Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk

Plasma levels of N6,N6,N6-trimethyl-L-lysine (TML) are associated with a 2.4 times higher risk of major adverse cardiovascular events within three years.

• TML levels are independently associated with a 2.9 times higher risk of mortality within five years.
• Genome-wide association studies suggest several loci for TML levels, but none reached genome-wide significance.
• TML can serve as a nutrient precursor for gut bacteria to produce trimethylamine (TMA) and trimethylamine N-oxide (TMAO), which are linked to cardiovascular disease.
• Both plant- and animal-derived foods contain abundant TML, but its conversion to TMA is slow in fecal cultures from both omnivores and vegans.
• TML supplementation in mice does not increase plasma TMAO levels or enhance thrombosis potential.

AI simplified