The Truth about Trimethylaminuria (TMAU) and the FMO3 Gene Mutation
Trimethylamine (TMA) is produced by gut bacteria from dietary ingredients. In individuals with a hereditary defect in flavin-containing monooxygenase 3 (FMO3), bacterial TMA production is believed to contribute to the symptoms of trimethylaminuria (TMAU; fish-odor syndrome). When FMO3 is not working correctly or if not enough enzyme is produced, the body loses the ability to properly convert trimethylamine (TMA) from precursor compounds in food digestion into trimethylamine oxide (TMAO), through a process called N-oxidation. Trimethylamine then builds up and is released in the person's sweat, urine, and breath, giving off a strong fishy odor or strong body odor. A variant of TMAU (secondary trimethylaminuria or TMAU2) exists where there is no genetic cause, yet excessive TMA is secreted, possibly due to intestinal dysbiosis, altered metabolism, or hormonal causes.
There are two types of TMAU: Type 1 is identified as those born with the condition due to a faulty gene (called the FMO3 gene) inherited from a parent. Type 2 is identified as those who acquire the condition later in life, this is thought to occur either following a gene mutation, or a due to changes in bacterial composition in the body. Most TMAU2 sufferers produce too much TMA from intestinal bacteria due to an excess of the specific strains of bacteria that breakdown choline, carnitine and lecithin in to TMA.
As TMAU is still under-recognized and often goes undiagnosed, those affected often suffer from psychological problems and social stress. Affected individuals experience shame and embarrassment, fail to maintain relationships, avoid contact with people who comment on their condition, and are obsessive about masking the odor with hygiene products and even smoking. The malodorous aspect can have serious and destructive effects on schooling, personal life, career and relationships, resulting in social isolation, low self-esteem, depression, paranoid behavior, and suicide. Delayed diagnosis, body odor and the lack of cure may lead to psychosocial issues.
The bacteria in our gut play a vital role in helping us break down and digest our food. The friendly strains of bacteria produce non-smelly substances as a product of their fermentation process, whereas pathogenic microbes often produce more four smelling substances. It is not the friendly strains of bacteria in the gut that break down and convert choline and other substances from the diet in to TMA. The major bacterial converters of choline, carnitine and lecithin are mostly neutral, pathogenic or opportunistic microbes.
So, it is thought that probiotics could potentially help in two ways. They can control the populations of pathogenic and opportunistic bacteria so that less TMA is released from the choline in our food. Secondly, they can help reduce transit time, so that there is less time for TMA to be released from food and then absorbed in to the blood stream.
Trimethylaminuria (abbreviated to TMAU and also known as ‘fish odour syndrome’) is a very distressing condition that often seriously affects the quality of life and confidence of sufferers. It is a metabolic condition, in which sufferers are unable to break down Trimethylamine (TMA) which is itself an end product of the bacterial breakdown of certain dietary compounds such as: choline, carnitine and lecithin, found in various foods, such as milk, red meat, eggs, liver, peas, beans and soy products. Due to the fact that gut bacteria are involved in the conversion of dietary compounds to TMA, probiotics could play a role in the management of symptoms of Trimethylaminuria (TMAU).
Origin and fate of TMA in the human gut, and the proposed Archaebiotics concept: Gut microbiota synthesis of TMA is realized from TMAO, choline, PC and L-carnitine. The TMA is then absorbed and goes to the liver, routes (A or (B). In the case of route (A), a partial or total defect in FMO3-oxidation into TMAO leads to increased level and diffusion of TMA in breath, urine and sweat. When FMO3 liver oxidation is functional (B), the increase of TMAO in blood is associated with atherosclerosis. Therefore, converting TMA directly in the gut using Archaebiotics belonging to the seventh methanogenic order, naturally-occurring in the gut: this would increase the efficiency of TMA conversion.
Drug substrates may also impair metabolism in TMAU individuals. Examples of FMO3 drug substrates include Drug Class of drug: Bupivacaine; Lidocaine Anaesthetics Benzydamine, Anti-inflammatory (throat lozenges and sprays) *Chlorpromazine, Anti-psychoticClozapine, Anti-psychoticFluphenazine, Anti-psychotic Olanzapine, Anti-psychotic Perazine,Anti-psychotic(S)-Nicotine Neuronal stimulant Tamoxifen Anti-estrogen.
What Disease States May be related to Trimethylaminuria?
Any disease state or compromise anywhere in the gastrointestinal tract or in the organs of detoxification and elimination (liver, kidneys, skin, lungs) can be related to TMAU, especially in the liver which may already be struggling due to the genetic component of TMAU. Small intestine bacterial overgrowth (SIBO), a type of dysbiosis or unbalanced microbiome, may increase TMA production, as may bacterial vaginosis (BV). Constipation can make matters worse by not moving food at a desirable pace through the digestive tract and by allowing dysbiosis to occur. GERD or reflux can result in dysbiosis.
Relationship: The Role of Probiotics, Enzymes & Trimethylaminuria
Intestinal bacteria break down digested food into trimethylamine (TMA). The major bacterial converters of carnitine, choline, phosphatidylcholine and betaine to TMA are mostly neutral, pathogenic or opportunistic microbes, rather than probiotics.
- Probiotics can help control the populations of neutral, opportunistic or pathogenic microbes so that less TMA is released from digested food.
Probiotics can help with GERD or reflux.
Probiotics can reduce constipation, speeding up the movement of food in the intestines so that there is less time for TMA to be released.
Dysbiosis (unbalanced microbiota) may be a problem in your gastrointestinal tract, however you can improve the balance of microbes in your GI tract towards probiotics. Not only will this help your prevention of potential TMAO/TMA problems but it will give you the numerous health benefits that probiotics and a healthy diet can provide.
The Synbiotics (Probiotic & Prebiotics) contained in the Probiotic Pack™ helps to balance the immune system, promote nutrient absorption and healthy microbiome. Serrapeptase, a main Ingredient in The Probiotic Pack™, helps immensely as it clears out all of the inflammation and dead tissue. By alleviating the inflammation and clearing away this problem tissue it relieves the symptoms and allows the healing system to rapidly repair the problem.
The Probiotic Pack™ contains quality systemic enzymes that work synergistically with the Synbiotics. Because of their variety of origins and substrates, wide ranges of optimal temperatures and pH levels, increased percentage of absorption, and increased level of effectiveness, enzyme blends have a wider range of advantages than do individual enzymes. Additionally, when enzymes are taken in combination with probiotics, vitamins, minerals, and herbs, the combination improves absorption and bioavailability of the ingredients.
It is recommended to take a high-quality multi-strain probiotic formula, with at least 11 strains to balance gut bacteria and promote a healthy digestive system. The best probiotics can withstand stomach acids and enable the bacteria reach the gut alive to perform their health-enhancing benefits. In terms of reducing inflammation, relieving symptoms and reducing or slowing the progressiveness of a disorder, the Probiotic Pack™ is a great natural alternative for Trimethylaminuria.
Promotes healthy digestion and nutrient absorption*
Promotes a balanced microflora recolonization*
Supports gastro-intestinal health*
Promotes healthy yeast levels*
Brugère, Jean-François, et al. “Archaebiotics- Proposed Therapeutic Use of Archaea to Prevent Trimethylaminuria and Cardiovascular Disease.” Gut Microbes, vol. 5, no. 1, 2013, pp. 5–10., doi:10.4161/gmic.26749.
Dimidi, E., et al. (2017). 'Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation'. Adv Nutr, 8(3): 484-494
Dorte Eskesen et al, (2015), Effect of the probiotic strain Bifidobacterium animalis subsp. lactis, BB-12®, on defecation frequency in healthy subjects with low defecation frequency and abdominal discomfort: a randomised, double-blind, placebo-controlled, parallel-group trial , British Journal of Nutrition (Human and Clinical Nutrition).
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Testimonials are Individual Results. Your results may vary. Copyright © 2018 FitCube Nutrition. All rights reserved Terms & Conditions.