Serum metabolite signature of the modified Mediterranean-DASH intervention for neurodegenerative delay (MIND) diet.

INTRODUCTION: There is a lack of biomarkers of clinically important diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. OBJECTIVES: Our study explored serum metabolites associated with adherence to the MIND diet. METHODS: In 3,908 Atherosclerosis Risk in Communities (ARIC) study participants, we calculated a modified MIND diet score based on a 66-item self-reported food frequency questionnaire (FFQ). The modified score did not include berries and olive oil, as these items were not assessed in the FFQ. We used multivariable linear regression models in 2 subgroups of ARIC study participants and meta-analyzed results using fixed effects regression to identify significant metabolites after Bonferroni correction. We also examined associations between these metabolites and food components of the modified MIND diet. C-statistics evaluated the prediction of high modified MIND diet adherence using significant metabolites beyond participant characteristics. RESULTS: Of 360 metabolites analyzed, 27 metabolites (15 positive, 12 negative) were significantly associated with the modified MIND diet score (lipids, n = 13; amino acids, n = 5; xenobiotics, n = 3; cofactors and vitamins, n = 3; carbohydrates n = 2; nucleotide n = 1). The top 4 metabolites that improved the prediction of high dietary adherence to the modified MIND diet were 7-methylxanthine, theobromine, docosahexaenoate (DHA), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF). CONCLUSION: Twenty-seven metabolomic markers were correlated with the modified MIND diet. The biomarkers, if further validated, could be useful to objectively assess adherence to the MIND diet.

Protein Biomarkers of Ultra-Processed Food Consumption and Risk of Coronary Heart Disease, Chronic Kidney Disease, and All-Cause Mortality.

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 (ß-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.

Serum Metabolomic Markers of Artificially Sweetened Beverage Consumption.

BACKGROUND: The consumption of artificially sweetened beverages is on the rise. Use of artificial sweeteners has been associated with adverse health outcomes. There is a need to identify novel objective biomarkers of artificially sweetened beverages in order to improve dietary assessment and to provide insight into their metabolic impact. OBJECTIVES: We aimed to identify serum metabolites that are associated with artificially sweetened beverage consumption. METHODS: In the Atherosclerosis Risk in Communities (ARIC) study, consumption of artificially sweetened beverages was assessed using a food frequency questionnaire and fasting serum samples were collected during the first study visit (1987-1989). Participants were categorized as nonusers if they reported almost never consumption of artificially sweetened beverages, moderate users for 1 glass/mo to 6 glasses/wk, and heavy users for ≥1 glasses/d. Untargeted metabolomic profiling was conducted in 2 subgroups (subgroup 1: n = 1866, profiled in 2010; subgroup 2 profiled in 2014: n = 2072), and 360 metabolites were analyzed. In this secondary data analysis, multivariable linear regression models were used, adjusting for demographics, health behaviors, health status, and dietary factors. Analyses were conducted in each subgroup and results meta-analyzed. RESULTS: In a meta-analysis of 3938 generally healthy participants (mean age, 54 y; 60% women; 62% Black participants) from ARIC study visit 1, 11 serum metabolites were significantly associated with artificially sweetened beverage consumption. Heavier consumption of artificially sweetened beverages was associated with higher concentrations of 10 metabolites (saccharin, threonate, erythronate, glycerate, gluconate, mannitol, glucose, tryptophan betaine, trehalose, and N6-acetyllysine) and lower concentrations of glycocholenate sulfate. CONCLUSIONS: Eleven serum metabolites are related to artificially sweetened beverage intake, which consist of known sugar substitutes, processed food additives, glucose-related compounds, and gut microbiome-related metabolites. These findings enhance our knowledge of the metabolic activity of artificial sweeteners and suggests new biomarkers for monitoring intake.

Sugar-Sweetened Beverages and Adverse Human Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies.

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health.

Plant-based diets for kidney disease prevention and treatment.

PURPOSE OF REVIEW: Plant-based diets are associated with a lower risk of hypertension, diabetes, cardiovascular disease, and mortality. Using the most recent evidence, we critically appraised the role of plant-based diets in primary and secondary prevention of chronic kidney disease (CKD) with a focus on key nutritional factors (dietary acid load, phosphorus, potassium, sodium, and fiber). RECENT FINDINGS: In healthy individuals, observational studies found that greater intake of plant protein and higher adherence to plant-based diets (overall, healthful, and provegetarian) was associated with a lower risk of CKD. In those with CKD, plant-based diets were associated with a lower risk of mortality, improved kidney function, and favorable metabolic profiles (fibroblast growth factor-23, uremic toxins, insulin sensitivity, inflammatory biomarkers). Only few studies reported nutrient content of plant-based diets. These studies found that plant-based diets had lower dietary acid load, lower or no significant difference in phosphorus and sodium, and higher potassium and fiber. One study reported that vegetarian diets were associated with severe vitamin D deficiency compared to nonvegetarian diets. SUMMARY: Plant-based diets provide several benefits for prevention and management of CKD, with little risk for individuals with CKD. Incorporation of vitamin D rich foods in plant-based diets may be helpful.

Magnesium-Rich Diet Score is Inversely Associated with Incident Cardiovascular Disease: The Atherosclerosis in Communities (ARIC) Study.

BACKGROUND: Numerous studies have shown inverse associations between serum magnesium (Mg) and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent. AIM: To examine the association of a Mg-rich diet score with risks of CVD, coronary heart disease (CHD), and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: There were 15,022 Black and White adults without prevalent CVD at baseline (1987-89) included in this analysis. Diet was assessed at two visits 6 years apart using an interviewer-administered 66-item food frequency questionnaire. A Mg-rich diet score was created that included servings of whole grain products, nuts, vegetables, fruit, legumes, coffee, and tea. Cox proportional hazard regression evaluated associations of incident CVD, CHD and stroke across quintiles of Mg-rich diet score, adjusting for demographics, lifestyle factors, and clinical characteristics. RESULTS: Over >30 years of follow-up, there were 3,531 incident CVD events (2,562 CHD, 1,332 ischemic stroke). Participants who consumed more Mg-rich foods were older, female, White, had lower blood pressure, fewer were not current smokers, and more reported being physically active. A Mg-rich diet was inversely associated with incident CVD (HRQ5 vs Q1=0.87, 95%CI: 0.77-0.98, ptrend=0.02) CHD (HRQ5 vs Q1=0.82, 95%CI: 0.71-0.95, ptrend=0.01); however, the diet-stroke association was null (HRQ5 vs Q1=1.00, 95%CI: 0.82-1.22, ptrend=0.97). CONCLUSIONS: Consuming a diet including Mg-rich foods, such as whole grains, nuts, vegetables, fruits, legumes, coffee and tea, is associated with lower risk of CVD and CHD, but not ischemic stroke.

This study showed an inversely association between a magnesium-rich (mg-rich) diet score and risk of cardiovascular disease (CVD) in adults aged 45-64 at baseline (1987-89) and followed for over 30 years. The mg-rich diet score was created by summing the reported number of daily servings consumed from whole grain products, fruit, vegetables, legumes, nuts, coffee and tea.A mg-rich diet score may be associated with lower risk of developing CVD and coronary heart disease, but not ischemic stroke.

Associations of Dietary Calcium and Phosphorus With Vascular and Valvular Calcification: The ARIC Study.

Background: High dietary calcium and phosphorus may accelerate vascular calcification, but epidemiological data are inconsistent. Most of those studies assessed diet at one point and have not been systematically evaluated. Objectives: The purpose of this study was to assess the associations of dietary calcium and phosphorus intakes in middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,914 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 80.5 years) without coronary heart disease who underwent chest computed tomography scans at visit 7 (2018-2019) and completed a 66-item food frequency questionnaire at 2 earlier visits (visit 1 [1987-1989] and visit 3 [1993-1995]). Dietary calcium and phosphorus intakes were averaged between these 2 visits. Calcification was quantified by the Agatston score in coronary artery, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. Results: Dietary calcium intake was inversely associated with coronary artery and ascending aorta calcification, whereas the association was not significant for other measures of extra-coronary calcification. For example, the highest vs lowest quartile of calcium intake showed an adjusted OR of 0.66 (95% CI: 0.45-0.98) for coronary artery calcification (Agatston score ≥75th percentile). Dietary phosphorus intake demonstrated similar results, but the magnitude of the association was weaker than dietary calcium intake. Conclusions: Dietary calcium and phosphorus intakes at middle age were not positively associated with vascular and valvular calcification at over 75 years old. Our findings did not support the link between a calcium or phosphorus-rich diet and vascular and valvular calcification.

Trends in Plant-Based Diets among United States Adults, 1999-March 2020.

BACKGROUND: Interest in plant-based eating has increased alongside increased variety and availability of highly processed plant-based meat and dairy alternatives. The impact of the shifting commercial landscape and public interest in plant-based eating on dietary intake is unknown. OBJECTIVES: To examine trends in the consumption and composition of plant-based diets in the United States adults. METHODS: Serial cross-sectional data from the National Health and Nutrition Examination Survey were used to assess trends in the proportion of United States adults aged ≥20 y consuming a plant-based diet (defined as ≥50% total protein from plants on a 24-h dietary recall) from 1999-2000 to 2017-March 2020 (n = 51,698). Trends in processing level (percentage energy intake from ultraprocessed foods) and diet quality [Healthy Eating Index (HEI)-2020 scores] were assessed in the subset of adults consuming plant-based diets (n = 8327). RESULTS: The proportion of United States adults consuming plant-based diets increased from 14.4% (95% CI: 12.9%, 16.0%) to 17.2% (95% confidence interval [CI]: 15.5%, 19.1%; P = 0.005 for trend). In all survey cycles, ultraprocessed foods accounted for the majority of energy intake, and ultraprocessed food intake in plant-based diets did not significantly change over time [50.7% kcal (95% CI: 47.3%, 54.1%) in 1999-2000 compared with 52.7% kcal (95% CI: 49.7%, 55.6%) in 2017-March 2020; P for trend = 0.34]. The quality of plant-based diets, measured by HEI-2020 scores, improved from 52.1 (95% CI: 49.7, 54.6) to 55.8 (95% CI: 54.1, 57.5; P for trend <0.001). CONCLUSIONS: Between 1999 and March 2020, the proportion of United States adults consuming a plant-based diet increased. Among people consuming plant-based diets, ultraprocessed foods contributed most to energy intake and there was no sustained change in intake over time. The mean diet quality was low but improved modestly.

Ultra-Processed Food Consumption and Risk of Incident Hypertension in US Middle-Aged Adults.

BACKGROUND: Consumption of ultra-processed food, which is manufactured food that is high in additives and sparse in intact foods, is adversely associated with cardiovascular health, primarily in non-US study populations. We aimed to estimate the association between ultra-processed food consumption and incident hypertension in middle-aged adults in the United States. METHODS AND RESULTS: We included 8923 ARIC (Atherosclerosis Risk in Communities) study participants who were hypertension free at baseline and had complete dietary, covariate, and hypertension data from visit 1 (1987-1989). Over a median (25th, 75th percentile) follow-up of 13 (6-21) years, 79% of participants developed hypertension. Participants in the highest quartile of ultra-processed food consumption had 15% higher risk of incident hypertension than those in the lowest quartile (hazard ratio [HR], 1.15 [95% CI, 1.08-1.23]). Participants in the highest quartile of consumption of sugar-sweetened beverages, red and processed meat, and margarine had 16% (HR, 1.16 [95% CI, 1.08-1.24]; p-trend <0.001), 10% (HR, 1.10 [95% CI, 1.03-1.19]; P trend = 0.005), and 6% (HR, 1.06 [95% CI, 0.99, 1.45]; P trend = 0.045) higher risk of incident hypertension, respectively, when compared with the lowest quartiles of consumption. Each additional serving of minimally or unprocessed food was associated with a 2% lower risk of incident hypertension (HR, 0.98 [95% CI, 0.98, 0.99], P<0.001). CONCLUSIONS: High consumption of ultra-processed foods, specifically of sugar-sweetened beverages, red and processed meat, and margarine, was associated with a higher incidence of hypertension, whereas minimally or unprocessed food consumption was associated with lower hypertension risk.

Serum protein responses to Dietary Approaches to Stop Hypertension (DASH) and DASH-Sodium trials and associations with blood pressure changes.

OBJECTIVES: The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure, but the mechanisms underlying DASH diet-blood pressure relations are not well understood. Proteomic measures may provide insights into the pathophysiological mechanisms through which the DASH diet reduces blood pressure. METHODS: The DASH (1994-1996) and DASH-Sodium (1997-1999) trials were multicenter, randomized-controlled feeding trials. Proteomic profiling was conducted in serum collected at the end of the feeding period (DASH, N = 215; DASH-Sodium, N = 390). Multivariable linear regression models were used to identify interactions between 71 DASH diet-related proteins and changes in systolic and diastolic blood pressure. Estimates were meta-analyzed across both trials. Elastic net models were used to identify proteins that predict changes in blood pressure. RESULTS: Ten significant interactions were identified [systolic blood pressure: seven proteins; diastolic blood pressure: three proteins], which represented nine unique proteins. A high level of renin at the end of the feeding period was associated with greater reductions in diastolic blood pressure in individuals consuming the control than DASH diets. A high level of procollagen c-endopeptidase enhancer 1 (PCOLCE) and collagen triple helix repeat-containing protein 1 (CTHRC1) were associated with greater reductions in systolic blood pressure in individuals consuming the DASH than control diets, and with elevations in systolic blood pressure in individuals consuming the control diets (P for interaction for all tests < 0.05). Elastic net models identified six additional proteins that predicted change in blood pressure. CONCLUSIONS: Several novel proteins were identified that may provide some insight into the relationship between the DASH diet and blood pressure.

Ultra-processed food consumption and risk of diabetes: results from a population-based prospective cohort.

AIMS/HYPOTHESIS: Understanding the impact of the overall construct of ultra-processed foods on diabetes risk can inform dietary approaches to diabetes prevention. In this study, we aimed to evaluate the association between ultra-processed food consumption and risk of diabetes in a community-based cohort of middle-aged adults in the USA. We hypothesised that a higher intake of ultra-processed foods is associated with a higher risk of incident diabetes. METHODS: The study included 13,172 participants without diabetes at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) study. Dietary intake was assessed with a 66-item semiquantitative food frequency questionnaire, and foods were categorised by processing level using the Nova classification system. Ultra-processed food was analysed categorically (quartiles of energy-adjusted intake) and continuously (per one additional serving/day). We used Cox regression to evaluate the association of ultra-processed food intake with risk of diabetes with adjustment for sociodemographic characteristics, total energy intake, health behaviours and clinical factors. RESULTS: Over a median follow-up of 21 years, there were 4539 cases of incident diabetes. Participants in the highest quartile of ultra-processed food intake (8.4 servings/day on average) had a significantly higher risk of diabetes (HR 1.13; 95% CI 1.03, 1.23) compared with participants in the lowest quartile of intake after adjustment for sociodemographic, lifestyle and clinical factors. Each additional serving of ultra-processed food consumed daily was associated with a 2% higher risk of diabetes (HR 1.02; 95% CI 1.00, 1.04). Highest quartile consumption of certain ultra-processed food groups, including sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks, was associated with a 29%, 21% and 16% higher risk of diabetes, respectively, compared with the lowest quartile. CONCLUSIONS/INTERPRETATION: We found that a higher intake of ultra-processed food was associated with higher risk of incident diabetes, particularly sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks. Our findings suggest interventions reducing ultra-processed food consumption and specific food groups may be an effective strategy for diabetes prevention.

An Early Gestation Plasma Inflammasome in Rural Bangladeshi Women.

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research.

Plasma proteins associated with plant-based diets: Results from the Atherosclerosis Risk in Communities (ARIC) study and Framingham Heart Study (FHS).

BACKGROUND & AIMS: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort. METHODS: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics. RESULTS: In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests). CONCLUSIONS: Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.

Rationale & Objective: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD. Study Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]). Setting & Participants: Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without diabetes in the ARIC, REGARDS, and MESA studies. Exposures: Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1. Outcome: Incident CKD or end-stage kidney disease. Analytical Approach: Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts. Results: 872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m2. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31). Limitations: Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts. Conclusions: In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.

This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.

Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study.

Rationale & Objective: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). Study Design: Prospective cohort study. Setting & Participants: A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. Exposures: Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites. Outcomes: Incident CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 with ≥25% estimated glomerular filtration rate decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease). Analytical Approach: Multivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C statistics assessed the ability of the metabolites to improve the discrimination of highest versus lower 3 quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and the intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident CKD. Results: Thirty significant associations were identified between protein-rich foods and serum metabolites (fish, n = 8; nuts, n = 5; legumes, n = 0; red and processed meat, n = 5; eggs, n = 3; and poultry, n = 9). Metabolites collectively and significantly improved the discrimination of high intake of protein-rich foods compared with covariates alone (difference in C statistics = 0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; P < 1.00 × 10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR, 0.82; 95% CI, 0.75-0.89; P = 7.81 × 10-6). Limitations: Residual confounding and sample-storage duration. Conclusions: We identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with a lower risk of CKD.

In this study, we aimed to identify associations between protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry) and serum metabolites, which are small biological molecules involved in metabolism. Metabolites significantly associated with a protein-rich food individually and collectively improved the discrimination of the respective protein-rich food, suggesting that these metabolites should be prioritized in future diet biomarker research. We also studied associations between significant diet-related metabolites and incident kidney disease. One fish-related metabolite was associated with a lower kidney disease risk. This finding supports the recent nutritional guidelines recommending a Mediterranean diet, which includes fish as the main dietary protein source.

Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses.

OBJECTIVE: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. DESIGN: Systematic umbrella review of existing meta-analyses. DATA SOURCES: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality. RESULTS: The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality. CONCLUSIONS: Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023412732.

Plant-Based Dietary Patterns and Incident Diabetes in the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Plant-based dietary patterns emphasize plant foods and minimize animal-derived foods. We investigated the association between plant-based dietary patterns and diabetes in a community-based U.S. sample of Black and White adults. RESEARCH DESIGN AND METHODS: We included middle-aged adults from the Atherosclerosis Risk in Communities (ARIC) study without diabetes at baseline who completed a food-frequency questionnaire (n = 11,965). We scored plant-based diet adherence according to three indices: overall, healthy, and unhealthy plant-based diet indices. Higher overall plant-based diet index (PDI) scores represent greater intakes of all plant foods and lower intakes of animal-derived foods. Higher healthy plant-based diet index (hPDI) scores represent greater healthy plant food intake and lower intakes of animal-derived and unhealthy plant foods. Higher unhealthy plant-based diet index (uPDI) scores represent greater unhealthy plant food intake and lower intakes of animal-derived and healthy plant foods. We used Cox regression to estimate hazard ratios (HRs) for incident diabetes (defined according to self-reported diagnosis, medication use, or elevated blood glucose) associated with each index. RESULTS: Over a median follow-up of 22 years, we identified 4,208 cases of diabetes among subjects. Higher PDI scores were associated with a lower risk of diabetes (quintile 5 vs. 1 HR 0.89 [95% CI 0.80, 0.98]; Ptrend = 0.01). hPDI scores were also inversely associated with diabetes risk (quintile 5 vs. 1 HR 0.85 [95% CI 0.77, 0.94]; Ptrend < 0.001). uPDI scores were not associated with diabetes risk. CONCLUSIONS: A dietary pattern that minimizes animal-derived foods and emphasizes plant foods may reduce diabetes risk.