Association of diet with circulating trimethylamine-N-oxide concentration

Abstract

Trimethylamine-N-oxide (TMAO) is a compound that is present in seafood and produced through human gut microbial metabolism of its precursors. Previous studies have suggested that elevated TMAO concentrations are associated with an increased risk of cardiovascular events. However, the association between diet and TMAO concentrations in free-living adult populations has not been adequately described. The objective of this study was to identify dietary predictors of plasma TMAO concentrations. TMAO concentrations were assessed in 2 fasting plasma samples collected 6 mo apart among 620 healthy men. Short-term and long-term dietary intakes were assessed during the same time-frame of blood collections via repeated 7-d dietary records (7DDRs) and a semiquantitative food-frequency questionnaire (SFFQ), respectively. We grouped individual food items into 21 groups and regressed against averaged TMAO concentrations. We also assessed the association between dietary scores and TMAO concentrations. In models adjusted for demographic characteristics and mutually adjusted for food groups, SFFQ-assessments of fish and egg intakes were significantly associated with increased TMAO concentration (β=0.082; 95% CI: 0.021, 0.14; P=0.009 for fish; β=0.065; 95% CI: 0.004, 0.13; P=0.039 for egg). The positive association between fish consumption and TMAO concentration was replicated in the 7DDR-assessments (β=0.12; 95% CI: 0.060, 0.18; P<0.001). There was no association between red meat intake and TMAO concentrations. The unhealthful plant-based diet index (uPDI) was inversely associated (β=-0.013; 95% CI: -0.021, -0.005; P=0.001) and healthy dietary scores were positively correlated with TMAO concentration. TMAO concentration was significantly associated with fish intake, but not with red meat consumption. uPDI, an unhealthy dietary pattern, was inversely related to TMAO concentration. As such, this study suggests that in free-living populations, higher circulating concentrations of TMAO cannot simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern.