Serum untargeted metabolomic profile of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern

Abstract

Background: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is recommended for cardiovascular disease risk reduction. Assessment of dietary intake has been limited to subjective measures and a few biomarkers from 24-h urine collections.

Objective: The aim of the study was to use metabolomics to identify serum compounds that are associated with adherence to the DASH dietary pattern.

Design: We conducted untargeted metabolomic profiling in serum specimens collected at the end of 8 wk following the DASH diet (n = 110), the fruit and vegetables diet (n = 111), or a control diet (n = 108) in a multicenter, randomized clinical feeding study (n = 329). Multivariable linear regression was used to determine the associations between the randomized diets and individual log-transformed metabolites after adjustment for age, sex, race, education, body mass index, and hypertension. Partial least-squares discriminant analysis (PLS-DA) was used to identify a panel of compounds that discriminated between the dietary patterns. The area under the curve (C statistic) was calculated as the cumulative ability to distinguish between dietary patterns. We accounted for multiple comparisons with the use of the Bonferroni method (0.05 of 818 metabolites = 6.11 × 10-5).

Results: Serum concentrations of 44 known metabolites differed significantly between participants randomly assigned to the DASH diet compared with both the control diet and the fruit and vegetables diet, which included an amino acid, 2 cofactors and vitamins (n = 2), and lipids (n = 41). With the use of PLS-DA, component 1 explained 29.4% of the variance and component 2 explained 12.6% of the variance. The 10 most influential metabolites for discriminating between the DASH and control dietary patterns were N-methylproline, stachydrine, tryptophan betaine, theobromine, 7-methylurate, chiro-inositol, 3-methylxanthine, methyl glucopyranoside, β-cryptoxanthin, and 7-methylxanthine (C statistic = 0.986).

Conclusions: An untargeted metabolomic platform identified a broad array of serum metabolites that differed between the DASH diet and 2 other dietary patterns. This newly identified metabolite panel may be used to assess adherence to the DASH dietary pattern. This trial was registered at http://www.clinicaltrials.gov as NCT03403166.

FIGURE 1

Plot of −log₁₀P values for the adjusted association between serum known metabolites and the DASH diet compared with the control diet (A) and fruit and vegetables diet (B). P values were calculated from multivariable regression models adjusted for age, sex, minority race, educational level, BMI, and hypertension status. The analysis was conducted in the 110 participants randomly assigned to the DASH diet and the 108 participants randomly assigned to the control diet in panel A and among 110 participants randomly assigned to the DASH diet and 111 participants randomly assigned to the fruit and vegetables diet in panel B. DASH, Dietary Approaches to Stop Hypertension.

FIGURE 2

Scores plot of principal components 1 and 2 for discriminating between the DASH diet and the control diet (A) and between the DASH diet and the fruit and vegetables diet (B). Plots were created from a partial least-squares discriminant analysis of 110 participants randomly assigned to the DASH diet and the 108 participants randomly assigned to the control diet in panel A and among 110 participants randomly assigned to the DASH diet and 111 participants randomly assigned to the fruit and vegetables diet in panel B. DASH, Dietary Approaches to Stop Hypertension.

FIGURE 3

VIP scores for the top 10 serum metabolites for discriminating between the DASH diet and the control diet (A) and between the DASH diet and the fruit and vegetables diet (B). VIP scores were calculated from a partial least-squares discriminant analysis among 110 participants randomly assigned to the DASH diet and the 108 participants randomly assigned to the control diet in panel A and among 110 participants randomly assigned to the DASH diet and 111 participants randomly assigned to the fruit and vegetables diet in panel B. Red boxes for the DASH diet (and green boxes for the control diet) indicate that serum concentrations of the metabolite were higher among those randomly assigned to the DASH diet compared with those randomly assigned to the control diet. Green boxes for the DASH diet (and red boxes for the control diet) indicate that serum concentrations of the metabolite were lower among those randomly assigned to the DASH diet compared with those randomly assigned to the control diet. DASH, Dietary Approaches to Stop Hypertension; VIP, Variable Importance in Projection.