We read with interest the correspondence titled “Gut Microbe-Generated Trimethylamine N-Oxide from Dietary Choline is Prothrombotic in Subjects”, published by Zhu et al . in the journal Circulation (1). This work builds on an emerging body of evidence which has suggested a role for the gut-derived metabolite, trimethylamine N -oxide (TMAO), in the development of cardiovascular disease (CVD). This current study is an important clinical test of hypotheses generated from innovative preclinical and observational evidence, and seeks to build upon the nature of TMAO’s relationship with CVD risk in humans. To assess this relationship, Zhu et al . enrolled 18 subjects (10 omnivores and 8 vegetarians) and provided choline bitartrate as a supplement (450 mg choline/day) for 2 months. Following choline supplementation, fasting plasma TMAO concentrations increased and were associated with increased ADP-induced platelet aggregation, an effect that was partially blunted by aspirin.