COVID

The Lyme Spiral

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The Lyme Spiral

Two of the most commonly asked questions I face as someone with Lyme disease is “when were you bitten by a tick?” and “when did you get Lyme?” To be honest, while I have my suspicions, I really have no idea. Many people are surprised to hear that the majority of people with Lyme disease never recall being bitten by a tick. The bullseye type rash that people assume is the hallmark of Lyme symptoms also doesn’t occur in many of us with Lyme, hence why we have no idea when we first contracted the disease.

Early History

I was an active child and a competitive swimmer. By high school, I was swimming at the state and national level. I was in great shape with great health, or so I thought, and had no obvious reason to be experiencing any medical abnormalities. However, over my freshman year in high school, I started experiencing widespread joint pain. Because I was in such good health and swimming and training up to four hours per day, it came as a surprise to my parents, coaches, and doctors when I was experiencing such pain. During this time, I did get tested for Lyme by my pediatrician. While he was fine testing for rheumatoid arthritis and lupus, we had to beg him to test for a Lyme test, even though it was common in our area. It was years later when we learned that traditional doctors typically do not test for or treat Lyme disease.

My test showed that I had one positive band of Lyme. He said that this was not enough for a diagnosis, and I was sent home without any answers. My sophomore year of high school, the joint pain continued and even began to get a bit worse. I went to a rheumatologist at the Children’s Hospital of Philadelphia and was diagnosed with Amplified Musculoskeletal Pain Syndrome, also known as AMPS. Their main treatment plan was exercise, which, with swimming, I was already doing. There wasn’t much else that could be done, but by junior year it seemed like I had grown out of AMPS. Whether it was really AMPS or had it been Lyme disease all along, I have no idea.

College Dorm Flu Masked My Infections – Until My Vocal Cords Went Haywire

My freshman year of college living in a dorm I was sick constantly. I missed several of my college swim meets from contracting the adenovirus, developing severe swimmer’s ear, and coming down with strep throat and bronchitis. Another strange thing I began to notice was that I was having low grade fevers nearly every day. I got tested for the mono virus, as many college students are, at one point or another, but the test came back negative. With the constant infections, along with many headaches and slight fatigue, a blood test showed that I had an underlying Epstein Barr virus from prior contraction. I do think they missed mono, and I can’t help but wonder if Lyme played a role.

During my sophomore year of college, I began the swimming season feeling strong until I developed a nasty virus along with a bad cough within the first few weeks of the semester. Luckily, the virus died down, however the cough never went away. The cough became worse as I swam and I was led to assume I had developed sports-induced asthma. I just couldn’t get in a good full breath. During fall break, I went to an allergy and asthma specialist. When I told her I couldn’t fully breathe in, she pointed out that with asthma, you typically have trouble breathing out. She performed a rhinoscopy, where they stick a camera in your nose down into your throat, and examined my vocal cords on a very fuzzy screen before diagnosing me with vocal cord dysfunction. This was a difficult diagnosis because it was hard to explain to friends and family. It is not commonly known, and somewhat misunderstood. People genuinely had no idea that when I was breathing in, my vocal cords were spasming closed. The only thing I could link this to was the virus I had a month prior.

It took months of my vocal cord dysfunction being taken lightly or just blatantly disbelieved until I went to an otolaryngology specialist in New York City. The specialist performed a rhinoscopy as well, but recorded everything on a crystal clear screen. He was able to visibly show my parents that my vocal cords were, in fact, spasming closed when I breathed in. My parents have since admitted they didn’t fully believe me until that appointment. The recommended treatment was Botox. This meant that I had to go into the city every few months to get Botox injected into my vocal cords. Eventually, the doctor recommended surgery because folds of tissue were leaning into my airway over my vocal cords, a condition known as laryngomalacia, making my vocal cord dysfunction worse. I got surgery and continued with my Botox appointments and my vocal cord dysfunction finally calmed down a bit. Again, here I had suspicions that this was related to Lyme disease as well. My first Lyme specialist commented that vocal cord dysfunction could have been a result of the disease. After hearing Shania Twain’s story about how Lyme disease affected her vocal cords, my suspicions were stronger, but, again, I will never know for sure.

Looking For a Zebra: Fatigue, Tachycardia, and Hypertension

I took a year off of school for a few different reasons, some of them being medical. I was still experiencing low grade fevers constantly, fatigue, tachycardia, and hypertension. I was still very active, going to OrangeTheory Fitness classes a few times a week, along with lifting weights and swimming. Currently, I can barely walk my dog and my exercise consists of physical therapy. A few times, I went to OrangeTheory Fitness with my mom, and when I looked up at my name on the screen, I saw the number 212, which I thought was my score (I thought I was winning), but my mom realized it was actually my heart rate. At another point during this year, my blood pressure was in the 200s over the 200s. I went to an endocrinologist for my fevers, fatigue, and the general feeling that something was very off. She told me I was on so many psychiatric medications that they were making me “sound slow,” and that I just had fever of unknown origin. She also said that she was going to visit her family in India and could bring me back herbal supplements for the fever of unknown origin.

That being said, I did have severe anxiety at the time and was dealing with post-traumatic stress disorder. I had no idea what this meant at the time, but my psychiatrist told me to go to my primary care doctor and tell him “we’re looking for a zebra,” and even a pheochromocytoma. I saw several doctors that year, each who ordered different types of blood work. One doctor was so unsure what was happening that she ordered twenty two vials of blood. Yet, I was still left without any answers.

And Then Came Covid

After my mental health and anxiety had not improved with medication and therapy, my mom felt there still had to be an underlying issue. This is when she found and took me to a Lyme specialist in the fall of 2019, who immediately diagnosed me with Lyme disease and bartonella, and later, mast cell activation syndrome (MCAS). Physically, my symptoms were manageable. However, I contracted the first strain of COVID-19 in May of 2020, and my life has never been the same. Within the next few months, I started experiencing joint pain, severe migraines, vertigo, severe fatigue, and continued mental health issues. I even had to drop all of my classes in the fall semester of 2020 because I missed nearly two weeks of school from having a fourteen day long migraine. I began developing neurological and cognitive issues, such as trouble focusing and thinking and I had with memory. I switched to a different Lyme specialist, and this time I even tested CDC positive, which is more uncommon than not in those with Lyme. I started yet again another regimen of antibiotics and herbs. I spent most of that year couch ridden, sleeping much of the day, and constantly in hot Epsom salt baths to ease the joint and muscle pain. It felt like my mind and body were completely outside of my control, almost like my autonomy was taken from me. I was on several combinations of antibiotics until I eventually switched doctors again. This new physician was recommended by my Lyme literate dietitian, and was extremely knowledgeable of complex cases. I still see her to this day.

The next year I went back to school part time, only taking two classes each semester. Before the fall semester, I was diagnosed with babesia, and a few months into the semester I was diagnosed with hypothyroidism. These diagnoses often come together in the case of Lyme disease, but a new diagnosis is always a lot to take in. In class, I would forget what I was saying mid-sentence, which made me self-conscious and hesitant to participate. I struggled to balance the fatigue, physical pain, and brain fog with school. Yet, I successfully completed those two semesters.

Medication-Induced Pancreatitis

Finally, my senior year began: Fall of 2022. I was still attending part-time, but was now taking three classes as well as a lab each semester. In late September, early October I started having these acute episodes of severe pain in my upper abdomen that spread to my back. Because I have been medically gaslit so many times and I also have a high pain tolerance, I was nervous to go to the doctor. These episodes felt like I should have been in the emergency room, but because they only lasted an hour I was afraid to go to the hospital in fear that they would brush me off as a young female having stomach aches. I dealt with the pain for almost four weeks before I finally went to a doctor.

As it turns out, I had pancreatitis. I had to go on a mostly liquid diet for two weeks, stop taking my antibiotics and other supplements for Lyme, as doctors believed it was drug induced, with the culprit suspected to be rifampin, or the combination of too many other medications and supplements. I had been on various psych meds for years. Initially they were prescribed for severe anxiety and panic attacks and when I began to get sick, it only worsened. Among the medications I have been prescribed and used are several SSRIs/SNRIs (Prozac, Zoloft, Lexapro, Luvox, and Effexor). I have used sleeping medications such as Prazosin, Seroquel, and trazodone, as well as a tricyclic antidepressant, some benzodiazepines, Wellbutrin, Buspar, hydroxyzine, and different ADHD medications (Concerta, Ritalin, Vyvanse, Adderall, Straterra).

While pancreatitis mostly resolved, my Lyme started to continue to progress. I was having many more neurological and cognitive symptoms, my whole body was tremoring nearly every day, and I knew that we had to take action before the Lyme and coinfections progressed any further. I went back on antibiotics at the beginning of the spring semester, but had many Herxheimer reactions. I was out of it and sweating with fevers in class, all while also managing an internship. Within a few months my tremors became much better, indicating that the antibiotics were working. It was a long and stressful year, but I graduated Magna Cum Laude after having periods of extreme sickness where I questioned whether I would ever graduate.

Right now I’m on Anafranil, Buspar, Trazodone, Hydroxyzine, and Valium. As for Lyme and coinfections, I’m on clarithromycin, Tinidaloze, Valtrex, Mepron, methylene blue, (recently started), low dose Naltrexone, liposomal oil of cinnamon clove and oregano, cryptolepis, Researched Nutritionals MycP, phosphatidylcholine, vit D and C, omegas, ATP360 and CoQ10 for mitochondrial dysfunction (my doctor has suspected mitochondrial death/dysfunction after having COVID the first time, followed by long covid). I’m on a whole bunch of other supplements too to support my immune system, help with mast cell activation/histamines, digestion, brain function, etc. I’m taking between 50-70 pills per day with a few liquids mixed in there. I’m also on thyroid Armour for hypothyroidism as well as migraine medications and Zofran.

Chronic Illness Limbo: Neither Disabled Nor Able Bodied

Something that healthy people may not think about is having to choose your battles in terms of symptoms and treatments. For example, I started methylene blue shortly after graduation. Methylene blue, which is a medical dye, is a relatively newer, yet promising treatment for Lyme disease, but it is a monoamine oxidase inhibitor (MAOI). This means it can interact with psychiatric medications, and, therefore, I had to go off of all of my ADHD medications. The combination of an MAOI and a serotonergic ADHD medication can lead to both serotonin syndrome and a hypertensive crisis. The idea is that over time and with building up the dosage of the methylene blue it will minimize brain fog, a huge Lyme symptom, and help to treat ADHD symptoms. However, it takes quite a while to build up to an adequate dosage of methylene blue, and it also takes some time for it to actually show effects and improvements. Methylene blue treatment has been a bit brutal here and there with Herxheimer reactions.

One of the most daunting and frustrating things about Lyme disease, especially when it becomes chronic, is that there is rarely a trajectory or expected timeline to start feeling better or to reach remission. I’m currently still trying to find my way to remission, but cannot say I am close. Lyme Disease has turned my life upside down. At this point in my life, I thought I would be living up my twenties with either having already started graduate school or a big girl job. Something that people with Lyme disease, and those with other chronic illnesses as well, deal with on a regular basis is not being able to keep up with productivity culture leading to feelings of failure, laziness, or character flaws. Chronic illness is isolating, and, for many, it may feel like there is no place in society for us when we’re neither fully able bodied nor fully disabled. Instead of living up my twenties, I spend most days with my parents and my dog, I rarely drink alcohol or go out with friends, as it is difficult to maintain friendships when chronically ill. I am still trying to find a place to fit into society post bachelor’s degree, without a master’s or doctoral degree. I feel resentful of all of the doctors who misdiagnosed me or gaslit me, letting me go longer and longer undiagnosed, and therefore, untreated, allowing the Lyme to progress. However, I have found friends in the chronic illness community that, even though we have a variety of illnesses and different symptoms, understand the common struggles of chronic illness.

If you suspect you have Lyme, the best thing you can do is go to a Lyme literate doctor in your area, whose names and locations are usually spread through word of mouth due to the politicization of Lyme Disease, which can lead to possible repercussions for doctors who treat Lyme without CDC positive tests, which, like I said earlier, are inaccurate and are not often used as a basis for diagnosis.

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Poor Diet, COVID, and Thiamine Deficiency: A Perfect Storm

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poor diet, covid, thiamine deficiency

A bit of information about me:  I am 24 year old man. I have always been fit, always exercised at least 5 times a week, and have had physical jobs. I never really cared about what I ate and my diet consisted of a load of protein (mainly protein shakes and chicken) with massively high carb/sugar consumption. I went out drinking with friends on most weekends. About two years ago, I had COVID and since then my health seemed to decline massively. I did not see a doctor initially, because I was not aware of how bad my health would become.

About a year after having COVID, my anxiety levels were through the roof. It was so bad, I couldn’t even leave the house without worrying something was going to happen. The symptoms I developed included: a change in personality, hand a feet neuropathy, shocking circulation to hands and feet, severe bowl issues, really low body temperature, extreme fatigue to the point where I was unable to get off the sofa after work most days, memory problems and an inability to think.

A year into this, I realized that I had to do something about my health. I was literally at breaking point. I did not know what was going on with my body or mind. At first, I thought I was diabetic because I matched so many symptoms but blood test showed normal sugar levels. I went back to the doctors numerous times. They basically told me that I was mad. They told my family all my symptoms and that I was really struggling, but no one believed that I was ill. They said it was all in my head and led me to believe that I was actually going mad.

Heart Problems, Breathlessness, and Thiamine Deficiency

Then the heart problems started. I have always played football, since I was 10 years old, and I have always been extremely fit, but I began having trouble breathing when playing. It gradually got worse and I became unable to walk the stairs without becoming breathless. As the breathing problems worsened, I had to stop all exercise. The exertion seemed to make me worse.

At this point, I was positive my symptoms were not imagined and so I did endless research online and found a video by Dr. Berg about thiamine/vitamin B1. I ordered some Benfotiamine and it definitely seemed to help. The anxiety vanished almost instantly and most of my symptoms went away except neurological ones. So I took about 4 tablets, 250mg each, per day for about 9 months. After this time, I felt I was not progressing any further. I thought I would never get circulation back in my hands and feet. My brain was still confused all the time and my breathing became slightly better but it was still nowhere near where I wanted to be.

I returned to internet for research and found Elliot Overton’s YouTube channel and ordered some TTFD, b-complex, magnesium, potassium. Thiamega, the product from Objective Nutrients, has 100mg thiamine HCL, 200mg Benfotiamine, 50mg Sulbutiamine and 50mg TTFD. At first, the paradox reaction, getting worse before getting better, was absolutely shocking. I remember being on the sofa each weekend and just sleeping most of the day. The brain fog was the worst it had been for months but after maybe a month that seemed to clear up and my brain problems seemed to have massively improved.

I forgot to mention earlier that prior to beginning supplementation with Benfotiamine and then TTFD, I had a private MRI scan on my brain. It showed high T2W right signal – a sign of lesions and demyelination and confirmation that I had thiamine deficiency. So, I went for another MRI with contrast recently to see if I have improved any. I am still waiting for the results on that one.

Improved But Still Missing Something

I am at the point now, where I feel I am back to normal health with most of my symptoms improved. All that remains to be resolved are the circulation and breathing problems. The rest do seem nearly resolved.

I have recently tried the carnivore/keto diet, but I usually get to day 3 or 4 and have to stop because it seems to make my symptoms worse especially the breathing and circulation. My current diet is mostly whole foods, with high protein, high fat and lower carbs. I try and eat a lot of red meat and that seems to help.

I was wondering if there was anything I can do to repair this issue, or is it for life now? Sugar and alcohol definitely seem to make me worse, but then so does keto and so I am unsure what to do. Maybe if I manage to push past the first week on keto I would feel better and my nerves would start to repair? All I know is that I must have had a serious case of beriberi disease, which has caused all this damage to my body. Obviously, I know it is my fault for not taking care of my diet, but I also feel the doctors are partly to blame as they seem to know absolutely nothing about thiamine deficiency. All they want to hear about is anxiety and depression. Any help at all would be massively appreciated. Thanks.

Photo by Paul Zoetemeijer on Unsplash.

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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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It All Comes Down to Energy

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It all comes down to energy

The Threat Around Us

Animals, including Homo Sapiens, survive in an essentially toxic environment, surrounded by microorganisms, potential poisons, the risk of trauma, and adverse weather conditions. Evolutionary development has equipped us with complex machinery that provides defensive mechanisms when any one of these factors has to be faced. Before the discovery of microorganisms, medical treatment had no rhyme or reason, but killing the microorganisms became the methodology. The research concentrated on ways and means of “killing the enemy”, the bacteria, the virus, the cancer cell. The discovery of penicillin reinforced this approach. We are now facing a period of potential impotence because of bacterial resistance, failure of attempts to kill viruses, and the resistance to chemotherapeutic agents in cancer. Louis Pasteur is purported to have said on his deathbed, “I was wrong, it is the terrain that matters”, meaning body defenses.

Hans Selye, whose research into how animals defend themselves when attacked by any form of stress, led to his description of the General Adaptation Syndrome (GAS). He recognized the necessity of energy in initiating the GAS and its failure in an animal that succumbed to stress. He labeled human disease as “the diseases of adaptation”. In Selye’s time, there was little information about energy metabolism but today, its details are fairly well-known. The suggestion of a new approach depends on the fact that our defenses are metabolic in character and require an increase in energy production over and above that required for homeostasis. If the GAS applies to human physiology and that we are facing the “diseases of adaptation”, it is hypothesized that research should be applied to methods by which energy metabolism can be stimulated and mobilized to meet the stress.

Energy Deficiency, Defective Immunity, and COVID-19

There is evidence that energy deficiency applies to each of the diseases described here. It may be the unrecognized cause of defective immunity in Covid-19 disease. Although in coronavirus disease the clinical manifestations are mainly respiratory, major cardiac complications are being reported involving hypoxia, hypotension, enhanced inflammatory status, and arrhythmic events that are not uncommon. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes may accompany acute viral infections or may follow infection by weeks, months, or longer in viral recovered patients. Electrocardiographic changes have been reported in Covid-19 patients. The authors suggest that it may be attributed to hypoxia as one possibility. Because the total body stores of thiamine are low, acute metabolic stress can initiate deficiency. Thiamine deficiency has a clinical expression similar to that observed in hypoxic stress and the authors referred to it as pseudo-hypoxia. It is therefore not surprising that defective energy metabolism can express itself clinically in many different ways.

The present medical model regards each disease as having a separate cause, but the large variety of symptoms induced by thiamine deficiency suggest the ubiquitous nature of energy deficiency as a cause in common. Obesity, a reflection of high calorie malnutrition, has been published as a risk factor for patients admitted to intensive care with Covid-19. Thiamine deficiency was reported in 15.5-29% of obese patients seeking bariatric surgery. Hannah Ferenchick M.D. an emergency room physician commented online that many of her patients with Covid-19 had what she called “silent hypoxemia”. These patients had an arterial oxygen saturation of only 85% but “looked comfortable” and their chest x-rays “looked more like edema”  It has long been known that patients with beriberi had low arterial oxygen and a high venous oxygen saturation. All that would be needed to support the hypothesis of thiamine deficiency in some Covid victims would be finding a high venous oxygen saturation at the same time as a low arterial saturation. Also, edema is a very important sign of beriberi, and thiamine deficiency has been noted in critical illness.

Disrupted Autonomic Function

There have been many articles in medical journals describing dysautonomia, mysteriously in association with a named disease, but with no suggestion that the dysautonomia is part of that disease. More recently, there is increasing evidence that dysautonomia is a feature of chronic fatigue syndrome (CFS), manifested primarily as disordered regulation of cardiovascular responses to stress. Manipulating the autonomic nervous system (ANS) may be effective in the treatment of CFS. Dysautonomia is also a characteristic of thiamine deficiency. Patients with Parkinson’s disease begin to lose weight several years before diagnosis and a study was undertaken to investigate this association with the ANS. Costantini and associates have shown that high dose thiamine treatment improves the symptoms of Parkinson’s disease, although the plasma thiamine concentration was normal. They have also shown that high dose thiamine treatment decreases fatigue in inflammatory bowel disease, Hashimoto’s disease, after stroke, and multiple sclerosis. As already noted, it is also an important consideration in critically ill patients.

Multiple System Atrophy is a devastating and fatal neurodegenerative disorder. The clinical presentation is highly variable and autonomic failure is one of its most common problems. Dysautonomia was found to be a clinical entity in Ehlers-Danlos syndrome, a musculoskeletal disease, and this syndrome frequently coexists with Postural Orthostatic Tachycardia Syndrome (POTS), a disease that is included in the group of diseases under the heading of dysautonomia. Some cases of POTS have been reported to be thiamine deficient. This common condition often involves chronic unexplained symptoms such as inappropriate fast heart rate, chronic fatigue, dizziness, or unexplained “spells” in otherwise healthy young individuals. Many of these patients have gastrointestinal or bladder disorders, chronic headaches, fibromyalgia, and sleep disturbances. Anxiety and depression are relatively common. Not surprisingly the many symptoms are often unrecognized for what they represent and the patient may have a diagnosis of psychosomatic disease.

Immune-Mediated Inflammatory Diseases (IMIDs) is a descriptive term coined for a group of conditions that share common inflammatory pathways and for which there is no definite etiology. These diseases affect the elderly most severely with many of the patients having two or more IMIDs. They include type I diabetes, obesity, hypertension, chronic pulmonary disease, coronary heart disease, inflammatory bowel disease, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus, psoriasis, psoriatic arthritis, and multiple sclerosis. The recent recognition of small fiber neuropathy in a large subgroup of fibromyalgia patients reinforces the dysautonomia-neuropathic hypothesis and validates fibromyalgia pain. These new findings support the disease as a primary neurological entity.

Energy Deficiency During Pregnancy: The Cause of Many Complications

Irwin emphasized the energy requirements of pregnancy in which the maternal diet and genetics have to be capable of producing energy for both mother and fetus. He found that preventive megadose thiamine, started in the third trimester, completely prevented all the common complications of pregnancy. Hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalization in pregnancy overall. This disease has been associated with Wernicke’s encephalopathy, well known to be due to brain thiamine deficiency. The traditional explanation is that vomiting is the cause, but since vomiting is a symptom of thiamine deficiency, it could just as easily be the cause rather than the effect. In spite of the fact that migraines are one of the major problems seen by primary care physicians, many patients do not obtain appropriate diagnoses or treatment. Migraine occurs in about 18% of women and is often aggravated by hormonal shifts. A complex neurological disorder involving multiple brain areas that regulate autonomic, affective, cognitive, and sensory functions, it occurs also in pregnancy. Features of the migraine attack that are indicative of altered autonomic function include nausea, vomiting, diarrhea, polyuria, eyelid edema, conjunctival injection, lacrimation, nasal congestion, and ptosis.

The Proteopathies: Disorders Involving Critical Enzymes

The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine. Multiple similarities exist between classical thiamine deficiency and Alzheimer’s disease (AD), in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients. Senile plaques and neurofibrillary tangles are the principal histopathological marks of AD and other proteopathies. The essential constituents of these lesions are structurally abnormal variants of normally generated proteins (enzymes). The crucial event in the development of transmissible spongiform encephalopathies is the conformational change of a host-encoded membrane protein into a disease associated, fibril forming isoform. A huge number of proteins that occur in the body have to be folded into a specific shape in order to become functional. When this folding process is inhibited, the respective protein is referred to as being mis-folded, nonfunctional, and causatively related to a disease process. These diseases are termed proteopathies and there are at least 50 different conditions in which the mechanism is importantly related to a mis-folded protein. Energy is required for this folding process. Because of their reported relationship with thiamine, it has been hypothesized that mis-folding might be related to its deficiency on an energy deficiency basis.

It All Comes Down to Energy

A hypothesis has been presented that the overlap of symptoms in different disease conditions represents cellular energy failure, particularly in the brain. If this should prove to be true, the present medical model would become outdated. An attack by bacteria, viruses or an oncogene might be referred to as “the enemy”. The defensive action, organized and controlled by the brain, may be thought of as “a declaration of war” and the illness that follows the evidence that “a war is being fought”. This concept is completely compatible with the research reported by Selye. It underlines his concept that human diseases are “the diseases of adaptation”, dependent on energy for a successful outcome in a “war” between an attacking agent and the complex defensive actions of the body. Killing the enemy is a valid approach to treatment if it can be done safely. Unfortunately, the side effects of most medications sometimes makes things worse and that is offensive to the Hippocratic Oath. We badly need to create an approach to research that explores ways and means of supporting and stimulating the normal mechanisms of defense.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on May 11, 2020.

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Serotonin Syndrome and Thiamine: Is There a Connection?

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Serotonin syndrome is described as a drug-related condition and is commonly believed to be rare. Serotonin is a neurotransmitter, but its actions make it sound like a hormone. It is made in the central nervous system and the gastrointestinal nerve complex. The symptoms of serotonin syndrome arise as a result of an over-abundance of its release from the nervous system into the blood and can be mild to severe, depending on the amount of serotonin in circulation. For normal function, serotonin is stored in a tiny cavity at the end of a nerve, known as a synaptosome and is released by passing through the membrane that surrounds the synaptosome, into the brain. The syndrome is caused by medications, either alone or in combination that increase serotonin levels, e.g. antidepressants, migraine medications, opioid pain medications, or illegal drugs. It is treated by the withdrawal of the causative drugs. There are multiple symptoms arising from an excess of serotonin in the brain and there are also symptoms arising from a deficiency. It is perhaps the prime example of the importance of moderation in everything.

Too Much or Too Little Serotonin

Just as excess serotonin is linked with a variety of symptoms, including: shivering, diarrhea, irritability and/or restlessness, confusion, increased heart rate, high blood pressure, dilated pupils, twitching muscles, muscle rigidity, excessive sweating, headache, tremors, goose bumps, hallucinations, and in more severe cases, unresponsiveness, high fever, seizures, irregular heartbeat, unconsciousness or coma, too little serotonin may be linked to mood disturbances. Deficiency is associated with several psychological symptoms, such as anxiety, depressed mood, aggression, irritability, low energy and low self-esteem. It can cause carbohydrate craving, weight gain, fatigue and nausea, but also, digestive or gastrointestinal motility problems such as irritable bowel syndrome and constipation. It is also a key neurotransmitter in the sleep cycle and is an essential brain chemical.

Thiamine Deficiency and Serotonin

Since many of the posts on this website discuss the problem of symptoms that are frequently associated with deficiency of vitamin B1 (thiamine), I turned to the literature to see if there was any connection between this deficiency and the role of serotonin. I found two important studies that demonstrate the critical role of this vitamin and its association with serotonin. In the first study, researchers explored the role of thiamine deficiency in synaptic transmission, the high affinity uptake and release systems for neurotransmitters using synaptosomal preparations isolated from different parts of the brain in thiamine deficient rats. There was significant decrease in the uptake of serotonin by the synaptosomal preparations of the cerebellum. The administration of the vitamin in vivo resulted in a significant reversibility of the inhibition of serotonin uptake, coinciding with dramatic clinical improvement. The study supports the possibility of an important innervation of the cerebellum by serotonin and suggests a selective involvement of this system in the pathogenesis of some of the neurologic manifestations of thiamine deficiency.

The negative societal impacts associated with the increasing prevalence of violence and aggression needs to be understood. In the second study, researchers investigated the role thiamine using a mouse model of aggression. Ultrasound aggression in mice was induced and the molecular and cellular changes were studied. They found that the ultrasound-induced effects were ameliorated by treatment with thiamine and benfotiamine, both of which were able to reverse the ultrasound-induced molecular changes.

The clinical effects of both deficiency and excess of serotonin are all well described online. The deficiency symptoms described are exactly those associated with beriberi, the vitamin B1 deficiency disease. Serotonin cannot cross the blood brain barrier. Therefore, it must be produced separately in the brain and the gastrointestinal system. Its association with thiamine in the bowel amply reinforces the mystery of gastrointestinal beriberi.

The many posts on thiamine deficiency in Hormones Matter suggests that a mild deficiency of thiamine is responsible for the large number of the polysymptomatic illnesses reported. High calorie malnutrition is a common cause by its increase in the calorie/thiamine ratio. The relationship with drugs is another matter. Although the mechanism of an excess of circulating serotonin is described as the drug-related cause of this syndrome, I could not help but notice that I have seen some of these symptoms corrected by the use of megadose thiamine. For example, excessive sweating, dilated pupils, increased heart rate and “goose bumps” are all caused by increased activity in the sympathetic branch of the autonomic nervous system. Thiamine deficiency is a prime cause of imbalance in this system. Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms and even a compromise of the patient’s life. Contemplating this made me wonder whether the vitamin might have an important bearing on maintaining serotonin in its median state of concentration, because of its vital role in energy metabolism.

Serotonin and COVID-19

Since it has been claimed that Americans consume a high calorie diet, it is important to stress the imbalance which is commonly high in carbohydrate and fat. Serotonin is synthesized from tryptophan, an amino acid that is found in first-class protein and is an essential component of the human diet. It plays a part in many metabolic functions including the synthesis of serotonin and melatonin. Supplementation of this amino acid is considered in the treatment of depression and sleep disorders. It is also used in helping to resolve cognitive disorders, anxiety, or even neurodegenerative diseases. Reduced secretion of serotonin is associated with autism spectrum disorder, obesity, anorexia and bulimia nervosa, as well as other diseases presenting with a variety of symptoms.

It has been hypothesized that aging occurs because of failure of the pineal gland to produce melatonin from serotonin. Evidence has been presented for a role of melatonin and serotonin in controlling the neuroendocrine and immune networks inhibiting the development of ischemic heart and Alzheimer’s disease, tumor formation and other degenerative processes associated with aging. However, a more modern concept for aging is that the production of intracellular reactive oxygen species is a major determinant of lifespan.

One important feature of Covid 19 pathophysiology is the activation of immune cells, with consequent massive production and release of inflammatory mediators that may cause impairment of several organ functions including the brain. In addition to its classical role as a neurotransmitter, serotonin has immunomodulatory properties, down regulating the inflammatory response by central and peripheral mechanisms. Although the interferon system is the first line of defense against viral infection in mammals, almost all viruses have evolved mechanisms to evade the interferon system by partially blocking their synthesis or action.

The Case for Thiamine Supplementation in COVID 19

Thiamine is an essential cofactor for four enzymes involved in the production of energy (ATP) and the synthesis of essential cellular molecules. The total body stores of the vitamin are relatively small and its deficiency can develop in patients secondary to inadequate nutrition, alcohol use disorders, increased urinary excretion and acute metabolic stress. Patients with sepsis are frequently thiamine deficient and patients undergoing surgical procedures can develop the deficiency. It can lead to congestive heart failure, peripheral neuropathy, Wernicke disease and gastrointestinal beriberi. It can result in the development of intensive care unit complications such as heart failure, delirium, critical care neuropathy, gastrointestinal dysfunction and unexplained lactic acidosis. Consequently clinicians need to consider thiamine deficiency in patients admitted to intensive care units and the development of this deficiency during the management of critically ill patients. Intravenous thiamine can correct lactic acidosis, improve cardiac function and treat delirium, without there being any possibility of toxicity. The many symptoms developed in Covid 19 patients are interpreted as a direct effect of the virus, whereas the evidence written in this post strongly suggests that deficiency or excess of serotonin are responsible and that intravenous thiamine could be given with impunity in the emergency room. The persistence of thiamine deficiency following the cessation of the acute phase of the disease would explain the long term symptoms that have been described, following what is generally accepted as recovery.

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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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Recovering from Long Covid with Thiamine

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After 15+ months with Long COVID or Post-Acute COVID-19 Syndrome (PACS), I can honestly say that I’m grateful for the experience. Without it, I probably wouldn’t have ever realized an underlying condition that would have severely jeopardized my health. In short, Drs. Marrs and Lonsdale have saved me from a lifetime of suffering.

Acute Covid

Like most people, I took last year’s COVID recommendations seriously. I began working from home and conducting meetings online. The only trips I took were to pick up groceries or water my plants at the office. Despite my precautions, I contracted the virus in May of 2020.

Four days after the exposure, I bent over to pick something off of the floor, and the room spun.

I’d dealt with vertigo off and on for years. I always considered dizziness to be my “early warning system.” If I was dehydrated or hungry or fatigued, dizziness let me know to care for my needs. I wasn’t surprised that a virus would intensify the experience.

Over the course of the disease, I dealt with fevers, gastrointestinal problems, loss of my senses of smell and taste, strange auditory and visual phenomena, persistent headaches that wrapped ear-to-ear across the front of my head, tingling in my arms and face, and a feeling of fatigue I had never experienced before.

On day 8, I found myself unable to rise from my chair, let alone climb the staircase. I had soiled the bed overnight and my heart rate was disturbingly high. I called a neighbor for help with the groceries I’d had delivered that morning, and she, a nursing home professional who’d recovered from the virus, listened to my symptoms and told me she thought I had COVID-19. She brought me her pulse oximeter.

Longer Term Symptoms

While the worst of the symptoms began to remit after a couple of weeks, the dizziness, the headaches, the fatigue, and the GI distress persisted for months. My vision was blurry and sounds were louder, even painfully so. I couldn’t stand for long without becoming faint, with a heart that beat out of my chest. My short-term memory was shot, and I needed alarms and lots of Post-It notes to keep me on track. I purchased and assembled a rollator, a walker on four wheels, to help me feel steadier while walking.

I began reading about Long COVID, and I found that physicians had no idea what to do for us. I learned we are much like patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who have been mocked and ignored for decades, accused of somaticizing emotional distress — or worse yet, purely confabulating their symptoms.

Those with Long COVID would also be disregarded by the medical community, I learned from online support groups. These groups were mostly comprised of our UK brothers and sisters who’d been hit with COVID before the US was. I may never forget the harsh response one sufferer received from her physician: “What do you expect me to do about this?” Countless others were told they merely had anxiety and sent home with antidepressants and anxiolytics.

Was Nicotinic Acid the Answer?

Although I loathe watching videos (let me read the transcript, please!), I took to YouTube for help. Gez Medinger, a UK filmmaker and fellow Long Hauler, offered a series of videos on coping with the condition. I started a stack of supplements proposed by various researchers he interviewed. I went on a low-histamine diet, as we learned the virus causes over-activation of mast cells. Finally I had some hope, I thought, but “The Stack,” which featured the use of nicotinic acid (B3), offered no relief.

In January I began taking higher doses of nicotinic acid on the recommendation of a health scientist on Twitter. The research appeared sound, and it looked like deficiency of nicotinamide adenine dinucleotide (NAD+) might explain Long COVID.

Nicotinic acid gained me improved clarity of thought and concentration, as well as increased energy. (I would later learn that the heart rate and blood pressure issues I experienced after each dose were due to methylation issues, for which TMG/betaine would be immensely helpful.) I tried the ever-evolving B3 protocols, but the balance issues remained, and I continued to walk like a toddler.

Discovering Thiamine Deficiency, Beriberi and Dysautonomia

My study of Vitamin B1 started as a result of a random tweet mentioning TTFD for Long COVID. In researching it, I found this life-saving website and the collective wisdom here. I saw myself in most of the symptoms of beriberi, a disease I discovered no one remembers from the science lesson on rickets, pellagra, and scurvy. I was surprised that few people have heard of Long COVID, but the lack of awareness of beriberi was shocking. Among my friends, only a Vietnam War medic had ever heard of the disease.

I learned there was an explanation for my dizziness and balance issues: dysautonomia. This website also explained other problems I’d learned to accept over my pre-COVID years: irritable bowel syndrome, night blindness, reduced body temperature (sometimes as low as 93.7º), occasional heart palpitations, and an inability to perspire.

I also learned that the medical community largely has no answers for dysautonomia except physical therapy exercises that debilitated people like me are advised not to implement. Nonetheless, I donned compression stockings as prescribed.

Antibiotic Induced Thiamine Deficiency

How did I get beriberi? I wondered. I don’t conform to the eating patterns Drs. Lonsdale and Marrs describe. After I’d developed hypoglycemia decades ago, I changed my diet to low-carb/high-protein. I am distinctly not a foodie. I see food as a health tool, not a treat, and I believed in the concept of “food as medicine.”

I don’t eat fast foods, I read labels and I don’t remember the last pizza I tasted. The most highly processed foods I’d eaten over the years were nitrate-free, organic craft chicken sausages. Lynne Campbell, a fellow beriberi sufferer who has been my rock of support and guidance throughout this thiamine adventure, had the answer. “You’ve been floxed.”

Yes, indeed, I had been. I was diagnosed with a pelvic infection many years ago, and my physicians treated me with months of antibiotics, including metronidazole, doxycycline, cephalexin, ciprofloxacin, levofloxacin, azithromycin, and nitrofurantoin. Readers of this site will recognize many of these for their thiamine-depleting potential.

I was also prescribed countless doses of fluconazole to combat fungal infections the antibiotics caused, as well as powerful medications to treat gastrointestinal upset and presumed bladder inflammation. We now know that antifungals like fluconazole, for example, can cause increases in oxidative stress, but who knows what damage was done by all of these medications?

I can’t overlook the impact of the emotional trauma as well. The horrific discovery of the original infection led me to make dramatic lifestyle changes, including physical relocation of my residence and months of legal proceedings. For a time, I used alcohol to help me fall asleep.

After a colonoscopy detected no explanations for the continued pelvic pain, an adhesiolysis was performed almost eleven months after the original infection was diagnosed. The persistent pelvic pain was not due to continued infection but to scar tissue that had developed as a result of infection.

I now believe that I developed a subclinical thiamine deficiency that grew gradually worse over the years. I was among those who Dr. Lonsdale calls “the walking sick,” and COVID, by intensifying these symptoms, made me pay attention.

The Thiamine Paradox and Recovery

I started Lipothiamine in late March of this year, and suffered through many weeks of the process known as “paradox.” The floor began to “move” on me; sometimes it felt like I was walking on water. I installed suction cup handles on my counters so I could perform activities with the other hand. Some days I was so disabled that all I could eat was mozzarella cheese sticks. There certainly was no way I could cook for myself.

Part of the misery was due to my inability to tolerate the alpha lipoic acid in the formulation, and some was caused by the above-mentioned methylation/B3 issues. But I persisted with the B1, as I knew dramatic reactions typically meant the individual is on the right track.

As my experimentation revealed I also had paradoxical reactions to the thiamine HCL in my B complex, I established that I had the transporters needed for this formulation, and I switched to 25 milligrams of HCL in late May, exactly a year since my COVID infection. Lynne and I giggled about it via Twitter direct messages. “I have the transporters! I have the transporters! Yea!”

I am now taking several 75mg doses of thiamine HCL throughout the day, increasing ever-so-slightly as I go. I learned that I can’t increase the dose except in small increments or my symptoms get worse.

I have recovered my ability to experience “goosebumps,” something I hadn’t even noticed I’d lost. And, unfortunately, I now perspire!

My breathing patterns are normal and effortless now. Prior to thiamine supplementation, I would catch myself holding my breath, and it was not unusual to wake up gasping for air.

My heart rate and body temperature are steady and I no longer have palpitations. My vision is much clearer, even in the dark. The floor almost never moves on me, except when I let my blood sugar drop or when terribly fatigued. I was recently able to use two hands to clean an overhead bedroom fan; this was something I was unable to comfortably do even before COVID.

Digestion is only rarely a problem. I suspect this is what it is like to be “normal.” I do believe supplementing with butyrate and probiotics has been helpful as well.

Lynne helped me realize the importance of tending to my potassium and calcium needs. I also added magnesium taurate to my magnesium glycinate. I continue to take “The Stack” from months ago, but in modified dosages. I take the other B vitamins separately.

Long Covid is Real and B Vitamins Are a Part of It

Long COVID is a very complicated condition with a large variety of symptoms. This is one reason why some people question the validity of the condition. However, recent research suggests there are three clusters of symptoms, with three treatment pathways. Those of us for whom the virus depleted thiamine may represent Cluster Two. Or it may be all that all Long Haulers are thiamine-depleted to some degree. We certainly know now that a viral infection can be all it takes for a B1 deficiency to manifest.

I’m still wondering about the recent speculation regarding brainstem damage in Long Haulers. Is it irreversible damage, as some say, or dysfunction caused by thiamine deficiency? There are a lot of questions for which we have no answers, but I can report that many of the people in our support groups are benefiting from thiamine, as I and others spread the word.

There is also evidence “the chronic disease [of COVID] is due to changes in the metabolism of tryptophan and the lack of niacin (NAD/NADH+).”

For me, the solution seems to be to address both B vitamins, along with the cofactors mentioned above.

I am a person of faith, which is why I emerged with my sanity from the nightmare that changed everything so many years ago. God’s mercy, I believe, also allowed me to find the breadcrumbs to eventually learn of beriberi, dysautonomia, and the thiamine remedy.

While I’m not cured yet, I couldn’t have accomplished what I have without the work of Dr. Derrick Lonsdale and Dr. Chandler Marrs, and of course the friendship and guidance of my Sister-In-Beriberi, Lynne. There are no words to express my gratitude.

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. 

This article was published originally on September 1, 2021.

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Coordinating the Body’s Defense

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Human beings live in a world where they are under continuous attack. In this post, I will outline the nature of the attack and how we defend ourselves.

Homeostasis

The prefix “homeo” means “the same, steady”, and the definition of homeostasis is “the tendency towards a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes”. Although we are surrounded by bacteria and viruses that are ready to attack us, generally speaking we remain healthy. We can assume that the body’s capacity for maintaining health has adequate energy to maintain homeostasis. That must mean that we are defending ourselves continuously, but any form of imposed stress, such as an infection, demands a surge of energy to meet it. The miracle of being alive means that our defensive machinery is always operating automatically. The body consists of between 70 and 100 trillion cells, each having a responsibility in its own right. We exist because we have inherited a code from our parents called DNA. If this is in a perfect state, all that is required is food to supply energy. The defense is referred to as “an illness”.

How We Defend Ourselves From Infection

As an illustration, I am going to use the form of a typical attack referred to as a streptococcal sore throat, whose technical name is “acute febrile lymphadenopathy”.

Why does the throat become sore?

As we all know, because of inflammation. This is a defensive process because the inflammation is an attempt to block the passage of the bacteria into the body.

Why do we get swollen glands in the neck?

The swollen glands are known as lymph nodes. They become enlarged because it is an attempt to capture and destroy the bacteria as they pass from the throat into the body.

Why do we develop a raised body temperature?

As we all know, the normal body temperature is 37° C.  This is the temperature at which bacteria are at their most efficient state. By raising the body temperature, the efficiency of the bacteria is reduced.

The Brain and the Inflammatory Reflex

We now know that inflammation is under the control of the brain. It sends signals through the nervous system that is known technically as “the inflammatory reflex”. In fact, the entire defensive system is under the control of the brain, as is illustrated by a case that I have already described on this forum, but bears repeating.

Years ago, I was confronted by the case of two boys, both of whom experienced recurrent acute febrile lymphadenopathy. Of course, they had been treated by repeated antibiotic therapy, even though any form of infection had not been proved. Cutting out the technicalities involved, I was able to show that both of these boys were deficient in thiamine, leading to a reduction in brain energy. Each of these two boys had been indulged throughout life with an ad lib ingestion of sweets. It was probably responsible for the thiamine deficiency. Again, without going into the necessary technical factors, the lower part of the brain that controls the defensive machinery becomes unduly sensitive from the energy-deficiency caused by the insufficiency of thiamine. What was really happening was that the part of the brain that controls the defensive machinery had become hypersensitive. It was reacting to a variety of otherwise harmless environmental stimuli under the false Impression that an Infective microorganism was the stressor. There were other factors that supported this explanation, but they are highly technical and inappropriate for this post. The case was published in the medical literature.

It is not easy to understand that the acute febrile lymphadenopathy in each of these 2 boys was really a perfectly appropriate defensive reaction to non-existent bacterial attack, if such an attack had been the reality. If we acknowledge that bacterial invasion of the body is a form of stress, we are supporting the conclusion that “stress” requires a surge of brain energy to operate the defense. This is true for any form of stress, including trauma and mental action.

Because lack of oxidation had made the brains of these boys hypersensitive to any form of stimulus, they must have been overreacting to the perception of some form of environmental stress under the false Impression that it represented a bacterial invasion. Of course, we cannot know if this is the truth, but all the biochemical studies supported this explanation of the observed facts.

Genetics

The perfect structure of the human body is undoubtedly the ideal. It would mean that we had inherited a perfect genetic code in DNA. It is unlikely that perfection in structure is ever achieved in any of us and that we each have a share of genetic mistakes known as polymorphisms. These are not sufficient to cause disease on their own, but perhaps they introduce genetic risk. Another factor may have to play a part. For example, type 1 diabetes has a gene or genes in its background. But the disease does not emerge until later in life, often after a minor stress such as a cold or injury. If the gene(s) were the sole cause, the symptoms of diabetes could be expected to appear at birth. What I am hypothesizing is that a breakdown in health requires more than a single factor. We have indicated that Imperfect genetics is one factor and some form of stress is another.

Nutrition and Malnutrition

We have indicated that a surge of energy is inevitably required for the automatic machinery to go into defensive action. That comes from our food whose efficiency in synthesizing that energy comes from two distinct parts. The first part is called calories and the second part is known as non-caloric micronutrients. Mother Nature “knows” the exact proportion of each part of the food. We do not! Is it not obvious that our food has to  be that supplied only by MN?

Because the brain is the organ that needs the largest amount of oxygen, it quickly reacts to a mild insufficiency by producing a variety of sensations called symptoms. It is almost as though the brain is trying to warn its owner that it is lacking energy. Of course, the trouble with that is that the cause has to be interpreted in practical terms. The lower brain that controls the autonomic nervous system (ANS) is highly sensitive to oxidative deficiency, so the many symptoms experienced by the patient come from dysregulation of that system. For example, a common symptom is heart palpitations. The explanation for them often given by the physician, is that it is from “heart disease”. Dysfunction of the ANS is not considered. A series of laboratory studies found to be abnormal in heart disease are applied. Abnormal laboratory results are essential to the present concept of “real disease” and when they are found to be normal, the interpretation of the palpitations is that it is “psychosomatic”. Unfortunately, there are millions of patients who go through a series of specialists seeking an answer to their multiple symptoms. Each specialist gives an answer that is governed by current diagnostic concepts or their particular specialist status. Some of these unfortunate patients have recorded their experiences by posting on Hormones Matter and anyone seeking help may find the solution in one or more posts that address this problem.

Chronic Illness and Covid Longhaulers

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

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 credit: fxxu via pixabay.com, cc0 license.

This article was published originally on August 9, 2021. 

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New Developments in High-Dose Thiamine: The Legacy of Antonio Costantini

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In partnership with his colleagues, the Italian doctor Antonio Costantini pioneered the use of high-dose thiamine for treating a range of neurological and inflammatory conditions, including Parkinson’s disease (and here), multiple sclerosis, fibromyalgia, inflammatory bowel disease, and chronic cluster headaches.

Sadly, in 2020, Dr. Costantini contracted COVID-19 and died. While his work is finished, his legacy of exploring the therapeutic benefits of high-dose thiamine endures. In the past year, several important studies on high-dose thiamine have been released. This review briefly describes two of these studies and several related resources.

High-Dose Thiamine for IBD Fatigue

In the January 2021 issue of Alimentary Pharmacology & Therapeutics, Palle Bager and colleagues published a randomized controlled trial examining whether oral high-dose thiamine helped relieve fatigue in patients with quiescent inflammatory bowel disease (IBD) and severe chronic fatigue. Following a regimen adapted from Costantini’s earlier pilot study and other Costantini studies, the patients in Bager’s trial received 600 to 1,800 mg of oral thiamine hydrochloride daily, based on weight and gender. The 40 patients in the study were randomized to either receive high-dose thiamine or a placebo for four weeks. Following a four-week washout period, the control and treatment groups switched for another four weeks of treatment/placebo, so that everyone in the study received both high-dose thiamine and a placebo. The trial found that high-dose thiamine produced large reductions in self-reported fatigue on the validated IBD fatigue scale that were both clinically and statistically significant. No statistically significant relationship was observed between the impact of high-dose thiamine and patients’ baseline thiamine deficiency status.

This study is significant for its use of a very rigorous evaluation method: a double-blind cross-over randomized controlled trial. Using this gold standard evaluation method, Bager and colleagues largely confirmed the findings of Costantini’s earlier pilot study. While the Bager study focused only on people with IBD, it provides reason to be optimistic that high-dose thiamine may be helpful for the other populations studied by Costantini and possibly for people with other neurological and inflammatory conditions.

Bager and colleagues suggest that the impact of thiamine in reducing fatigue among patients with IBD and chronic fatigue may be related to problems the patients experience with the active transport mechanism for thiamine:

While the effect of high-dose oral thiamine was highly significant in our study, its exact mechanisms still need to be explored and investigated. The theory of a dysfunction in thiamine transport from blood to mitochondria remains a plausible explanation. The participants in our study were exposed to high doses of thiamine which induces passive diffusion that will add thiamine to the cells and the mitochondria. Consequently, the carbohydrate metabolism can normalise, and a reduction of fatigue is likely to follow.

In a Letter to the Editor of Alimentary Pharmacology & Therapeutics, I urged consideration of an alternative hypothesis, grounded in thiamine’s property as a carbonic anhydrase inhibitor:

The inhibition of carbonic anhydrase isoenzymes by high-dose thiamine and the resulting production of carbon dioxide could lead to reductions in fatigue and other symptomatic improvement through one or more of four potential pathways: (a) by reducing intracranial hypertension and/or ventral brainstem compression; (b) by increasing blood flow to the brain; (c) by facilitating aerobic cellular respiration and lactate clearance through the Bohr effect; or (d) by dampening the pro-inflammatory Th-17 pathway, again through the Bohr effect, potentially mediated by reductions in hypoxia-inducible factor 1.

More background on my hypotheses on the potential mechanisms for the impact of high-dose thiamine, with full citations, may be found here. The authors’ thoughtful reply to my letter may be found here.

High-Dose Thiamine for COVID-19

Another important recent study on high-dose thiamine has been released on a preprint server and is currently under consideration at the journal Critical Care. The study found that administration of high-dose thiamine to 83 patients in Saudi Arabia who were critically ill with COVID-19 was associated with a 55% reduction in 30-day ICU mortality and a 51% reduction in in-hospital mortality, as well as a reduction of 81% in the incidence of thrombosis during their ICU stay. The patients received a median of 100 mg of thiamine (presumably intravenously) for a median of 7 days.

Unlike the Bager study, the COVID-19 study by Al Sulaiman and colleagues was a retrospective study using a case matching approach, rather than a prospective study using random assignment. The authors matched the patients treated with high-dose thiamine to other critically ill COVID-19 patients using propensity scores based on baseline characteristics and controlling for the use of systemic corticosteroids. Based on correspondence with the authors, I understand that the patients’ baseline thiamine levels were not measured and thus unavailable as a matching variable.

This study is significant for providing evidence of the potential of high-dose thiamine to help treat critically ill patients with COVID-19. As I noted in an earlier Hormones Matter blog post, a prior study had found that high-dose thiamine damped down the pro-inflammatory th-17 pathway associated with the COVID-19 cytokine storm, but that study did not involve the treatment of actual COVID-19 patients.  Outcome data from the Front Line COVID-19 Critical Care Alliance suggests that the combined use of Methylprednisolone, Ascorbic Acid (Vitamin C), Thiamine and Heparin  (the so-called MATH+ protocol) may be helpful for COVID-19, but those data do not isolate the impact of high-dose thiamine and do not compare outcomes for treated households to those of a comparison group.

A randomized controlled trial is needed to verify the results found by Al Sulaiman and colleagues and assess whether high-dose thiamine can reduce mortality from COVID-19 among critically ill patients. It would also be valuable to rigorously evaluate whether oral high-dose thiamine could help early stage COVID-19 outpatients avoid hospitalization by reducing the incidence of the COVID-19 cytokine storm. This could help reduce the burdens of hospitals in India, Brazil, and other countries with high COVID-19 caseloads.

Future Directions

I am hopeful that additional rigorous research will be conducted to assess the potential of high-dose thiamine to treat a range of neurological and inflammatory conditions. It is hard to imagine a better tribute to Costantini’s work than a series of additional randomized controlled trials evaluating whether the observations he made in his pilot and case studies hold up when tested with larger samples using rigorous methods.

In addition to the conditions studied by Costantini, I would also encourage research into whether high-dose thiamine could be helpful for people with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and the neurological complications of Ehlers-Danlos Syndrome (EDS) (such as those experienced by my daughter). In this Medium post (more technical discussion) and Health Rising post (less technical discussion), I explain why I think these populations could benefit from high-dose thiamine.

More recently, I documented the retrospective self-reported outcomes for 55 individuals with ME/CFS, EDS or Fibromyalgia who reported taking 200 mg of more daily of high-dose thiamine. Nearly two-thirds of the participants in this retrospective survey reported large benefits, most commonly in reducing fatigue, post-exertional malaise, and brain fog.  Interestingly, benefits were reported across a range of doses, including doses below those used by Costantini and Bager. Several study participants described high-dose thiamine as a game-changer that brought them substantial relief. The study has many limitations. For example, it was a small non-representative sample and based on self-reports only, but it is consistent with the potential of high-dose thiamine to provide large therapeutic benefits. I am hopeful it will help make the case for conducting more rigorous research in the future.

To the extent that Long COVID is similar to ME/CFS, I would also encourage the study of high-dose thiamine for people with this debilitating condition.

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 AJS1 from Pixabay.

This article was published originally on June 10, 2021.

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Two of the most commonly asked questions I face as someone with Lyme disease is “when were you bitten by

COVID Notes: Platelets, Endothelial Damage, and Mitochondria

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covid notes - platelets, endothelial damage, mitochondri

Among the more consistent observations regarding COVID are disturbed platelet and endothelial -function, the time frame where severe illness presents (7-10 days into the infection), and the apparently self-reinforcing cycle of dysregulated immune function (cytokine storm). The prevailing hypothesis suggests that the SARS-CoV-2 pathogen causes platelet and monocyte hyper-activation and aggregation, inducing endothelial damage marked by micro-thrombi. These events initiate the formation of something called circulating immune complexes (CICs). The formation of CICs then drives excessive inflammation and further platelet activation, which, if not halted, becomes the self-reinforcing cycle of severely and ever-escalating immunopathology known as the cytokine storm. The net result of this mess can be everything from excessive lung damage and multi-organ damage to death. With this characterization in mind, the key questions that remain are 1) whether this cascade is unique to the SARS-COV-2 pathogen, 2) what sets off this cascade, and 3) why does all of this seem to kick in around days 7-10?

Is COVID Immunopathology Unique?

Currently, there is much debate as to whether this response is similar to other severe viral illnesses and simply more readily observed because of the scale of the pandemic or truly unique to the SARS-CoV-2 pathogen. Digging through the literature, it appears that while there are some unique features to this pathogen, as there are to all pathogens, neither the host response nor the time frame are particularly unique. The cascade may be simply ramped up in terms of severity and scale, and arguably, against a backdrop of increasingly poor metabolic health of the general population, while the time frame may reflect nothing more than the time it takes for mitochondrial exhaustion to develop.

Regarding the immunopathogenic cascades observed with COVID-19, we know that similar patterns are observed with other viral pathogens. For example, platelet and monocyte hyperactivation are common with severe flu and other viruses, as are endothelia damage and micro-thrombi and the CICs. Platelet and monocyte regulation are influenced in large part, by the severity of the threat, while the health of the host an his/her metabolic capacity determine homeostasis is managed and maintained. Similarly, the formation of CICs does not appear to unique to COVID. CICs are simply multiple antibodies and antigens bound together in one clump that circulate systemically to wreak havoc. They are very common with both bacterial and viral infection and in a variety of autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis. Even the cytokine storm and subsequent multi-organ failure, viewed with much novelty at the onset of COVID, is common with severe illness or trauma and with various viral pathogens. A cytokine storm is an umbrella term used to describe the late phase host response to a variety of pathogens and stressors; the onset and duration of which vary according to the type of stressor and treatments administered. The self-reinforcing nature of hyper-cytokinemia may be linked more with host resources than with the actual pathogen. With the flu virus:

Clinical observations and animal experiments indicate that severe H5N1 and 1918 H1N1 virus disease is associated with cytokine dysregulation. However, because effects of multiple cycles of viral replication and host responses are inextricably intertwined, it is not clear whether cytokine dysregulation is a consequence of the severe disease (caused by direct viral damage) or contributes to pathology in its own right.

Although none these responses appears to be wholly unique and specifically related to the SARS-CoV-2 pathogen, the frequency with which this pathogen evokes these patterns, typically associated with only the most severe illnesses in the most severely compromised individuals cannot be discounted. Inasmuch as these are typical patterns, it is difficult not to question what about the interaction between this pathogen and the environment into which it proliferates is so different from other pandemics that precipitates such severe illness in so many individuals.

Host Mitochondrial Capacity

A paper published in 2015 found a similar, and perhaps even more rapid, progression of disturbed immune function and endothelial damage in cases of severe influenza A (IAV). Importantly, these events were attributed to mitochondrial collapse in the host, in part mediated by the pathogen, but mostly mediated by the host metabolic health. In other words, individuals with co-morbid health issues, the risk for mitochondrial collapse during a severe infection was greater than in healthy individuals. This makes sense when we consider that for survival, viral pathogens usurp and rewire host metabolic capacity e.g. mitochondrial energy production. In a healthy individual, this may not be problematic, but in a metabolically challenged individual the threat of mitochondrial energy collapse becomes greater because the very same pathways re-regulated by the virus are already stressed by existing illness, lifestyle, and diet. Specifically, in the case of IAV, and I suspect COVID and other severe viral pathogens, an enzyme called pyruvate dehydrogenase kinase (PDK – there are four isoforms of PDK with varying activity) is upregulated, while another enzyme called carnitine palmitoyltransferase II (CPT II) is downregulated. This limits mitochondrial energy (ATP) production capacity significantly by downregulating both glucose and fatty acid oxidation.

You may recall from previous posts, that glucose oxidation/oxidative phosphorylation begins in earnest with the enzyme complex called the pyruvate dehydrogenase complex (PDC). PDK, in its various isoforms, disables an important subunit of the PDC, which in turn reduces the amount of pyruvate that can be converted into acetyl-CoA and enter the tricarboxylic cycle (TCA; also called the Krebs or citric acid cycle) to produce ATP – energy. Simultaneously, these viruses downregulate CPT II, which limits the breakdown of long chain fatty-acids. Fatty acids are key fuel source for the mitochondria of many cells, including those of cardiomyocytes in the heart and endothelial cells that line the vasculature. That viral pathogens usurp these pathways is particularly problematic when one considers that these same patterns – upregulated PDK and downregulated CPT II (among others) are observed with obesity, diabetes, heart disease and cancer. With 476 million and 523 million people diagnosed with type 2 diabetes and cardiovascular disease respectively worldwide, this presents a problem.

From the standpoint of viral (or cancer cell) replication, this Warburg-like metabolic reprograming is a boon to the pathogen’s survival. It is not so helpful to the host, however, especially if the host’s metabolic capacity is already impaired with the aforementioned disease processes. It is entirely possible that, while COVID is certainly a serious viral pathogen, part of its capacity for destruction, lays not in the virus itself, but in the environment into which it enters. Data are clear that COVID severity is predicated on poor metabolic health. What is often missing from the conversation is how large a percentage of the worldwide population suffers from poor metabolic health. In the US, research estimates that only 12-20% of the population, depending criteria used, may be considered metabolically healthy.

Using a war analogy, with poor metabolic capacity/limited energy, everything is shifted towards fighting/winning the frontline battles e.g. activation of inflammatory cytokines. Few resources are allocated containing the damage e.g. activation of the anti-inflammatory cytokines. It is a metabolic blitz of sorts; hard, fast, and incredibly deadly, burning everything in its wake. The immune system recognizes the threat to survival and goes all in against the pathogen. The problem with such an approach is that there are no resources to tamp down the fighting as the enemy retreats and nothing to stop or even limit the damage to immediate landscape (tissue and organs). This, in turn, evokes a self-reinforcing cycle of increasing inflammation; one that become independent of the original response and further derails energy production.

This potentially fatal immune response has been termed the cytokine storm. Such hypercytokinemia alters the cellular redox state through different cytokine receptor and reduces the expression of our complex I subunits, oxygen consumption [7,8] and ATP synthesis in mitochondria, as well increasing mitochondrial O2_ production and the intracellular calcium concentration[Ca2þ]i [9] (Fig. 1). ATP depletion causes dissociation of zonula occludens- 1, an intracellular tight junction component, from the actin cytoskeleton and thus increases junctional permeability.

All of this is a result of poor metabolic fitness. With hyperglycemia, in particular, micronutrients deficiencies abound necessitating a shift from the primary and secondary pathways of glucose metabolism (OXPHOS and the pentose phosphate pathway) to tertiary pathways (the polyol/sorbitol, hexosamine, diacylglycerol/PKC, AGE pathways). This necessarily leads to a reduction in ATP, which in turn leads to micro – and microvascular cell damage. It is conceivable that the damage to vasculature presumed directly related to COVID, may have been there already and simply worsened or expedited with the addition of the virus. That we are seeing it so clearly now, may be only related to the scale of this pandemic.

Why the 7-10 Day Shift in Severity?

All of this appears to manifest around days 7-10. Before then, patients are said to be able to persevere from home, but between days 7-10, either the patient begins to recover or everything hits the fan and hospitalization is required. What underlies that critical shift in severity? Once again, mitochondrial collapse is likely to play a role. While altered metabolic capacity would affect the individual systemically, I believe that we see some of the more obvious issues evolving from platelet dysfunction.

The body carries about 150,000-450,000 platelets per liter of blood. In addition to their most well-known role in clotting and blood hemostasis, platelets are also active immune mediators (hence, their relationship with the circulating immune complexes), involved in wound healing, inflammation (elevated cytokine and cytokine storm if unregulated), infection control, endothelial function (platelet aggregation/clots adhere to endothelium causing stress and damage), and angiogenesis and tumor metastasis.

Managing these functions is done largely by the release of various signaling molecules, like serotonin and adenosine diphosphate (ADP) from dense granules within the platelets, and clotting, growth and immune factors like fibrinogen, platelet derived growth factor, and cytokines from the alpha granules. Platelet serotonin release may be particularly relevant to question of time and severity of COVID illness, as it occurs readily in damaged and dying platelets, drives immune reaction, and when severe enough, may elicit something called a serotonin storm, which symptomatically is almost identical to the cytokine storm (and to acute thiamine deficiency). In other words, when platelets are hyper-activated and spill their contents, if not tempered appropriately, there can be system-wide damage.

Importantly, platelets are quite small, have no nucleus, and carry only 5-8 mitochondria per cell, upon which they are critically dependent for energy production and survival. About 40% of platelet energy production is derived from the mitochondrial process called oxidative phosphorylation. The remaining 60% is derived from glycolysis. In both cases, however, micronutrients are required to power the various reactions involved in the production of ATP. Thiamine is top among them and is critical for both pathways. It is also commonly deficient in type 2 diabetes, heart disease and can be easily depleted in any severe illness or trauma.

I believe the purported gearshift from manageable to deadly results from the interplay between failing energy capacity, failing mitochondria, and platelet life and death cycles. This time frame parallels the natural lifecycle of the platelet and overlaps a cycle or two of platelet biogenesis from the megakaryocytes (5 days) suggesting problems with the equilibrium between platelet apoptosis and biogenesis. This time frame also represents a simple case of energy depletion, where not enough ATP is available to manage the immune response to the virus and maintain normal functions simultaneously. Seven to 10 days of a hypermetabolic state in individuals who, because of pre-existing metabolic disorders are likely poorly nourished in advance of the illness, and may not eat during this illness due to both the loss of smell and taste and severity of infection itself, will deplete energy reserves. This will affect immune response generally and platelet response specifically.

So Now What?

Feed the damned mitochondria! This may not prevent symptoms and other treatments may be required, but if we were to just support the damned mitochondria with the appropriate micronutrients, it would certainly help the patient to meet the energetic demands of the illness.

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