Diet patterns associated with cognitive decline: methods to harmonize data from European and US cohort studies.

The impact of dietary intake on cognitive outcomes and dementia prevention is a topic of increasing interest. Meta-analyses of observational studies, mostly conducted within US and European populations, have reported benefits of healthy diet patterns on cognitive performance, but results from individual studies have been inconsistent. These inconsistencies are likely due to the diverse methodology used in studies, including different diet and cognitive function assessment instruments, follow-up periods, and analytical methods, which make drawing conclusions relevant to dietary guidance challenging. The objective of this project is to describe a protocol to conduct a retrospective harmonization study on dietary intake and cognitive health using data from European and US studies. The recommendations resulting from the project can be used to support evidence-based synthesis for future iterations of the Dietary Guidelines for Americans or other population-based dietary guidance. Additionally, this study will serve as a harmonization guide for future research on the relationship between diet patterns and cognition. The approach outlined ultimately aims to optimize resources and expedite research efforts for dementia prevention.

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.

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.

Added sugar intake is associated with weight gain and risk of developing obesity over 30 years: The CARDIA study.

BACKGROUND AND AIMS: Numerous prospective studies have examined sugar sweetened beverage (SSB) intake associated with weight gain or incident obesity. Because SSB accounts for only 33 % of added sugar (AS) intake, we investigated the associations of AS intake with change in weight and waist circumference and risk of developing obesity. METHODS AND RESULTS: At baseline (1985-86) Black and White women and men, aged 18-30 years, enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study and were followed for 30 years (2015-16). A diet history assessed dietary intake 3 times over 20 years. Multivariable linear regression evaluated the associations of change in weight (n = 3306) and waist circumference (n = 3296) across quartiles of AS, adjusting for demographics, lifestyle factors, and anthropometrics. Proportional hazards regression analysis evaluated the associations of time-varying cumulative AS intake with risk of incident obesity (n = 4023) and abdominal obesity (n = 3449), adjusting for the same factors. Over 30 years of follow-up, greater AS intake was associated with gaining 2.3 kg more weight (ptrend = 0.01) and 2.2 cm greater change in waist circumference (ptrend = 0.005) as well as increased risk of incident obesity (HR 1.28; 95 % CI: 1.08-1.53) and incident abdominal obesity (HR 1.27; 95 % CI:1.02-1.60). CONCLUSION: Our findings are consistent with recommendations from the 2020-2025 U S. Dietary Guidelines for Americans to limit daily AS intake.

Relationship of calcium and magnesium intakes with the dietary approaches to stop hypertension score and blood pressure: the International Study of Macro/micronutrients and Blood Pressure.

OBJECTIVE: Research investigating calcium and magnesium intakes from the Dietary Approaches to Stop Hypertension (DASH) pattern and other sources in association with blood pressure is limited. We aimed to characterize sources/intake levels of calcium and magnesium in relation to overall diet quality (DASH-score) and determine modification effects with DASH score and blood pressure. METHODS: Cross-sectional United States data (average dietary and supplement intake from four 24 h recalls and eight blood pressure measurements) from two separate visits, 2195 men and women (40-59 years) in the International Study of Macro/Micronutrients and Blood Pressure were analysed. Food-based adherence to the DASH diet was estimated. Linear models tested associations between each 1-point DASH score with blood pressure. Participants were stratified by adherence to sex-specific recommended allowance for magnesium and calcium intakes. Effect-modification was tested across DASH-score quintiles and median of urinary sodium. RESULTS: DASH-score was inversely associated with SBP in fully adjusted models (-0.27; 95%CI: -0.38 to -0.15 mmHg). SBP was inversely associated with dietary calcium intake from DASH food groups: -1.54 (95% CI: -2.65 to -0.43) mmHg; calcium intake from other non-DASH food groups: -1.62 (95% CI: -2.94 to -0.29) mmHg. Dietary magnesium intake from DASH food groups (-1.59; 95% CI: -2.79, -0.40 mmHg) and from other non-DASH foods (-1.92; 95% CI: -3.31, -0.53 mmHg) was inversely associated with SBP. CONCLUSION: A higher DASH score showed a consistent association with lower BP suggesting a relationship between intakes of calcium and Mg with BP regardless of whether the source is part of the DASH diet or not, even when adjusted for supplement intakes.The INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov .

Consumption of foods and beverages rich in added sugar associated with incident metabolic syndrome: Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIMS: Numerous studies report positive associations between total carbohydrate (CHO) intake and incident metabolic syndrome (MetS), but few differentiate quality or type of CHO relative to MetS. We examined source of CHO intake, including added sugar (AS), AS-rich CHO foods and sugar-sweetened beverages (SSBs) associated with incident MetS in adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS: Among 3154 Black American and White American women and men aged 18-30 years at baseline, dietary intake was assessed by diet history three times over 20 years. Sources of AS-rich CHO foods and beverages include sugar-rich refined grain products, candy, sugar products, and SSBs. Incident MetS was created according to standard criteria. Time-dependent Cox proportional-hazards regression analysis evaluated the associations of incident MetS across quintiles of cumulative intakes of AS-rich CHO foods and beverages, AS, and SSBs adjusted for potential confounding factors over 30 years of follow-up. RESULTS: The associations of AS-rich CHO foods and beverages, AS, and SSB intakes with incident MetS were consistent. Compared to the lowest intake, the greatest intake of AS-rich CHOs, AS, and SSBs were associated with 59% (ptrend<0.001), 44% (ptrend=0.01), and 34% (ptrend=0.03) higher risk of developing MetS, respectively. As expected, diet quality was lower across increasing quintiles of AS-rich CHO foods and beverages, AS, and SSBs (all ptrend<0.001). CONCLUSION: Our study findings are consistent with an elevated risk of developing MetS with greater consumption of AS, AS-rich CHO foods, and SSBs which support consuming fewer AS-rich CHO foods and SSBs.

Metabolic syndrome (MetS) is a condition consisting of 3 out of 5 heart disease risk factors. Researchers have found that the risk of developing MetS increases as carbohydrate (CHO) intake also increases. However, how this risk is related is to the type and quality of CHO has not been well studied. To study this, we used data from 3154 African American and White American women and men aged 18-30 years old at baseline (1985-86). Information was collected about their health and what they ate. This allowed us to find out if MetS occurred over time if it ever did. We determined how much added sugar (AS), sugar-sweetened beverages (SSBs), and AS-rich CHO foods and beverages they ate. AS-rich foods and beverages contain sugars, syrups, and caloric sweeteners added to them during production or preparation. CHO foods containing AS include refined grain breads, rolls, bakery products, candy, jellies, and more. We found that people with the greatest intake of AS, SSBs, and AS-rich CHO foods and beverages had a higher risk of developing MetS compared to those with the lowest intake. These results align with US Dietary Guidelines as well as European guidelines to consume less AS; therefore, to consume fewer AS-rich CHO foods and SSBs.

Diet quality is associated with adipose tissue and muscle mass: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: Aging is associated with changes in body composition, and preventing loss of muscle mass and accumulation of excess adipose tissue in middle-aged adults may reduce age-related conditions at older ages. Dietary intake is one lifestyle factor shown to improve or maintain body composition. However, few studies have examined the Healthy Eating Index2015 (HEI2015), a measure of diet quality, and the association with body composition in adult men and women. METHODS: Participant data (n = 3017) from the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the associations of the HEI2015 with body composition measures at Year 25 (Y25), including (1) 25 year-change in weight, body mass index (BMI), and waist circumference and (2) a computed tomography (CT) scan at Y25 measured muscle mass, muscle quality (better quality = less lipid within the muscle), and adipose tissue depots visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and adipose within skeletal muscle (intermuscular adipose tissue; IMAT). Dietary intake was assessed by a diet history three times over 20 years, at years 0, 7, and 20. HEI2015, averaged over three exams, was created and categorized into quintiles. Multiple regression analysis evaluated the associations of body composition stratified across quintiles of HEI2015 adjusted for demographic characteristics, energy intake, lifestyle factors, and baseline anthropometric measures as appropriate. Race-sex interaction was tested (Pinteraction  > 0.30). RESULTS: Over 25 years of follow-up, averaged HEI2015 was significantly and inversely associated with weight gain (Quintile 1 (Q1) 37.3 lb vs. 32.9 in Q5; Ptrend  = 0.01), change in BMI (Q1 5.8 kg/m2 vs. 5.0 in Q5; Ptrend  = 0.005), and change in waist circumference (Q1 17.5 cm vs. 15.2 cm in Q5; Ptrend  < 0.001). By Y25, HEI2015 was inversely associated with VAT Q1 136.8 cm3 vs. 116.6 in Q5; Ptrend  < 0.001) and IMAT volumes (Q1 9.52 vs. 8.12 cm3 in Q5; Ptrend  < 0.001). Although total muscle volume declined (Ptrend  = 0.03), lean muscle mass volume was similar across quintiles (Ptrend  = 0.55). The IMAT/total muscle mass ratio declined across HEI2015 quintiles (Ptrend  < 0.001). Finally, higher HEI2015 was associated with better muscle quality at Y25 (higher value = less lipid within the muscle; Q1 41.1 vs. 42.2 HU in Q5; Ptrend  = 0.002). HEI2015 was nonlinearly, but inversely, associated with SAT (nonlinear P = 0.011). CONCLUSIONS: Improving diet quality in young to middle-aged adults is a recommended strategy to promote better measures of body composition. Our study findings suggest that healthier food choices may influence body composition.

Measures of MRI Brain Biomarkers in Middle Age According to Average Modified Mediterranean Diet Scores Throughout Young and Middle Adulthood.

BACKGROUND: The Mediterranean diet (MedDiet) has been linked with better cognitive function and brain integrity. OBJECTIVE: To examine the association of modified Mediterranean diet (mMedDiet) scores from early through middle adulthood in relation to volumetric and microstructural midlife MRI brain measures. Assess the association of mMedDiet and brain measures with four cognitive domains. If variables are correlated, determine if brain measures mediate the relationship between mMedDiet and cognition. METHODS: 618 participants (mean age 25.4±3.5 at year 0) of the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Cumulative average mMedDiet scores were calculated by averaging scores from years 0, 7, and 20. MRI scans were obtained at years 25 and 30. General linear models were used to examine the association between mMedDiet and brain measures. RESULTS: Higher cumulative average mMedDiet scores were associated with better microstructural white matter (WM) integrity measured by fractional anisotropy (FA) at years 25 and 30 (all ptrend <0.05). Higher mMedDiet scores at year 7 were associated with higher WM FA at year 25 (ß= 0.003, ptrend = 0.03). Higher mMedDiet scores at year 20 associated with higher WM FA at years 25 (ß= 0.0005, ptrend = 0.002) and 30 (ß= 0.0003, ptrend = 0.02). mMedDiet scores were not associated with brain volumes. Higher mMedDiet scores and WM FA were both correlated with better executive function, processing speed, and global cognition (all ptrend <0.05). WM FA did not mediate the association between mMedDiet scores and cognition. CONCLUSIONS: mMedDiet scores may be associated with microstructural WM integrity at midlife.

A Plant-Centered Diet is Inversely Associated with Radiographic Emphysema: Findings from the CARDIA Lung Study.

Chronic obstructive pulmonary disease (COPD) is a significant public health concern and intercepting the development of emphysema is vital for COPD prevention. Smokers are a high-risk population for emphysema with limited prevention strategies. We aimed to determine if adherence to a nutritionally rich plant-centered diet among young ever-smokers is associated with reduced risk of future radiographic emphysema. We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Lung Prospective Cohort Study who were 18-30 years old at enrollment and followed for 30 years. We analyzed 1,706 adults who reported current or former smoking by year 20. Repeated measures of diet history were used to calculate A Priori Diet Quality Scores (APDQS), and categorized into quintiles, with higher quintiles representing higher nutritionally rich plant-centered food intake. Emphysema was assessed at year 25 (n=1,351) by computed tomography (CT). Critical covariates were selected, acknowledging potential residual confounding. Emphysema was observed in 13.0% of the cohort, with a mean age of 50.4 ± 3.5 years. The prevalence of emphysema was 4.5% in the highest APDQS quintile (nutritionally rich), compared with 25.4% in the lowest quintile. After adjustment for multiple covariates, including smoking, greater adherence to a plant-centered diet was inversely associated with emphysema (highest vs lowest quintile odds ratio: 0.44, 95% CI 0.19-0.99, ptrend=0.008). To conclude, longitudinal adherence to a nutritionally rich plant-centered diet was associated with decreased risk of emphysema development in middle adulthood, warranting further examination of diet as a strategy for emphysema prevention in a high-risk smoking population.

Plant-Based Diets and Risk of Hospitalization with Respiratory Infection: Results from the Atherosclerosis Risk in Communities (ARIC) Study.

The benefits of plant-based diets may depend on the type of plant. To determine the associations of healthy and unhealthy plant-based diet types on risk of hospitalization with respiratory infections or any infection, we used dietary intake data reported in a food frequency questionnaire from the Atherosclerosis Risk in Communities Study to calculate a plant-based diet index (PDI), a healthy PDI (HPDI), and an unhealthy PDI (UPDI). Cox regression was used to calculate hazard ratios for the associations of the three plant-based diet indices with the risk of hospitalization with respiratory infections and any infection-related hospitalization. Comparing the highest to lowest quintiles, HPDI was associated with a lower risk of hospitalization with respiratory infections (HR 0.86, 95% CI: 0.75, 0.99), and a lower risk of hospitalization with any infections (HR 0.87, 95% CI: 0.78, 0.97). The PDI was associated with a lower risk of hospitalization with any infections (HR 0.86, 95% CI: 0.76, 0.96). Significant associations were not observed with the UPDI. Adults with a high PDI and HPDI had a lower risk of hospitalization with any infections, whereas adults with a high HPDI had lower risk of hospitalizations with respiratory infections.

Serum Metabolomic Markers of Dairy Consumption: Results from the Atherosclerosis Risk in Communities Study and the Bogalusa Heart Study.

BACKGROUND: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake. OBJECTIVES: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults. METHODS: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in 2 subgroups of the Atherosclerosis Risk in Communities study (ARIC; n = 3776). Results from the 2 subgroups were meta-analyzed using fixed effects meta-analysis. Significant meta-analyzed associations in the ARIC study were then tested in the Bogalusa Heart Study (BHS; n = 785). RESULTS: In the ARIC study and BHS, the mean age was 54 and 48 years, 61% and 29% were Black, and the mean dairy intake was 1.7 and 1.3 servings/day, respectively. Twenty-nine significant associations between dietary intake of dairy and serum metabolites were identified in the ARIC study (total dairy, n = 14; low-fat dairy, n = 10; high-fat dairy, n = 5). Three associations were also significant in BHS: myristate (14:0) was associated with high-fat dairy, and pantothenate was associated with total dairy and low-fat dairy, but 23 of the 27 associations significant in the ARIC study and tested in BHS were not associated with dairy in BHS. CONCLUSIONS: We identified metabolomic associations with dietary intake of dairy, including 3 associations found in 2 independent cohort studies. These results suggest that myristate (14:0) and pantothenate (vitamin B5) are candidate biomarkers of dairy consumption.

Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10-8, we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2, SLC29A2, ANKRD13D and POLD4, and spanning a > 9 Mb region on chromosome 11 (57.5 Mb ~ 67.1 Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.

Investigating Associations of Omega-3 Fatty Acids, Lung Function Decline, and Airway Obstruction.

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health. Objectives: To investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in a diverse sample of adults from general-population cohorts. Methods: Complementary study designs: 1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1 and FVC measures in the NHLBI Pooled Cohorts Study and 2) two-sample Mendelian randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid levels were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for the most metabolically downstream omega-3 fatty acid, docosahexaenoic acid (DHA). An increase in DHA of 1% of total fatty acids was associated with attenuations of 1.4 ml/yr for FEV1 (95% confidence interval [CI], 1.1-1.8) and 2.0 ml/yr for FVC (95% CI, 1.6-2.4) and a 7% lower incidence of spirometry-defined airway obstruction (95% CI, 0.89-0.97). DHA associations persisted across sexes and smoking histories and in Black, White, and Hispanic participants, with associations of the largest magnitude in former smokers and Hispanic participants. The MR study showed similar trends toward positive associations of genetically predicted downstream omega-3 fatty acids with FEV1 and FVC. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher levels of downstream omega-3 fatty acids, especially DHA, on lung health.

Long-term aspartame and saccharin intakes are related to greater volumes of visceral, intermuscular, and subcutaneous adipose tissue: the CARDIA study.

BACKGROUND: Artificial sweetener (ArtSw) intakes have been previously associated with higher BMI in observational studies and may promote visceral and skeletal muscle adipose tissue (AT) accumulation. This study aimed to determine whether habitual, long-term ArtSw or diet beverage intakes are related to greater AT depot volumes and anthropometry-related outcomes. METHODS: A validated diet history questionnaire was administered at baseline, year 7, and year 20 examinations in 3088 men and women enrolled in the Coronary Artery Risk Development in Young Adults cohort (CARDIA), mean age of 25.2 years and mean BMI of 24.5 kg/m2 at baseline. Volumes of visceral (VAT), intermuscular (IMAT), and subcutaneous adipose tissue (SAT) were assessed by computed tomography at year 25. Linear regression evaluated associations of aspartame, saccharin, sucralose, total ArtSw, and diet beverage intakes with AT volumes, anthropometric measures, and 25-year change in anthropometry. Cox regression estimated associations of ArtSw with obesity incidence. Adjustments were made for demographic and lifestyle factors, total energy intake, and the 2015 healthy eating index. RESULTS: Total ArtSw, aspartame, saccharin, and diet beverage intakes were positively associated with VAT, SAT, and IMAT volumes (all ptrend ≤ 0.001), but no associations were observed for sucralose intake (all ptrend > 0.05). In addition, total ArtSw, saccharin, aspartame, and diet beverage intakes were associated with greater body mass index, body weight, waist circumference, and their increases over a 25-year period. Except for saccharin (ptrend = 0.13), ArtSw, including diet soda, was associated with greater risks of incident obesity over a median 17.5-year follow-up (all ptrend < 0.05). CONCLUSIONS: Results suggest that long-term intakes of aspartame, saccharin, or diet soda may increase AT deposition and risk of incident obesity independent of diet quality or caloric intake. Coupled with previous evidence, alternatives to national recommendations to replace added sugar with ArtSw should be considered since both may have health consequences.

Metabolomics of Dietary Intake of Total, Animal, and Plant Protein: Results from the Atherosclerosis Risk in Communities (ARIC) Study.

Background: Dietary consumption has traditionally been studied through food intake questionnaires. Metabolomics can be used to identify blood markers of dietary protein that may complement existing dietary assessment tools. Objectives: We aimed to identify associations between 3 dietary protein sources (total protein, animal protein, and plant protein) and serum metabolites using data from the Atherosclerosis Risk in Communities Study. Methods: Participants' dietary protein intake was derived from a food frequency questionnaire administered by an interviewer, and fasting serum samples were collected at study visit 1 (1987-1989). Untargeted metabolomic profiling was performed in 2 subgroups (subgroup 1: n = 1842; subgroup 2: n = 2072). Multivariable linear regression models were used to assess associations between 3 dietary protein sources and 360 metabolites, adjusting for demographic factors and other participant characteristics. Analyses were performed separately within each subgroup and meta-analyzed with fixed-effects models. Results: In this study of 3914 middle-aged adults, the mean (SD) age was 54 (6) y, 60% were women, and 61% were Black. We identified 41 metabolites significantly associated with dietary protein intake. Twenty-six metabolite associations overlapped between total protein and animal protein, such as pyroglutamine, creatine, 3-methylhistidine, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. Plant protein was uniquely associated with 11 metabolites, such as tryptophan betaine, 4-vinylphenol sulfate, N-δ-acetylornithine, and pipecolate. Conclusions: The results of 17 of the 41 metabolites (41%) were consistent with those of previous nutritional metabolomic studies and specific protein-rich food items. We discovered 24 metabolites that had not been previously associated with dietary protein intake. These results enhance the validity of candidate markers of dietary protein intake and introduce novel metabolomic markers of dietary protein intake.

Associations of 5-year changes in alcoholic beverage intake with 5-year changes in waist circumference and BMI in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: This study aimed to shed light on contradictory associations of alcohol intake with waist circumference (WC) and body mass index (BMI) by examining 5-yr changes in alcohol intake in relation to 5-yr WC and BMI changes. METHODS: This prospective study included 4,355 participants (1,974 men and 2,381 women) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study at baseline (1985-1986) and followed over 25 years (2010-2011). Longitudinal random effects linear regression models were used to test whether changes in drinking (defined categorically) as starting to drink, increasing, decreasing, stable drinking or stopping drinking (versus stable non-drinking) over a series of 5-yr periods were associated with corresponding 5-yr WC and BMI changes. Associations with 5-yr changes (defined categorically as starting, stable or stopping) in drinking level (i.e., light/moderate and excessive) and 5-yr changes (defined categorically as increasing, no change, or decreasing) by beverage type (i.e., beer, wine and liquor/mixed drinks) were also examined. RESULTS: In men, compared to stable non-drinking, decreasing total alcohol intake was associated with lower 5-yr WC (ß:-0.62 cm; 95% CI: -1.09, -0.14 cm) and BMI gains (ß:-0.20 kg/m2; 95% CI: -0.30, -0.03 kg/m2) and stopping excessive drinking was associated with lower 5-yr WC gains (ß:-0.77 cm; 95% CI: -1.51, -0.03 cm). In women, compared to those with stable non-drinking habits, starting light/moderate drinking was associated with lower 5-yr WC (ß: -0.78 cm; 95% CI: -1.29, -0.26 cm) and BMI gains (ß:-0.42 kg/m2; 95% CI: -0.64, -0.20 kg/m2). Increasing wine intake was associated with a lower 5-yr BMI gain (ß:-0.27 kg/m2; 95% CI: -0.51, -0.03 kg/m2). Decreasing liquor/mixed drink (ß:-0.33 kg/m2; 95% CI: -0.56, -0.09 kg/m2) intake was associated with lower 5-yr WC (ß:-0.88 cm; 95% CI: -1.43, -0.34 cm) and BMI (ß:-0.33 kg/m2; 95% CI: -0.56, -0.09 kg/m2) gains. CONCLUSIONS: Associations of alcohol intake with obesity measures are complex. In women, wine and liquor/mixed drink intakes had contrasting associations with WC and BMI change. In men, decreasing weekly alcoholic beverage intake with an emphasis on stopping excessive consumption may be beneficial in managing WC and BMI gains.

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

Investigating associations of omega-3 fatty acids, lung function decline, and airway obstruction.

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have anti-inflammatory properties and may benefit lung health. Objectives: Investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in adults of diverse races/ethnicities from general population cohorts. Methods: Complementary study designs: (1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV 1 and FVC measures in the National Heart, Lung, and Blood Institute Pooled Cohorts Study, and (2) two-sample Mendelian Randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid concentrations were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for docosahexaenoic acid (DHA). One standard deviation higher DHA was associated with an attenuation of 1.8 mL/year for FEV 1 (95% confidence interval [CI] 1.3-2.2) and 2.4 mL/year for FVC (95% CI 1.9-3.0). One standard deviation higher DHA was also associated with a 9% lower incidence of spirometry-defined airway obstruction (95% CI 0.86-0.97). DHA associations persisted across sexes, smoking histories, and Black, white and Hispanic participants, with the largest magnitude associations in former smokers and Hispanics. The MR study showed positive associations of genetically predicted omega-3 fatty acids with FEV 1 and FVC, with statistically significant findings across multiple MR methods. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher circulating omega-3 fatty acids, especially DHA, on lung health.

Dietary metabolic signatures and cardiometabolic risk.

AIMS: Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood. METHODS AND RESULTS: In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study. CONCLUSION: Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.

Association of nut consumption with CVD risk factors in young to middle-aged adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND AND AIMS: Few studies have examined long-term associations of walnut, other nut, and no nut consumption with cardiovascular disease (CVD) risk factors. Results from prospective studies with long-term follow-up can provide further evidence for dietary guideline messaging to consume nuts. Therefore, we examined the associations of walnut, other nut, and no nut consumption with diet quality and CVD risk factors over 30 years of follow-up. METHODS AND RESULTS: Data were analyzed from 3092 young adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary intake, including walnuts and other nuts, was assessed 3 times over 20 years. CVD risk factors were measured at multiple exams. General linear regression evaluated the associations of walnut, other nut, and no nut consumption with CVD risk factors over 30 years (Y30) of follow-up. The 20-year cumulative mean intake of walnuts (0.74 oz/d), other nuts (1.6 oz/d), or no nut consumption was differentially associated with HEI-2015 and CVD risk factors by Y30. Generally, walnut consumers had significantly higher HEI-2015, lower body mass index, waist circumference, blood pressure, and triglyceride concentration, and gained less weight since baseline than other nut consumers (p ≤ 0.05 for all). Further, walnut consumers had lower fasting blood glucose than no nut consumers (p ≤ 0.05). CONCLUSION: Study findings that walnut and other nut consumption was associated with better CVD risk factors and diet quality aligns with the 2020-2025 US. Dietary Guidelines for Americans recommendation to consume nuts, such as walnuts, within the context of a healthy diet.