Urine Metabolites Associated with the Dietary Approaches to Stop Hypertension (DASH) Diet: Results from the DASH-Sodium Trial

Abstract

Scope: Serum metabolomic markers of the Dietary Approaches to Stop Hypertension (DASH) diet are previously reported. In an independent study, the similarity of urine metabolomic markers are investigated.

Methods and results: In the DASH-Sodium trial, participants are randomly assigned to the DASH diet or control diet, and received three sodium interventions (high, intermediate, low) within each randomized diet group in random order for 30 days each. Urine samples are collected at the end of each intervention period and analyzed for 938 metabolites. Two comparisons are conducted: 1) DASH-high sodium (n = 199) versus control-high sodium (n = 193), and 2) DASH-low sodium (n = 196) versus control-high sodium. Significant metabolites identified using multivariable linear regression are compared and the top 10 influential metabolites identified using partial least-squares discriminant analysis to the results from the DASH trial. Nine out of 10 predictive metabolites of the DASH-high sodium and DASH-low sodium diets are identical. Most candidate biomarkers from the DASH trial replicated. N-methylproline, chiro-inositol, stachydrine, and theobromine replicated as influential metabolites of DASH diets.

Conclusions: Candidate biomarkers of the DASH diet identified in serum replicated in urine. Replicated influential metabolites are likely to be objective biomarkers of the DASH diet.

Trial registration: ClinicalTrials.gov NCT00000608.

Keywords: biomarkers; dietary patterns; feeding study; metabolomics.

Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts of interests to disclose.

© 2020 Wiley-VCH GmbH.

Figures

Figure 1.

Flow diagram of participant selection DASH, Dietary Approaches to Stop Hypertension

Figure 2.

Number and percentages of metabolites by metabolite categories significantly different between the DASH diets and the control-high sodium diet Numbers within the graph represents number of metabolites (%). “Measured urine metabolites” represents the distribution of all measured metabolites in our study. DASH, Dietary Approaches to Stop Hypertension

Figure 3.

Volcano plots of P-values and β coefficients for the association between individual metabolites and DASH diets The red horizontal dashed line represents the Bonferroni-adjusted threshold (5.33 × 10−5) and the red vertical dashed line is set at β coefficient=0. Positive β coefficients (to the right of the red vertical dashed line) indicate that the level of metabolites was higher in individuals randomly assigned to DASH diet relative those assigned to the control diet. Negative β coefficients (to the left of the red vertical dashed line) indicate that the level of metabolites was lower in individuals randomly assigned to DASH diet relative those assigned to the control diet. The top 10 metabolites representative of the DASH-high sodium diet and DASH-low sodium diet relative to the control-high sodium diet are labeled. * Metabolites that are not officially confirmed based on a standard.

Figure 4.

Scores plot derived from principal component analysis of significant metabolites for the DASH diets and control-high sodium diet Plots were created from partial least squares-discriminant analysis. DASH, Dietary Approaches to Stop Hypertension