Trimethylamine N-Oxide as a Potential Biomarker for Cardiovascular Disease: Its Association with Dietary Sources of Trimethylamine N-Oxide and Microbiota

Trimethylamine N-oxide (TMAO), the oxidized form of trimethylamine (TMA), was previously thought to be a waste product but is now considered an important risk factor for cardiovascular disease (CVD) and its comorbidities. Foods or supplements containing choline and carnitine are major precursors of TMA in the diet and are metabolized by gut microbiota. Trimethylamine N-oxide is produced through the oxidation of this compound by flavin-containing monooxygenase (FMO) in the liver. The organ responsible for the removal of TMAO from body fluids is the kidneys. Therefore, plasma TMAO levels are influenced by multiple complex factors, especially the amount of TMA precursors and dietary TMAO sources in the diet, the dominant genera in the gut microbiota, FMO3 enzyme activity, and kidney functions. Among these, the quantity of TMAO and its precursors in the diet and microbiota can be considered modifiable risk factors. However, discussions continue regarding how plasma TMAO levels reach pathological levels and their role (consequence or cause) in CVD. This review presents the current scientific evidence on the relationship and underlying mechanisms between CVD and TMAO and provides an overview of the association of plasma TMAO levels with modifiable risk factors, such as dietary TMAO precursors, dietary TMAO sources, and microbiota.