Eggs, dietary choline, and nonalcoholic fatty liver disease in the Framingham Heart Study.

BACKGROUND: Eggs are rich in bioactive compounds, including choline and carotenoids, that may benefit cardiometabolic outcomes. However, little is known about their relation with nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We investigated the association between intakes of eggs and selected egg-rich nutrients (choline, lutein and zeaxanthin) and NAFLD risk and changes in liver fat over approximately 6 years of follow-up in the Framingham Offspring and Third Generation cohorts. METHODS: On two separate occasions (2002-2005 and 2008-2011), liver fat was assessed using a computed tomography scan to estimate the average liver fat attenuation relative to a control phantom to create the liver phantom ratio (LPR). In 2008-2011, cases of incident NAFLD were identified as an LPR ≤0.33 in the absence of heavy alcohol use, after excluding prevalent NAFLD (LPR ≤0.33) in 2002-2005. Food frequency questionnaires were used to estimate egg intakes (classified as <1, 1, and ≥2 per week) and dietary choline (adjusted for body weight using the residual method), and the combined intakes of lutein and zeaxanthin. Multivariable modified Poisson regression and general linear models were used to compute incident risk ratios (RR) of NAFLD and adjusted mean annualized liver fat change. RESULTS: NAFLD cumulative incidence was 19% among a total of 1414 participants. We observed no associations between egg intake or the combined intakes of lutein and zeaxanthin with an incident NAFLD risk or liver fat change. Other diet and cardiometabolic risk factors did not modify this association. However, dietary choline intakes were inversely associated with NAFLD risk (RR for tertile 3 vs. 1: 0.69, 95% CI: 0.51-0.94). CONCLUSIONS: While egg intake was not directly associated with NAFLD risk, eggs are a major source of dietary choline, which was strongly inversely associated with NAFLD risk in this community-based cohort.

A Healthy Diet is Associated with a Lower Risk of Hepatic Fibrosis.

BACKGROUND: Higher diet quality is associated with a lower risk of NAFLD. OBJECTIVES: We examined the relationship between diet quality and hepatic fibrosis. METHODS: We analyzed cross-sectional associations between 3 a priori diet quality scores-the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), and a modified Mediterranean-style Diet Score (MDS)-and hepatic fat [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)] measured by vibration-controlled transient elastography (VCTE) in 2532 Framingham Heart Study (FHS) participants and 3295 participants of the National Health and Nutrition Examination Survey (NHANES). RESULTS: Higher diet quality scores were associated with lower LSM in both FHS and NHANES after adjustment for demographic and lifestyle factors. Additional adjustment for CAP or BMI attenuated the observed associations. Association strength was similar across all 3 diet quality scores. Fixed-effect meta-analysis demonstrated that, under CAP-adjusted models, the LSM decreases associated with 1-SD increase of the DASH, AHEI, and MDS scores were 2% (95% CI: 0.7%, 3.3%; P = 0.002), 2% (95% CI: 0.7%, 3.3%; P = 0.003), and 1.7% (95% CI: 0.7%, 2.6%; P = 0.001), respectively, whereas in the meta-analysis of BMI-adjusted models, LSM reductions associated with 1-SD increase of the DASH, AHEI, and MDS scores were 2.2% (95% CI: -0.1%, 2.2%; P = 0.07), 1.5% (95% CI: 0.3%, 2.7%; P = 0.02), and 0.9 (95% CI: -0.1%, 1.9%; P = 0.07), respectively. CONCLUSIONS: We demonstrated associations of higher diet quality with favorable hepatic fat and fibrosis measures. Our data suggest that a healthy diet may reduce the likelihood of obesity and hepatic steatosis as well as the progression of steatosis to fibrosis.

A beneficial cardiometabolic health profile associated with dietary supplement use: A cross-sectional study.

As a follow-up to an earlier study demonstrating healthier cardiometabolic profiles among long-term multiple dietary supplement (LTMDS) users, we examined if cardiometabolic health benefits associated with LTMDS use persisted with aging. The study is based on LTMDS users from North America and 2007-2010 NHANES participants who were used for comparison to the LTMDS users. NHANES subjects were classified as non-dietary supplement (NS) users, single supplement/single purpose supplement (SS) users, multivitamin/mineral supplement (MVMS) users, and multiple dietary supplement (MDS) users. Supplement groups were compared for total, HDL and LDL cholesterol; triglycerides; glucose; insulin; CRP and HbA1c ≥ 6.5%, adjusting for age, sex, income, education, BMI, history of CVD, and medications for hypercholesterolemia and diabetes. Geometric mean (95% confidence interval) LDL cholesterol was significantly lower (P < 0.05) for all supplement groups (SS: 110 (104-117) mg/dL; MVMS: 113 (107-119) mg/dL; MDS: 115 (111-118) mg/dL; LTMDS: 112 (105, 119) mg/dL) compared with the NS users (122 (118-126) mg/dL). Compared with the NS group, MDS users had significantly (P < 0.05) lower mean total cholesterol (198 (194-201) vs 201 (197, 206) mg/dL), MDS and LTMDS users higher mean HDL cholesterol (54.2 (53.3-55.1) and 60.0 (57.4, 62.7) mg/dL vs 52.0 (50.8-53.3) mg/dL), LTMDS users lower fasting glucose (100 (98-103) vs 105 (103-106) mg/dL), SS and MDS users lower insulin (8.4 (7.4-9.6) and 9.1 (8.3-9.9) vs 10.2 (9.4-11.1) µIU/mL), and MDS users lower CRP (% ≥ 1.5 mg/L, 50.8 (47.9-53.6) vs 57.0 (52.4-61.6) %). These findings add to the evidence that use of dietary supplements may provide cardiometabolic health benefits.

Higher Dietary Inflammatory Index scores are associated with brain MRI markers of brain aging: Results from the Framingham Heart Study Offspring cohort.

INTRODUCTION: We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort. METHODS: A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI). RESULTS: Higher (pro-inflammatory) DII scores, averaged across a maximum of three time points, were associated with smaller total brain volume (beta ± standard error: -0.16 ± 0.03; P < .0001) after adjustment for demographic, clinical, and lifestyle covariates. In addition, higher DII scores were associated with smaller total gray matter volume (-0.08 ± 0.03; P = .003) and larger lateral ventricular volume (0.04 ± 0.02; P = .03). No associations were observed with other brain MRI measures. DISCUSSION: Our findings showed associations between higher DII scores and global brain MRI measures. As we are one of the first groups to report on the associations between higher DII scores and brain volume, replication is needed to confirm our findings.

Early Childhood Lutein and Zeaxanthin Intake Is Positively Associated with Early Childhood Receptive Vocabulary and Mid-Childhood Executive Function But No Other Cognitive or Behavioral Outcomes in Project Viva.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition in older adults. Recent evidence suggests that their dietary intake may also have cognitive implications in childhood. OBJECTIVE: The aim was to examine associations of early childhood lutein and zeaxanthin (L/Z) intake with cognition in early and mid-childhood. METHODS: Among 1378 children in Project Viva, a prospective cohort, mothers reported their child's dietary intake in early childhood (median: 3.2 y) using a food-frequency questionnaire. Child cognition and behavior were assessed at the same time point using the Peabody Picture Vocabulary Test (PPVT-III) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) and at mid-childhood (median: 7.7 y) using the Kaufman Brief Intelligence Test, the WRAVMA drawing subtest, the Wide Range Assessment of Memory and Learning, the Behavior Rating Inventory of Executive Function (BRIEF), and the Strengths and Difficulties Questionnaire. RESULTS: Children consumed a daily mean (SD) of 1.0 (0.4) mg L/Z in early childhood. Children in the third-quartile category of L/Z intake had a mean PPVT-III score 2.40 (95% CI: 0.27, 4.53) points higher than children in the lowest quartile category in early childhood, suggesting better receptive vocabulary. Children in the highest quartile category of L/Z intake had a parent-reported mean BRIEF Global Executive Composite score 1.65 (95% CI: -3.27, -0.03) points lower than children in the lowest quartile category in mid-childhood, indicating better executive function. We did not observe associations between L/Z intake and any of the other cognitive or behavioral outcomes assessed. CONCLUSIONS: The overall findings do not provide strong evidence of an association between child L/Z intake and cognition and behavior. However, the positive associations found between early childhood L/Z intake and early childhood receptive vocabulary and mid-childhood executive function, in addition to previous evidence of neurodevelopmental benefit of L/Z intake, suggest that this relation deserves further investigation.

Sugar-Sweetened Beverage Consumption and Plasma Lipoprotein Cholesterol, Apolipoprotein, and Lipoprotein Particle Size Concentrations in US Adults.

BACKGROUND: Prospective cohort studies have found a relation between sugar-sweetened beverage (SSB) consumption (sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations. OBJECTIVES: To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults. METHODS: We examined participants from the Framingham Offspring Study (FOS; 1987-1995, n = 3047) and the Women's Health Study (1992, n = 26,218). Concentrations of plasma LDL cholesterol, apolipoprotein B (apoB), HDL cholesterol, apolipoprotein A1 (apoA1), triglyceride (TG), and non-HDL cholesterol, as well as total cholesterol:HDL cholesterol ratio and apoB:apoA1 ratio, were quantified in both cohorts; concentrations of apolipoprotein E, apolipoprotein C3, RLP-TG, and RLP cholesterol (RLP-C) were measured in the FOS only. Lipoprotein particle sizes were calculated from nuclear magnetic resonance signals for lipoprotein particle subclass concentrations (TG-rich lipoprotein particles [TRL-Ps]: very large, large, medium, small, and very small; LDL particles [LDL-Ps]: large, medium, and small; HDL particles [HDL-Ps]: large, medium, and small). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors such as lifestyle, diet, and traditional lipoprotein risk factors. RESULTS: SSB consumption was positively associated with LDL cholesterol, apoB, TG, RLP-TG, RLP-C, and non-HDL cholesterol concentrations and total cholesterol:HDL cholesterol and apoB:apoA1 ratios; and negatively associated with HDL cholesterol and apoA1 concentrations (P-trend range: <0.0001 to 0.008). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes; lower concentrations of large LDL-Ps and medium HDL-Ps; and higher concentrations of small LDL-Ps, small HDL-Ps, and large TRL-Ps (P-trend range: <0.0001 to 0.001). CONCLUSIONS: Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study.

BACKGROUND: The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. METHODS: Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. RESULTS: During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04-1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01-1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87-1.64)]. CONCLUSIONS: Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.

Adverse effects related to methotrexate polyglutamate levels: adjudicated results from the cardiovascular inflammation reduction trial.

OBJECTIVES: Methotrexate is widely used at low dosages (LD-MTX) for non-oncologic indications and is associated with a variety of adverse effects (AEs). We sought to determine whether concentrations of the active metabolite, MTX polyglutamates (MTX-PGs) 1-5, correlate with AEs. METHOD: We examined data from the LD-MTX arm of the randomized double-blind Cardiovascular Inflammation Reduction Trial (CIRT). All AEs were blindly adjudicated and monitoring laboratories were tested centrally. The MTX-PGs 1-5 were assessed in one reference laboratory using liquid chromatography-tandem mass spectrometry. Based on prior literature, MTX-PGs 3-5 were chosen as the exposure of interest and quartiles of MTX-PGs 3-5 were assessed for their relationship with all AEs and each pre-specified category of AE using adjusted Cox proportional hazards regression. RESULTS: Of the 2391 subjects randomized to LD-MTX, MTX-PG levels were available for 1319 subjects (median dosage 16.1 mg/week) from the 8 month visit. We followed these subjects for a median of 2.2 years [interquartile range (IQR) 1.5-2.9]. Higher MTX-PG3-5 levels were related to an increased risk of anaemia [compared with quartile 1 (Q1); hazard ratio (HR) for Q4 1.27 (95% CI 0.98, 1.65), P for trend = 0.05] and a decreased risk of thrombocytopenia [HR for Q4 0.52 (95% CI 0.32, 0.84), P for trend = 0.05]. MTX-PG3-5 levels >134 nmol/l were associated with an increased risk of liver abnormalities [HR 1.36 (95% CI 1.08, 1.72)]. CONCLUSIONS: Higher MTX- PG3-5 levels were modestly associated with LD-MTX AEs, including anaemia and liver function abnormalities, but a reduced risk of thrombocytopenia and haemorrhage. CLINICAL TRIAL REGISTRATION: NCT01594333.

Water Intake and Markers of Hydration Are Related to Cardiometabolic Risk Biomarkers in Community-Dwelling Older Adults: A Cross-Sectional Analysis.

BACKGROUND: Emerging evidence links underhydration and habitual low water intake to higher cardiometabolic risk, but evidence is limited in community-dwelling older adults. OBJECTIVES: The objective is to examine if higher water intake and better hydration are associated with better cardiometabolic health. METHODS: This cross-sectional analysis using general linear models included 2238 participants from the Framingham Heart Study Second Generation and First Generation Omni cohorts with an estimated glomerular filtration rate >30 mL·min-1·1.73 m-2 and a valid FFQ for assessment of water intake. Of these participants, 2219 had fasting spot urinary creatinine data and 950 had 24-h urine creatinine data to assess hydration. Cardiometabolic risk factors included fasting glucose, triglycerides (TGs), total cholesterol (TC), HDL cholesterol, and calculated LDL cholesterol; glycated hemoglobin (HbA1c); C-reactive protein (CRP); and systolic (SBP) and diastolic (DBP) blood pressure. RESULTS: The combined cohorts were on average aged 70 y; 55% were women. Mean (95% CI) daily total water intakes were 2098 (2048, 2150) mL for men and 2109 (2063, 2156) mL for women. Total daily water, beverage (including plain water), and plain water intakes demonstrated significant positive trends with HDL cholesterol (P < 0.01). TG concentrations were significantly lower among the highest plain water consumers (P < 0.05). The 24-h urine concentration, as measured by creatinine, was positively associated with LDL cholesterol and TG concentrations ( P < 0.01) and inversely associated with HDL cholesterol concentrations (P < 0.002). Neither water intake nor urine concentration was associated with glucose or HbA1c (P > 0.05). CONCLUSIONS: Our findings of a consistent pattern between circulating lipid concentrations and different water sources and hydration markers support an association between hydration and lipid metabolism in older adults and add to the growing evidence that inadequate water intake and underhydration may lead to higher cardiometabolic risk.

Whole- and Refined-Grain Consumption and Longitudinal Changes in Cardiometabolic Risk Factors in the Framingham Offspring Cohort.

BACKGROUND: Greater whole grain (WG) consumption is associated with reduced risk of cardiovascular disease (CVD); however, few prospective studies have examined WG or refined grain (RG) intake and intermediate cardiometabolic risk factors. OBJECTIVES: We examined the longitudinal association between WG and RG intake on changes in waist circumference (WC); fasting HDL cholesterol, triglyceride, and glucose concentrations; and blood pressure. METHODS: Subjects were participants in the Framingham Offspring cohort study [n = 3121; mean ± SD baseline age: 54.9 ± 0.2 y; BMI (kg/m2) 27.2 ± 0.1]. FFQ, health, and lifestyle data were collected approximately every 4 y over a median 18-y follow-up. Repeated measure mixed models were used to estimate adjusted mean changes per 4-y interval in risk factors across increasing categories of WG or RG intake. RESULTS: Greater WG intake was associated with smaller increases in WC (1.4 ± 0.2 compared with 3.0 ± 0.1 cm in the highest compared with the lowest category, respectively; P-trend < 0.001), fasting glucose concentration (0.7 ± 0.4 compared with 2.6 ± 0.2 mg/dL; P-trend < 0.001), and systolic blood pressure (SBP; 0.2 ± 0.5 compared with 1.4 ± 0.3 mm Hg; P-trend < 0.001) per 4-y interval. When stratified by sex, a stronger association with WC was observed among females than males. Higher intake of WG was associated with greater increases in HDL cholesterol and declines in triglyceride concentrations; however, these differences did not remain significant after adjustment for change in WC. Conversely, greater RG intake was associated with greater increases in WC (2.7 ± 0.2 compared with 1.8 ± 0.1 cm, P-trend < 0.001) and less decline in triglyceride concentration (-0.3 ± 1.3 compared with -7.0 ± 0.7 mg/dL, P-trend < 0.001). CONCLUSIONS: Among middle- to older-age adults, replacing RG with WG may be an effective dietary modification to attenuate abdominal adiposity, dyslipidemia, and hyperglycemia over time, thereby reducing the risk of cardiometabolic diseases.

Maternal Intake of Lutein and Zeaxanthin during Pregnancy Is Positively Associated with Offspring Verbal Intelligence and Behavior Regulation in Mid-Childhood in the Project Viva Cohort.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition at older age. To our knowledge, no previous study has evaluated their cognitive implications in the prenatal period, when the brain undergoes its most rapid development. OBJECTIVE: The objective of this study was to examine associations of maternal lutein and zeaxanthin (L/Z) intake during pregnancy with child cognition. DESIGN: Among 1580 mother-child pairs in Project Viva, a prospective cohort, we assessed maternal intake of L/Z during pregnancy using food frequency questionnaires and offspring cognition by the Visual Recognition Memory paradigm in infancy, the Peabody Picture Vocabulary Test and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) in early childhood, and the Kaufman Brief Intelligence Test (KBIT-II), the WRAVMA drawing subtest, and the Wide Range Assessment of Memory and Learning in mid-childhood. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Strengths and Difficulties Questionnaire. RESULTS: Mothers consumed a daily mean (SD) of 2.6 (2.0) mg L/Z in the first and second trimesters of pregnancy. Mean mid-childhood KBIT-II verbal scores were higher with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: 2.67 (95% CI: 0.13, 5.20) and for second trimester: 3.55 (95% CI: 0.81, 6.28)], indicating better verbal intelligence. Secondary analyses on cognitive subtests showed that mean mid-childhood BRIEF Behavioral Regulation Index scores were lower with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: -1.63 (95% CI: -3.22, -0.04) and for second trimester: -1.89 (95% CI: -3.58, -0.21)], indicating better behavior regulation ability. CONCLUSIONS: Higher maternal L/Z intake during pregnancy was associated with better offspring verbal intelligence and behavior regulation ability in mid-childhood, suggesting a potential benefit during prenatal development. We did not find a benefit of higher maternal L/Z intake on other child cognitive or behavioral outcomes. Project Viva is registered at clinicaltrials.gov as NCT02820402.

Dairy versus other saturated fats source and cardiometabolic risk markers: Systematic review of randomized controlled trials.

To analyze the effects of dairy intake on cardiometabolic risk markers compared to other dietary fat sources in adults. Literature database and gray literature were searched for studies published up to October 2018. Two independent authors selected and extracted data from articles. Summary tables were constructed to present data for all outcomes. The intake of dairy appears to have a protective effect on some cardiovascular risk factors, or it is not worse than other SFA sources. The higher intake of dairy can decrease total cholesterol and reduce waist circumference and increase HDL cholesterol. However, it can also increase LDL and triglycerides, although those were small changes. It was observed that the effect of dairy on several serum lipids varied according to the type dairy product used on intervention. Dairy products seem to present a different effect on cardiometabolic risk factors than other fat sources, with evidence of improvement on metabolic parameters compared to another animal source of SFA.

Associations of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet with cardiac remodelling in the community: the Framingham Heart Study.

Normal cardiac function is directly associated with the maintenance of cerebrovascular health. Whether the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet, designed for the maintenance of neurocognitive health, is associated with cardiac remodelling is unknown. We evaluated 2512 Framingham Offspring Cohort participants who attended the eighth examination cycle and had available dietary and echocardiographic data (mean age 66 years; 55 % women). Using multivariable regression, we related the cumulative MIND diet score (independent variable) to left ventricular (LV) ejection fraction, left atrial emptying fraction, LV mass (LVM), E/e' ratio (dependent variables; primary), global longitudinal strain, global circumferential strain (GCS), mitral annular plane systolic excursion, longitudinal segmental synchrony, LV hypertrophy and aortic root diameter (secondary). Adjusting for age, sex and energy intake, higher cumulative MIND diet scores were associated with lower values of indices of LV diastolic (E/e' ratio: logß = -0·03) and systolic function (GCS: ß = -0·04) and with higher values of LVM (logß = 0·02), all P ≤ 0·01. We observed effect modification by age in the association between the cumulative MIND diet score and GCS. When we further adjusted for clinical risk factors, the associations of the cumulative MIND diet score with GCS in participants ≥66 years (ß = -0·06, P = 0·005) and LVM remained significant. In our community-based sample, relations between the cumulative MIND diet score and cardiac remodelling differ among indices of LV structure and function. Our results suggest that favourable associations between a higher cumulative MIND diet score and indices of LV function may be influenced by cardiometabolic and lifestyle risk factors.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Dairy Intake in 2 American Adult Cohorts Associates with Novel and Known Targeted and Nontargeted Circulating Metabolites.

BACKGROUND: The role of dairy in health can be elucidated by investigating circulating metabolites associated with intake. OBJECTIVES: We sought to identify metabolites associated with quantity and type of dairy intake in the Framingham Heart Study Offspring and Third Generation (Gen3) cohorts. METHODS: Dairy intake (total dairy, milk, cheese, yogurt, and cream/butter) was analyzed in relation to targeted (Offspring, n = 2205, 55.1 ± 9.8 y, 52% female, 217 signals; Gen3, n = 866, 40.5 ± 8.8 y, 54.9% female, 79 signals) and nontargeted metabolites (Gen3, ∼7031 signals) in a 2-step analysis including orthogonal projections to latent structures with discriminant analysis (OPLS-DA) in discovery subsets to identify metabolites distinguishing between high and low intake; and linear regression in confirmation subsets to assess putative associations, subsequently tested in the total samples. Previously reported associations were also investigated. RESULTS: OPLS-DA in the Offspring targeted discovery subset resulted in a variable importance in projection (VIP) >1 of 65, 60, 58, 66, and 60 metabolites for total dairy, milk, cream/butter, cheese, and yogurt, respectively, of which 5, 3, 1, 6, and 4 metabolites, respectively, remained after confirmation. In the Gen3 targeted discovery subset, OPLS-DA resulted in a VIP >1 of 17, 15, 13, 7, and 6 metabolites for total dairy, milk, cream/butter, cheese, and yogurt, respectively. In the Gen3 nontargeted discovery subset, OPLS-DA resulted in a VIP >2 of 203, 503, 78, 186, and 206 metabolites, respectively. Combining targeted and nontargeted results in Gen3, significant associations of 7 (6 unannotated), 2, 12 (11 unannotated), 0, and 61 (all unannotated) metabolites, respectively, remained. Candidate identities of unannotated signals included fatty acids and food flavorings. Results supported relations previously reported for C14:0 sphingomyelin, and marginal associations for deoxycholates. CONCLUSIONS: Dairy in 2 American adult cohorts associated with numerous circulating metabolites. Reports about diet-metabolite relations and confirmation of previous findings might be limited by specificity of dietary intake and breadth of measured metabolites.

Flavonoid Intake and MRI Markers of Brain Health in the Framingham Offspring Cohort.

BACKGROUND: Although greater flavonoid intake is associated with a reduced risk of Alzheimer's disease (AD) and related dementias (ADRD), evidence relating dietary flavonoid intake to brain health based on MRI is lacking. OBJECTIVE: The objective of this study was to explore the association between dietary flavonoid intake and MRI measures of brain health, including total brain tissue volume (TBV), white matter hyperintensities volume (WMHV), and hippocampal volume (HV). METHODS: Eligible subjects included members of the Framingham Heart Study Offspring Cohort who were free of stroke at exam 7 and had at least 1 valid food frequency questionnaire from exams 5, 6, or 7 (n = 2086; mean age at exam 7, 60.6 y). Flavonoid intakes represented the cumulative mean of intakes across the 3 exams and were categorized based on quartiles categories of intake. TBV, WMHV, and HV were assessed at exam 7. Multiple linear regression models were used to examine the cross-sectional association between total and the 6 classes of flavonoids and the 3 aforementioned MRI measures. RESULTS: The mean (95% CI) of the WMHV of subjects in the highest quartile category of flavan-3-ols [0.56 (0.52, 0.61)] and flavonoid polymers [0.57 (0.52, 0.61)] intake was significantly smaller relative to that of subjects in the lowest quartile category of flavan-3-ols [0.65 (0.60, 0.71)] and flavonoid polymers [0.66 (0.60, 0.71)] after accounting for important demographic, lifestyle, and clinical factors. Inverse trend associations with WMHV were also seen for flavan-3-ols (P = 0.01) and flavonoid polymers (P = 0.01) as well as for total flavonoids (P = 0.01). TBV and HV were not associated with dietary flavonoid intake following the adjustment for potential confounders. CONCLUSIONS: Our results contribute to the literature on flavonoids and ADRD as they suggest that higher flavonoid intakes may affect ADRD risk in middle-aged and older adults by reducing WMHV, a marker strongly associated with ADRD.

Short-Term Tea Consumption Is Not Associated with a Reduction in Blood Lipids or Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: A recent systematic review of epidemiological evidence suggests that higher amounts of tea intake are associated with lower risks of cardiovascular disease (CVD) incidence and mortality. OBJECTIVES: Our study objective was to assess mechanisms by which tea consumption may influence CVD risks. METHODS: A systematic review and meta-analysis was conducted to investigate the effects of green and/or black tea consumption (≥4 wk) on systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride (TG) in healthy populations and among at-risk adults (analyzed separately) with metabolic syndrome, prediabetes, and hypercholesterolemia. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the strength of evidence (SoE). RESULTS: A total of 14 unique RCTs which randomly assigned 798 participants to either green tea, black tea, or placebo controls were included in our analyses. Intervention durations ranged from 4 to 24 wk (mean: 7.4 wk). Individual studies were judged as moderate to high quality based on risk of bias assessments. SoE was low to moderate owing to low sample sizes and insufficient power for most included studies to observe changes in the measured CVD biomarkers. Meta-analyses showed no significant effects of tea consumption on SBP, DBP, total cholesterol, LDL cholesterol, HDL cholesterol, and TG in healthy and at-risk adults (i.e., adults with obesity, prediabetes, borderline hypercholesterolemia, and metabolic syndrome). CONCLUSIONS: Short-term (4-24 wk) tea consumption does not appear to significantly affect blood pressure or lipids in healthy or at-risk adults, although the evidence is limited by insufficient power to detect changes in these CVD biomarkers. High-quality RCTs with longer durations and sufficient sample sizes are needed to fully elucidate the effects of tea. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020134513.

Dietary Patterns, Ceramide Ratios, and Risk of All-Cause and Cause-Specific Mortality: The Framingham Offspring Study.

BACKGROUND: Prior evidence suggests that diet modifies the association of blood ceramides with the risk of incident cardiovascular disease (CVD). It remains unknown if diet quality modifies the association of very long-chain-to-long-chain ceramide ratios with mortality in the community. OBJECTIVES: Our objectives were to determine how healthy dietary patterns associate with blood ceramide concentrations and to examine if healthy dietary patterns modify associations of ceramide ratios (C22:0/C16:0 and C24:0/C16:0) with all-cause and cause-specific mortality. METHODS: We examined 2157 participants of the Framingham Offspring Study (mean age = 66 y, 55% women). Blood ceramides were quantified using a validated assay. We evaluated prospective associations of the Dietary Guidelines Adherence Index (DGAI) and Mediterranean-style Diet Score (MDS) with incidence of all-cause and cause-specific mortality using Cox proportional hazards models. Cross-sectional associations of the DGAI and MDS with ceramides were evaluated using multivariable linear regression models. RESULTS: The C22:0/C16:0 and C24:0/C16:0 ceramide ratios were inversely associated with all-cause, CVD, and cancer mortality; multivariable-adjusted HRs (95% CIs) were 0.73 (0.67, 0.80) and 0.70 (0.63, 0.77) for all-cause mortality, 0.74 (0.60, 0.90) and 0.69 (0.55, 0.86) for CVD mortality, and 0.75 (0.65, 0.87) and 0.75 (0.64, 0.88) for cancer mortality, respectively. Inverse associations of the C22:0/C16:0 and C24:0/C16:0 ceramide ratios with cancer mortality were attenuated among individuals with a higher diet quality (DGAI or MDS above the median, all P-interaction ≤0.1). The DGAI and MDS had distinct associations with ceramide ratios (DGAI: lower C22:0/C16:0 across quartiles; MDS: higher C24:0/C16:0 across quartiles; all P-trend ≤0.01). CONCLUSION: In our community-based sample, ceramide ratios (C22:0/C16:0 and C24:0/C16:0) were associated with a lower risk of all-cause and cause-specific mortality. Further, we observed that a higher overall diet quality attenuates the association between blood ceramide ratios and cancer mortality and that dietary patterns have distinct relations with ceramide ratios.

Long-term dietary flavonoid intake and change in cognitive function in the Framingham Offspring cohort.

OBJECTIVE: To examine the association between long-term intake of total and the six classes of dietary flavonoids and decline in cognitive function over a follow-up period of up to 15 years. DESIGN: In this longitudinal study, we evaluated change in eight cognitive domain scores (verbal and visual memory, verbal learning, attention and concentration, abstract reasoning, language, visuoperceptual organisation and the global function) based on three neuropsychological exams and characterised the annualised change between consecutive exams. Long-term intakes of total and six flavonoid classes were assessed up to four times by a validated FFQ. Repeated-measures regression models were used to examine the longitudinal association between total and six flavonoid classes and annualised change in the eight cognitive domains. SETTING: The Framingham Heart Study (FHS), a prospective cohort study. PARTICIPANTS: One thousand seven hundred and seventy-nine subjects who were free of dementia, aged ≥45 years and had attended at least two of the last three FHS Offspring cohort study exams. RESULTS: Over a median follow-up of 11·8 years with 1779 participants, nominally significant trends towards a slower decline in cognitive function were observed among those with higher flavanol and flavon-3-ol intakes for global function, verbal and visual memory; higher total flavonoids and flavonoid polymers for visual memory; and higher flavanols for verbal learning. CONCLUSIONS: In spite of modest nominal trends, overall, our findings do not support a clear association between higher long-term flavonoid intake and slowing age-related cognitive decline.

Participant characteristics and self-reported weight status in a cross-sectional pilot survey of self-identified followers of popular diets: Adhering to Dietary Approaches for Personal Taste (ADAPT) Feasibility Survey.

OBJECTIVE: To describe characteristics of self-identified popular diet followers and compare mean BMI across these diets, stratified by time following diet. DESIGN: Cross-sectional, web-based survey administered in 2015. SETTING: Non-localised, international survey. PARTICIPANTS: Self-selected followers of popular diets (n 9019) were recruited to the survey via social media and email announcements by diet community leaders, categorised into eight major diet groups. RESULTS: General linear models were used to compare mean BMI among (1) short-term (<1 year) and long-term (≥1 year) followers within diet groups and (2) those identifying as 'try to eat healthy' (TTEH) to all other diet groups, stratified by time following the specific diet. Participants were 82 % female, 93 % White and 96 % non-Hispanic. Geometric mean BMI was lower (P < 0·05 for all) among longer-term followers (≥1 year) of whole food, plant-based (WFPB), vegan, whole food and low-carb diets compared with shorter-term followers. Among those following their diet for 1-5 years (n 4067), geometric mean BMI (kg/m2) were lower (P < 0·05 for all) for all groups compared with TTEH (26·4 kg/m2): WFPB (23·2 kg/m2), vegan (23·5 kg/m2), Paleo (24·6 kg/m2), vegetarian (25·0 kg/m2), whole food (24·6 kg/m2), Weston A. Price (23·5 kg/m2) and low-carb (24·7 kg/m2). CONCLUSION: Our findings suggest that BMI is lower among individuals who made active decisions to adhere to a specific diet, particularly more plant-based diets and/or diets limiting highly processed foods, compared with those who simply TTEH. BMI is also lower among individuals who follow intentional eating plans for longer time periods.