From the Guidelines
Trimethylamine N-oxide (TMAO) is a compound produced in the body when gut bacteria metabolize certain nutrients found in animal products, particularly L-carnitine and phosphatidylcholine, which are then oxidized by hepatic flavin-containing monooxygenases (FMOs) to form TMAO 1. TMAO has been implicated in various health outcomes, including cardiovascular disease, with studies suggesting that elevated blood levels of TMAO are associated with increased risk of cardiovascular disease, including heart attacks and strokes. Key points to consider about TMAO include:
- TMAO is produced by the gut microbiome in response to certain nutrients found in animal products, such as red and processed meats 1.
- The production of TMAO involves the conversion of L-carnitine and phosphatidylcholine to trimethylamine, which is then oxidized by the liver to form TMAO 1.
- Elevated TMAO levels have been linked to increased risk of cardiovascular disease, although the evidence is not entirely consistent and may be confounded by other factors, such as reduced kidney function 1.
- Foods high in L-carnitine and phosphatidylcholine, such as red meat and processed meats, may contribute to higher TMAO production, while plant-based diets may result in lower TMAO levels 1.
- Further research is needed to fully understand the relationship between TMAO and cardiovascular disease, as well as the potential benefits and limitations of TMAO testing in clinical practice 1.
From the Research
Definition and Formation of TMAO
- Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism 2.
- TMAO is synthesized through a meta-organismal stepwise process that involves the microbial production of TMA in the gut from dietary precursors and its subsequent oxidation to TMAO by flavin-containing monooxygenases in the liver 3.
- TMAO can also be absorbed directly from the gastrointestinal tract after the intake of TMAO-rich foods such as fish and shellfish 3.
Dietary Precursors of TMAO
- Choline, l-carnitine, betaine, and other TMA-containing compounds are the major dietary precursors of TMA 3, 4.
- Diet is an important factor as it provides the nutritional precursors to eventually produce TMAO 3.
Health Implications of TMAO
- Elevated circulating TMAO levels have been linked to an increased risk of developing adverse cardiovascular outcomes such as atherosclerosis and thrombosis 3, 5, 6.
- TMAO has been associated with various diseases, including cardiovascular diseases, cardiorenal disorders, diabetes mellitus, metabolic syndrome, cancers, and neurological disorders 5.
- The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways, and promotion of foam cell formation 2.