constipation thiamine

Gastrointestinal Disease and Thiamine

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The gastrointestinal (GI) tract, long thought to be specific only to the process of digestion, starts at the mouth and ends at the anus. Modern research has revealed that it has a very complex relationship with the rest of the body, especially the brain, and this post is aimed at giving the reader a glimpse of this research.

The Impact of Medication on the GI Tract

Every year many new medications are approved for clinical use, several of which can cause clinically significant GI tract toxicity. An article in the medical literature describes the drug-induced injury to the fragile lining of the tract. A drug by the name of Flagyl is used for resistant bacterial infections. Its chemical name is metronidazole and occasionally it results in the complication of encephalopathy (brain disease). It has been proposed that the adverse effects of the drug may be due wholly or in part to its conversion to a thiamine analog (the drug has a similar formula to thiamine and acts as an antagonist to the action of the vitamin). It seems that this happens enough that a Metronidazole Toxicity group has been formed online and has a considerable number of people with complaints regarding the use of this drug. Because the encephalopathy is said to be uncommon, it is apparently accepted as an occasional side effect, even though many people have been crippled from its use. The number of people reporting serious symptoms in the Toxicity group tends to negate the conclusions of officialdom that this encephalopathy is “uncommon, if not rare”.

Thiamine Deficiency and Obesity

This is defined by a formula known as the body mass index. Obesity is a growing worldwide epidemic currently affecting one in 10 adults. In the United States the incidences is as high as 40%. A publication claims that the only proven long-term treatment of severe obesity is surgical modification of the gastrointestinal anatomy, termed bariatric surgery. Complications are seen in patients who fail to follow the recommended changes in lifestyle. They include nausea, vomiting, so-called dumping syndrome, acid reflux and nutritional deficiencies. The authors note that “despite caloric density, the diet of patients prior to bariatric surgery is often of poor nutrient quality“. Unfortunately it needs to be pointed out that it is exactly why they became obese in the first place. Bariatric surgery is “shutting the stable door after the horse has gone”. Although obesity has been viewed traditionally as a disease of excess nutrition, the evidence suggests that it may also be a disease of malnutrition. Thiamine deficiency (TD) was found in as many as 29% of obese patients seeking bariatric surgery. They can present with vague signs and symptoms. In many posts on this website it has been pointed out that high calorie malnutrition is a widespread scourge in America and is responsible for the high incidence of obesity. The “vague signs and symptoms” are typical of early TD (beriberi) and are often misdiagnosed as psychosomatic.

Constipation or Diarrhea

The commonest form of bypass surgery for obesity, without going into the details, is known as Roux-en-Y. I do not know the reason for this nomenclature, but for surgeons it defines the technique. A publication in the medical literature described thiamine deficiency after gastric bypass and hypothesized that this is common. Of 151 patients, 27 met the criteria for thiamine deficiency, a prevalence of 18%. Eleven of these patients reported constipation after the surgery and treatment with thiamine improved it.

A 29-year-old patient has been described who had experienced sudden blindness and a disturbance of consciousness after two months of chronic diarrhea and minimal food intake. Amongst other physical signs, hemorrhages were seen in the eye. Leaking of blood from capillaries has long been recognized as a phenomenon that might be found in thiamine deficiency. It is of particular interest that the examination of cerebrospinal fluid revealed it to be normal, but magnetic resonance imaging showed changes that were interpreted as typical of thiamine deficiency. After administration of intravenously administered thiamine, both visual acuity and the visual field rapidly improved with the simultaneous recovery of consciousness. No indication was provided to explain a two-month period of diarrhea, although it was accompanied by “minimal food intake”.

A patient with Crohn’s disease and long-standing diarrhea resulted in combined thiamine and magnesium deficiency. Despite massive doses of thiamine given intravenously the symptoms of the deficiency could not be suppressed until the magnesium deficiency was also corrected. Many posts on Hormones Matter have discussed the relationship of magnesium with thiamine. Both of them work together as cofactors for a number of vitally important enzymes that govern energy metabolism. Obviously, literally any lapse of health can occur if energy is insufficient to meet the demands of living. Therefore, it is possible to understand that fatigue and other disorders related to ulcerative colitis and Crohn’s disease are the manifestation of an intracellular mild thiamine deficiency.

It is important to note that, in spite of finding the levels of thiamine and thiamine pyrophosphate in the blood to be normal, 10 patients out of 12 showed complete regression of fatigue and 2 patients showed partial regression when thiamine was administered. Note the doses of thiamine that were given. They ranged from 600 to 1500 mg/day given by mouth. The thing to understand here is that this was not simple vitamin replacement. These authors were using thiamine as a completely non-toxic drug, revealing genuine pioneering. Other authors have noted that micronutrient deficiencies occur in Crohn’s disease. They reported two patients with Crohn’s disease who complained of sudden-onset eye and brain dysfunction and confusion while receiving prolonged total parenteral nutrition. Magnetic resonance imaging allowed definitive diagnosis of Wernicke encephalopathy, a well-known brain disease occurring as a result of thiamine deficiency.

The Gut – Brain Connection

Within the last decade, the complement of bacteria living in the human bowel, now known as the gut microbiome, has become a focus of attention. The GI tract was once regarded simply as a digestive organ, but recent research has led to finding that the microbiome may have an impact on human health and disease. Surprisingly, it has become a focus of research for those interested in the brain and behavior. Multiple routes of communication between the gut and the brain have been established. Recently the gut microbiota (the complement of bacteria) has been profiled in a variety of conditions, including autism, major depression and Parkinson’s disease. Of course, there is still debate as to whether or not the changes observed are primary in causing the disease or merely a reflection of it. Other authors have raised the question of the importance of the microbiota in the pathology associated with autism, dementia, mood disorders and schizophrenia. It is interesting that the GI microbiome has been regarded as a complex ecosystem that reportedly establishes a symbiotic mutually beneficial relation with the host. It is said to be rather stable in health, but affected by age, drugs, diet, alcohol and smoking. Smoking leads to modifications of the bacterial complement and is linked with absence of a protective effect toward ulcerative colitis, and deleterious for Crohn’s disease.

An interesting slant has been placed on this problem of relationship between the host and the bacteria which make up the microbiome. It is pointed out that thiamine is an essential cofactor for all organisms, including bacteria and the role that gut microbes play in modulating thiamine availability is poorly understood. Little is known about how thiamine impacts the stability of microbial gut communities. In order to study this, a model gut microbe (Bacteroides thetaiotaomicron) was chosen. The study showed that thiamine acquisition mechanisms used by this microorganism not only are critical for its physiology and fitness but also provide the opportunity to model how other gut microbes may respond to the shifting availability of thiamine in the gut. Importance of this means that the variation in the ability of gut microbes to transport, synthesize and compete for thiamine is expected to impact on the structure and stability of the microbiota. The authors conclude that this variation may have both direct and indirect effects on human health.

The Role of Energy Metabolism

The question of whether bacterial changes in the gut are primary or secondary makes us think of which is the “chicken” and which is the “egg”. Bacteria are complex one-celled organisms and they require energy to perform their normal function, just the same as our body cells. Therefore, thiamine is as important to bacteria as it is to us, bringing us back to considering the frontier of medical thinking that energy metabolism is the core issue of health and disease.

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Image by Andrew Martin from Pixabay.

This article was published originally on May 6, 2019. 

Quick Thoughts: Hyperemesis and Early Thiamine Deficiency

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A while back, I published an article about expanding the symptoms considered to be associated with thiamine deficiency. Conventionally, we tend to look only at the end stage results of long term thiamine deficiency as being the indicators of disease, forgetting that to get to this stage there was a prodrome, which, except in rare cases, proceeds across many months, if not years. Even with a severely thiamine restricted diet, it can be weeks to months before the more traditionally recognized neurological or cardiovascular symptoms manifest. A series of studies conducted in early 1940s found that among the most common early symptom of thiamine deficiency was GI dysfunction ranging from nausea, vomiting, and constipation, to severe food intolerances and complete anorexia. The prominence of vomiting in this scenario got me thinking about hyperemesis, the severe and near continuous vomiting experienced by some women during pregnancy, but also, about the exploding numbers of illnesses that involve GI dysmotility and dysbiosis. From IBS to SIBO, gastroparesis to constipation and really everything in between, could they also be a consequence of insufficient thiamine? According to the research, yes. Indeed, these non-pregnant cases of GI dysfunction, easily fall under the umbrella of gastrointestinal beriberi – thiamine deficiency that manifests in GI system, sometimes months before the onset of the more traditional cardiovascular or neurological forms.

Pregnancy, Vomiting, and Thiamine

With pregnancy, we know that the energy demands upon the mom are enormous, which means that given its role in energy metabolism, thiamine demands are enormous as well. Some older research estimates the demand for thiamine increases by at least 5X that of a non-pregnant woman. Other research, which I seem to have lost the reference for, posited the demand increased by a factor of 10. Personally, I believe the demand and need for thiamine and other nutrients during pregnancy is higher yet.

The RDA for thiamine during pregnancy is 1.4mg per day, just a fraction over the RDA for non-pregnant women (1.1mg). A quick scan of prenatal vitamins shows that most include from 1.5mg – 3mg of thiamine, woefully below the estimated need of 5-10X non-pregnant levels. That discrepancy alone could cause problems in women who may have been borderline thiamine deficient pre-pregnancy. The pregnancy itself would tip her over into deficiency territory. This then could very easily lead to increased vomiting, which then would further hamper the intake and absorption of thiamine, exacerbating the deficiency, and cause more vomiting; a cycle that becomes especially dangerous to both mom and the baby as time progresses.

While it is easy to see how thiamine deficiency is a common consequence of hyperemesis, it is possible that it is also a contributing cause. Dr. Lonsdale and others have long asserted a role for thiamine deficiency as a causative contributor to hyperemesis. Just based upon the estimated need versus the availability in prenatals and diet, especially once vomiting has begun, this makes sense. Importantly, these types of symptoms have been observed across many case studies unrelated to pregnancy, so much so that gastrointestinal beriberi is a legitimate, though woefully under-recognized form of thiamine deficiency disease. As mentioned previously, the symptoms include GI distress in the form of vomiting, gastroparesis (delayed stomach emptying, which results in vomiting), disturbed GI dysmotility, either too much or too little, and dysbiosis. All of this is documented to be attributable to insufficient thiamine in non-pregnant people. Is it so difficult to see that pregnancy too could elicit or exacerbate gastrointestinal beriberi?

But Wait, What About Carnitine and CoQ10?

If you follow my work, a few years back I mapped one of the causes of hyperemesis to a carnitine deficiency. Carnitine is critical to the metabolism of fatty acids, and its deficiency along with another mitochondrial co-factor, CoQ10, have been linked to a condition called Cyclic Vomiting Syndrome (CVS). Supplementation with l-carnitine and CoQ10 appears to resolve the vomiting with CVS. After publishing that paper, anecdotal reports came back suggesting that l-carnitine and CoQ10 was useful in preventing and resolving hyperemesis. I believe that it is still involved in many cases, but it is possible that thiamine is involved as well and it may be a contributing factor to the carnitine deficiency. Thiamine, in addition to its role in key enzymes involved in carbohydrate and protein metabolism, is also involved in fatty acid metabolism and positionally, it sits a step above carnitine.

Here we have a few options beyond the traditional and largely ineffective anti-emetic medications given to women with hyperemesis; options that I would argue are significantly safer and healthier for mom and baby and likely far more effective. If thiamine and/or l-carnitine deficiency are at the root of hyperemesis, correcting those deficiencies early should give women a much easier and healthier pregnancy.

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 May 24, 2021.