Effects of dietary choline, betaine, and L‐carnitine on the generation of trimethylamine‐N‐oxide in healthy mice

Abstract

Trimethylamine‐N‐oxide (TMAO) is considered to have negative effect on human health. Different precursors of TMAO, such as choline, betaine, and L‐carnitine, are commonly found in daily foods. The aim of the present study was to compare the ability of different precursors to be metabolized into TMAO, as well as the possible effect of chronic administration with TMAO precursors on TMAO production. The rate of TMAO generation after single gavage with different precursors was L‐carnitine > choline >betaine. Moreover, the serum TMAO level of mice increased more than twofold after administration with choline for 3 weeks compared with L‐carnitine and betaine groups, which was accompanied by the change of intestinal flora. After the gavage of choline chloride, the production for TMAO was 2.8 and 1.6 times higher in chronic choline‐treated group compared with L‐carnitine and betaine groups, respectively. In addition, administration with choline increased the lowest TMAO level after intraperitoneal injection of trimethylamine (TMA) hydrochloride among the three treated groups. These findings indicated that different TMAO precursors had different ability to form TMAO in vivo, and long‐term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by dietary intervention.Practical ApplicationDiverse TMAO precursors exhibited different ability to be converted into TMAO in vivo. The ability of choline to produce TMAO was stronger than that of betaine and L‐carnitine. Long‐term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by adjustment of dietary structure.

Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice

“…Since plasma TMAO levels are highly correlated with dietary patterns and the nutritional composition of foods [ 17 , 18 ], dietary intervention may be an alternative strategy for inhibiting TMAO production [ 19 ]. A methionine-restricted (MR) diet has emerged as a highly preferable dietary intervention strategy since it is reported to exert many beneficial effects including the promotion of vascular health [ 20 ], reduction in fat deposition [ 21 ], improvement of glucose homeostasis [ 22 ], improving oxidative stress and inflammation [ 23 , 24 ], and a prolonged life span [ 25 ].…”

Trimethylamine-N-Oxide Pathway: A Potential Target for the Treatment of MAFLD

“…A study conducted by demonstrated that the rate of TMAO generation after single gavage with different precursors is L-carnitine > choline > betaine; However, long-term dietary intervention showed that the production for TMAO in chronic choline-treated group is 2.8 and 1.6 times than that in L-carnitine and betaine groups, respectively (Yu et al, 2020). Priscilla and colleagues also investigated TMA production from dietary precursors in an in-vitro model of the human colon, they found that the rate of TMA production from precursors is choline > L-carnitine > betaine > γ-butyrobetaine, and conversion of L-carnitine to TMA is slower than that of choline (Day-Walsh et al, 2021).…”

Docosahexaenoic acid-acylated curcumin diester alleviates cisplatin-induced acute kidney injury by regulating the effect of gut microbiota on the lipopolysaccharide- and trimethylamine-N-oxide-mediated PI3K/Akt/NF-κB signaling pathway in mice

“…The levels of TMAO and TMA in serum were measured according to the previous methods by liquid chromatography with tandem mass spectrometry (LCMS/MS). 16…”