough and laugh, examples of an important relationship between the voluntary and automatic mechanisms of a complex nervous system. If a failure occurs in the centers in the brainstem that control mechanisms of automatic breathing, this action ceases. Of course, when we are asleep, our voluntary control of breathing stops and we rely on the brainstem centers to control automatic breathing. A genetic defect in the brainstem centers causes a rare disease that has been called “Ondine’s Curse”. The patient can breathe voluntarily but automatic breathing ceases intermittently during the night, sometimes causing awakening with a startle. Life expectancy is short and the affected individual may die suddenly during the night. Many people reading this will become aware that I am also describing sleep apnea, which is really a less severe example of the same thing. Sudden infant death syndrome (SIDS) has a similar history.

Thiamine Deficiency and Brainstem Function

It has long been known that the lower part of the brain that includes the brainstem is highly susceptible to metabolic breakdown from thiamine deficiency. This metabolism is governed by an array of genes, some of which are activated in response to hypoxia (lack of oxygen). Because thiamine is absolutely essential to the consumption of oxygen (oxidation), lack of this vitamin is sometimes referred to as pseudo-hypoxia (false lack of oxygen). Therefore, a genetic defect in the automatic breathing mechanism might be affected by either hypoxia or pseudo-hypoxia, strongly implicating that a damaging effect might arise from either one, the other, or both together in combination.

I have successfully treated sleep apnea and threatened SIDS with pharmacological doses of thiamine and magnesium. A genetic error may not be a self-sufficient cause, requiring the addition of thiamine deficiency to precipitate the disaster. Now that we have the science of epigenetics (the ability of nutrients to react with the gene defect), it is, in my view, mandatory for a physician facing a clinical problem of this type to use pharmacological doses of thiamine and magnesium empirically. Even if it does not work, it can do no harm and might just save the day. To my knowledge, there are no pharmaceutical approaches available and it is unlikely that there ever will be unless the technique of gene replacement becomes a reality. Thiamine treatment even then should be the first line of approach because it is totally unstressful, nontoxic, cheap and I have seen some dramatic responses in my practice.

A Patient with Ondine’s Curse

Many years ago I had the care of a 12 year old girl who suffered from this disease. She was the child of a first cousin marriage and had lost two brothers from sudden death at night, so it was clearly genetically determined. I cannot remember the details, except that she was forced to use mechanical breathing assistance. As would be expected, she subsequently died. One day when we were studying her case, I was walking through the pediatric ward and noticed that she was sitting on the side of her bed. Her hands were raised in front of her with the fingers widespread; her eyes were staring and she was cyanotic (blue skin color). This was the position of great anxiety or panic, representing a fight-or-flight reflex. When she received oxygen administration, the cyanosis disappeared and she relaxed.

The Fight-or-flight Reflex

In many posts on this website, we have indicated that we have two types of nervous system. One enables us to move at will. The other one, known as the autonomic, is automatic and almost totally involuntary. This system, controlled by the lower part of the brain, including the brainstem, enables us to adapt to environmental change and governs the mechanisms for a number of important life-saving reflexes, the fight-or-flight being the best known. It can initiate mental and physical activity when a person is placed in a position of danger. It is not clear how the decision is made for flight or fight and this may depend on other factors in the personality of the individual. For example, a soldier may race up a hill, capture a machine-gun post and not know that he had a finger shot off in the process. It can imbue a feat of strength that enables a mother to lift the front end of a small car off her child who has been run over. Oxygen lack, as being experienced by my patient, was obviously exceedingly dangerous to her and fired the reflex, demonstrated by the characteristic positioning of panic. I treated this patient with thiamine, without effect, but had no regrets because I tried and there was no other treatment known.

Brain Chemistry and Genetics

The lower part of the human brain works rather like a computer or an information processor. It receives messages from the outside environment and signals the body organs through the autonomic nervous system. It is in constant communication with the rest of the brain. One of its important tasks is the maintenance of appropriate breathing. In the brainstem there are a series of cellular collections that since the status of oxygen concentration in the blood, thus enabling an adjustment in breathing appropriate to the oxygen concentration of the surrounding air. These centers are also sensitive to the efficiency of oxidation, the consumption of oxygen in the synthesis of energy. The first cousin marriage strongly suggests that my patient and her siblings succumbed to the effects of a genetic error. Aside from a genetic cause, one of the well-known weaknesses within this system is that this part of the brain is highly sensitive to a deficiency of thiamine, illustrated by the following case.

Mountain Sickness and Brainstem Thiamine Deficiency

A 75 year old woman came to my attention with a curious story. Every two weeks she would indulge in square dancing. On returning home she would succumb to a feverish episode that would last for several days. These episodes had, of course, been treated as infections, with little or no thought given to the association with square dancing. Laboratory studies revealed that she was deficient in thiamine, but in addition she had an abnormally high red blood cell count and hemoglobin. This is known as hemoconcentration and it would be expected to occur as an adaptive response to living at high altitude. In other words, an increase in hemoglobin and red cells would compensate for the low concentration of oxygen at high altitude. I concluded that the febrile episodes were an imitation of a well-known phenomenon known as mountain fever. Her brainstem was behaving as though the ambient oxygen concentration was equivalent to that of high altitude. However, the hemoconcentration compensation was insufficient because she had pseudo-hypoxia from thiamine deficiency.

Mountain fever occurs in people that have difficulty when they ascend to altitude and are said to be unfit for mountain climbing. Here was a woman that was developing this phenomenon at sea level. My explanation was as follows: her brain was marginally deficient in the vitamin necessary for oxidation and energy production for ordinary everyday purposes. The square dancing represented an additional consumption of energy for which some chemical adjustment had been made in her own system. Because this was insufficient the febrile episode imitated mountain sickness. These episodes disappeared after she was treated with pharmacological doses of thiamine.

Variation in Symptomology

It is obviously important to point out that this patient did not have Ondine’s Curse, even though oxidation was compromised in brainstem. Neither did my patient with Ondine’s Curse have mountain sickness. It represents an enormous difficulty in defining a clinical situation where two conditions are represented in different ways, although the underlying mechanism is similar if not identical. If this is the truth about disease, the symptoms that develop really represent an alarm system that has to be interpreted in terms of the underlying biochemical cause. Perhaps the focus on genetic causes may be too narrow and this seems to be true in cancer research. There is insufficient attention to epigenetic influence of nutrients on the action of genes and more attention should be paid to the nature of energy production in the mitochondria. Although both patients in this post had a widely different presentation, the underlying mechanism was similar if not identical.

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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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Image credit: Arthur Rackham, Public domain, via Wikimedia Commons.

This article was published originally on June 25, 2018.

Rest in peace Derrick Lonsdale, May 2024.

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Paradoxical Reactions With TTFD: The Glutathione Connection

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TTFD and Low Glutathione

Some individuals experience negative reactions and the worsening of symptoms when they begin thiamine repletion therapies using the more biologically available formulations like thiamine tetrahydrofurfuryl disulfide (TTFD). Dr. Lonsdale calls these paradoxical reactions. In this article, I examine the chemistry beyond these reactions and provide some hypotheses regarding why they happen and how to mitigate them.

TTFD Basics

In order to understand why some individuals react negatively to TTFD supplementation, it is essential to understand the basics behind TTFDs molecular configuration and how it is processed by cells. The primary difference between ordinary thiamine and TTFD is an extra chemical group called a mercaptan group. The mercaptan is derived from allicin, a compound found in garlic, and is connected to the thiamine molecule via a special sulfur-sulfur bond called a disulfide bond. Importantly, it is this unique chemical group that accounts for TTFD’s ability to traverse membranes in the body without the need for a transport system.

Upon ingestion, TTFD is mostly absorbed into the blood from the gastrointestinal tract in whole form as TTFD. As it travels through the blood, it can penetrate the brain and other organs without cellular transporters. One of the main sites of absorption is the red blood cells. Upon penetration of the red blood cell membrane, TTFD must first be processed or “broken apart” before it can release the thiamine contained within its chemical structure. After thiamine is released into the cell, the ancillary mercaptan group must also be processed and/or detoxified through alternative pathways. It is therefore theoretically plausible that errors involved in the processing of TTFD could contribute toward negative side effects or reactions to this nutrient.

How TTFD Is Processed Inside the Cell: The Glutathione Connection

For TTFD to “release” its thiamine, its disulfide bond must gain electrons from another donor molecule. In chemical terms, this process is referred to as reduction. Once this reduction occurs, thiamine is freed and can then go on to participate in cellular biochemical reactions.

Of the few molecules which have been shown to reduce TTFD, glutathione performs this function most effectively. As the cell’s primary antioxidant, glutathione is responsible for donating electrons to neutralize reactive oxygen species, and can either be found in its reduced form or its oxidized form. Once a reduced glutathione molecule (GSH) has donated its electron, it bridges with another to molecule to form oxidized glutathione (GSSG). GSSG is then recycled back to two GSH molecules through accepting electrons from NADPH via the enzyme glutathione reductase (vitamin B2 as FAD dependent). TTFD and Glutathione

When TTFD enters cells, GSH in red blood cells chemically reduces TTFD via a process called “disulfide exchange” (presumably using a protein called glutaredoxin). Reduced glutathione becomes oxidized glutathione and TTFD “releases” thiamine to producing free thiamine inside the cell with an extra TFD mercaptan group left over.

The initial phase of processing TTFD requires that cells have enough reduced glutathione. Furthermore, the more GSH you have – the faster the rate of this reaction. So in simple terms, to obtain thiamine from TTFD the cells “use up” their reduced glutathione.

I recently had correspondence with one individual who only gained tolerance of TTFD after supplementing with 200mcg of selenium in the form of sodium selenite. Selenium supplementation in different forms has been shown to increase red blood cell GSH levels by up to 35%. This is thought to occur due to selenium’s ability increase glutathione synthesis through upregulating the enzyme gamma-glutamylcysteine synthetase. I suspect that poor glutathione status might be one of the reasons for benefit from selenium.

Having enough glutathione is clearly very important, but recycling it is also essential to maintain a pool of glutathione in its reduced form. Unfortunately TTFD can place a burden on this system, and this was demonstrated in one old study from Japan which showed that TTFD administration rapidly lowered red blood cell GSH. Interestingly enough, that same experiment showed that GSH levels were restored within 5-10 minutes. This restoration was accomplished by the vitamin B2 (as FAD)-dependent enzyme glutathione reductase, which donates electrons to GSSG with the reducing power of NADPH to recycle it back to two GSH.

What this basically means is that cells require a robust antioxidant system to properly process TTFD and return back to their original state. First, cells need enough of the antioxidant GSH to cleave thiamine. Second, cells also need to be able to recycle the oxidized glutathione back to its reduced state.

Poor Glutathione Status and Difficulty With TTFD

Immediately, we see two potential issues that could arise from TTFD supplementation which might provide a better understanding of why some people may not tolerate this molecule.

In someone who has poor glutathione (GSH) status, they might theoretically be less able to cleave thiamine from TTFD. There are many reasons why someone may have poor glutathione status:

  • Low precursors (cysteine, glutamate, glycine)
  • Chronic oxidative burden and/or inflammation
  • Deficiencies in the nutrients required to generate, process, or utilize glutathione (B6 or selenium)
Alternatively, an individual may have enough resources to make glutathione, but if they cannot recycle it through the necessary machinery (i.e glutathione reductase), then taking a substance which depletes their GSH (like TTFD) might further contribute towards their oxidative burden.

A total and/or functional riboflavin deficiency is the probably the most common culprit responsible for poor glutathione reductase activity. The glutathione reductase enzyme also requires adequate reducing power from NADPH to drive the enzymatic reaction. NADPH is derived from niacin (vitamin B3) and is generated in the pentose phosphate pathway which, ironically, requires the thiamine-dependent enzyme transketolase.

In the context of poor enzyme activity, without the reducing powder to drive GSSG back to GSH, the oxidized form of glutathione can theoretically drift towards the path of generating a free radical called the glutathione radical. This alone could further contributes to oxidative stress and cell damage.

Below is a hypothetical scenario to demonstrate my point:

  1. An individual suffers from long-term thiamine deficiency and has suboptimal riboflavin status
  2. Thiamine deficiency leads to lower activity of transketolase
  3. Low transketolase activity produces a lack of NADPH
  4. A lack of NADPH and a lack of FAD means that glutathione reductase is unable to efficiently recycle glutathione, which produces an imbalance between reduced/oxidized glutathione.
  5. Intracellular GSH is further lowered by taking high dose TTFD, and there is not enough enzyme activity to recycle it back
  6. Oxidative stress is made worse

In the above scenario, taking a high dose of TTFD may not be appropriate. Rather, restoring NADPH levels through supplementing with ordinary thiamine and supporting the glutathione system via other measures might be advised before starting with TTFD. Optimal riboflavin status is also necessary for the above processes to run smoothly.

Older research in Japan showed that TTFD supplementation could lead to a secondary B2 deficiency through increased urinary excretion. The increased need for glutathione reductase could at least also contribute to this effect. When taking TTFD, it has downstream effects on other nutrients. Hence, these supporting nutrients should also be taken in conjunction when someone is supplementing TTFD in high doses.

Some basic laboratory measurements of glutathione status include:

  • Whole blood glutathione (low)
  • Gamma-glutamyl-transpeptidase (high)
  • Urinary pyroglutamic acid (high)

Furthermore, there are several functional markers which can be measured to assess riboflavin status, including direct measurement of red blood cell glutathione reductase activity:

  • Urinary glutaric acid (high)
  • Whole blood B2
  • Urinary adipic, suberic, ethylmalonic acids (high)
  • Urinary succinic acid (high) can also be suggestive along with a few other organic acids
  • Erythrocyte glutathione reductase activity (low)

To summarize, the initial cellular processing of TTFD requires adequate levels of reduced glutathione. Glutathione becomes oxidized, and so TTFD has can have a depleting effect on GSH and increase the requirement for recycling. If there is insufficient active B2 (as FAD) or NADPH levels, glutathione is not likely to be recycled sufficiently and may lead to GSSG radical formation.

It is therefore possible that the glutathione-depleting effect of TTFD could be responsible for some of the side effects associated with supplementation. This is probably most applicable in individuals with poor glutathione recycling and underlying oxidative stress. Therefore, nutrient therapies that may support this initial phase of TTFD metabolism include:

  • Selenium (improve GSH levels)
  • Riboflavin (improve GSSG-GSH recycling)
  • Niacin (increase NADPH)
  • Ordinary thiamine (increase NAPH via PPP)
  • NAC, glycine and/or glutathione TAKEN HOURS AWAY from TTFD (GSH precursors)

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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.

Yes, I would like to support Hormones Matter.   

Image by Layers from Pixabay.
This article was published originally on October 26, 2020. 

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Recurrent Fever With Swollen Glands: Febrile Lymphadenopathy and Thiamine

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fever swollen glands - Febrile Lymphadenopathy.

Every profession has its jargon and the medical profession is no exception. Perhaps it is even more addicted to jargon than other professions. The title used here refers to an extremely common disease, particularly in children. Febrile is the word used to describe fever. Lymphadenopathy simply means that lymph glands are swollen. The mechanism is as follows: the throat becomes infected, often with streptococcus and may affect the tonsils or adenoids. A message is sent from the throat to the brain that reacts to cause the body temperature to be raised. We will see why later. The lymph glands in the neck are stimulated to get bigger as part of the immune response. The child feels sick and accepts bed rest and these essentially defensive reactions are referred to as the “illness”. Often a treatment such as aspirin is given to the child to bring the temperature down under the mistaken concept that this is the dangerous part of the illness. A previous post on this website described a case of Reye’s syndrome, a deadly disease known to occur as a result of giving aspirin to bring the fever down. It is of course true that a very high temperature such as 106°F is considered to be dangerous. But this is because the brain mechanism that initiates this temperature is itself in an abnormal state and may be the actual source of the danger.

Understanding Fever as an Immune Response

If we look at this situation in the cold light of day, we can come to false conclusions. Yes, this is the expected situation with an infected throat and it is invariably treated with antibiotics. But let us see what is really happening in all cases of this common affliction. The brain has received a message from the throat that an attack by a microorganism is occurring. The brain sets up a defense mechanism and I refer to the microorganism as a “stressor” (the enemy). The brain is programmed to recognize the attack as dangerous to the organism. The physical aspects of the infection and the brain mechanisms that receive the message and activate the defense are in constant communication. The body temperature is raised by the brain as part of this defense.

Microorganisms, the stressors, are programmed by Mother Nature to operate at maximum efficiency at 37°C, the normal temperature of the human body. By raising the body temperature, the environment for the microorganisms is detrimental to its action and decreases its virulence. No rise in body temperature indicates that the brain is sick!

Inflammation Is an Immune Response: Resting Boosts Immune Function

The inflammation of the throat makes it harder for the microorganism to gain entrance and is also part of the defense. Strangely enough, we now know that inflammation is controlled and governed by the brain. A message to the lymph glands in the neck increases their size to cope with the expected passage and trapping of bacteria from the infected area and is part of the immune response.

The bed rest or fatigue that occurs with illness is yet another part of the immune mechanism. Bed rest conserves the cellular energy needed to activate the defense mechanisms.

You can readily see that all of these reactions that we call sickness are scripted and controlled completely by the brain. It may come as a surprise to many readers, but fever, inflammation and energy conservations are necessary immune reactions. Diminishing or overriding those reactions, usually by trying to reduce fever with a drug or failing to rest rather than assisting the body’s defense systems, may only prolong the illness and perhaps even create new ones.

The modern method of treatment is, of course, to kill the organism. Little thought is given to whether the supply of energy in the brain is sufficient to run the complex organization of defense. It also assumes that the genes that oversee the immune response are intact and functionally healthy.

Nutrient Interactions With Immune Response

Now I must tell you about two children, both of whom had suffered from repeated episodes of febrile lymphadenopathy (Lonsdale D. Recurrent febrile lymphadenopathy treated with large doses of vitamin B1: report of two cases). Each child had been treated by antibiotic therapy with their recurrent episodes over a two or three-year period on the assumption that they were caused by bacterial infection. Both were medical puzzles because evidence of bacterial infection was lacking and it was assumed that the recurrent episodes were viral in nature. I had the opportunity to study one of them in detail.

The child had been admitted to a prestigious hospital and a swollen gland in the neck had been biopsied under the impression that it might explain the disease. The pathologist had reported an enlarged but otherwise perfectly normal gland structure. The mother told me that at this hospital he had also had the concentrations of vitamin B12 and folic acid measured in the blood, presumably because they were looking for evidence of deficiency. She volunteered that “the doctors told me that I was giving him too many vitamins”, apparently because the two vitamins had been found to be in an unusually high concentration. She also volunteered that this was very strange to her “because I had not been giving him any vitamins at all. The doctors didn’t believe me”. This naturally intrigued me.

Without going into the technical details, I found that he had evidence of abnormal thiamine metabolism. The folic acid and B12 concentrations were indeed extremely high. When I gave him the big daily doses of thiamine, these two vitamins each fell into its range of normal blood concentration. I discharged him from the hospital where these studies had been carried out, continuing the high dose treatment with thiamine. Two or three months later, the mother called me to say that her child had not had any episodes of fever and was extremely well. I responded to her by asking if she was interested in stopping the thiamine in the interests of science. She did stop it and three weeks later he had an episode of sleep walking, spontaneous urination as he went down the stairs and another episode of febrile lymphadenopathy.

You may well ask how the sleep disturbance could possibly be associated with the throat problem, so continue reading. I readmitted him to the hospital and clinical examination revealed the sore throat and a very large lymph gland in the neck. The folic acid and B12 concentrations were once more elevated. I restarted the thiamine and the two vitamin concentrations again fell into the normal range. The enlarged lymph gland disappeared and I discharged him from the hospital with instructions to continue the high dose thiamine. About a year later she reported that the episodes had begun again. I told her to add a multivitamin to the thiamine and again the episodes ceased. The other child also had evidence of abnormal thiamine metabolism that was resolved by the administration of large doses of thiamine, but unfortunately, I was not able to study him further. Please note that both children had been indulged with ad lib candy and soft drinks.

Nutrient Deficiency in the Face of High Sugar Intake: Altered Immune Responses

The explanation is construed from a rational approach to the genius of Mother Nature. I have already described the normal mechanism of defense to infection organized by the brain. Think of the body as being like an old-fashioned fortress. When an approaching enemy is spotted by soldiers on the Eastern battlements, a message is sent to the commander. The commander is then able to plan the defense and off duty soldiers are deployed to the scene of impending attack.  Imagine that the commander is drunk and he sends the reserve soldiers to the Western battlements. Or perhaps the commander imagines falsely that he has received a message and deploys his defensive soldiers throughout the fortress unnecessarily, a “May Day” without reason. Obviously the commander would be to blame.

This is an analogy for the brain/body response to infection. Messages throughout the body are automatically relayed through the autonomic (automatic) nervous system and by the hormones released from the endocrine glands. Hormones, carried in the blood stream, are messengers. White blood cells are “the defending soldiers”. Both the autonomic and endocrine systems are under the control of the more primitive lower part of the brain, the commander in the analogy and the part of the brain that is known to be peculiarly sensitive to thiamine deficiency. There is good scientific evidence that thiamine deficiency will make the “commander” much more sensitive to incoming signals from the “battlements”.  Like the “drunk commander”, it organizes a complete defensive reaction without there being any need.

To be a little more scientific, thiamine deficiency causes reactions in the lower brain that are exactly like a mild to moderate deprivation of oxygen. That is why thiamine deficiency is reported scientifically to cause pseudo-hypoxia (pseudo, false: hypoxia, deficiency of oxygen). These children had been indulged with ad lib. candy and soft drinks. Even if they had had the average intake of thiamine from the diet, essential to the processing of sugar, it was insufficient to metabolize the sugar. You might say that this was an increased sugar/thiamine ratio, equivalent to dietary thiamine deficiency with a normal healthy diet.

Microorganisms Attack: The Immune Response Defends

Each case of the usual form of febrile lymphadenopathy can be visualized as a hostile attack by a microorganism (a stressor) requiring a defense response. However, in the case of these two  children, when the brain ”commander” was exposed to thiamine deficiency  (pseudo-hypoxia), itself imposing  brain stress, it  became hypersensitive to virtually any form  of incoming signal from the environment. It is therefore possible that a change such as ambient temperature was being perceived falsely as a dangerous threat to the organism (the patient). Hence, it is hypothesized that any proposed minor form of stress initiated the defensive response, mediated and organized by the lower brain that is programmed to perceive danger. It is possible that a virus in each case may or may not have been responsible for being the “stressor” but it is more likely that the “commander” was initiating an unnecessary defense based on a false perception of a non-existent attack such as ambient temperature change.

I have to turn to analogy once more.  A car has an engine. Its essential function is to produce energy. The energy has to be transmitted to the wheels through individual mechanical parts that are connected together to form an energy consuming transmission. In the human body each cell has its own engines and they are called mitochondria. Their function is also to produce energy that has to be converted into mental and physical action. Thiamine is essential to energy production from the mitochondria and a series of enzymes are the equivalent of the mechanical parts of the transmission in a car and therefore can be thought of as an energy consuming biochemical device. Therefore, mitochondria produce energy; the transmission consumes it in mental and physical action. Folate (folic acid) and vitamin B12 are essential to this biochemical transmission. Because thiamine deficiency depletes cellular energy, the enzyme dependent (energy hungry) transmission developed problems. Folate and B12 accumulated in the blood simply because they were not being used. When thiamine was given to this boy, cellular energy improved and the two vitamins were consumed in their actions and their concentrations decreased in the blood.

Sleepwalking: An Example of Brain Dysfunction?

Sleepwalking has always been a puzzle. A sleepwalker is not consciously aware of what he or she is doing. I remember the case of a man who drove his car for 70 miles and had no recollection of doing it. I had found from my clinical experience that sleepwalking children would stop doing this with the administration of nutrients, particularly thiamine and magnesium. The fact that the subject of this discussion urinated as he descended the stairs indicated abnormal automatic autonomic nervous system activity. This was pretty good evidence that it was oxidative deficiency in the brain that was responsible for both physical and mental abnormal activity after therapeutic thiamine had been withdrawn.

The Use of a Multivitamin: Completing the Nutrient Team

As the story above indicated, the episodes of febrile lymphadenopathy began to return about one year after he had been discharged with instructions to take only thiamine. There is a particular relationship between thiamine and magnesium because both of them are cofactors together for the same enzymes. However, vitamins and minerals are non caloric nutrients that work as a complex team. There might still be nutrients in naturally occurring food that await discovery. Mother Nature knows how they all should be balanced. The further we move from our biologic origins by the introduction of artificial foods in our hedonistic pursuit of pleasure, the more illness can be expected. Our present medical model is concerned only with killing the attacking agent. Rather simple clinical research revealed an anomaly of this nature in the organization of defense, without knowing how common it is. It should surely focus our attention on the role of nutrition in providing the raw materials for this organization. An infection gives rise to a battle. There are only three possible outcomes: the enemy wins: the defense wins: there is stalemate. The stalemate possibility suggests that chronic long term infection can be tackled by the use of energy producing nutrients that improve the efficiency of a defensive program.

Unfortunately, there are problems with what appears to be a simple solution. Even natural food does not have the nutrient density that it used to have because of changes in farming practices. Also, whether we like it or not, evolution is going on all the time and in the modern world, the smartest brains have the greatest evolutional advantage. Those interested in following the numerous posts on this website will note that post Gardasil thiamine deficiency appears to affect the brightest and the best. I have suggested that relatively poor nutrition, coupled with a smart brain, creates a greater risk of succumbing to a risk from vaccination, mild infection or trauma.

I have seen several articles that state the uselessness of dietary supplements, claiming that the numerous vendors are cheating the public. My own library research reveals numerous papers on the subject of supplementary nutrients coming from many parts of the world other than America. Although they are not cheap, the expense is very much less than the drugs issued by pharmaceutical companies and their curative or preventive properties are huge. Humanitarian research in this area of relative ignorance is a modern necessity.

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 Kelly Sikkema on Unsplash.

This article was published originally on April 19, 2016.

Rest in peace Derrick Lonsdale, May 2024.

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