Abstract
BACKGROUND: The Western dietary pattern (WD) is positively associated with risk of coronary artery disease (CAD) and cancer, whereas the Prudent dietary pattern (PD) may be protective. Foods may influence metabolite concentrations as well as oxidative stress and lipid dysregulation, biological mechanisms associated with CAD and cancer. OBJECTIVE: The aim was to assess the association of 2 derived dietary pattern scores with serum metabolites and identify metabolic pathways associated with the metabolites. METHODS: We evaluated the cross-sectional association between each dietary pattern (WD, PD) and metabolites in 2199 Women's Health Initiative (WHI) participants. With FFQ and factor analysis, we determined 2 dietary patterns consistent with WD and PD. Metabolites were measured with LC-tandem MS. Metabolite discovery among 904 WHI Observational Study (WHI-OS) participants was replicated among 1295 WHI Hormone Therapy Trial (WHI-HT) participants. We analyzed each of 495 metabolites with each dietary score (WD, PD) in linear regression models. RESULTS: The PD included higher vegetables and fruit intake compared with the WD with higher saturated fat and meat intake. Independent of energy intake, BMI, physical activity, and other confounding variables, 45 overlapping metabolites were identified (WHI-OS) and replicated (WHI-HT) with an opposite direction of associations for the WD compared with the PD [false discovery rate (FDR) P < 0.05]. In metabolite set enrichment analyses, phosphatidylethanolamine (PE) plasmalogens were positively enriched for association with WD [normalized enrichment score (NES) = 2.01, P = 0.001, FDR P = 0.005], and cholesteryl esters (NES = -1.77, P = 0.005, FDR P = 0.02), and phosphatidylcholines (NES = -1.72, P = 0.01, P = 0.03) were negatively enriched for WD. PE plasmalogens were positively correlated with saturated fat and red meat. Phosphatidylcholines and cholesteryl esters were positively correlated with fatty fish. CONCLUSIONS: Distinct metabolite signatures associated with Western and Prudent dietary patterns highlight the positive association of mitochondrial oxidative stress and lipid dysregulation with a WD and the inverse association with a PD.