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

Overview

Journal Hypertension

Date 2023 May 10

PMID 37161796

Authors

Hyunju Kim

Lawrence J Appel

Alice H Lichtenstein

Kari E Wong

Nilanjan Chatterjee

Eugene P Rhee

Casey M Rebholz

Affiliations

Soon will be listed here.

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 ( 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 ( 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/NCT00000608; Unique identifier: NCT00000608 (DASH-Sodium trial).

Citing Articles

Nutrition and Hypertension Researches in 2023: focus on salt intake and blood pressure.

Matsumoto C Hypertens Res. 2025; .

PMID: 39871003 DOI: 10.1038/s41440-024-02089-5.

A Metabolome Wide Association Study of Fruit and Vegetable Consumption and Associations with Cardiovascular Disease Risk Factors: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) Study.

Oude Griep L, Chekmeneva E, Van Horn L, Chan Q, Daviglus M, Frost G J Nutr. 2024; 155(1):122-131.

PMID: 39536968 PMC: 11795696. DOI: 10.1016/j.tjnut.2024.11.004.

Plant Protein but Not Animal Protein Consumption Is Associated with Frailty through Plasma Metabolites.

Tanaka T, Das J, Jin Y, Tian Q, Moaddel R, Moore A Nutrients. 2023; 15(19).

PMID: 37836476 PMC: 10574762. DOI: 10.3390/nu15194193.

References

DiNicolantonio J, Niazi A, Lavie C, OKeefe J, Ventura H . Thiamine supplementation for the treatment of heart failure: a review of the literature. Congest Heart Fail. 2013; 19(4):214-22. DOI: 10.1111/chf.12037. View

Svetkey L, Sacks F, Obarzanek E, Vollmer W, Appel L, Lin P . The DASH Diet, Sodium Intake and Blood Pressure Trial (DASH-sodium): rationale and design. DASH-Sodium Collaborative Research Group. J Am Diet Assoc. 1999; 99(8 Suppl):S96-104. DOI: 10.1016/s0002-8223(99)00423-x. View

Sumner L, Amberg A, Barrett D, Beale M, Beger R, Daykin C . Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics. 2013; 3(3):211-221. PMC: 3772505. DOI: 10.1007/s11306-007-0082-2. View

Landberg R, Aman P, Friberg L, Vessby B, Adlercreutz H, Kamal-Eldin A . Dose response of whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine in relation to intake. Am J Clin Nutr. 2008; 89(1):290-6. DOI: 10.3945/ajcn.2008.26709. View

Wang D, Toledo E, Hruby A, Rosner B, Willett W, Sun Q . Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevención con Dieta Mediterránea). Circulation. 2017; 135(21):2028-2040. PMC: 5496817. DOI: 10.1161/CIRCULATIONAHA.116.024261. View

Kim H, Hu E, Wong K, Yu B, Steffen L, Seidelmann S . Serum Metabolites Associated with Healthy Diets in African Americans and European Americans. J Nutr. 2020; 151(1):40-49. PMC: 7779213. DOI: 10.1093/jn/nxaa338. View

Appel L, Moore T, Obarzanek E, Vollmer W, Svetkey L, Sacks F . A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997; 336(16):1117-24. DOI: 10.1056/NEJM199704173361601. View

Tanaka T, Sohmiya K, Kono T, Terasaki F, Horie R, Ohkaru Y . Thiamine attenuates the hypertension and metabolic abnormalities in CD36-defective SHR: uncoupling of glucose oxidation from cellular entry accompanied with enhanced protein O-GlcNAcylation in CD36 deficiency. Mol Cell Biochem. 2006; 299(1-2):23-35. DOI: 10.1007/s11010-005-9032-3. View

Loo R, Zou X, Appel L, Nicholson J, Holmes E . Characterization of metabolic responses to healthy diets and association with blood pressure: application to the Optimal Macronutrient Intake Trial for Heart Health (OmniHeart), a randomized controlled study. Am J Clin Nutr. 2018; 107(3):323-334. DOI: 10.1093/ajcn/nqx072. View

10.

Sun H, Zhu X, Cai W, Qiu L . Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway. Int J Mol Sci. 2017; 18(4). PMC: 5412428. DOI: 10.3390/ijms18040844. View

11.

Stamler J, Brown I, Daviglus M, Chan Q, Kesteloot H, Ueshima H . Glutamic acid, the main dietary amino acid, and blood pressure: the INTERMAP Study (International Collaborative Study of Macronutrients, Micronutrients and Blood Pressure). Circulation. 2009; 120(3):221-8. PMC: 4048930. DOI: 10.1161/CIRCULATIONAHA.108.839241. View

12.

Zhu Y, Frank J, Riphagen I, Minovic I, Vos M, Eggersdorfer M . Associations of 24 h urinary excretions of α- and γ-carboxyethyl hydroxychroman with plasma α- and γ-tocopherol and dietary vitamin E intake in older adults: the Lifelines-MINUTHE Study. Eur J Nutr. 2022; 61(7):3755-3765. PMC: 9464128. DOI: 10.1007/s00394-022-02918-8. View

13.

Wagner-Golbs A, Neuber S, Kamlage B, Christiansen N, Bethan B, Rennefahrt U . Effects of Long-Term Storage at -80 °C on the Human Plasma Metabolome. Metabolites. 2019; 9(5). PMC: 6572224. DOI: 10.3390/metabo9050099. View

14.

Prasad A, Andrews N, Padder F, Husain M, Quyyumi A . Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. J Am Coll Cardiol. 1999; 34(2):507-14. DOI: 10.1016/s0735-1097(99)00216-8. View

15.

Elliott P, Stamler J, Dyer A, Appel L, Dennis B, Kesteloot H . Association between protein intake and blood pressure: the INTERMAP Study. Arch Intern Med. 2006; 166(1):79-87. PMC: 6593153. DOI: 10.1001/archinte.166.1.79. View

16.

Giffen C, Carroll L, Adams J, Brennan S, Coady S, Wagner E . Providing Contemporary Access to Historical Biospecimen Collections: Development of the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biopreserv Biobank. 2015; 13(4):271-9. PMC: 4559201. DOI: 10.1089/bio.2014.0050. View

17.

Ma T, Liu T, Xie P, Jiang S, Yi W, Dai P . UPLC-MS-based urine nontargeted metabolic profiling identifies dysregulation of pantothenate and CoA biosynthesis pathway in diabetic kidney disease. Life Sci. 2020; 258:118160. DOI: 10.1016/j.lfs.2020.118160. View

18.

McCullough M, Maliniak M, Stevens V, Carter B, Hodge R, Wang Y . Metabolomic markers of healthy dietary patterns in US postmenopausal women. Am J Clin Nutr. 2019; 109(5):1439-1451. DOI: 10.1093/ajcn/nqy385. View

19.

Walker M, Song R, Xu X, Gerszten R, Ngo D, Clish C . Proteomic and Metabolomic Correlates of Healthy Dietary Patterns: The Framingham Heart Study. Nutrients. 2020; 12(5). PMC: 7284467. DOI: 10.3390/nu12051476. View

20.

Sacks F, Obarzanek E, Windhauser M, Svetkey L, Vollmer W, McCullough M . Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure. Ann Epidemiol. 1995; 5(2):108-18. DOI: 10.1016/1047-2797(94)00055-x. View