bacterial overgrowth

SIBO, IBS, and Constipation: Unrecognized Thiamine Deficiency?

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

GI Motility and Thiamine

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

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

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

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

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

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

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

Malnutrition Induced Malnutrition

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

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

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

TTFD and Gut Motility

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

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

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

To learn more about how thiamine affects gut health:

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

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Thiamine Deficiency: A Slow Road to Dementia

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‘Jo, you’ll be relieved to hear the tests are all normal.’

I’d heard this line so many times, and it wasn’t reassuring. Each time it became less likely that I had an illness that could be defined, diagnosed, and consequently cured, or even treated. If there was nothing wrong with me, why did I feel so awful? I had been gradually deteriorating over months, perhaps longer.

Fatigue and Other Seemingly Innocuous Symptoms

It’s difficult to say when I first felt unwell. One of the initial symptoms was terrific fatigue – struggling to find the energy to carry on each day at work. I was taking longer and more frequent tea breaks and relying on sugar to give me the buzz to carry on. Of course, it didn’t help that I didn’t sleep well. I would fall into a deep sleep early evening and then wake feeling strangely on edge with a racing heart, unable to sleep for most of the night. Even if I could sleep, it didn’t make me feel any better.

There were several other symptoms, which I could explain away, but one odd symptom was muscle twitches or fasciculations. These were worse when I was tired or had been more active. I also had dodgy guts – more about this later.

Even though I was exhausted I could continue working, being a mother to our four children – albeit a rather terrible one that repeatedly fell asleep in the middle of bedtime stories, until I developed brain fog. I felt like my thinking was occurring at less than half the usual speed. I struggled to hold a conversation, as this required listening, interpreting the other person’s words, formulating an answer, and talking. I would have to really concentrate to think about anything. I would forget things unless I wrote them down, which just meant I had unfinished lists scattered everywhere.

After falling on the ward where I had been working as a doctor, I finally acknowledged that I was sick, even if there was nothing apparently wrong with me. Once I stopped working, I deteriorated further, such that I was unable to recognize people and even places.

A Slow Road to Dementia

This was over 10 years ago. Clearly, I’ve improved since then. I’ve written a book to try to characterize my symptoms, explain what caused them, and why it was difficult to make a diagnosis. This seems even more pertinent since a lot of the symptoms I suffered with then resemble long Covid now.

My main concern was that I had developed dementia. I had many of the features: I struggled to remember recent events, I had problems following conversations, I was forgetting the names of friends and even commonly used objects, and I was repeating myself and having problems with thinking and reasoning. I also had difficulty recognizing where I was — this is visuospatial disorientation — a key marker of dementia.

Since the medical profession seemed to have no idea how to treat me I decided to try to work it out for myself. What choice did I have? Away from work, I had time to slowly read through medical papers, whilst I rested. I recognized that my symptoms improved after taking antibiotics for a gum infection. Any exertion made me markedly worse, but not immediately afterward, it would be the following day and last for several days. I improved if I rested. My other symptoms included pains in my hands and feet. I thought this was arthritis initially, but when I developed pins and needles and subsequently numbness, I realized this was a peripheral neuropathy – a problem with the sensory nerves in my extremities.

Some months earlier a close colleague had told me I was thiamine deficient, mainly because I had lost a lot of weight. I was taken aback, assuming he thought my diet was poor, or that I was drinking alcohol. I hadn’t drunk any alcohol for years as it made me feel rough after a few sips. I investigated thiamine deficiency and found that it causes loss of sensation as well as loss of balance; I already knew it affected memory from treating alcoholics under my care.

My friend kindly agreed to try high-dose intravenous thiamine on the ward. Neither of us really thought it would work, but it was worth a shot. I was astounded when after a few minutes of the infusion I started to be able to think clearer and even the pains in my hands and feet disappeared. I practically skipped off the ward to buy oral thiamine and dose up. Sadly, thiamine tablets didn’t work and two days later I was back on the unit begging for more shots. This thrice-weekly dosing of thiamine infusions continued for months.

The Gut Connection

I trained in Gastroenterology and General Medicine. They say doctors make the worst patients. For as long as I could remember I had suffered from intermittent severe central abdominal pains, which usually occurred after eating quickly on an empty stomach. According to my mother, I had been a colicky baby and had also returned to the hospital as a new baby with uncontrollable vomiting. Nothing abnormal was found.

In fact, not all the tests I had were normal. After several second opinions, I had a few abnormal tests. I had a CT scan of my abdomen, which showed that I had gut malrotation. The severe pains I had experienced throughout life were due to small bowel volvulus – twisting. I learned that if I stopped eating and lay down on my back the pain would gradually subside. Each time my guts twisted scar tissue formed adhesions, slowing down my gut movements.

My guts had been noticeably abnormal for many years. I had noisy guts and passed very loose, frequent motions. I don’t know many slim 20-year-olds who suffered from severe gastro-esophageal reflux as I did. As this progressed, I developed recurrent chest infections and required multiple courses of antibiotics. Eventually, I worked out that I was aspirating gut contents into my lungs each night, and I stopped eating in the evening and propped myself up with many pillows. All sorted – no more chest infections – no more antibiotics.

One of the other abnormal tests was an incredibly low vitamin D. Through late-night searches of anything vaguely relevant and my gastroenterology knowledge I worked out that a low vitamin D occurred in bacterial overgrowth. This made sense. I had developed bacterial overgrowth in my small intestines — the part of the gut responsible for the absorption of nutrients from food.

Small intestinal bacterial overgrowth or SIBO is due to an excess of bacteria in the small intestines. There are many risk factors including sluggish guts from adhesions, previous surgery, medications that slow the gut, but also multiple courses of antibiotics, poor immune system, and use of drugs that block acid production in the stomach, as well as pancreatitis. I’m sure that a diet high in sugar didn’t help.

I had another test specifically looking for bacterial overgrowth, which the nurse (a colleague I’d worked with many times) and I interpreted as abnormal. The consultant I saw thought the machine must have broken. This was frustrating; after so many normal tests to have a wildly abnormal test attributed to faulty equipment. I decided it was better to treat the patient (me) rather than a dubious test result. After starting antibiotics, I no longer needed the thiamine infusions. The diarrhea also improved.

I worked out that I had bacterial overgrowth from mal-rotated guts, obstructed from adhesions, which improved with antibiotics and were eventually treated with corrective surgery. I also had severe vitamin D deficiency, which was corrected with injections, and thiamine deficiency, which I subsequently managed with a fat-soluble thiamine analogue — benfotiamine. I found a paper online reporting thiamine deficiency in extremely obese patients who had undergone surgery on their small intestines to aid weight loss. Many of these patients had thiamine deficiency; they also had high folate, which was thought to be a marker of bacterial overgrowth. Oral thiamine had no effect on their thiamine levels, but after taking antibiotics the patients’ thiamine returned to normal. Interestingly, my folate was high.

What was less well known was that some bacteria produce an enzyme called thiaminase, which destroys thiamine. I can only assume that I had these kinds of bacteria in my gut. Interestingly these bacterial enzymes do not destroy benfotiamine.

I followed up on my theory of the underlying cause of dementia: that too many bacteria, producing a lot of thiaminase enzyme, destroy the thiamine in our food rendering us thiamine deficient. I found out that thiamine is essential for all living things, and it is necessary for the release of energy from food, particularly sugar or glucose. The brain only uses glucose as an energy supply. There are reports of low thiamine levels in the brain in patients who have died of dementia. Glucose metabolism in the brain is never normal in dementia. Benfotiamine has been shown to improve mild cognitive impairment. I speculated that this was the cause of my brain fog.

Thiamine Deficiency: The Missed Diagnosis

Why was it so difficult to make a diagnosis? I believe there are several reasons. Firstly, thiamine levels are rarely tested in the UK. Even though I had worked in the NHS for over 20 years I had never requested a thiamine test. Secondly, thiamine deficiency is known to present in widely differing ways. This is like many of the mysterious syndromes — a constellation of recognizable symptoms and signs with largely normal tests: irritable bowel syndrome, fibromyalgia, etc., and also long Covid. Thirdly, I wasn’t listened to. I’m not sure whether this is because I’m female, but I became extremely sick before anyone really tried to help, and even then I was reliant on friends I have in the medical profession.

I’m remarkably well now. I regained my memory and ability to think, although it probably took a couple of years. My guts still aren’t completely normal, but bacterial overgrowth is often a chronic condition. I still take supplements and I’m careful with my diet, avoiding sugar and alcohol. My diet is quite restrictive, but it’s worth it. I wouldn’t want to go back to how I was.

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This article was published originally on June 30, 2022. 

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Finasteride, SIBO, and Metabolic Disruption

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I am 26 years old and living in Switzerland. I work in marketing. I currently weigh only 62kg (136lbs) even though I am 184 cm (6 ft) tall. Two years ago, I developed a small intestinal bacterial overgrowth (SIBO) infection suddenly after taking 20g of a probiotic called Perfect Pass Prebiotic. It contains partially hydrolyzed guar gum. I was also taking two lactobacillus probiotics per day during during the two months leading up to the SIBO. For the SIBO, I was treated with Atrantil and Xifaxan 4 times per day for two weeks. Antratil is an herb combination used to treat SIBO and Xifaxan (rifaximin) is a broad spectrum antibiotic. After these treatments, I developed an overgrowth of bilophilia and desulfurio bacteria. This has led to a severe sulfur intolerance. I have not found any treatment for this yet. Before developing SIBO, I used antihistamine (desloratadine, 5mg every day for two years) and Finacapil (finasteride) for the last 8 years, but I stopped taking it four months ago.

Since developing the SIBO, I have developed several food sensitivities including: oxalate, salicylate, and sulfur and histamine intolerances. I have lost 5kgs. I have also developed very high ammonia. That is my biggest issue. I had blood tests to confirm the high ammonia. It seems that I can only eat five foods without triggering a reaction: rice, chicken, carrots, fennel, and gluten free bread. When I eat anything else, I have almost all the symptoms possible. Before developing SIBO, I could eat anything. My diet was diverse and healthy.

Genetic Polymorphisms

I have since learned that I have several genetic polymorphisms which either upregulate or downregulate the activity of several enzymes involved in energy production and antioxidant processes. I have a fast cystathionine beta-synthase (CBS) enzyme, which may be at the root of my current problems. The CBS enzyme uses vitamin B6 to convert the amino acids homocysteine and serine into something called cystathionine, which then converts to cysteine and glutathione, a critical antioxidant pathway. Individuals with high CBS activity, end up with high levels of taurine and ammonia and lower levels of cystathionine and homocysteine, and importantly, lower levels of glutathione, making them more apt to suffer from infections and reactions to foods and medications. CBS upregulation also upsets the urea cycle, which means that I have problems with methylation.

If that were not bad enough, I have learned that I also have several SNPs that impact metabolism.

  • FUT2 +/+
  • GAD1 (2) +/- (1) +/+
  • HFE H63D +/+
  • MAT1A +/+
  • CBS C699T +/-
  • MTRR K350A +/-
  • NOS3 (3) +/-
  • PEMT (2) +/-
  • BCMO1 (4) +/-
  • AGXT +/-
  • MTHFR +/+
  • BHMT+/+

I have low homocysteine in blood, low lactic acid, high histamine, high bilirubin.

Nutrient Deficiencies

Nutrient testing shows that I have very low blood ceruloplasmin and copper but normal intracellular copper.  Testing showed that I am also low in vitamins A, C, K2, manganese, selenium, magnesium, and low in vitamins B2, B3, B5, B9, and B12. Because I also have gastritis, sulfate reducing bacteria overgrowth and high ammonia, issues with sulphur, oxalates and salicylates etc., I don’t tolerate most oral supplements or things like natural vitamin C or beef liver. I also can’t tolerate methyl and sulfur vitamins and minerals.

I found a solution with IV multivitamin and mineral but it contained glycine and way too much chromium and iron and because of my hemochromatosis, it probably depleted my manganese, folate, etc. My manganese and folate concentrations are very low in blood. The IV was helping me a lot first but the ammonia issue began to be way too high and as did the blood chromium, so I stopped. The IV had all the vitamins and minerals, plus glycine and phosphatidylcholine.

I had an ADK supplement with 5000UI Vitamin A, 5000UI Vitamin D, and 600mg Vitamin K2, MK7 synthetic and it was helping a lot with the ammonia but gave me bad oxalate burning bladder. Manganese helped a lot, but since I don’t have enough vitamin C, my CYP7A1 enzyme, which manganese triggers, is not working well. The CYP7A1 enzyme converts cholesterol into bile acid. As a result of the manganese supplement, I developed cholestasis, but when I take vitamin C, which is the missing piece here, I get oxalate issues. It seems that I cannot win. The manganese may cause a loss of choline or glycine but both contain ammonia and sulfur, so I can’t take it.

I did tolerate the vitamin C in the IV mix, though. It could have been because it came with the other B vitamins. This leads me to believe that perhaps I can tolerate transdermal vitamins or another formulation of the IV nutrients.

I know that I need thiamine (vitamin B1) but I have normal TPP in blood and when I tried to take it in HCL, mononitrate, TPP even at 1 mg, it gave me the sulfur issue and high ammonia. More recently, I had an organic acid test (OAT). It showed that I have low vitamin B6 in urine test, but it was high in the blood, I have very high inorganic phosphate in blood, normal magnesium in blood but low intracellular magnesium. Both probably are caused by too much iron. I really need vitamin C, but because of oxalate issue I cannot take it, and if I take vitamin B6, it will further upregulate my CBS and produce more sulfite, sulfate, ammonia, and hydrogen sulfide.

I should note that I always have gallbladder pain, and flow issue, and I can’t digest fat, but all gallbladder supplements that contain sulfur give me issues. So I don’t know how to take manganese without cholestasis, vitamin c without oxalate issue and B1 without sulfur issue and folinic acid without glutamate issue. I have run out of idea to cure myself. If anyone can help, it would be great!

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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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