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Randomized Controlled Trial
. 2023 Jul;80(7):1494-1506.
doi: 10.1161/HYPERTENSIONAHA.123.20901. Epub 2023 May 10.

Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions

Hyunju Kim  1   2 , Lawrence J Appel  1   3 , Alice H Lichtenstein  2   4 , Kari E Wong  5 , Nilanjan Chatterjee  6 , Eugene P Rhee  7 , Casey M Rebholz  1   2
Affiliations
Randomized Controlled Trial

Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions

Hyunju Kim et al. Hypertension. 2023 Jul.

Abstract

Background: The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies-the DASH and DASH-Sodium trials.

Methods: Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395). Using multivariable linear regression models, associations were examined between metabolites and change in systolic BP and DBP. Tested for interactions between diet interventions and metabolites were the following comparisons: (1) DASH versus control diets in the DASH trial (serum), (2) DASH high-sodium versus control high-sodium diets in the DASH-Sodium trial (urine), and (3) DASH low-sodium versus control high-sodium diets in the DASH-Sodium trial (urine).

Results: Sixty-five significant interactions were identified (DASH trial [serum], 12; DASH high sodium [urine], 35; DASH low sodium [urine], 18) between metabolites and systolic BP or DBP. In the DASH trial, serum tryptophan betaine was associated with reductions in DBP in participants consuming the DASH diets but not control diets (P interaction, 0.023). In the DASH-Sodium trial, urine levels of N-methylglutamate and proline derivatives (eg, stachydrine, 3-hydroxystachydrine, N-methylproline, and N-methylhydroxyproline) were associated with reductions in systolic BP or DBP in participants consuming the DASH diets but not control diets (P interaction, <0.05 for all tests).

Conclusions: We identified metabolites that were associated with BP lowering in response to dietary interventions.

Registration: URL: https://www.

Clinicaltrials: gov/ct2/show/NCT03403166; Unique identifier: NCT03403166 (DASH trial). URL: https://www.

Clinicaltrials: gov/ct2/show/NCT00000608; Unique identifier: NCT00000608 (DASH-Sodium trial).

Keywords: blood pressure; dietary approaches to stop hypertension; hypertension; metabolic networks and pathways; metabolomics.

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Conflict of interest statement

Disclosures None.

Figures

Figure 1.
Figure 1.
Associations between Dietary Approaches to Stop Hypertension (DASH) diet–related serum metabolites and systolic or diastolic blood pressure in the DASH trial. β coefficients and 95% CIs were calculated using multivariable linear regression models for 1 SD higher in metabolite, adjusting for age, sex, race, education, body mass index, and hypertension. Only metabolites with significant interaction with diet interventions (P for interaction, <0.05) are presented. *Metabolites with a tier 2 certainty, which were not confirmed by a reference standard.
Figure 2.
Figure 2.
Associations between Dietary Approaches to Stop Hypertension (DASH) diet–related urine metabolites and systolic or diastolic blood pressure in the DASH-Sodium trial. We compared DASH high-sodium diet and control high-sodium diet interventions. β coefficients and 95% CIs were calculated using multivariable linear regression models for 1 SD higher in metabolite, adjusting for age, sex, race, income, body mass index, and 24-hour urine creatinine. Only metabolites with significant interaction with diet interventions (P for interaction, <0.05) are presented. CEHC indicates carboxyethylhydroxychroman. *Metabolites with a tier 2 certainty, which were not confirmed by a reference standard.
Figure 3.
Figure 3.
Scatterplots of Dietary Approaches to Stop Hypertension (DASH) diet–related metabolites and systolic blood pressure (SBP) or diastolic blood pressure (DBP). A, Serum tryptophan betaine in the DASH and control diet interventions in the DASH trial. B, Urine stachydrine in the DASH high-sodium compared with control high-sodium diet interventions in the DASH-Sodium trial. C, Urine N-methylglutamate in the DASH low-sodium compared with control high-sodium diet interventions in the DASH-Sodium trial. Blue line represents linear regression line, and gray shaded area represents 95% CIs.
Figure 4.
Figure 4.
Associations between Dietary Approaches to Stop Hypertension (DASH) diet–related urine metabolites and systolic or diastolic blood pressure in the DASH-Sodium trial. We compared DASH low-sodium diet and control high-sodium diet interventions. β coefficients and 95% CIs were calculated using multivariable linear regression models for 1 SD higher in metabolite, adjusting for age, sex, race, income, body mass index, and 24-hour urine creatinine. Only metabolites with significant interaction with diet interventions (P for interaction, <0.05) are presented. CEHC indicates carboxyethylhydroxychroman. *Metabolites with a tier 2 certainty, which were not confirmed by a reference standard.
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