Metabolomic profiles associated with blood pressure reduction in response to the DASH and DASH-Sodium dietary interventions

Authors: KIM, HYUNJU - Johns Hopkins University; APPEL, LAWRENCE - Johns Hopkins University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WONG, KARI - Metabolon, Inc; CHATTERJEE, NILANJAN - Johns Hopkins University; RHEE, EUGENE - Massachusetts General Hospital; REBHOLZ, CASEY - Johns Hopkins University

Submitted to: Hypertension
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2023
Publication Date: 7/1/2023
Citation: Kim, H., Appel, L.J., Lichtenstein, A.H., Wong, K.E., Chatterjee, N., Rhee, E.P., Rebholz, C.M. 2023. Metabolomic profiles associated with blood pressure reduction in response to the DASH and DASH-Sodium dietary interventions. Hypertension. https://doi.org/10.1161/HYPERTENSIONAHA.123.20901.
DOI: https://doi.org/10.1161/HYPERTENSIONAHA.123.20901

Interpretive Summary: Elevated blood pressure is a risk factor for stroke and heart disease. Diet plays an important role in maintaining a healthy blood pressure. Two studies had previously been conducted to compare the impact of different dietary patterns on blood pressure lowering. Participants were provided with all their food and beverages. We used the urine and plasma samples collected during the course of those studies to determine if specific marker (metabolite) concentrations resulting from the different dietary patterns were associated with blood pressure lowering. Identified were 41 potential markers that were both associated with blood pressure lowering and differed among dietary intervention. If validated, these markers may help identify individuals with dietary patterns that would benefit from modification to promote blood pressure lowering and determine the mechanisms of how certain dietary patterns affect blood pressure.

Technical Abstract: Background: The Dietary Approaches to Stop Hypertension (DASH) diets significantly reduced blood pressure in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. Objectives: We identified metabolites associated with systolic or diastolic blood pressure changes induced by dietary interventions during randomized controlled intervention trials. Methods: Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions for two multicenter, randomized controlled feeding trials: DASH (N=219) and DASH-Sodium (N=395). Using multivariable linear regression models associations were examined between metabolites and change in systolic and diastolic blood pressure. Tested for interactions between diet interventions and metabolites were 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 conducted for metabolites identified as significantly different. Results: Sixty-five significant interactions were identified [DASH=12; DASH-high sodium=35; DASH-low sodium=18] between metabolites and systolic or diastolic blood pressure. In the DASH trial, serum tryptophan betaine was associated with reductions in diastolic blood pressure in participants consuming the DASH diets, but not control diets. In the DASH-Sodium trial, urine levels of N-methylglutamate, and proline derivatives (e.g., stachydrine, 3-hydroxystachydrine, N-methylproline, N-methylhydroxyproline) were associated with reductions in systolic or diastolic blood pressure in participants consuming the DASH diets, but not control diets. Seven pathways, such as tocopherol metabolism, tyrosine metabolism, thiamine metabolism, pantothenate and CoA metabolism, and ceramides, were overrepresented. Conclusions: Using data from randomized feeding studies, we identified metabolites that were associated with blood pressure lowering in response to a dietary intervention. These metabolites highlight pathways through which the DASH diet reduced blood pressure.