Trimethylamine N-oxide

Trimethylamine N-oxide (TMAO) is an organic compound with the formula (CH3)3NO. It is in the class of amine oxides. Although the anhydrous compound is known, trimethylamine N-oxide is usually encountered as the dihydrate. It is a product of the oxidation of trimethylamine, a common metabolite in animals. Both the anhydrous and hydrated materials are white, water-soluble solids. Trimethylamine N-oxide (TMAO) is an organic compound with the formula (CH3)3NO. It is in the class of amine oxides. Although the anhydrous compound is known, trimethylamine N-oxide is usually encountered as the dihydrate. It is a product of the oxidation of trimethylamine, a common metabolite in animals. Both the anhydrous and hydrated materials are white, water-soluble solids. Trimethylamine N-oxide is an osmolyte found in saltwater fishes, sharks, rays, molluscs, and crustaceans. It is considered as a protein stabilizer that may serve to counteract urea, the major osmolyte of sharks, skates and rays. It is also higher in deep-sea fishes and crustaceans, where it may counteract the protein-destabilizing effects of pressure. TMAO decomposes to trimethylamine (TMA), which is the main odorant that is characteristic of degrading seafood. TMAO is biosynthesized from trimethylamine, which is derived from choline. Trimethylaminuria is a rare defect in the production of the enzyme flavin-containing monooxygenase 3 (FMO3). Those suffering from trimethylaminuria are unable to convert choline-derived trimethylamine into trimethylamine oxide. Trimethylamine then accumulates and is released in the person's sweat, urine, and breath, giving off a strong fishy odor. The order Clostridiales, the genus Ruminococcus, and the taxon Lachnospiraceae are positively associated with TMA and TMAO levels. In contrast, proportions of S24-7, an abundant family from Bacteroidetes, are inversely associated with TMA and TMAO levels. A study published in 2013, assessing 513 adults with a history of major adverse cardiovascular events, an average age of 68, and 69% of whom previously or currently smoke, may indicate that high levels of TMAO in the blood are associated with an increased risk of additional cardiovascular events. The concentration of TMAO in the blood increases after consuming foods containing carnitine or lecithin if the bacteria that convert those substances to TMAO are present in the gut. High concentrations of carnitine are found in red meat, some energy drinks, and some dietary supplements. Some types of normal gut bacteria (e.g. species of Acinetobacter) in the human microbiome convert dietary carnitine to TMAO. TMAO alters cholesterol metabolism in the intestines, in the liver, and in artery walls. In the presence of TMAO, there is increased deposition of cholesterol in, and decreased removal of cholesterol from peripheral cells such as those in artery walls. Lecithin is found in soy, eggs, as an ingredient in processed food, is sold as a dietary supplement, is used as an emulsifier, and is used to prevent sticking (for example in non-stick cooking spray). The link between cardiovascular diseases and TMAO is disputed by other researchers. Clouatre et al. argue that choline sources and dietary L-carnitine do not contribute to a significant elevation of blood TMAO, and the main TMAO source in the diet is fish. Another source of TMAO is dietary phosphatidylcholine, again by way of bacterial action in the gut. Phosphatidyl choline is present at high concentration in egg yolks and some meats. It has been suggested that TMAO may be involved in the regulation of arterial blood pressure and etiology of hypertension and thrombosis (blood clots) in atherosclerotic disease. A 2017 meta-analysis found higher circulating TMAO was associated with 23% higher risk of cardiovascular events and a 55% higher risk of mortality.