Dataset Information

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

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).

SUBMITTER: Kim H

PROVIDER: S-EPMC10262995 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Kim Hyunju H Appel Lawrence J LJ Lichtenstein Alice H AH Wong Kari E KE Chatterjee Nilanjan N Rhee Eugene P EP Rebholz Casey M CM

Hypertension (Dallas, Tex. : 1979) 20230510 7

<h4>Background</h4>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.<h4>Methods</h4>Metabolomic profiling was conducted in serum and urine samples collected at the en ...[more]

PMID: 37161796

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Project description:BackgroundBoth sodium reduction and the DASH (Dietary Approaches to Stop Hypertension) diet, a diet rich in fruits, vegetables, and low-fat dairy products, and reduced in saturated fat and cholesterol, lower blood pressure. The separate and combined effects of these dietary interventions by baseline blood pressure (BP) has not been reported.ObjectivesThe authors compared the effects of low versus high sodium, DASH versus control, and both (low sodium-DASH vs. high sodium-control diets) on systolic blood pressure (SBP) by baseline BP.MethodsIn the DASH-Sodium (Dietary Patterns, Sodium Intake and Blood Pressure) trial, adults with pre- or stage 1 hypertension and not using antihypertensive medications, were randomized to either DASH or a control diet. On either diet, participants were fed each of 3 sodium levels (50, 100, and 150 mmol/day at 2,100 kcal) in random order over 4 weeks separated by 5-day breaks. Strata of baseline SBP were <130, 130 to 139, 140 to 149, and ≥150 mm Hg.ResultsOf 412 participants, 57% were women, and 57% were black; mean age was 48 years, and mean SBP/diastolic BP was 135/86 mm Hg. In the context of the control diet, reducing sodium (from high to low) was associated with mean SBP differences of -3.20, -8.56, -8.99, and -7.04 mm Hg across the respective baseline SBP strata listed (p for trend = 0.004). In the context of high sodium, consuming the DASH compared with the control diet was associated with mean SBP differences of -4.5, -4.3, -4.7, and -10.6 mm Hg, respectively (p for trend = 0.66). The combined effects of the low sodium-DASH diet versus the high sodium-control diet on SBP were -5.3, -7.5, -9.7, and -20.8 mm Hg, respectively (p for trend <0.001).ConclusionsThe combination of reduced sodium intake and the DASH diet lowered SBP throughout the range of pre- and stage 1 hypertension, with progressively greater reductions at higher levels of baseline SBP. SBP reductions in adults with the highest levels of SBP (≥150 mm Hg) were striking and reinforce the importance of both sodium reduction and the DASH diet in this high-risk group. Further research is needed to determine the effects of these interventions among adults with SBP ≥160 mm Hg. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH-Sodium]; NCT00000608).

Project description:BackgroundAdherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear.ObjectivesAmong free-living populations, we delineated metabolic signatures associated with the DASH diet adherence, 24-hour urinary sodium and potassium excretions, and the potential metabolic pathways involved.MethodsWe used 24-hour urinary metabolic profiling by proton nuclear magnetic resonance spectroscopy to characterize the metabolic signatures associated with the DASH dietary pattern score (DASH score) and 24-hour excretion of sodium and potassium among participants in the United States (n = 2164) and United Kingdom (n = 496) enrolled in the International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP). Multiple linear regression and cross-tabulation analyses were used to investigate the DASH-BP relation and its modulation by sodium and potassium. Potential pathways associated with DASH adherence, sodium and potassium excretion, and BP were identified using mediation analyses and metabolic reaction networks.ResultsAdherence to the DASH diet was associated with urinary potassium excretion (correlation coefficient, r = 0.42; P < 0.0001). In multivariable regression analyses, a 5-point higher DASH score (range, 7 to 35) was associated with a lower systolic BP by 1.35 mmHg (95% CI, -1.95 to -0.80 mmHg; P = 1.2 × 10-5); control of the model for potassium but not sodium attenuated the DASH-BP relation. Two common metabolites (hippurate and citrate) mediated the potassium-BP and DASH-BP relationships, while 5 metabolites (succinate, alanine, S-methyl cysteine sulfoxide, 4-hydroxyhippurate, and phenylacetylglutamine) were found to be specific to the DASH-BP relation.ConclusionsGreater adherence to the DASH diet is associated with lower BP and higher potassium intake across levels of sodium intake. The DASH diet recommends greater intake of fruits, vegetables, and other potassium-rich foods that may replace sodium-rich processed foods and thereby influence BP through overlapping metabolic pathways. Possible DASH-specific pathways are speculated but confirmation requires further study. INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov.

Project description:BackgroundThe blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and reduced sodium intake are well established. The effects on other biomarkers related to vascular health are of interest and might assist in explaining the effects of the DASH diet and sodium reduction.ObjectivesWe hypothesized that a low-sodium DASH diet improves (lowers) biomarkers of inflammation [C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR)] and mineral metabolism [phosphorus and fibroblast growth factor-23 (FGF23)].MethodsWe conducted a secondary analysis of the DASH-Sodium trial using frozen serum samples. This controlled feeding study randomly assigned 412 adults (≥22 y) with elevated blood pressure (120-159/80-95 mmHg) to consume either a DASH diet or control diet. Within each arm, participants received 3 sodium levels [low (1150 mg), intermediate (2300 mg), high (3450 mg)] in random sequence, each for 30 d. To maximize contrast, samples collected at the end of the low-sodium DASH (n = 198) and high-sodium control (n = 194) diets were compared. Between-diet differences in serum CRP, suPAR, phosphorus, and FGF23 concentrations were assessed using linear regression adjusted for age, sex, race, income, education, smoking status, and BMI.ResultsCRP concentrations did not differ between groups (P = 0.83), but suPAR was higher after the low-sodium DASH diet than the high-sodium control [geometric mean 2470 pg/mL (95% CI: 2380, 2560 pg/mL), compared with 2290 pg/mL (95% CI: 2210, 2380 pg/mL); P = 0.006]. Phosphorus was higher after the low-sodium DASH diet [geometric mean 3.50 mg/dL (95% CI: 3.43, 3.57 mg/dL)] compared with the high-sodium control diet [geometric mean 3.39 mg/dL (95% CI: 3.33, 3.46 mg/dL); P = 0.04]. FGF23 was also higher after the low-sodium DASH diet [geometric mean 35.3 pg/mL (95% CI: 33.3, 37.3 pg/mL) compared with 28.2 pg/mL (95% CI: 26.6, 29.8 pg/mL); P < 0.001].ConclusionsContrary to our hypothesis, biomarkers of inflammation and mineral metabolism were increased or unchanged by a low-sodium DASH diet compared with a high-sodium control diet in adults with elevated blood pressure.

Project description:Background and objectivesMetabolomics is a relatively new field of "-omics" research, focusing on high-throughput identification of small molecular weight metabolites. Diet has both acute and chronic effects on metabolic profiles; however, alterations in response to dietary sodium restriction (DSR) are completely unknown. The goal of this study was to explore changes in urine metabolites in response to DSR, as well as their association with previously reported improvements in vascular function with DSR.Design, setting, participants, & measurementsUsing stored urine samples from a 10-week randomized placebo-controlled crossover study of DSR in 17 middle-aged/older adults (six men and 11 women; mean age 62±8 years) who had moderately elevated systolic BP (130-159 mmHg) and were otherwise healthy, a liquid chromatography/mass spectrometry-based analysis of 289 metabolites was performed. This study identified metabolites that were significantly altered between the typical (153±29 mmol/d) and low (70±29 mmol/d) sodium conditions, as well as their baseline (typical sodium) association with responsiveness to previously reported improvements in vascular endothelial function (brachial artery flow-mediated dilation) and large elastic artery stiffness (aortic pulse wave velocity).ResultsOf the 289 metabolites surveyed, 10 were significantly altered (nine were upregulated and one was downregulated) during the low sodium condition, and eight of these exceeded our prespecified clinically significant threshold of a >40% change. These metabolites were involved in biologic pathways broadly related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. One metabolite, serine, was independently (positively) associated with previously reported improvements in the primary vascular outcome of brachial artery flow-mediated dilation.ConclusionsThis proof-of-concept study provides the first evidence that DSR is a stimulus that induces significant changes in urinary metabolomic profiles. Moreover, serine was independently associated with corresponding changes in vascular endothelial function after DSR. Larger follow-up studies will be required to confirm and further elucidate the metabolic pathways that are altered in response to DSR.

Project description:BackgroundThe relationship between dietary sodium intake and blood pressure (BP) has been tested in clinical trials and nonexperimental human studies, indicating a direct association. The exact shape of the dose-response relationship has been difficult to assess in clinical trials because of the lack of random-effects dose-response statistical models that can include 2-arm comparisons.MethodsAfter performing a comprehensive literature search for experimental studies that investigated the BP effects of changes in dietary sodium intake, we conducted a dose-response meta-analysis using the new 1-stage cubic spline mixed-effects model. We included trials with at least 4 weeks of follow-up; 24-hour urinary sodium excretion measurements; sodium manipulation through dietary change or supplementation, or both; and measurements of systolic and diastolic BP at the beginning and end of treatment.ResultsWe identified 85 eligible trials with sodium intake ranging from 0.4 to 7.6 g/d and follow-up from 4 weeks to 36 months. The trials were conducted in participants with hypertension (n=65), without hypertension (n=11), or a combination (n=9). Overall, the pooled data were compatible with an approximately linear relationship between achieved sodium intake and mean systolic as well as diastolic BP, with no indication of a flattening of the curve at either the lowest or highest levels of sodium exposure. Results were similar for participants with or without hypertension, but the former group showed a steeper decrease in BP after sodium reduction. Intervention duration (≥12 weeks versus 4 to 11 weeks), type of study design (parallel or crossover), use of antihypertensive medication, and participants' sex had little influence on the BP effects of sodium reduction. Additional analyses based on the BP effect of difference in sodium exposure between study arms at the end of the trial confirmed the results on the basis of achieved sodium intake.ConclusionsIn this dose-response analysis of sodium reduction in clinical trials, we identified an approximately linear relationship between sodium intake and reduction in both systolic and diastolic BP across the entire range of dietary sodium exposure. Although this occurred independently of baseline BP, the effect of sodium reduction on level of BP was more pronounced in participants with a higher BP level.

Dataset Information

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

Background

Methods

Results

Conclusions

Registration

Clinicaltrials

Clinicaltrials

Publications

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

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