Precision health targeting TMAO in postmenopausal women: polyphenol effects modulated by urolithin A and equol metabotypes in a randomised, placebo-controlled crossover trial

baseline and placebo. The effects varied by metabotype. TMAO reduction was significant in urolithin A metabotype (UMA), equol producers (EP), and lunularin non-producers (LNP). Reductions and effect sizes were most pronounced in the metabotype clusters MC3 (UMA + EP + LP) and MC7 (UMA + EP + LNP), which represented 39% of participants. DMA decreased selectively in UMA. No correlations were found between TMAO or DMA changes and BMI, age at menopause onset, or years since menopause. These findings show that polyphenol supplementation reduces urinary TMAO in a metabotype-dependent manner and support metabotyping as a precision-health strategy to mitigate cardiometabolic risk after menopause.