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Abstract. 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

Prospective cohort studies have found a relation between sugar-sweetened beverage consumption (SSB; 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.To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults.We examined participants from the Framingham Offspring Study (FOS) (1987-1995; n = 3047) and the Women's Health Study (1992; n = 26,218). Plasma LDL-C, apolipoprotein (apo) B, HDL-C, apoA1, triglyceride (TG), non-HDL-C, total: HDL-cholesterol ratio, and apoB: apoA1 concentrations were quantified in both cohorts, and apoE, apoC3, RLP-TG, and RLP-cholesterol concentrations in FOS only. Lipoprotein particle sizes were calculated from NMR signals for lipoprotein particle subclass concentrations (triglyceride-rich lipoprotein particles [TRL-P; very large, large, medium, small, and very small], LDL-particles [LDL-P; large, medium, and small], HDL-particles [HDL-P; 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.SSB consumption was positively associated with LDL-C, apoB, TG, RLP-TG, RLP-C, non-HDL-C concentrations and total: HDL cholesterol and apoB: apoA1 ratio, and negatively associated with HDL-C and apoA1 concentrations (P-trend ranges from 0.0001 to 0.003). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes, lower concentrations of large LDL-P and medium HDL-P, and higher concentrations of small LDL-P, small HDL-P, and large TRL-P (P-trend ranges from 0.0001 to 0.0009).Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

Vitamin D status has been found to be inversely associated with metabolic syndrome (MetS) in some studies. Vitamin D status varies by race and ethnicity, and the association of MetS with Vitamin D status in U.S. adults and by race and Hispanic origin has not been evaluated extensively.To examine the associations between Vitamin D status and MetS overall, and across race and Hispanic origin groups in a nationally representative sample of U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014.The total sample included 8,639 adults, 20 years of age and over. Serum Vitamin D was measured using a standardized liquid chromatography-tandem mass spectrometry method and was categorized using data driven tertiles. MetS was defined using measured waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were fitted (accounting for sociodemographic and lifestyle factors, dietary supplement use, and BMI) to examine the associations of serum Vitamin D with MetS among adults overall, and by race and Hispanic origin.Serum Vitamin D in the lowest tertile (≤ 56 nmol/L) was significantly associated with increased odds of MetS compared to the highest tertile (77.9 nmol/L); fully adjusted model OR: 1.85 and 95% CI: 1.51, 2.27. Inverse associations were noted for all race-Hispanic origin groups: non-Hispanic White (OR: 2.24; and 95% CI: 1.67, 3.01), non-Hispanic Black (OR: 1.56; and 95% CI: 1.06, 2.29) and Hispanic (OR: 1.48; and 95% CI: 1.03, 2.14) adults.Lower Vitamin D status was significantly associated with MetS among U.S. adults after adjusting for sociodemographic and lifestyle factors, dietary supplement use, and BMI. This finding was noted across all race and Hispanic origin groups, although the strength of the association varied being strongest for non-Hispanic White adults.

By 2060, the number of adults aged ≥65 y is expected to double, and the ≥85 y segment of the population is expected to triple in the United States. US federal nutrition guidance is based on the premise that healthy diets contribute to delaying the onset and progression of many age-related diseases and disability. Yet, little is known about the dietary intakes or nutritional needs across the older adulthood age span. This review aims to identify community-based cohorts that collected information on dietary intake of adults ≥65 y in the United States. Thirty-two cohorts met all inclusion criteria. We summarized information on the cohorts’ design, demographics, and diet assessment. We also identified key gaps in the existing databases that, if filled, could enhance their utility to address certain research questions. This review serves as a valuable inventory of cohorts that can be leveraged to answer key questions about the diet and nutritional needs of the oldest old, who represent the fastest growing segment of the population in the United States.

Background Dysfunction in blood vessel dynamics may contribute to changes in muscle measures. Therefore, we examined associations of vascular health measures with grip strength and gait speed in adults from the Framingham Heart Study. Methods The cross-sectional study (1998–2001) included participants with 1 measure of grip strength (kg, dynamometer) or gait speed (4-m walk, m/s) and at least 1 measure of aortic stiffness (carotid–femoral pulse wave velocity, brachial pulse pressure, and brachial flow pulsatility index) or brachial artery structure and function (resting flow velocity, resting brachial artery diameter, flow-mediated dilation %, hyperemic brachial blood flow velocity, and mean arterial pressure [MAP]) assessed by tonometry and brachial artery ultrasound. The longitudinal study included participants with ≥1 follow-up measurement of gait speed or grip strength. Multivariable linear regression estimated the association of 1 standard deviation (SD) higher level of each vascular measure with annualized percent change in grip strength and gait speed, adjusting for covariates. Results In cross-sectional analyses (n = 2 498, age 61 ± 10 years; 56% women), higher resting brachial artery diameter (β ± standard error [SE] per 1 SD: 0.59 ± 0.24, p = .01) and MAP (β ± SE: 0.39 ± 0.17, p = .02) were associated with higher grip strength. Higher brachial pulse pressure (β ± SE: −0.02 ± 0.01, p = .07) was marginally associated with slower gait speed. In longitudinal analyses (n = 2 157), higher brachial pulse pressure (β ± SE: −0.19 ± 0.07, p = .005), was associated with slowing of gait speed but not with grip strength. Conclusions Higher brachial artery pulse pressure (measure of aortic stiffness) was associated with loss of physical function over ~11 years, although we found no evidence that microvascular function contributed to the relation.

Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vitamin B-12 deficiency has many identifiable causes, including autoimmune and other gastrointestinal malabsorption disorders, dietary deficiency, and congenital defects in genes that are involved in vitamin B-12 trafficking and functions. Another putative cause of vitamin B-12 deficiency is the high-folate-low vitamin B-12 interaction, first suspected as the cause for observed relapse and exacerbation of the neurological symptoms in patients with pernicious anemia who were prescribed high oral doses of folic acid. We propose that this interaction is real and represents a novel cause of vitamin B-12 depletion with specific etiology. We hypothesize that excessive intake of folic acid depletes serum holotranscobalamin (holoTC), thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues. This effect is specific for holoTC and does not affect holohaptocorrin, the inert form of serum vitamin B-12. Depletion of holoTC by folic acid in individuals with already low vitamin B-12 status further compromises the availability of vitamin B-12 coenzymes to their respective enzymes, and consequently a more pronounced state of biochemical deficiency. This hypothesis is drawn from evidence of observational and intervention studies of vitamin B-12-deficient patients and epidemiological cohorts. The evidence also suggests that, in a depleted state, vitamin B-12 is diverted to the hematopoietic system or the kidney. This most likely reflects a selective response of tissues expressing folate receptors with high affinity for unmetabolized folic acid (UMFA; e.g., hematopoietic progenitors and renal tubules) compared with those tissues (e.g., liver) that only express the reduced folate carrier, which is universally expressed but has poor affinity for UMFA. The biochemical and physiological mechanisms underlying this interaction require elucidation to clarify its potential public health significance.

Nutrient profiling systems (NPS) aim to discriminate the healthfulness of foods for front-of-package labelling, warning labels, taxation, company ratings and more. Existing NPS often assess relatively few nutrients and ingredients, use inconsistent criteria across food categories and have not incorporated the newest science. Here, we developed and validated an NPS, the Food Compass, to incorporate a broader range of food characteristics, attributes and uniform scoring principles. We scored 54 attributes across 9 health-relevant domains: nutrient ratios, vitamins, minerals, food ingredients, additives, processing, specific lipids, fibre and protein, and phytochemicals. The domain scores were summed into a final Food Compass Score (FCS) ranging from 1 (least healthy) to 100 (most healthy) for all foods and beverages. Content validity was confirmed by assessing nutrients, food ingredients and other characteristics of public health concern; face validity was confirmed by assessing the FCS for 8,032 foods and beverages reported in NHANES/FNDDS 2015–16; and convergent and discriminant validity was confirmed from comparisons with the NOVA food processing classification, the Health Star Rating and the Nutri-Score. The FCS differentiated food categories and food items well, with mean ± s.d. ranging from 16.4 ± 17.7 for savoury snacks and sweet desserts to 78.6 ± 17.4 for legumes, nuts and seeds. In many food categories, the FCS provided important discrimination of specific foods and beverages as compared with NOVA, the Health Star Rating or the Nutri-Score. On the basis of demonstrated content, convergent and discriminant validity, the Food Compass provides an NPS scoring a broader range of attributes and domains than previous systems with uniform and transparent principles. This publicly available tool will help guide consumer choice, research, food policy, industry reformulations and mission-focused investment decisions. A nutrient profiling system is developed to incorporate 54 attributes across 9 domains, bringing together a broad and unique range of food characteristics and uniform scoring principles. The Food Compass presents a detailed profiling system for the healthfulness of foods.

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

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 0.05). 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.

Background: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS). Objectives: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength. Methods: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and

Lutein and zeaxanthin are carotenoids associated with better cognition in older adults. Recent evidence suggest that their dietary intake may also have cognitive implications in childhood.To examine associations of early childhood lutein and zeaxanthin (L/Z) intake with cognition in early and mid-childhood.Among 1378 children in Project Viva, a prospective cohort, mothers reported their child's dietary intake in early childhood (median 3.2 years) using a food frequency questionnaire. Child cognition and behavior were assessed at the same timepoint 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 years) 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.Children consumed a daily mean (SD) of 1.0 (0.4) mg of 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.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 relationship deserves further investigation.

The positive association of choline for cognition has been reported in both animal and human studies, yet the association of choline with the risk of incident dementia or Alzheimer's disease (AD) in humans is unclear.Our objective was to test the hypothesis that lower (higher) dietary choline intake is associated with increased (decreased) risk of incident dementia or AD.Data from the Framingham Heart Study (FHS) Offspring Cohort Exam 5 to Exam 9 were used. Participants were free of dementia and stroke with valid self-report 126-item Harvard food-frequency questionnaire (FFQ) at Exam 5. The intakes of total choline, its contributing compounds, and betaine were estimated based on a published nutrient database. The intakes were updated at each exam to represent the cumulative average intake across the five exams. The associations between dietary choline intake and incident dementia and AD were examined in the mixed effect Cox proportional hazard models, adjusting for covariates.A total of 3,224 participants (53.8% female, mean ± SD age 54.5 ± 9.7 year) were followed up for a mean ± SD of 16.1 ± 5.1 years (1991-2011). There were 247 incident dementia cases, of which 177 were AD. Dietary choline intake showed non-linear relationship with incident dementia and AD. After adjusting for covariates, low choline intake (defined as choline/100 ≤ 2.19 and choline/100 ≤ 2.15 in our sample) was significantly associated with incident dementia or incident AD.Low choline intake was associated with increased risk of incident dementia or AD.

Nutrients, including protein, calcium, and fat may be associated with risk of frailty, yet specific contributions from whole dairy foods rich in these nutrients remain understudied.To determine associations between dairy intake (milk, yogurt, cheese, total (milk + yogurt + cheese), low-fat and high-fat dairy, and servings per week) and frailty onset and frailty phenotype components.Prospective cohort study. All dairy intake exposures (servings per week) were assessed via a food frequency questionnaire.Participants (aged 33 to 86 years) from the Framingham Offspring Study who were not frail at baseline (1998-2001) completed a food frequency questionnaire and had 1 or 2 follow-up frailty assessments (2005-2008 and 2011-2014) were included.Frailty was defined as the presence of ≥3 Fried frailty phenotype components: unintentional weight-loss, exhaustion, slowness (gait speed), weakness (grip strength), and low physical activity. Individuals with zero to two components were considered nonfrail.Repeated measures logistic regression estimated odds ratios and 95% CIs for frailty onset. Logistic (exhaustion and weight loss) and linear regression (gait speed, grip strength, and physical activity) estimated the association between baseline dairy intake and each frailty component at follow-up, adjusting for baseline values for age, sex, energy intake (residual analysis), current smoking, and multivitamin use. Models were further adjusted for health status in a secondary analysis.Mean baseline age ± SD was 61 ± 9 years (range = 33 to 87 years), and 54% were women. Of 2,550 nonfrail individuals at baseline, 8.8% (2005-2008) and 13.5% (2011-2014) became frail. Higher yogurt intake was associated with decreased odds of frailty (odds ratio 0.96, 95% CI 0.93 to 0.99; P = 0.02). Each additional serving of yogurt (β ± SE) .004 ± .001; P0.01) and low-fat dairy (β ± SE) .001 ± .0006; P = 0.04) was associated with significantly faster follow-up gait speed. Dietary intakes of high-fat dairy were associated with increased odds of frailty (odds ratio 1.02, 95% CI 1.00 to 1.04; P = 0.05), but the P value was of borderline significance. No associations were observed for other dairy foods. After adjusting for health status, the associations of high-fat dairy and yogurt with frailty became nonsignificant, although the magnitudes of the associations did not change. The association between yogurt and gait speed decreased in magnitude after adjusting for health status (β ± SE) .002 ± .001; P = 0.01).Dietary intakes of yogurt were modestly associated with reduced frailty onset and dietary intakes of high-fat dairy had a borderline association with increased odds of frailty, but other dairy food intakes showed no association in this study of healthy adults. Some dairy food intakes were modestly associated with follow-up gait speed. However, effect sizes were small, and the clinical importance of these associations remains undetermined.

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.

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.

Understanding the health effects of protein intake is bedeviled by a number of factors, including protein quality and source. In addition, different units, including grams, grams per kilogram body weight (g/kg BW), and percent energy, may contribute to confusion about protein's effects on health, especially BW-based units in increasingly obese populations. We aimed to review the literature and to conduct a modeling demonstration of various units of protein intake in relation to markers of cardiometabolic health. Data from the Framingham Heart Study Offspring (n = 1847; 60.3 y; 62.5% women) and Third Generation (n = 2548; 46.2 y; 55.3% women) cohorts and the NHANES 2003–04 (n = 1625; 46.2 y; 49.7% women) and 2005–06 (n = 1347; 43.7 y; 49.5% women) cycles were used to model cross-sectional associations between 7 protein units (grams, percent energy, g/kg ideal BW, g/kg actual BW, BW-adjusted g/kg actual BW, g/kg lean BW, and g/kg fat-free BW) and 9 cardiometabolic outcomes (fasting glucose, systolic and diastolic blood pressure, total and HDL cholesterol, triglycerides, BMI, waist circumference, and estimated glomerular filtration rate). The literature review indicated the use of myriad units of protein intake, with differential results on cardiometabolic outcomes. The modeling demonstration showed units expressed in BW were confounded by BW, irrespective of outcome. Units expressed in grams, percent energy, and ideal BW showed similar results, with or without adjustment for body size. After adjusting for BW, results of units expressed in BW aligned with results of grams, percent energy, and ideal BW. In conclusion, protein intake in cardiometabolic health appears to depend on protein's unit of expression. Authors should be specific about the use of WHO (g/kg ideal BW) compared with US (g/kg actual BW) units, and ideally use gram or percent energy in observational studies. In populations where overweight/obesity are prevalent, intake based on actual BW should be reevaluated., Protein units vary across the literature, likely obscuring true relationships between protein intake and cardiometabolic outcomes. A narrative review and modeling demonstration illustrate these problems, followed by recommendations for best practices.

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.A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI).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.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.

BACKGROUND Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due to limitations of these studies. OBJECTIVES To examine the prospective relation between total and 6 classes of dietary flavonoid intake and risk of ADRD and Alzheimer disease (AD) while addressing limitations of earlier observational studies. METHODS We used data from the Framingham Heart Study Offspring Cohort exams 5 through 9. Participants were ADRD-free with a valid FFQ at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average intake across the 5 exams, and were expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to handle their nonlinear relation with ADRD and AD. Cox proportional hazards regression was used to estimate the HRs for the association between the flavonoid intakes and incidence of ADRD and AD. RESULTS Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, individuals with the highest (>60th percentile) intakes of flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD relative to individuals with the lowest intakes (≤15th percentile), with HRs (95% CI; P-trend) of 0.54 (0.32, 0.90; P = 0.003) for flavonols, 0.24 (0.15, 0.39; P

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 (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.

Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL) increase in daily tea consumption (estimated 280 mg and 338 mg total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I(2) = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I(2) = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.

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.

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 flavan-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.

BACKGROUND: The benefit of a Mediterranean-style diet in reducing frailty is not well established in older Americans. OBJECTIVES: We sought to determine associations of a Mediterranean-style dietary pattern and related antioxidants with frailty onset and worsening of the Fried phenotype in adults. METHODS: This prospective study included 2384 nonfrail adults from the Framingham Offspring Study with a Mediterranean-style dietary pattern score (MSDPS) and data on antioxidant intakes (vitamin C, E, and total carotenoids) estimated from an FFQ at the index examination (1998–2001) and 1 prior examination (if available), as well as a frailty assessment at the index examination and at least 1 follow-up. Frailty onset was defined as ≥3 of 5 Fried frailty phenotype criteria at follow-up and the worsening of the Fried frailty phenotype was defined as an increased number of frailty criteria over follow-up (yes or no). Logistic regression with generalized estimating equations estimated ORs and 95% CIs, adjusting for confounders. Analyses were stratified by age (

A Mediterranean-style diet is a healthy eating pattern that may benefit cancer risk, but evidence among Americans is scarce. We examined the prospective association between adherence to such a diet pattern and total cancer risk. A Mediterranean-style dietary pattern (MSDP) score was derived from a semi-quantitative food frequency questionnaire at exam 5 (1991–1995). Subjects included 2966 participants of the Framingham Offspring Study who were free of prevalent cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, lifestyle, and anthropometric measures. Cox-models were also used to examine effect modification by lifestyle and anthropometric measures. During 18 years of median follow-up, 259 women and 352 men were diagnosed with cancer. Women with moderate or higher adherence to the MSDP had ≥25% lower risks of cancer than women with the lowest MSDP (HR (moderate vs. lowest): 0.71, 95% CI: 0.52–0.97 and HR (highest vs. lowest): 0.74, 95% CI: 0.55–0.99). The association between MSDP score and cancer risk in men was weaker except in non-smokers. Beneficial effects of the MSDP in women were stronger among those who were not overweight. In this study, higher adherence to MSDP was associated with lower cancer risk, especially among women.

Background: Adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy. Objective: We evaluated whether adherence to the MIND diet associated with superior cognitive function, larger brain volumes, fewer SBIs, and less cognitive decline in the community-based Framingham Heart Study. Methods: 2,092 participants (mean±SD, age 61±9) completed Food Frequency Questionnaires, averaged across a maximum of 3-time points (examination cycles 5, 6, and 7), cognitive testing at examination cycle 7 (present study baseline: 1998–2001) and after a mean±SD of 6.6±1.1 years from baseline (n = 1,584). A subset of participants also completed brain magnetic resonance imaging (MRI) at examination cycle 7 (n = 1,904). In addition, participants with dementia, stroke, and other relevant neurological diseases such as significant head trauma, subdural hematoma, or multiple sclerosis were excluded from the analyses. Results: Higher MIND diet scores were associated with better global cognitive function (β±SE,+0.03SD±0.01; p = 0.004), verbal memory, visual memory, processing speed, verbal comprehension/reasoning, and with larger total brain volume (TBV) following adjustments for clinical, lifestyle and demographic covariates, but not with other brain MRI measures (i.e., hippocampal volume, lateral ventricular volume, white matter hyperintensity volume, and SBIs) or cognitive decline. Conclusion: Higher MIND diet scores associated with better cognitive performance and larger TBV at baseline, but not with cognitive decline. Clinical trials are needed to ascertain whether adopting the MIND diet affects trajectories of cognitive decline.

OBJECTIVES: Metabolomic markers may provide deeper insight into the underlying biology of frailty. Yet, little data exist characterizing metabolomic correlates of frailty. The objective of this cross-sectional study was to determine the association of serum metabolites with frailty. METHODS: We evaluated 2187 participants from the Framingham Offspring Study (mean age; 62y; 53% women) with metabolomic and frailty data. Metabolites (n = 217) were quantified using liquid chromatography/tandem mass spectrometry (1990–95). Frailty was assessed using Fried's frailty phenotype (1998–01). Multivariable logistic regression models were used to relate individual metabolites with odds of frailty. In 1,815 participants, we created a metabolomic signature: sum of (serum metabolite concentration*β coefficient). Metabolites were included based on the strength of their individual association with frailty (FDR ≤ 0.05). Logistic regression was used to relate the metabolomic signature with odds of frailty. C-statistics determined if the metabolomic signature improved the prediction of frailty beyond a standard model. Models were adjusted for age, sex, BMI, and smoking. RESULTS: Adjusting for age and sex, 24 metabolites were significantly associated with frailty (22 positive and 2 negative; all FDR ≤ 0.05). A majority of metabolites were lipids (n = 19) of the phosphatidylcholine (n = 7) and triacylglycerol (n = 10) sub-classes with high degree of saturation (n = 13 with

The amount of time spent in poor health at the end of life is increasing. This narrative review summarizes consistent evidence indicating that healthy dietary patterns and maintenance of a healthy weight in the years leading to old age are associated with broad prevention of all the archetypal diseases and impairments associated with aging including: noncommunicable diseases, sarcopenia, cognitive decline and dementia, osteoporosis, age-related macular degeneration, diabetic retinopathy, hearing loss, obstructive sleep apnea, urinary incontinence, and constipation. In addition, randomized clinical trials show that disease-specific nutrition interventions can attenuate progression-and in some cases effectively treat-many established aging-associated conditions. However, middle-aged and older adults are vulnerable to unhealthy dietary patterns, and typically consume diets with inadequate servings of healthy food groups and essential nutrients, along with an abundance of energy-dense but nutrient-weak foods that contribute to obesity. However, based on menu examples, diets that are nutrient-dense, plant-based, and with a moderately low glycemic load are better equipped to meet the nutritional needs of many older adults than current recommendations in US Dietary Guidelines. These summary findings indicate that healthy nutrition is more important for healthy aging than generally recognized. Improved public health messaging about nutrition and aging, combined with routine screening and medical referrals for age-related conditions that can be treated with a nutrition prescription, should form core components of a national nutrition roadmap to reduce the epidemic of unhealthy aging.

Background The conjoint associations of adherence to the recent physical activity and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods and Results We evaluated 2379 FHS (Framingham Heart Study) Third Generation participants (mean age, 47 years; 54.4% women) attending examination cycle 2. We examined the cross‐sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (binary; moderate‐to‐vigorous physical activity ≥150 versus Conclusions Maintaining both regular physical activity and a healthy diet in midlife may be required for optimal cardiometabolic health in later life.

BACKGROUND: Dietary fiber reduces body weight and inflammation in clinical trials. It is unclear whether body mass index (BMI) and inflammation might explain the observed association between higher fiber intake and the lower risk of symptomatic knee osteoarthritis (SXKOA). OBJECTIVES: We quantified the extent to which BMI and inflammation influenced the relation between dietary fiber and SXKOA. METHODS: We used longitudinal data from the Osteoarthritis Initiative (OAI) and the Framingham Offspring Osteoarthritis Study. At baseline of each study, men and women (mean age: 61 y) with or at risk of knee osteoarthritis were followed for 48 mo in the OAI. Adults (mean age: 53 y) were followed for 9.5 y in the Framingham study. Dietary fiber intake was estimated using a validated food-frequency questionnaire. Measured weight and height were used to calculate BMI. Serum high-sensitivity C-reactive protein (CRP) was measured in the Framingham study only. Incident SXKOA was defined as new onset of a combination of knee pain and radiographic osteoarthritis. We applied marginal structural models to quantify the mediation through BMI in the OAI and the sequential mediation through BMI and CRP in the Framingham study. RESULTS: Incident SXKOA occurred in 861 knees among 2876 persons in the OAI and in 143 knees among 971 persons in the Framingham study. In persons whose fiber intake was ≥21 g/d compared with those with intakes

Background Maternal intake of several nutrients during pregnancy is linked to offspring cognition. The relation between maternal dietary patterns and offspring cognition is less established. Objectives We aimed to examine associations of maternal diet quality during pregnancy with child cognition and behavior. Methods Among 1580 mother–child pairs in Project Viva, a prospective prebirth cohort, we assessed maternal diet during pregnancy using FFQs and evaluated diet quality using versions modified for pregnancy of the Mediterranean Diet Score (MDS-P) and Alternate Healthy Eating Index (AHEI-P). Child cognitive and behavioral outcomes were assessed using standardized tests and questionnaires at infancy and in early and mid-childhood. We conducted multivariable linear regression analyses. Results Mothers were predominantly white, college-educated, and nonsmokers. After adjustment for child age and sex and maternal sociodemographic and lifestyle characteristics, maternal high (6–9) compared with low (0–3) MDS-P during pregnancy was associated with higher child Kaufman Brief Intelligence Test (KBIT-II) nonverbal (mean difference for first trimester: 4.54; 95% CI: 1.53, 7.56) and verbal scores (3.78; 95% CI: 1.37, 6.19) and lower Behavioral Rating Inventory of Executive Function (BRIEF) Metacognition Index (−1.76; 95% CI: −3.25, −0.27), indicating better intelligence and fewer metacognition problems in mid-childhood. Maternal Q4 compared with Q1 AHEI-P during pregnancy was associated with higher Wide Range Assessment of Visual Motor Abilities matching scores in early childhood (mean difference for first trimester: 2.79; 95% CI: 0.55, 5.04) and higher KBIT-II verbal scores (2.59; 95% CI: 0.13, 5.04) and lower BRIEF Global Executive Composite scores in mid-childhood (−1.61; 95% CI: −3.20, −0.01), indicating better visual spatial skills, verbal intelligence, and executive function. Conclusions Maternal intake of a better-quality diet during pregnancy was associated with better visual spatial skills in the offspring at early childhood and with better intelligence and executive function in the offspring at mid-childhood.

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: logβ = −0·03) and systolic function (GCS: β = −0·04) and with higher values of LVM (logβ = 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 (β = −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.

Background The conjoint associations of adherence to the recent physical activity (PA) and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods We evaluated 2,379 Framingham Heart Study Third Generation participants (mean age 47 years, 54.4% women) attending examination cycle 2. We examined the cross-sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (PAG, binary; moderate to vigorous PA [MVPA] ≥ 150 minutes/week vs.

OBJECTIVES: Frailty occurs in 10–15% of community-living older adults. The benefit of a Mediterranean style diet in reducing frailty is not well established in older Americans. The aim was to determine the association of Mediterranean-Style Dietary Pattern and related antioxidants (vitamin C, E and total carotenoids from diet and supplements) with the odds of frailty over 9y in older adults from the Framingham Offspring study. METHODS: The Mediterranean-style dietary pattern score (MSDPS) was used to characterize a Mediterranean-style diet in 2541 men and women with completed food frequency questionnaires at baseline (1998–2001). Average intake of each antioxidant (vitamin C, E and total carotenoids, mg/d) at baseline and one prior exam (1995–98) was calculated. Total carotenoids were calculated as the sum of intake of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin. Frailty was assessed using Fried's frailty criteria at baseline and follow-up exam (2005–08). Participants categorized as frail at baseline were excluded (n = 27). Logistic regression was used to calculate odds ratios and 95% confidence intervals (95% CI) adjusting for age, sex, follow-up time, BMI, energy intake, current smoking and multivitamin use. Antioxidants were adjusted for each other in the same model. RESULTS: Mean age (±SD) was 60 ± 9y (range 33–86), 55% were female and mean follow-up time was 6.6y (range 3.7–9.1). Mean (±SD) was 45 ± 13 (range: 10.8–84.1) for the MSDPS, 36.5 (±32.3) mg/d for vitamin C, 16.4 (±199) mg/d for vitamin E and 1.8 (±0.8) mg/d for carotenoids. Prevalent frailty at follow-up exam was 5%. Although not significant, a 10 unit increase in MSDPS reduced the odds of frailty by 8.7% (95% CI: 0.78–1.08, P = 0.28) in the combined sample of men and women. Each 10 mg increase in total carotenoid intake reduced the odds of frailty by 29% (95% CI: 0.53–1.01, P = 0.02). Neither Vitamin C (P = 0.79) or E (P = 0.25) were individually associated with frailty. CONCLUSIONS: A Mediterranean style diet was not significantly associated with frailty in this sample of largely older adults. However, total carotenoids intake reduced the odds of frailty. Future work should consider if a Mediterranean style diet and related antioxidants delay the progression of frailty. FUNDING SOURCES: Boston Claude D. Pepper Center OAIC and Peter and Barbara Sidel Fund.

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 NCT 01594333.

Data on proteomic and metabolomic signatures of healthy dietary patterns are limited. We evaluated the cross-sectional association of serum proteomic and metabolomic markers with three dietary patterns: the Alternative Healthy Eating Index (AHEI), the Dietary Approaches to Stop Hypertension (DASH) diet, and a Mediterranean-style (MDS) diet. We examined participants from the Framingham Offspring Study (mean age, 55 years, 52% women) who had complete proteomic (n = 1713) and metabolomic (n = 2284) data, using food frequency questionnaires to derive dietary pattern indices. Proteins and metabolites were quantified using the SomaScan platform and liquid chromatography/tandem mass spectrometry, respectively. We used multivariable-adjusted linear regression models to relate each dietary pattern index (independent variables) to each proteomic and metabolomic marker (dependent variables). Of the 1373 proteins, 103 were associated with at least one dietary pattern (48 with AHEI, 83 with DASH, and 8 with MDS, all false discovery rate [FDR] &le, 0.05). We identified unique associations between dietary patterns and proteins (17 with AHEI, 52 with DASH, and 3 with MDS, all FDR &le, 0.05). Significant proteins enriched biological pathways involved in cellular metabolism/proliferation and immune response/inflammation. Of the 216 metabolites, 65 were associated with at least one dietary pattern (38 with AHEI, 43 with DASH, and 50 with MDS, 0.05). All three dietary patterns were associated with a common signature of 24 metabolites (63% lipids). Proteins and metabolites associated with dietary patterns may help characterize intermediate phenotypes that provide insights into the molecular mechanisms mediating diet-related disease. Our findings warrant replication in independent populations

BackgroundA 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.ObjectivesOur study objective was to assess mechanisms by which tea consumption may influence CVD risks.MethodsA 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).ResultsA 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).ConclusionsShort-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.

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.

Background Epigenome-wide association studies for cardiometabolic risk factors have discovered multiple loci associated with incident cardiovascular disease (CVD). However, few studies have sought to directly optimize a predictor of CVD risk. Furthermore, it is challenging to train multivariate models across multiple studies in the presence of study- or batch effects. Methods and Results Here, we analyzed existing DNA methylation data collected using the Illumina HumanMethylation450 microarray to create a predictor of CVD risk across 3 cohorts: Women's Health Initiative, Framingham Heart Study Offspring Cohort, and Lothian Birth Cohorts. We trained Cox proportional hazards-based elastic net regressions for incident CVD separately in each cohort and used a recently introduced cross-study learning approach to integrate these individual scores into an ensemble predictor. The methylation-based risk score was associated with CVD time-to-event in a held-out fraction of the Framingham data set (hazard ratio per SD=1.28, 95% CI, 1.10-1.50) and predicted myocardial infarction status in the independent REGICOR (Girona Heart Registry) data set (odds ratio per SD=2.14, 95% CI, 1.58-2.89). These associations remained after adjustment for traditional cardiovascular risk factors and were similar to those from elastic net models trained on a directly merged data set. Additionally, we investigated interactions between the methylation-based risk score and both genetic and biochemical CVD risk, showing preliminary evidence of an enhanced performance in those with less traditional risk factor elevation. Conclusions This investigation provides proof-of-concept for a genome-wide, CVD-specific epigenomic risk score and suggests that DNA methylation data may enable the discovery of high-risk individuals who would be missed by alternative risk metrics. This work was supported by the US Department of Agriculture, Agriculture Research Service (8050–51000-098-00D). Dr. Westerman was additionally supported by National Institutes of Health predoctoral training grant 5T32HL069772-14. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This article was prepared in collaboration with investigators of the WHI but has not been reviewed by the WHI and does not necessarily reflect the opinions of the WHI investigators or the National Heart, Lung, and Blood Institute. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with Boston University (Contract No. N01-HC-25195 and HHSN268201500001I). This article was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or National Heart, Lung, and Blood Institute. The LBC 1936 is supported by Age UK (Disconnected Mind program) and the Medical Research Council (MR/M01311/1). Methylation typing in LBC 1936 was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. LBC 1936 work was conducted in the Centre for Cognitive Ageing and Cognitive Epidemiology, which supported Dr. Deary and is supported by the medical Research Council and Biotechnology and Biological Sciences Research Council (MR/K026992/1). Sí

There is increasing evidence that both black and green tea are beneficial for prevention of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes.Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥ 4 studies were performed. 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, eachcup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87- 1.00) with large heterogeneity (I2 = 81.4%; p = 0.005). Current evidence indicates that increased tea consumption may reduce cardiovascular and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO.