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Background: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health., Objectives: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk., Methods: A total of 9361 participants from the Atherosclerosis Risk in Communities visit 3 (1993-1995) were included. Dietary intake was assessed using a 66-item food-frequency questionnaire and the processing levels were categorized on the basis of the Nova classification. Plasma proteins were detected using an aptamer-based proteomic assay. We used multivariable linear regressions to examine the association between ultra-processed food and proteins, and Cox proportional hazard models to identify associations between ultra-processed food-related proteins and health outcomes. Models extensively controlled for sociodemographic characteristics, health behaviors, and clinical factors., Results: Eight proteins (6 positive, 2 negative) were identified as significantly associated with ultra-processed food consumption. Over a median follow-up of 22 y, there were 1276, 3084, and 5127 cases of CHD, CKD, and death, respectively. Three, 5, and 3 ultra-processed food-related proteins were associated with each outcome, respectively. One protein (β-glucuronidase) was significantly associated with a higher risk of all 3 outcomes, and 3 proteins (receptor-type tyrosine-protein phosphatase U, C-C motif chemokine 25, and twisted gastrulation protein homolog 1) were associated with a higher risk of 2 outcomes., Conclusions: We identified a panel of protein biomarkers that were significantly associated with ultra-processed food consumption. These proteins may be considered potential biomarkers for ultra-processed food intake and may elucidate the biological processes through which ultra-processed foods impact health outcomes., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Adherence 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., Objectives: Among 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., Methods: We 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., Results: Adherence 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., Conclusions: Greater 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Online tools are increasingly utilized in clinical trial recruitment. A/B testing is an effective technology used in political campaigns and commercial marketing to improve contributions or sales. However, to our knowledge, A/B has not been described in the context of clinical trial recruitment., Methods: Two A/B testing experiments were implemented on the recruitment website of the Study To Understand Fall Reduction and Vitamin D in You (STURDY), a response-adaptive, two-stage, randomized controlled trial. Commercial A/B platforms randomized web-users to different versions of the trial's website landing page; Experiment 1 included two infographic versions and Experiment 2 included three video versions. We compared web-user engagement metrics between each version and the original landing page. We determined the effect of each version compared to the original landing page on the likelihood of a web-user to (1) request more information about the trial, (2) complete a screening visit, or (3) enroll in the trial., Results: A total of 2605 and 374 web-users visited the trial's website during Experiment 1 and 2, respectively. Response to the online interest form significantly differed by infographic version in Experiment 1. The number of individuals who engaged with website content and pages significantly differed by video in Experiment 2., Conclusion: In a pilot study implementing A/B testing of a clinical trial recruitment website, different versions of the website led to differences in web-user engagement and interest in the trial. A/B testing tools offer a promising approach to test the effectiveness of clinical trial recruitment materials and to optimize recruitment campaigns., Clinical Trial Registration: This trial is registered at ClinicalTrials.gov. The trial registration number is NCT02166333. The URL is: https://clinicaltrials.gov/ct2/show/NCT02166333 Trial Registration Number: NCT02166333 Trial Register: ClinicalTrials.gov., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The 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., Objectives: We 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)]., Methods: We 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., Results: CRP 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]., Conclusions: Contrary 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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: In individuals with chronic kidney disease (CKD), healthy dietary patterns are inversely associated with CKD progression. Metabolomics, an approach that measures many small molecules in biofluids, can identify biomarkers of healthy dietary patterns., Objectives: We aimed to identify known metabolites associated with greater adherence to 4 healthy dietary patterns in CKD patients., Methods: We examined associations between 486 known plasma metabolites and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and alternate Mediterranean diet (aMED) in 1056 participants (aged 21-74 y at baseline) in the Chronic Renal Insufficiency Cohort (CRIC) Study. Usual dietary intake was assessed using a semiquantitative FFQ. We conducted multivariable linear regression models to study associations between healthy dietary patterns and individual plasma metabolites, adjusting for sociodemographic characteristics, health behaviors, and clinical factors. We used principal component analysis to identify groups of metabolites associated with individual food components within healthy dietary patterns., Results: After Bonferroni correction, we identified 266 statistically significant diet-metabolite associations (HEI: n = 60; AHEI: n = 78; DASH: n = 77; aMED: n = 51); 78 metabolites were associated with >1 dietary pattern. Lipids with a longer acyl chain length and double bonds (unsaturated) were positively associated with all 4 dietary patterns. A metabolite pattern low in saturated diacylglycerols and triacylglycerols, and a pattern high in unsaturated triacylglycerols was positively associated with intake of healthy food components. Plasmalogens were negatively associated with the consumption of nuts and legumes and healthy fat, and positively associated with the intake of red and processed meat., Conclusions: We identified many metabolites associated with healthy dietary patterns, indicative of food consumption. If replicated, these metabolites may be considered biomarkers of healthy dietary patterns in patients with CKD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The Dietary Approaches to Stop Hypertension (DASH) diet, a high-carbohydrate diet, is highly recommended based on its cardiovascular risk benefits, yet adherence remains persistently low. How subjective impressions of this diet contribute to adherence has not been thoroughly explored. The OmniCarb trial, which compared DASH-style diets varying in glycemic index (GI) and carbohydrate amount, surveyed subjective impressions of such diets., Objectives: We examined the effects of GI and carbohydrate amount on qualitative aspects of diet acceptability through secondary outcomes in the OmniCarb trial., Methods: OmniCarb was a randomized, crossover trial of 4 DASH-style diets varying by GI (≥65 compared with ≤45) and carbohydrate amount (40% compared with 58% kcal) in overweight or obese (BMI ≥25 kg/m2) adults (n = 163). Participants consumed each diet in random order over 5-wk periods, separated by 2-wk washouts. At baseline and the end of each feeding period, participants rated hunger, diet satisfaction, and gastrointestinal symptoms (diarrhea/loose stools, constipation, bloating, nausea, and heartburn)., Results: Participant mean age was 52 y, with 52% women, 51% non-Hispanic black, and 56% obese (BMI ≥30). Compared with baseline, all intervention diets decreased heartburn, increased diarrhea/loose stools, and increased bloating, but did not significantly affect constipation or nausea. Compared with lower carbohydrate diets, higher carbohydrate diets increased hunger (RR: 1.16; 95% CI: 1.04, 1.30), increased diet satisfaction (RR: 1.10; 95% CI: 1.01, 1.20), and increased heartburn (RR: 1.49; 95% CI: 1.09, 2.04). Compared with lower GI diets, higher GI diets did not affect hunger (RR: 0.92; 95% CI: 0.83, 1.02), decreased diet satisfaction (RR: 0.83; 95% CI: 0.75, 0.92), and did not affect heartburn (RR: 0.89; 95% CI: 0.70, 1.13). There were no between-diet differences for diarrhea/loose stools, constipation, bloating, and nausea., Conclusions: Although a higher carbohydrate amount in DASH-style diets can increase diet satisfaction, it can also decrease satiety and increase heartburn in adults with overweight or obesity.This trial is registered at clinicaltrials.gov as NCT00608049., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Background: Dietary recommendations to prevent gout emphasize a low-purine diet. Recent evidence suggests that the Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate while also improving blood pressure and lipids., Objective: To compare the effects of DASH-style diets emphasizing different macronutrient proportions on serum urate reduction., Methods: We conducted a secondary analysis of the Optimal Macronutrient Intake Trial to Prevent Heart Disease feeding study, a 3-period, crossover design, randomized trial of adults with prehypertension or hypertension. Participants were provided with 3 DASH-style diets in random order, each for 6 wk. Each DASH-style diet emphasized different macronutrient proportions: a carbohydrate-rich (CARB) diet, a protein-rich (PROT) diet, and an unsaturated fat-rich (UNSAT) diet. In the PROT diet, approximately half of the protein came from plant sources. We compared the effects of these diets on serum urate at weeks 4 and 6 of each feeding period., Results: Of the 163 individuals included in the final analysis, the mean serum urate at baseline was 5.1 mg/dL. Only the PROT diet reduced serum urate from baseline at the end of the 6-wk feeding period (-0.16 mg/dL; 95% CI: -0.28, -0.04; P = 0.007). Neither the CARB diet (-0.03 mg/dL; 95% CI: -0.14, 0.09; P = 0.66) nor the UNSAT diet (-0.01 mg/dL; 95% CI: -0.12, 0.09; P = 0.78) reduced serum urate from baseline. The PROT diet lowered serum urate by 0.12 mg/dL (95% CI: -0.20, -0.03; P = 0.006) compared with CARB and by 0.12 mg/dL (95% CI: -0.20, -0.05; P = 0.002) compared with UNSAT., Conclusions: A DASH-style diet emphasizing plant-based protein lowered serum urate compared with those emphasizing carbohydrates or unsaturated fat. Future trials should test the ability of a DASH-style diet emphasizing plant-based protein to lower serum urate and prevent gout flares in patients with gout. This trial was registered at clinicaltrials.gov as NCT00051350., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Healthy diet is essential in the management of chronic kidney disease (CKD) and preventing related comorbidities. Food outlet access has been studied in the general population; however, the influence of the local food environment on dietary intake among people with CKD has not been evaluated., Objectives: This study examined the associations of food outlet density and type of outlets with dietary intake in a multicenter cohort of racially and ethnically diverse patients with CKD., Methods: The Chronic Renal Insufficiency Cohort Study is a multicenter prospective study of patients with CKD that used a validated food frequency questionnaire to capture dietary intake at the baseline visit. This is a cross-sectional analysis of 2,484 participants recruited in 2003-2006 from seven Chronic Renal Insufficiency Cohort Study centers. Food outlet data were used to construct a count of the number of fast-food restaurants, convenience stores, and grocery stores per 10,000 population for each geocoded census block group. Multivariable linear and logistic regression models were used to evaluate the associations between measures of food outlet availability and dietary factors., Results: The proportion of participants living in zero-, low-, and high-food outlet density areas differed by gender, race or ethnicity, and income level. Among male subjects, living in areas with zero or the highest number of outlets was associated with having the highest caloric intakes in multivariable models. Male subjects living in areas with zero outlets consumed the highest levels of sodium and phosphorous. Female subjects living in areas with zero outlets had the lowest average intake of calories, sodium, and phosphorous. Among low-income female subjects, close proximity to more outlets was associated with higher calorie consumption. Among all participants, access to fast-food restaurants was not associated with an unhealthy diet score, and access to grocery stores was not associated with a healthy diet score., Conclusions: Average caloric and nutrient intakes differed by outlet availability; however, there were no strong associations with type of food outlet. This should be considered when developing food-focused public health policies., Competing Interests: Author Contributions J. P. Lash, E. Cedillo-Couvert, and A. C. Ricardo conceived the research idea and study design. E. Cedillo-Couvert performed the geocoding and data linkage. J. M. Madrigal completed the analyses and led the writing. All authors assisted with data interpretation, writing, editing, and the final review of the manuscript., (Copyright © 2020 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Excess salt intake contributes to hypertension and increased cardiovascular disease risk. Efforts to implement effective salt-reduction strategies require accurate data on the sources of salt consumption. We therefore performed a systematic review to identify the sources of dietary salt around the world. We systematically searched peer-reviewed and gray literature databases for studies that quantified discretionary (salt added during cooking or at the table) and nondiscretionary sources of salt and those that provided information about the food groups contributing to dietary salt intake. Exploratory linear regression analysis was also conducted to assess whether the proportion of discretionary salt intake is related to the gross domestic product (GDP) per capita of a country. We identified 80 studies conducted in 34 countries between 1975 and 2018. The majority (n = 44, 55%) collected data on dietary salt sources within the past 10 y and were deemed to have a low or moderate risk of bias (n = 75, 94%). Thirty-two (40%) studies were judged to be nationally representative. Populations in Brazil, China, Costa Rica, Guatemala, India, Japan, Mozambique, and Romania received more than half of their daily salt intake from discretionary sources. A significant inverse correlation between discretionary salt intake and a country's per capita GDP was observed (P < 0.0001), such that for every $10,000 increase in per capita GDP, the amount of salt obtained from discretionary sources was lower by 8.7% (95% CI: 5.1%, 12%). Bread products, cereal and grains, meat products, and dairy products were the major contributors to dietary salt intake in most populations. There is marked variation in discretionary salt use around the world that is highly correlated with the level of economic development. Our findings have important implications for the type of salt-reduction strategy likely to be effective in a country., (Copyright © The Author(s) 2020.)

Background: Short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate) are produced by microbial fermentation of fiber in the colon. Evidence is lacking on how high-fiber diets that differ in macronutrient composition affect circulating SCFAs., Objectives: We aimed to compare the effects of 3 high-fiber isocaloric diets differing in %kcal of carbohydrate, protein, or unsaturated fat on circulating SCFAs. Based on previous literature, we hypothesized that serum acetate, the main SCFA in circulation, increases on all high-fiber diets, but differently by macronutrient composition of the diet., Methods: OmniHeart is a randomized crossover trial of 164 men and women (≥30 y old); 163 participants with SCFA data were included in this analysis. We provided participants 3 isocaloric high-fiber (∼30 g/2100 kcal) diets, each for 6 wk, in random order: a carbohydrate-rich (Carb) diet, a protein-rich (Prot) diet (protein predominantly from plant sources), and an unsaturated fat-rich (Unsat) diet. We used LC-MS to quantify SCFA concentrations in fasting serum, collected at baseline and the end of each diet period. We fitted linear regression models with generalized estimating equations to examine change in ln-transformed SCFAs from baseline to the end of each diet; differences between diets; and associations of changes in SCFAs with cardiometabolic parameters., Results: From baseline, serum acetate concentrations were increased by the Prot (β: 0.24; 95% CI: 0.12, 0.35), Unsat (β: 0.21; 95% CI: 0.10, 0.33), and Carb (β: 0.12; 95% CI: 0.01, 0.24) diets; between diets, only Prot compared with Carb was significant (P = 0.02). Propionate was decreased by the Carb (β: -0.10; 95% CI: -0.16, -0.03) and Unsat (β: -0.10; 95% CI: -0.16, -0.04) diets, not the Prot diet; between diet comparisons of Carb vs. Prot (P = 0.006) and Unsat vs. Prot (P = 0.002) were significant. The Prot diet increased butyrate (β: 0.05; 95% CI: 0.00, 0.09) compared with baseline, but not compared with the other diets. Increases in acetate were associated with decreases in insulin and glucose; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin (Ps < 0.05)., Conclusions: Macronutrient composition of high-fiber diets affects circulating SCFAs, which are associated with measures of appetite and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT00051350., (Copyright © The Author(s) 2020.)

Background: The Healthy Eating Index-2015 (HEI-2015) score measures adherence to recommendations from the 2015-2020 Dietary Guidelines for Americans. The HEI-2015 was altered from the HEI-2010 by reclassifying sources of dietary protein and replacing the empty calories component with 2 new components: saturated fats and added sugars., Objectives: Our aim was to assess whether the HEI-2015 score, along with 3 other previously defined indices, were associated with incident cardiovascular disease (CVD), CVD mortality, and all-cause mortality., Methods: We conducted a prospective analysis of 12,413 participants aged 45-64 y (56% women) from the Atherosclerosis Risk in Communities (ARIC) Study. The HEI-2015, Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean (aMed) diet, and Dietary Approaches to Stop Hypertension Trial (DASH) scores were computed using the average dietary intakes of Visits 1 (1987-1989) and 3 (1993-1995). Incident CVD, CVD mortality, and all-cause mortality data were ascertained from baseline through 31 December, 2017. We used Cox proportional hazards models to estimate HRs and 95% CIs., Results: There were 4509 cases of incident CVD, 1722 cases of CVD mortality, and 5747 cases of all-cause mortality over a median of 24-25 y of follow-up. Compared with participants in the lowest quintile of HEI-2015, participants in the highest quintile had a 16% lower risk of incident CVD (HR: 0.84; 95% CI: 0.76-0.93; P-trend < 0.001), 32% lower risk of CVD mortality (HR: 0.68; 95% CI: 0.58-0.80; P-trend < 0.001), and 18% lower risk of all-cause mortality (HR: 0.82; 95% CI: 0.75-0.89; P-trend < 0.001) after adjusting for demographic and lifestyle covariates. There were similar protective associations for AHEI-2010, aMed, and DASH scores, and no significant interactions by race., Conclusions: Higher adherence to the 2015-2020 Dietary Guidelines for Americans was associated with lower risks of incident CVD, CVD mortality, and all-cause mortality among US adults., (Copyright © American Society for Nutrition 2019.)

Background: Despite diet being a first-line strategy for preventing cardiovascular disease, the optimal macronutrient profile remains unclear. We studied the effects of macronutrient profile on subclinical cardiovascular injury and inflammation., Methods: OmniHeart was a randomized 3-period, crossover feeding study in 164 adults with high blood pressure or hypertension (SBP 120-159 or DBP 80-99 mm Hg). Participants were fed each of 3 diets (emphasizing carbohydrate (CARB), protein (PROT), or unsaturated fat (UNSAT)) for 6-weeks, with feeding periods separated by a washout period. Weight was held constant. Fasting serum was collected at baseline while participants ate their own diets and after each feeding period. High-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity C-reactive protein (hs-CRP) were measured in stored specimens., Results: The average age was 53.6 years, 55% were African American, and 45% were women. At baseline, the median (25th-percentile, 75th-percentile) hs-cTnI was 3.3 ng/L (1.9, 5.6) and hs-CRP was 2.2 mg/L (1.1, 5.2). Compared to baseline, all 3 diets reduced hs-cTnI: CARB -8.6% (95%CI: -16.1, -0.4), PROT -10.8% (-18.4, -2.5), and UNSAT -9.4% (-17.4, -0.5). Hs-CRP was similarly changed by -13.9 to -17.0%. Hs-cTnI and hs-CRP reductions were of similar magnitudes as SBP and low-density lipoprotein cholesterol (LDLc) but were not associated with these risk-factor reductions (P-values = 0.09). There were no between-diet differences in hs-cTnI and hs-CRP reductions., Conclusions: Healthy diet, regardless of macronutrient emphasis, directly mitigated subclinical cardiac injury and inflammation in a population at risk for cardiovascular disease. These findings support dietary recommendations emphasizing healthy foods rather than any one macronutrient., Trial Registration: This trial is registered at clinicaltrials.gov, number: NCT00051350; URL: https://clinicaltrials.gov/ct2/show/NCT00051350., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To assess the effects of comprehensive lifestyle modification on low-density lipoprotein cholesterol (LDL-C) levels and whether greater participation in counseling sessions was associated with greater LDL-C reductions., Methods: Multicenter trial of Pre- or Stage 1 hypertensive adults randomized to: (1)Advice alone, (2)'Established' lifestyle intervention implementing physical activity, sodium reduction, and weight loss, if overweight, or (3)'Established + DASH' lifestyle intervention with DASH diet counseling. Both intervention groups received behavioral counseling. We used generalized estimating equations to model the intervention's effects on lipid outcomes. Analyses of number of sessions and lipids were adjusted for demographics and medical history., Results: Among 756 participants (mean age 49.7, 63.2% women, 34.7% black), both lifestyle interventions reduced LDL-C, triglycerides, and total cholesterol (TC) at six months. Compared to the 'Advice' arm, net mean lipid changes in the Established group were: LDL-C of -5.6 mg/dL (p=0.001) and TC of -7.3 mg/dL (p<0.001). Similarly, changes in the 'Established + DASH' group were: LDL-C of -4.0 mg/dL (p=0.03) and TC of -5.7 mg/dL (p=0.006). In dose-response analyses, for every 10-session increase, LDL-C changed by -6.2 mg/dL (p=0.003)., Conclusions: Comprehensive lifestyle modification lowers LDL-C with greater benefit among persons who attend more counseling sessions., Practice Implications: Patient engagement is a critical aspect of effective lifestyle interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Adherence to healthy dietary patterns, measured by the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), and alternate Mediterranean diet (aMed) scores, is associated with a reduced risk of cardiovascular disease. The association between these scores and chronic kidney disease (CKD) is undetermined., Objective: We aimed to estimate the association between the HEI, AHEI, and aMed scores and risk of incident CKD., Methods: We conducted a prospective analysis in 12,155 participants aged 45-64 y from the Atherosclerosis Risk in Communities (ARIC) Study. We calculated HEI-2015, AHEI-2010, and aMed scores for each participant and categorized them into quintiles of each dietary score. Incident CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 accompanied by ≥25% decline in estimated glomerular filtration rate, a kidney disease-related hospitalization or death, or end-stage renal disease. We used cause-specific hazard models to estimate risk of CKD from the quintile of the dietary score through to 31 December 2017., Results: There were 3980 cases of incident CKD over a median follow-up of 24 y. Participants who had higher adherence to the HEI-2015, AHEI-2010, and aMed scores were more likely to be female, have higher educational attainment, higher income level, be nonsmokers, more physically active, and diabetic compared with participants who scored lower. All 3 dietary scores were associated with lower CKD risk (P-trend < 0.001). Participants who were in the highest quintile of HEI-2015 score had a 17% lower risk of CKD (HR: 0.83; 95% CI: 0.74, 0.92) compared with participants in the lowest quintile. Those in quintile 5 of AHEI-2010 and aMed scores, respectively, had a 20% and 13% lower risk of CKD compared with those in quintile 1., Conclusion: Higher adherence to healthy dietary patterns during middle age was associated with lower risk of CKD., (Copyright © American Society for Nutrition 2019.)

Background: Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association., Objectives: We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis., Methods: We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies' risk of bias in their assessment of phosphorus exposure and BP., Results: We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively., Conclusions: We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489., (Copyright © American Society for Nutrition 2019.)

Background: Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors., Objective: We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial., Methods: DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test., Results: At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons)., Conclusions: These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054., (Copyright © American Society for Nutrition 2019.)

Background: Dietary acid load is a clinically important aspect of the diet that reflects the balance between acid-producing foods, for example, meat and cheese, and base-producing foods, for example, fruits and vegetables., Methods: We used metabolomics to identify blood biomarkers of dietary acid load in 2 independent studies of chronic kidney disease patients: the African American Study of Kidney Disease and Hypertension (AASK, n = 689) and the Modification of Diet in Renal Disease (MDRD, n = 356) study. Multivariable linear regression was used to assess the cross-sectional association between serum metabolites whose identity was known (outcome) and dietary acid load (exposure), estimated with net endogenous acid production (NEAP) based on 24-h urine urea nitrogen and potassium, and adjusted for age, sex, race, randomization group, measured glomerular filtration rate, log-transformed urine protein-to-creatinine ratio, history of cardiovascular disease, BMI, and smoking status., Results: Out of the 757 known, nondrug metabolites identified in AASK, 26 were significantly associated with NEAP at the Bonferroni threshold for significance (P < 6.6 × 10-5). Twenty-three of the 26 metabolites were also identified in the MDRD study, and 13 of the 23 (57%) were significantly associated with NEAP (P < 2.2 × 10-3), including 5 amino acids (S-methylmethionine, indolepropionylglycine, indolepropionate, N-methylproline, N-δ-acetylornithine), 2 cofactors and vitamins (threonate, oxalate), 1 lipid (chiro-inositol), and 5 xenobiotics (methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate). Higher levels of all 13 replicated metabolites were associated with lower NEAP in both AASK and the MDRD study., Conclusion: Metabolomic profiling of serum specimens from kidney disease patients in 2 study populations identified 13 replicated metabolites associated with dietary acid load. Additional studies are needed to validate these compounds in healthy populations. These 13 compounds may potentially be used as objective markers of dietary acid load in future nutrition research studies., (copyright © American Society for Nutrition 2019.)

Background: Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake., Objectives: The goal of this study was to identify serum metabolites associated with dietary protein intake., Methods: Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography-tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25-55 mL · min-1 · 1.73 m-2) and 192 participants in study B (glomerular filtration rate: 13-24 mL · min-1 · 1.73 m-2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10-5., Results: In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine., Conclusions: Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease.This trial was registered at clinicaltrials.gov as NCT03202914., (© 2019 American Society for Nutrition.)

Background: Persons with serious mental illnesses (SMI) such as schizophrenia and bipolar disorder have an increased risk of obesity and related chronic diseases and die 10-20years earlier than the overall population, primarily due to cardiovascular disease. In the ACHIEVE trial, a behavioural weight loss intervention led to clinically significant weight loss in persons with SMI. As the field turns its attention to intervention scale-up, it is important to understand whether the effectiveness of behavioural weight loss interventions for people with SMI, like ACHIEVE, differ for specific subgroups., Methods: This study examined whether the effectiveness of the ACHIEVE intervention differed by participant characteristics (e.g. age, sex, race, psychiatric diagnosis, body mass index) and/or their weight-related attitudes and behaviours (e.g. eating, food preparation, and shopping habits). We used likelihood-based mixed effects models to examine whether the baseline to 18 month effects of the ACHIEVE intervention differed across subgroups., Results: No statistically significant differences were found in the effectiveness of the ACHIEVE intervention across any of the subgroups examined., Conclusions: These findings suggest that the ACHIEVE behavioural weight loss intervention is broadly applicable to the diverse population of individuals with SMI., (Copyright © 2019. Published by Elsevier Ltd.)

Prior evidence suggests that vitamin D supplementation may reduce fall risk, but existing data are inconsistent and insufficient to guide policy. We designed a two-stage Bayesian response-adaptive dose-finding and seamless confirmatory randomized trial of vitamin D supplementation to prevent falls. Up to 1200 community-dwelling persons, aged ≥70 years, of predominantly white and African-American race, with serum 25(OH)D concentrations of 10-29 ng/mL and at elevated fall risk, will be randomized to one of four vitamin D3 (cholecalciferol) supplement doses: 200 (control), 1000, 2000, or 4000 IU/day and treated for up to 2 years. Stage 1 is designed to identify the best of the non-control doses for fall prevention. If a best dose is selected, Stage 2 will start seamlessly, with enrollees assigned to control or the best dose in Stage 1 continuing on that dose unchanged, enrollees assigned to the two non-control, non-best doses in Stage 1 switched to the best dose, and new enrollees randomly assigned 1:1 to control or the best dose. In Stage 2, we will compare the control dose group to the best dose group to potentially confirm the efficacy of that dose for fall prevention. The primary outcome measure in both stages is time to first fall or death, whichever comes first. Falls are ascertained from calendars, scheduled interviews, or interim self-reports. Secondary outcome measures include time to each component of the composite primary outcome and gait speed. Additional outcomes include the Short Physical Performance Battery score, physical activity level (assessed by accelerometry), and frailty score., Clinical Trial Registration: NCT02166333., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is recommended for cardiovascular disease risk reduction. Assessment of dietary intake has been limited to subjective measures and a few biomarkers from 24-h urine collections., Objective: The aim of the study was to use metabolomics to identify serum compounds that are associated with adherence to the DASH dietary pattern., Design: We conducted untargeted metabolomic profiling in serum specimens collected at the end of 8 wk following the DASH diet (n = 110), the fruit and vegetables diet (n = 111), or a control diet (n = 108) in a multicenter, randomized clinical feeding study (n = 329). Multivariable linear regression was used to determine the associations between the randomized diets and individual log-transformed metabolites after adjustment for age, sex, race, education, body mass index, and hypertension. Partial least-squares discriminant analysis (PLS-DA) was used to identify a panel of compounds that discriminated between the dietary patterns. The area under the curve (C statistic) was calculated as the cumulative ability to distinguish between dietary patterns. We accounted for multiple comparisons with the use of the Bonferroni method (0.05 of 818 metabolites = 6.11 × 10-5)., Results: Serum concentrations of 44 known metabolites differed significantly between participants randomly assigned to the DASH diet compared with both the control diet and the fruit and vegetables diet, which included an amino acid, 2 cofactors and vitamins (n = 2), and lipids (n = 41). With the use of PLS-DA, component 1 explained 29.4% of the variance and component 2 explained 12.6% of the variance. The 10 most influential metabolites for discriminating between the DASH and control dietary patterns were N-methylproline, stachydrine, tryptophan betaine, theobromine, 7-methylurate, chiro-inositol, 3-methylxanthine, methyl glucopyranoside, β-cryptoxanthin, and 7-methylxanthine (C statistic = 0.986)., Conclusions: An untargeted metabolomic platform identified a broad array of serum metabolites that differed between the DASH diet and 2 other dietary patterns. This newly identified metabolite panel may be used to assess adherence to the DASH dietary pattern. This trial was registered at http://www.clinicaltrials.gov as NCT03403166.

Background: Interindividual variation in the response to diet is common, but the underlying mechanism for such variation is unclear., Objective: The objective of this study was to use a metabolic profiling approach to identify a panel of urinary metabolites representing individuals demonstrating typical (homogeneous) metabolic responses to healthy diets, and subsequently to define the association of these metabolites with improvement of risk factors for cardiovascular diseases (CVDs)., Design: 24-h urine samples from 158 participants with pre-hypertension and stage 1 hypertension, collected at baseline and following the consumption of a carbohydrate-rich, a protein-rich, and a monounsaturated fat-rich healthy diet (6 wk/diet) in a randomized, crossover study, were analyzed by proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Urinary metabolite profiles were interrogated to identify typical and variable responses to each diet. We quantified the differences in absolute excretion of metabolites, distinguishing between dietary comparisons within the typical response groups, and established their associations with CVD risk factors using linear regression., Results: Globally all 3 diets induced a similar pattern of change in the urinary metabolic profiles for the majority of participants (60.1%). Diet-dependent metabolic variation was not significantly associated with total cholesterol or low-density lipoprotein (LDL) cholesterol concentration. However, blood pressure (BP) was found to be significantly associated with 6 urinary metabolites reflecting dietary intake [proline-betaine (inverse), carnitine (direct)], gut microbial co-metabolites [hippurate (direct), 4-cresyl sulfate (inverse), phenylacetylglutamine (inverse)], and tryptophan metabolism [N-methyl-2-pyridone-5-carboxamide (inverse)]. A dampened clinical response was observed in some individuals with variable metabolic responses, which could be attributed to nonadherence to diet (≤25.3%), variation in gut microbiome activity (7.6%), or a combination of both (7.0%)., Conclusions: These data indicate interindividual variations in BP in response to dietary change and highlight the potential influence of the gut microbiome in mediating this relation. This approach provides a framework for stratification of individuals undergoing dietary management. The original OmniHeart intervention study and the metabolomics study were registered at www.clinicaltrials.gov as NCT00051350 and NCT03369535, respectively.

While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for recommending potassium intake and often limits the use of renin-angiotensin-aldosterone system blockers in patients with heart failure and chronic kidney diseases. New agents for managing hyperkalemia may alter the long-term management of heart failure and the hypertension, proteinuria, and further function loss in chronic kidney diseases. In this jointly sponsored effort between the American Society of Hypertension and the National Kidney Foundation, 3 panels of researchers and practitioners from various disciplines discussed and summarized current understanding of the role of potassium in health and disease, focusing on cardiovascular, nutritional, and kidney considerations associated with both hypo- and hyperkalemia., (Copyright © 2017 Journal of the American Society of Hypertension and American Journal of Kidney Disease. Published by Elsevier Inc. All rights reserved.)

Introduction: Cognitive decline is common and increases mortality risk in hemodialysis patients. Intradialytic interventions like cognitive training (CT) and exercise training (ET) may preserve cognitive function., Methods: We conducted a pilot randomized controlled trial of 20 hemodialysis patients to study the impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET (foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function. Global cognitive function was measured by the Modified Mini Mental Status Exam (3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and TMTB), and executive function was assessed by subtracting (TMTB - TMTA). Lower 3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P values for differences were generated using analysis of variance, and 95% confidence intervals (CIs) and P values were generated from linear regression., Results: Patients with SC experienced a decrease in psychomotor speed and executive function by 3 months (TMTA: 15 seconds; P  = 0.055; TMTB: 47.4 seconds; P  = 0.006; TMTB - TMTA; 31.7 seconds; P  = 0.052); this decline was not seen among those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean change in 3MS score was -3.29 points (95% CI: -11.70 to 5.12; P  = 0.42) for CT and 4.48 points (95% CI: -4.27 to 13.22; P  = 0.30) for ET. Compared with SC, the difference in mean change for TMTA was -15.13 seconds (95% CI: -37.64 to 7.39; P  = 0.17) for CT and -17.48 seconds (95% CI: -41.18 to 6.22; P  = 0.14) for ET, for TMTB, the difference was -46.72 seconds (95% CI: -91.12 to -2.31; P  = 0.04) for CT and -56.21 seconds (95% CI: -105.86 to -6.56; P  = 0.03) for ET, and for TMTB - TMTA, the difference was -30.88 seconds (95% CI: -76.05 to 14.28; P  = 0.16) for CT and -34.93 seconds (95% CI: -85.43 to 15.56; P  = 0.16) for ET., Conclusion: Preliminary findings of our pilot study suggested that cognitive decline in psychomotor speed and executive function is possibly prevented by intradialytic CT and ET. These preliminary pilot findings should be replicated.

Evidence supports that multiple dietary factors affect blood pressure (BP). Dietary changes that effectively lower BP are weight loss, reduced sodium intake, increased potassium intake, moderation of alcohol intake, and Dietary Approaches to Stop Hypertension-style and vegetarian dietary patterns. In view of the increasing levels of BP in children and adults and the continuing epidemic of BP-related cardiovascular and renal diseases, efforts to reduce BP in both nonhypertensive and hypertensive individuals are warranted. The challenge to health care providers, researchers, government officials, and the general public is developing and implementing clinical and public health strategies that lead to sustained dietary changes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 status modifies the association between strict versus usual blood pressure control and mortality risk. We performed a retrospective analysis of the African American Study of Kidney Disease and Hypertension trial that randomized black participants with CKD to strict versus usual blood pressure control from 1995 to 2001. This included 682 participants with known APOL1 genotype (157 with high-risk genotype) previously assigned to either strict (mean arterial pressure [MAP] 92 mm Hg or less) versus usual blood pressure control (MAP 102-107 mm Hg) during the trial. During a median follow-up of 14.5 years, risk of death did not differ between individuals with high- versus low-risk APOL1 genotypes (unadjusted hazard ratio 1.00 [95% confidence interval 0.76-1.33]). However, a significant interaction was detected between the APOL1 risk group and blood pressure control strategy. In the APOL1 high-risk group, the risk of death was 42% lower comparing strict versus usual blood pressure control (0.58 [0.35-0.97]). In the APOL1 low-risk group, the risk of death comparing strict versus usual blood pressure control was not significantly different (1.09 [0.84-1.43]). Thus, strict blood pressure control during CKD associates with a lower risk of death in blacks with the high-risk CKD APOL1 genotype. Knowledge of APOL1 status could inform selection of blood pressure treatment targets in black CKD patients., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Higher diet-dependent nonvolatile acid load is associated with faster chronic kidney disease (CKD) progression, but most studies have used estimated acid load or measured only components of the gold standard, net acid excretion (NAE). Here we measured NAE as the sum of urine ammonium and titratable acidity in 24-hour urines from a random subset of 980 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. In multivariable models accounting for demographics, comorbidity and kidney function, higher NAE was significantly associated with lower serum bicarbonate (0.17 mEq/l lower serum bicarbonate per 10 mEq/day higher NAE), consistent with a larger acid load. Over a median of 6 years of follow-up, higher NAE was independently associated with a significantly lower risk of the composite of end-stage renal disease or halving of estimated glomerular filtration rate among diabetics (hazard ratio 0.88 per 10 mEq/day higher NAE), but not those without diabetes (hazard ratio 1.04 per 10 mEq/day higher NAE). For comparison, we estimated the nonvolatile acid load as net endogenous acid production using self-reported food frequency questionnaires from 2848 patients and dietary urine biomarkers from 3385 patients. Higher net endogenous acid production based on biomarkers (urea nitrogen and potassium) was modestly associated with faster CKD progression consistent with prior reports, but only among those without diabetes. Results from the food frequency questionnaires were not associated with CKD progression in any group. Thus, disparate results obtained from analyses of nonvolatile acid load directly measured as NAE and estimated from diet suggest a novel hypothesis that the risk of CKD progression related to low NAE or acid load may be due to diet-independent changes in acid production in diabetes., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Reducing uric acid is hypothesized to lower blood pressure, although evidence is inconsistent. In this ancillary of the DASH-Sodium trial, we examined whether sodium-induced changes in serum uric acid (SUA) were associated with changes in blood pressure. One hundred and three adults with prestage or stage 1 hypertension were randomly assigned to receive either the DASH diet or a control diet (typical of the average American diet) and were fed each of the three sodium levels (low, medium, and high) for 30 days in random order. Body weight was kept constant. SUA was measured at baseline and following each feeding period. Participants were 55% women and 75% black. Mean age was 52 (SD, 10) years, and mean SUA at baseline was 5.0 (SD, 1.3) mg/dL. Increasing sodium intake from low to high reduced SUA (-0.4 mg/dL; P < .001) but increased systolic (4.3 mm Hg; P < .001) and diastolic blood pressure (2.3 mm Hg; P < .001). Furthermore, changes in SUA were independent of changes in systolic (P = .15) and diastolic (P = .63) blood pressure, regardless of baseline blood pressure, baseline SUA, and randomized diet, as well as sodium sensitivity. Although both SUA and blood pressure were influenced by sodium, a common environmental factor, their effects were in opposite directions and were unrelated to each other. These findings do not support a consistent causal relationship between SUA and BP., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Introduction: Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function., Methods: Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population)., Results: In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively)., Conclusions: Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures., Competing Interests: The authors have no competing interest with any organization(s) with a financial interest in the subject matter. Declaration of Interests: No conflicts of interest exist., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of ≥30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of ≥30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of ≥30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of ≥30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between the patient-provider relationship, satisfaction with primary care provider's (PCP) involvement and weight loss in a practice-based weight loss trial., Methods: POWER was a practice-based randomized controlled behavioral weight loss trial. Participants completed questionnaires about patient-provider relationship and satisfaction with their PCPs' involvement in the trial. PCPs completed a demographics and practice survey. The main outcome was the mean weight change from baseline to 24 months. We created mixed-effect models, accounting for the random effects of patients clustering with the PCP and the repeated outcome assessments within patient over time, and adjusted for randomization assignment, age, gender, race and clinical site., Results: 347 (of 415) were included. Mean age was 54.8 years, mean BMI was 36.3 kg/m(2). Participants reported high quality patient-provider relationships (mean summary score=29.1 [range 14-32]). Patient-provider relationship quality was not associated weight loss in either the intervention or control groups. Among intervention participants, higher ratings of the helpfulness of the PCPs' involvement was associated with greater weight loss (p=0.005)., Conclusion: Patient-provider relationship quality was not associated with weight loss in a practice-based weight loss trial but rating PCPs as helpful in the intervention was associated with weight loss., Practice Implications: Partnering with PCPs to deliver weight loss programs may promote greater participant satisfaction and weight loss., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: For decades, dietary sodium intake in the United States has remained high, and few studies have examined strategies for maintaining recommended intakes., Objective: We examined the effects of a behavioral intervention, which emphasized spices and herbs, on the maintenance of sodium intake at the recommended intake of 1500 mg/d in individuals to whom the US Dietary Guidelines for Americans apply., Design: We conducted a 2-phase study that included adults ≥18 y of age for whom Dietary Guidelines for Americans recommends 1500 mg Na/d. The study was conducted in Baltimore, Maryland, from 2012 to 2014. In phase 1, 55 individuals consumed a low-sodium diet for 4 wk. Participants were provided all foods, snacks, and calorie-containing drinks. In phase 2, 40 participants from phase 1 were randomly assigned to either a behavioral intervention to reduce sodium intake (n = 20) or a self-directed control group (n = 20) for 20 wk. The primary study outcome was the change in mean 24-h urinary sodium excretion during phase 2. Linear regression analyses were used to determine intervention effects on urinary sodium excretion., Results: Participant characteristics were as follows: women: 65%; African American: 88%; hypertension: 63%; diabetes: 18%; mean age: 61 y; and mean body mass index (in kg/m(2)): 30. At the end of phase 2, mean 24-h sodium excretion was lower in the behavioral intervention than in the self-directed group (mean difference: -956.8 mg/d; 95% CI: -1538.7, -374.9 mg/d) after sodium intake at screening was controlled for (P = 0.002). These findings persisted in sensitivity analyses that excluded potentially incomplete urine collections [Mage's equation mean difference: -1090 mg/d (P = 0.001); Joosens' equation mean difference: -796 mg/d (P = 0.04)]., Conclusions: A multifactorial behavioral intervention emphasizing spices and herbs significantly reduced sodium intake. Because of the ubiquity of sodium in the US food supply, multilevel strategies addressing individual behaviors and the food supply are needed to improve adherence to recommendations. This trial was registered at clinicaltrials.gov as NCT01615159., (© 2015 American Society for Nutrition.)

Serum carbon isotope values [13C-to-12C serum carbon isotope ratio (δ(13)C)], which reflect consumption of corn- and cane-based foods, differ between persons consuming high and low amounts of sugar-sweetened beverages (SSBs). In this study, we determined whether serum δ(13)C changes in response to change in SSB intake during an 18-mo behavioral intervention trial. Data were from a subset of 144 participants from the PREMIER trial, a completed behavioral intervention (Maryland, 1998-2004). SSB intake was assessed using 2 24-h dietary recall interviews. Blinded serum samples were assayed for δ(13)C by natural abundance stable isotope mass spectroscopy. Multiple linear regression models with generalized estimating equations and robust variance estimation were used. At baseline, mean SSB intake was 13.8 ± 14.2 fl oz/d, and mean δ(13)C serum value was -19.3 ± 0.6 units per mil (designated ‰). A reduction of 12 oz (355 mL)/d SSB (equivalent to 1 can of soda per day) was associated with 0.17‰ (95% CI: 0.08‰, 0.25‰ P < 0.0001) reduction in serum δ(13)C values over 18 mo (equivalent to a 1% reduction in δ(13)C from baseline). After adjusting for potential confounders, a reduction of 12 oz/d SSB (equivalent to 1 can of soda per day), over an 18-mo period, was associated with 0.12‰ (95% CI: 0.01‰, 0.22‰ P = 0.025) reduction in serum δ(13)C. These findings suggest that serum δ(13)C can be used as a measure of dietary changes in SSB intake., (© 2014 American Society for Nutrition.)

Background: Elevated serum phosphorus is associated with all-cause mortality, but little is known about risk associated with dietary phosphorus intake., Objective: We investigated the association between phosphorus intake and mortality in a prospective cohort of healthy US adults (NHANES III; 1998-1994)., Design: Study participants were 9686 nonpregnant adults aged 20-80 y without diabetes, cancer, or kidney or cardiovascular disease. Exposure to dietary phosphorus, which was assessed by using a 24-h dietary recall, was expressed as the absolute intake and phosphorus density (phosphorus intake divided by energy intake). All-cause and cardiovascular mortality was assessed through 31 December 2006., Results: Median phosphorus intake was 1166 mg/d (IQR: 823-1610 mg/d); median phosphorus density was 0.58 mg/kcal (0.48-0.70 mg/kcal). Individuals who consumed more phosphorus-dense diets were older, were less often African American, and led healthier lifestyles (smoking, physical activity, and Healthy Eating Index). In analyses adjusted for demographics, cardiovascular risk factors, kidney function, and energy intake, higher phosphorus intake was associated with higher all-cause mortality in individuals who consumed >1400 mg/d [adjusted HR (95% CI): 2.23 (1.09, 4.5) per 1-unit increase in ln(phosphorus intake); P = 0.03]. At <1400 mg/d, there was no association. A similar association was seen between higher phosphorus density and all-cause mortality at a phosphorus density amount >0.35 mg/kcal [adjusted HR (95% CI): 2.27 (1.19, 4.33) per 0.1-mg/kcal increase in phosphorus density; P = 0.01]. At <0.35 mg/kcal (approximately the fifth percentile), lower phosphorus density was associated with increased mortality risk. Phosphorus density was associated with cardiovascular mortality [adjusted HR (95% CI): 3.39 (1.43, 8.02) per 0.1 mg/kcal at >0.35 mg/kcal; P = 0.01], whereas no association was shown in analyses with phosphorus intake. Results were similar by subgroups of diet quality and in analyses adjusted for sodium and saturated fat intakes., Conclusions: High phosphorus intake is associated with increased mortality in a healthy US population. Because of current patterns in phosphorus consumption in US adults, these findings may have important public health implications.

Background: The 2010 Dietary Guidelines Advisory Committee report contained dietary patterns developed by using nutrient-dense foods. In most cases, low-sodium forms of foods were incorporated into the patterns., Objectives: We wanted to determine whether choosing lower-sodium foods could lower the sodium content to 1500 mg without compromising nutrient adequacy. We also explored the effect of choosing typical foods (more calories with higher sodium) and the feasibility of implementing sodium recommendations on a density basis (mg Na/kcal)., Design: Food patterns developed during the 2010 Dietary Guidelines development process were used as the base for this analysis. Modeling was then used to analyze the effect of substituting lower-sodium foods on nutrient adequacy., Results: Sodium amounts in the base model varied directly with energy level (1.0 mg Na/kcal) and ranged from 996 to 3176 mg/d. Amounts in the lowest-sodium model also varied with energy level (~0.5 mg/kcal) and ranged from 500 to 1250 mg/d. A comparison of sodium density for the base and the lowest sodium models showed that sodium in the lowest model is ~50% of the base. For typical food choices, sodium amounts were much higher (1.6-2.0 mg/kcal and 1715-5078 mg/d). Comparison of sodium density for the base and the typical food choice models showed that amounts were 1.6-2.0 times greater than the base., Conclusions: By choosing only low-sodium foods, it was possible to construct nutritionally adequate dietary patterns with 1500 mg Na/d. Sodium density (mg Na/kcal) is a practical approach for expressing sodium recommendations.

Background: The benefits of regular physical activity are particularly salient to persons with serious mental illness (SMI) who have increased prevalence of obesity, diabetes, and earlier mortality from cardiovascular disease., Methods: The Activating Consumers to Exercise through Peer Support (ACE) trial will examine the effectiveness of peer support on adherence to a 4-month pilot exercise program for adults with SMI. Design, rationale and baseline data are reported. Baseline measures included: graded treadmill test; six-minute walk; height, weight and blood pressure; body composition; fasting blood; and self-reported psychiatric symptoms. Fitness levels were compared with national data and relationships among fitness parameters, psychological factors and cardiovascular disease risk factors were examined., Results: There were 93 participants and 18 peer leaders recruited from community psychiatry programs with an average age of 47 years (SD 10). There were no differences in demographics (76% female, 72% African American) or mental health symptoms between participants and peer leaders. Ninety-five percent of the sample had below average fitness levels for their age and sex with average MET levels of 5.9(SD 2.2) for participants and 6.2(SD 2.3) for peer leaders. Fitness evaluated during the treadmill test and the six-minute-walk were associated (r s = 0.36, p<.001). Lower MET levels were associated with a higher BMI (r s = -0.35, p<.001) and percent body fat (r s = -0.36, p <.001)., Conclusion: The uniformly low baseline cardiovascular fitness and the association of fitness with BMI and adiposity underscore the importance of suitably tailored programs to increase physical activity among adults with SMI.