Endpoint: mixed — an acute human egg/PC-challenge biomarker result (surrogate) + a prospective hard-event cohort (MACE).
In 40 healthy volunteers, ingesting 2 hard-boiled eggs plus 250 mg deuterium-labeled phosphatidylcholine produced a time-dependent rise in plasma/urinary TMAO (and other choline metabolites); the rise was abolished by antibiotic suppression of gut flora and reappeared on antibiotic withdrawal, directly demonstrating gut-microbial dependence. Separately, in a prospective cohort of 4,007 patients undergoing elective coronary angiography (the Cleveland Clinic “GeneBank” cohort), higher fasting plasma TMAO independently predicted incident major adverse cardiovascular events (death, MI, stroke) over 3 years.
relevance_note: the direct primary evidence that an egg-derived phosphatidylcholine challenge raises TMAO in humans, combined with the largest early prospective TMAO→events cohort. NOTE data-basis: this GeneBank cohort recurs in Zhu 2016 (this pool) and in Wang Z et al. 2014 EHJ (found but not minted, see orientation note) — treat as one underlying dataset for correlation purposes.