Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far?

Background Trimethylamine N-oxide (TMAO) is a metabolite that has attracted attention due to its positive association with several chronic non-communicable diseases such as insulin resistance, atherosclerotic plaque formation, diabetes, cancer, heart failure, hypertension, chronic kidney disease, liver steatosis, cardiac fibrosis, endothelial injury, neural degeneration and Alzheimer's disease. TMAO production results from the fermentation by the gut microbiota of dietary nutrients such as choline and carnitine, which are transformed to trimethylamine (TMA) and converted into TMAO in the liver by flavin-containing monooxygenase 1 and 3 (FMO1 and FMO3). Considering that TMAO is involved in the development of many chronic diseases, strategies have been found to enhance a healthy gut microbiota. In this context, some studies have shown that nutrients and bioactive compounds from food can modulate the gut microbiota and possibly reduce TMAO production. Objective This review has as main objective to discuss the studies that demonstrated the effects of food on the reduction of this harmful metabolite. Methods All relevant articles until November 2020 were included. The articles were searched in Medline through PubMed. Results Both the food is eaten acutely and chronically, by altering the nature of the gut microbiota, influencing colonic TMA production. Furthermore, hepatic production of TMAO by the flavin monooxygenases in the liver may also be influenced by phenolic compounds present in foods. Conclusion The evidence presented in this review shows that TMAO levels can be reduced by some bioactive compounds. However, it is crucial to notice that there is significant variation among the studies. Further clinical studies should be conducted to evaluate these dietary components’ effectiveness, dose, and intervention time on TMAO levels and its precursors.