Abstract
Introduction: The Dietary Approaches to Stop Hypertension (DASH) diet significantly reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. Hypothesis: We hypothesized that certain metabolites will be associated with BP reductions. Methods: Metabolomic profiling was conducted at the end of the diet interventions for participants randomly assigned to the DASH or control diet in multicenter, controlled feeding studies: DASH (N=219) and DASH-Sodium trials (N=395). Using multivariable linear regression models to examine the association between metabolites and BP change, we tested for interactions between diet and metabolites for the following comparisons: 1) DASH vs. control diets in the DASH trial, 2) DASH-high sodium vs. control-high sodium diets in the DASH-Sodium trial, and 3) DASH-low sodium vs. control-high sodium diets in the DASH-Sodium trial. Pathway overrepresentation analysis was constructed for significant metabolites. Results: Identified were 65 significant interactions [DASH=12; DASH-high sodium=35; DASH-low sodium=18]. Most amino acids (16/19), cofactors and vitamins (15/15), xenobiotics (9/13), peptides (4/5), and a nucleotide (1/1) were higher in participants consuming the DASH diets vs. the control diets. These metabolites were associated with BP reductions in participants consuming the DASH diets, but not control diets ( Figure ). Many lipid metabolites (10/12) were lower in participants consuming the DASH vs. the control diets. Lipid concentrations were associated with BP elevations in participants consuming the DASH diets and with BP reductions in participants consuming the control diets. Metabolites associated with tocopherol metabolism, ceramides, and pantothenate and CoA metabolism were overrepresented. Conclusions: Using data from randomized feeding studies, we identified metabolites that were associated with BP lowering. These metabolites highlight the pathways through which DASH diet reduced BP.
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