Developing and Evaluating the Construct Validity of a Dietary Pattern Predictive of Plasma TMAO and Choline

Background and Aims The metabolism of choline (highly present in animal products) can produce trimethylamine N-oxide (TMAO), a metabolite with atherosclerotic effects; however, dietary fiber may suppress this metabolic pathway. This study aimed to develop a dietary pattern predictive of plasma TMAO and choline concentrations using reduced rank regression (RRR) and to evaluate its construct validity. Methods and Results Diet and plasma concentrations of choline (μmol/L) and TMAO (μmol/L) were assessed in 1,724 post-menopausal women who participated in an ancillary study within the Women's Health Initiative Observational Study (1993-1998). The TMAO dietary pattern was developed using RRR in half of the sample (Training Sample) and applied to the other half of the sample (Validation Sample) to evaluate its construct validity. Energy-adjusted food groups were the predictor variables and plasma choline and TMAO, the response variables. ANCOVA and linear regression models were used to assess associations between each biomarker and the dietary pattern score. Discretionary fat, potatoes, red meat, and eggs were positively associated with the dietary pattern, while yogurt, fruits, added sugar, and starchy vegetables were inversely associated. Mean TMAO and choline concentrations significantly increased across increasing quartiles of the dietary pattern in the Training and Validation samples. Positive associations between the biomarkers and the TMAO dietary pattern were also observed in linear regression models (Validation Sample: TMAO, adjusted beta-coefficient=0.03650 (p-value=0.0088); Choline, adjusted beta-coefficient=0.01083 (p-value=0.0224). Conclusion We established the TMAO dietary pattern, a dietary pattern reflecting the potential of the diet to contribute to plasma concentrations of TMAO and choline.