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Urine Metabolites Associated with the Dietary Approaches to Stop Hypertension (DASH) Diet: Results from the DASH-Sodium Trial.
Kim, H, Lichtenstein, AH, Wong, KE, Appel, LJ, Coresh, J, Rebholz, CM
Molecular nutrition & food research. 2021;(3):e2000695
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Abstract
SCOPE Serum metabolomic markers of the Dietary Approaches to Stop Hypertension (DASH) diet are previously reported. In an independent study, the similarity of urine metabolomic markers are investigated. METHODS AND RESULTS In the DASH-Sodium trial, participants are randomly assigned to the DASH diet or control diet, and received three sodium interventions (high, intermediate, low) within each randomized diet group in random order for 30 days each. Urine samples are collected at the end of each intervention period and analyzed for 938 metabolites. Two comparisons are conducted: 1) DASH-high sodium (n = 199) versus control-high sodium (n = 193), and 2) DASH-low sodium (n = 196) versus control-high sodium. Significant metabolites identified using multivariable linear regression are compared and the top 10 influential metabolites identified using partial least-squares discriminant analysis to the results from the DASH trial. Nine out of 10 predictive metabolites of the DASH-high sodium and DASH-low sodium diets are identical. Most candidate biomarkers from the DASH trial replicated. N-methylproline, chiro-inositol, stachydrine, and theobromine replicated as influential metabolites of DASH diets. CONCLUSIONS Candidate biomarkers of the DASH diet identified in serum replicated in urine. Replicated influential metabolites are likely to be objective biomarkers of the DASH diet.
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Impact of Moderate Sodium Restriction and Hydrochlorothiazide on Iodine Excretion in Diabetic Kidney Disease: Data from a Randomized Cross-Over Trial.
Binnenmars, SH, Corpeleijn, E, Kwakernaak, AJ, Touw, DJ, Kema, IP, Laverman, GD, Bakker, SJL, Navis, G
Nutrients. 2019;(9)
Abstract
Sodium restriction may potentially reduce iodine intake. This study aimed to determine the effect of sodium restriction (dietary counseling) on 24-h urinary iodine excretion. Diuretics provide an alternative to sodium restriction and are frequently added to sodium restriction, so the effects of hydrochlorothiazide (50 mg daily) and combined therapy were also studied. We performed a post-hoc analysis of a Dutch multi-center, randomized cross-over trial in 45 patients with diabetic kidney disease with a mean age of 65 ± 9 years, mean eGFR of 65 ± 27 mL/min/1.73 m2, median albuminuria of 648 [230-2008] mg/24 h and 84% were male. During regular sodium intake with placebo, mean 24 h urinary sodium and iodine excretion were 224 ± 76 mmol/24 h and 252 ± 94 ug/24 h, respectively (r = 0.52, p < 0.001). Mean iodine excretion did not change significantly if sodium restriction and hydrochlorothiazide were applied separately; mean difference -8 ug/day (95% CI -38, 22; p = 0.6) and 14 ug/day (95% CI -24, 52; p = 0.5), respectively. Combined therapy induced a significant decrease in mean iodine excretion (-37 ug/day; 95% CI -67, -7; p = 0.02), yet this was not seen to a clinically meaningful level. The number of patients with an estimated intake below recommended daily allowances did not differ significantly between the four treatment periods (p = 0.3). These findings show that sodium restriction is not a risk factor for iodine deficiency.
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Relationship of Sodium Intake and Blood Pressure Varies With Energy Intake: Secondary Analysis of the DASH (Dietary Approaches to Stop Hypertension)-Sodium Trial.
Murtaugh, MA, Beasley, JM, Appel, LJ, Guenther, PM, McFadden, M, Greene, T, Tooze, JA
Hypertension (Dallas, Tex. : 1979). 2018;(5):858-865
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Dietary Na recommendations are expressed as absolute amounts (mg/d) rather than as Na density (mg/kcal). Our objective was to determine whether the strength of the relationship of Na intake with blood pressure (BP) varied with energy intake. The DASH (Dietary Approaches to Stop Hypertension)-Sodium trial was a randomized feeding trial comparing 2 diets (DASH and control) and 3 levels of Na density. Participants with pre- or stage 1 hypertension consumed diets for 30 days in random order; energy intake was controlled to maintain body weight. This secondary analysis of 379 non-Hispanic black and white participants used mixed-effects models to assess the association of Na and energy intakes with BP. The relationships between absolute Na and both systolic and diastolic BP varied with energy intake. BP rose more steeply with increasing Na at lower energy intake than at higher energy intake (P interaction<0.001). On the control diet with 2300 mg Na, both systolic and diastolic BP were higher (3.0 mm Hg; 95% confidence interval, 0.2-5.8; and 2.7 mm Hg; 95% confidence interval, 1.0-4.5, respectively) among those with lower energy intake (higher Na density) than among those with higher energy intake (lower Na density). The association of Na with systolic BP was stronger at lower levels of energy intake in both blacks and whites (P<0.001). The association of Na and diastolic BP varied with energy intake only among blacks (P=0.001). Sodium density should be considered as a metric for expressing dietary Na recommendations.
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Adherence to hemodialysis dietary sodium recommendations: influence of patient characteristics, self-efficacy, and perceived barriers.
Clark-Cutaia, MN, Ren, D, Hoffman, LA, Burke, LE, Sevick, MA
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2014;(2):92-9
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OBJECTIVE To identify characteristics of hemodialysis patients most likely to experience difficulty adhering to sodium restrictions associated with their dietary regimen. DESIGN Secondary analysis using baseline data from an ongoing randomized clinical trial examining the effects of a technology-supported behavioral intervention on dietary sodium intake in hemodialysis patients. SETTING Thirteen dialysis centers in southwestern Pennsylvania. SUBJECTS We included 122 participants (61% women; 48% African American) aged 61 ± 14 years undergoing maintenance, intermittent hemodialysis for end-stage renal disease. MAIN OUTCOME MEASURES Normalized dietary sodium intake, adjusted interdialytic weight gain, perceived problems, and self-efficacy for restricting dietary sodium. RESULTS Younger participants were more likely to report problems managing their hemodialysis diet and low self-efficacy for restricting sodium intake. Consistent with these findings, younger participants had a higher median sodium intake and higher average adjusted interdialytic weight gain. Females reported more problems managing their diet. Race, time on dialysis, and perceived income adequacy did not seem to influence outcome measures. CONCLUSION Our findings suggest that patients who are younger and female encounter more difficulty adhering to the hemodialysis regimen. Hence, there may be a need to individualize counseling and interventions for these individuals. Further investigation is needed to understand the independent effects of age and gender on adherence to hemodialysis dietary recommendations and perceived self-efficacy.
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Blood pressure differences associated with Optimal Macronutrient Intake Trial for Heart Health (OMNIHEART)-like diet compared with a typical American Diet.
Molitor, J, Brown, IJ, Chan, Q, Papathomas, M, Liverani, S, Molitor, N, Richardson, S, Van Horn, L, Daviglus, ML, Dyer, A, et al
Hypertension (Dallas, Tex. : 1979). 2014;(6):1198-204
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The Dietary Approaches to Stop Hypertension-Sodium (DASH-Sodium) trial demonstrated beneficial effects on blood pressure (BP) of the DASH diet with lower sodium intake when compared with typical American diet. The subsequent Optimal Macronutrient Intake Trial for Heart Health (OMNIHEART) trial reported additional BP benefits from replacing carbohydrate in the DASH diet with either protein or monounsaturated fats. The primary aim of this study is to assess possible BP benefits of an OMNIHEART-like diet in free-living Americans using cross-sectional US population data of the International Study of Macronutrients, Micronutrients and Blood Pressure (INTERMAP) study. The INTERMAP data include four 24-hour dietary recalls, 2 timed 24-hour urine collections, 8 BP readings for 2195 individuals aged 40 to 59 years from 8 US INTERMAP population samples. Analyses are conducted using 2 approaches: (1) regression of BP on a linear OMNIHEART nutrient score calculated for each individual and (2) a Bayesian approach comparing estimated BP levels of an OMNIHEART-like nutrient profile with a typical American nutrient profile. After adjustment for potential confounders, an OMNIHEART score higher by 1 point was associated with systolic/diastolic BP differences of -1.0/-0.5 mm Hg (both P<0.001). Mean systolic/diastolic BPs were 111.3/68.4 and 115.2/70.6 mm Hg for Bayesian OMNIHEART and Control profiles, respectively, after controlling for possible confounders, with BP differences of -3.9/-2.2 mm Hg, P(difference≤0)=0.98/0.96. Findings were comparable for men and women, for nonhypertensive participants, and with adjustment for antihypertensive treatment. Our findings from data on US population samples indicate broad generalizability of OMNIHEART results beyond the trial setting and support recommendations for an OMNIHEART-style diet for prevention/control of population-wide adverse BP levels.
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Effects of sodium intake and diet on racial differences in urinary potassium excretion: results from the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial.
Turban, S, Thompson, CB, Parekh, RS, Appel, LJ
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2013;(1):88-95
Abstract
BACKGROUND We previously showed that African Americans excreted less urinary potassium than whites, even while consuming similar diets in the Dietary Approaches to Stop Hypertension (DASH) trial. We hypothesized that a low-sodium diet may eliminate these differences. STUDY DESIGN Data from the DASH-Sodium randomized controlled feeding trial were analyzed. SETTING & PARTICIPANTS 412 adults with prehypertension or stage 1 hypertension. INTERVENTION Random assignment to either a typical American "control" diet (1.7 g [43 mEq] potassium/2,100 kcal/d) or the DASH diet (4.1 g [105 mEq] potassium/2,100 kcal/d). Within each diet, participants received 3 levels of sodium intake in random order for 30 days. OUTCOMES & MEASUREMENTS 24-hour urine samples were analyzed at the end of each period. The primary outcome was urinary potassium excretion. RESULTS On the DASH diet, African Americans consistently excreted significantly less urinary potassium (mean 24-hour urinary potassium excretion, 2,594 ± 961 mg [66 ± 25 mEq]) than whites (3,412 ± 1,016 mg [87 ± 26 mEq]) at the highest sodium level; adjusted (P < 0.001); this difference was not altered by sodium level (P = 0.6 comparing white to African American difference in urinary potassium excretion on high- vs low-sodium diet). In contrast, there was a smaller but significant white-African American difference in mean daily urinary potassium excretion in participants fed the control/high-sodium diet that was not present in the control/low-sodium diet (adjusted differences of 281 mg [7 mEq]/d vs 20 mg [0.5 mEq]/d, respectively; P = 0.007). Significant interactions were found between race and diet (P < 0.001) and between race and sodium (P = 0.02). LIMITATIONS Single rather than multiple urine collections were available at each time. Lack of stool potassium and sweat potassium values. CONCLUSIONS Racial differences in urinary potassium excretion depend on sodium intake and diet. Our results may help explain the previously documented large variability in urinary potassium excretion.
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Estimating 24-hour urinary sodium excretion from casual urinary sodium concentrations in Western populations: the INTERSALT study.
Brown, IJ, Dyer, AR, Chan, Q, Cogswell, ME, Ueshima, H, Stamler, J, Elliott, P, ,
American journal of epidemiology. 2013;(11):1180-92
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High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984-1987 at the ages of 20-59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were -1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and -1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity.
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Urinary sodium and potassium excretion and risk of cardiovascular events.
O'Donnell, MJ, Yusuf, S, Mente, A, Gao, P, Mann, JF, Teo, K, McQueen, M, Sleight, P, Sharma, AM, Dans, A, et al
JAMA. 2011;(20):2229-38
Abstract
CONTEXT The precise relationship between sodium and potassium intake and cardiovascular (CV) risk remains uncertain, especially in patients with CV disease. OBJECTIVE To determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and CV events in patients with established CV disease or diabetes mellitus. DESIGN, SETTING, AND PATIENTS Observational analyses of 2 cohorts (N = 28,880) included in the ONTARGET and TRANSCEND trials (November 2001-March 2008 from initial recruitment to final follow-up). We estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample (Kawasaki formula). We used restricted cubic spline plots to describe the association between sodium and potassium excretion and CV events and mortality, and to identify reference categories for sodium and potassium excretion. We used Cox proportional hazards multivariable models to determine the association of urinary sodium and potassium with CV events and mortality. MAIN OUTCOME MEASURES CV death, myocardial infarction (MI), stroke, and hospitalization for congestive heart failure (CHF). RESULTS At baseline, the mean (SD) estimated 24-hour excretion for sodium was 4.77 g (1.61); and for potassium was 2.19 g (0.57). After a median follow-up of 56 months, the composite outcome occurred in 4729 (16.4%) participants, including 2057 CV deaths, 1412 with MI, 1282 with stroke, and 1213 with hospitalization for CHF. Compared with the reference group with estimated baseline sodium excretion of 4 to 5.99 g per day (n = 14,156; 6.3% participants with CV death, 4.6% with MI, 4.2% with stroke, and 3.8% admitted to hospital with CHF), higher baseline sodium excretion was associated with an increased risk of CV death (9.7% for 7-8 g/day; hazard ratio [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for >8 g/day; HR, 1.66; 95% CI, 1.31-2.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for >8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for >8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.12-2.05 for >8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for <2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n = 2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for >3 g/day) on multivariable analysis. CONCLUSIONS The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.
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Modulation of the BP response to diet by genes in the renin-angiotensin system and the adrenergic nervous system.
Svetkey, LP, Harris, EL, Martin, E, Vollmer, WM, Meltesen, GT, Ricchiuti, V, Williams, G, Appel, LJ, Bray, GA, Moore, TJ, et al
American journal of hypertension. 2011;(2):209-17
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BACKGROUND Essential hypertension results from the interaction of several genetic and environmental factors. Identification of genetic factors that modulate blood pressure (BP) response to interventions can lead to improved strategies for prevention and control. The purpose of this study was to identify genes that modulate BP response to dietary interventions. METHODS We used data and samples collected in two randomized feeding studies to determine the extent to which genetic architecture is associated with the effect on BP of sodium intake and the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. Participants in both trials were adults with above-optimal BP or unmedicated stage 1 hypertension. Genomic DNA was typed for several candidate genes. RESULTS The effect of sodium intake on BP differed by genotype at the angiotensinogen, β2-adrenergic receptor, and kallikrein loci. The effect of DASH dietary pattern on BP differed by genotype at the β2-adrenergic receptor locus. CONCLUSIONS These findings have implications for understanding the mechanism(s) through which diet affects BP, the heterogeneity of these effects, and the extent to which dietary interventions can modulate genetic predisposition.
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Differential associations of dietary sodium and potassium intake with blood pressure: a focus on pulse pressure.
Buyck, JF, Blacher, J, Kesse-Guyot, E, Castetbon, K, Galan, P, Safar, M, Hercberg, S, Czernichow, S
Journal of hypertension. 2009;(6):1158-64
Abstract
OBJECTIVE Dietary sodium and potassium intakes are factors known to influence blood pressure (BP) through different pathways. These mechanisms likely result in differential effects on parameters characterizing BP. The aim of the study was to evaluate relationships between both sodium and potassium intake and all BP parameters--namely systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP)--simultaneously in a large general population. METHODS The present cross-sectional analysis was performed on 4919 middle-aged men and women, participants in the SU.VI.MAX study. Dietary intake was assessed through at least three 24-h dietary records. SBP and DBP were measured twice at a single visit after 10 min rest and averaged. Analysis of covariance was used to test for difference in BP parameters across tertiles of dietary sodium and potassium intakes. RESULTS In univariate analysis, increased dietary sodium and potassium intakes were both significantly associated with increased BP parameters (P < 0.0001). After relevant adjustments, sodium intake remained positively associated with PP (P = 0.006), whereas potassium intake became negatively associated with SBP, DBP and MAP (P < or = 0.02) but was not linked to PP (P = 0.56). CONCLUSION The positive association between dietary sodium intake and PP observed in the present study provides further evidence for the current concept linking sodium to rise in BP through modification and stiffening of the arterial wall, whereas negative associations between dietary potassium intake and both SBP and DBP, hence MAP, support the vasodilator properties of this latter nutrient.