Publications by authors named "Paul Jacques"

293 Publications

Mind Diet Adherence and Cognitive Performance in the Framingham Heart Study.

J Alzheimers Dis 2021 Jun 1. Epub 2021 Jun 1.

The Framingham Heart Study, Framingham, MA, USA.

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, 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.
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http://dx.doi.org/10.3233/JAD-201238DOI Listing
June 2021

Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

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 <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing.

Results: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified.

Conclusions: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.
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http://dx.doi.org/10.1093/ajcn/nqab093DOI Listing
May 2021

Healthy Aging-Nutrition Matters: Start Early and Screen Often.

Adv Nutr 2021 Apr 10. Epub 2021 Apr 10.

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/advances/nmab032DOI Listing
April 2021

Comparison of Indices of Carbohydrate Quality and Food Sources of Dietary Fiber on Longitudinal Changes in Waist Circumference in the Framingham Offspring Cohort.

Nutrients 2021 Mar 19;13(3). Epub 2021 Mar 19.

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.

The long-term impact of carbohydrate quality on abdominal weight gain is not fully understood. We aimed to examine the prospective relation of a carbohydrate quality index (CQI; defined by four criteria: dietary fiber, glycemic index, whole grain-to-total grain ratio, and solid-to-total carbohydrate ratio), total, cereal grain, vegetable, and fruit fiber, carbohydrate-to-total fiber ratio, and carbohydrate-to-cereal fiber ratio with changes in waist circumference (WC). Subjects were middle-aged to older, mostly white, participants in the Framingham Offspring cohort ( = 3101 subjects), with mean baseline age 54.9 ± 0.2 years (mean ± SE) and body mass index (BMI) 27.2 ± 0.1 kg/m. Food frequency questionnaire (FFQ), health, and lifestyle data were collected approximately every four years over a median total follow-up of 18 years. Repeated measure mixed models were used to estimate adjusted mean change in WC per four-year interval across quartiles of carbohydrate variables. In the most adjusted model, a higher CQI was marginally associated with a smaller increase in WC (2.0 ± 0.1 vs. 2.4 ± 0.1 cm in highest vs. lowest quartile, -trend = 0.04). Higher ratios of carbohydrate-to-fiber and carbohydrate-to-cereal fiber were associated with greater increases in WC per four-year interval (2.6 ± 0.1 vs. 2.0 ± 0.1 cm, -trend < 0.001, and 2.5 ± 0.1 vs. 2.1 ± 0.1 cm in highest versus lowest categories, -trend = 0.007, respectively); whereas higher intake of total fiber (1.8 ± 0.1 vs. 2.7 ± 0.1 cm, -trend < 0.001), cereal fiber (2.0 ± 0.1 vs. 2.5 ± 0.1 cm, -trend = 0.001), and fruit fiber (2.0 ± 0.1 vs. 2.7 ± 0.1 cm, -trend < 0.001) were associated with smaller increases in WC compared to lower intakes. There was a significant interaction between total fiber and total carbohydrate (as % of total energy intake). After stratification, the association between fiber intake and change in WC was not maintained in the context of a high carbohydrate diet. Better carbohydrate quality, primarily higher fiber intake and lower carbohydrate-to-fiber ratios, may help attenuate increases in abdominal adiposity over time.
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http://dx.doi.org/10.3390/nu13030997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003409PMC
March 2021

Conjoint Associations of Adherence to Physical Activity and Dietary Guidelines With Cardiometabolic Health: The Framingham Heart Study.

J Am Heart Assoc 2021 Apr 31;10(7):e019800. Epub 2021 Mar 31.

Section of Preventive Medicine and Epidemiology Boston University School of Medicine Boston MA.

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 <150 min/wk) and 2015 Dietary Guidelines for Americans (binary; 2015 Dietary Guidelines for Americans Adherence Index ≥median versus
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http://dx.doi.org/10.1161/JAHA.120.019800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174320PMC
April 2021

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

Nephrol Dial Transplant 2021 Mar 24. Epub 2021 Mar 24.

Center for Primary Care, Prevention, Brown University, Providence, RI, USA.

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 CVD outcomes, all-cause mortality, or transplant failure in kidney transplant recipients. 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 4,110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Non fasting remnant cholesterol levels were calculated based upon lipid profiles in 3,812 FAVORIT trial participants at randomization. Wilcoxon-type test for trend were 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, 452 All-Cause deaths. When comparing highest quartile 4 to quartile 1, proportional hazards modeling revealed a significant increase in CVD risk (HR, 1.32; 95% CI, 1.04-1.67) and all-cause mortality risk (HR, 1.34; 95% CI, 1.01-1.69). A non-significant increase in transplant failure was seen as well (HR, 1.20; 95% CI, 0.87-1.64).

Conclusion: Remnant cholesterol is associated with CVD and all-cause mortality in long-term kidney transplant recipients KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.
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http://dx.doi.org/10.1093/ndt/gfab068DOI Listing
March 2021

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

Int J Vitam Nutr Res 2021 Mar 1:1-11. Epub 2021 Mar 1.

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1024/0300-9831/a000701DOI Listing
March 2021

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

Br J Nutr 2021 Feb 23:1-9. Epub 2021 Feb 23.

Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.

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.
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http://dx.doi.org/10.1017/S0007114521000660DOI Listing
February 2021

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.

J Nutr 2021 03;151(3):615-627

Dorothy J and Gerald R Friedman School of Nutrition and Science Policy at Tufts University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/jn/nxaa348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948203PMC
March 2021

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.

J Nutr 2020 12;150(12):3269-3279

Department of Nutrition and Food Studies, George Mason University, Fairfax, VA, USA.

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.
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http://dx.doi.org/10.1093/jn/nxaa295DOI Listing
December 2020

Total carotenoid intake is associated with reduced loss of grip strength and gait speed over time in adults: The Framingham Offspring Study.

Am J Clin Nutr 2021 02;113(2):437-445

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

Background: Lower antioxidant serum concentrations have been linked to declines in lean mass and physical function in older adults. Yet population data on the effect of dietary antioxidants on loss of muscle strength and physical function are lacking.

Objective: We sought to determine the association of antioxidant intake [vitamin C, vitamin E, and total and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin)] with annualized change in grip strength and gait speed in adults from the Framingham Offspring study.

Methods: This prospective cohort study included participants with a valid FFQ at the index examination and up to 2 prior examinations and at ≥2 measures of primary outcomes: grip strength (n = 2452) and/or gait speed (n = 2422) measured over 3 subsequent examinations. Annualized change in grip strength (kg/y) and change in gait speed (m/s/y) over the follow-up period were used. Linear regression was used to calculate β coefficients and P values, adjusting for covariates.

Results: Mean ± SD age of participants was 61 ± 9 y (range: 33-88 y). Median intakes (IQR, mg/d) of vitamin C, vitamin E, and total carotenoid across available examinations were 209.2 (133.1-394.2), 27.1 (7.4-199.0), and 15.3 (10.4-21.3), respectively. The mean follow-up time was ∼12 ± 2 y (range: 4.5-15.4 y). In the sex-combined sample, higher intakes of total carotenoids, lycopene, and lutein + zeaxanthin were associated with increased annualized change in grip strength [β (SE) per 10-mg higher intake/d, range: 0.0316 (0.0146) to 0.1223 (0.0603) kg/y)]. All antioxidants except for vitamin C were associated with faster gait speed [β (SE) per 10-mg higher intake/d, range: 0.00008 (0.00004) to 0.0187 (0.0081) m/s/y].

Conclusions: Higher antioxidant intake was associated with increase in grip strength and faster gait speed in this cohort of adults. This finding highlights the need for a randomized controlled trial of dietary antioxidants and their effect on muscle strength and physical function.
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http://dx.doi.org/10.1093/ajcn/nqaa288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851823PMC
February 2021

Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop.

Am J Clin Nutr 2020 11;112(5):1390-1403

Division of Geriatrics and Clinical Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Folate, an essential nutrient found naturally in foods in a reduced form, is present in dietary supplements and fortified foods in an oxidized synthetic form (folic acid). There is widespread agreement that maintaining adequate folate status is critical to prevent diseases due to folate inadequacy (e.g., anemia, birth defects, and cancer). However, there are concerns of potential adverse effects of excess folic acid intake and/or elevated folate status, with the original concern focused on exacerbation of clinical effects of vitamin B-12 deficiency and its role in neurocognitive health. More recently, animal and observational studies have suggested potential adverse effects on cancer risk, birth outcomes, and other diseases. Observations indicating adverse effects from excess folic acid intake, elevated folate status, and unmetabolized folic acid (UMFA) remain inconclusive; the data do not provide the evidence needed to affect public health recommendations. Moreover, strong biological and mechanistic premises connecting elevated folic acid intake, UMFA, and/or high folate status to adverse health outcomes are lacking. However, the body of evidence on potential adverse health outcomes indicates the need for comprehensive research to clarify these issues and bridge knowledge gaps. Three key research questions encompass the additional research needed to establish whether high folic acid or total folate intake contributes to disease risk. 1) Does UMFA affect biological pathways leading to adverse health effects? 2) Does elevated folate status resulting from any form of folate intake affect vitamin B-12 function and its roles in sustaining health? 3) Does elevated folate intake, regardless of form, affect biological pathways leading to adverse health effects other than those linked to vitamin B-12 function? This article summarizes the proceedings of an August 2019 NIH expert workshop focused on addressing these research areas.
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http://dx.doi.org/10.1093/ajcn/nqaa259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657327PMC
November 2020

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

J Nutr 2020 11;150(11):2994-3004

Division of Nutrition Data Science, Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/jn/nxaa269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675031PMC
November 2020

Protein Intake and Human Health: Implications of Units of Protein Intake.

Adv Nutr 2021 02;12(1):71-88

Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/advances/nmaa097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850043PMC
February 2021

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.

Public Health Nutr 2020 10 27;23(15):2717-2727. Epub 2020 Jul 27.

Nutritional Epidemiology Program, Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA.

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.
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http://dx.doi.org/10.1017/S1368980020001330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477369PMC
October 2020

Proteomic and Metabolomic Correlates of Healthy Dietary Patterns: The Framingham Heart Study.

Nutrients 2020 May 19;12(5). Epub 2020 May 19.

Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

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 ( = 1713) and metabolomic ( = 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] ≤ 0.05). We identified unique associations between dietary patterns and proteins (17 with AHEI; 52 with DASH; and 3 with MDS; all FDR ≤ 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; all FDR ≤ 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.
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http://dx.doi.org/10.3390/nu12051476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284467PMC
May 2020

Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort.

Am J Clin Nutr 2020 08;112(2):343-353

Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

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 < 0.001) for anthocyanins, and 0.58 (0.35, 0.94; P = 0.03) for flavonoid polymers. The same pattern of associations was seen with AD for flavonols and anthocyanins but not for flavonoid polymers.

Conclusions: Our findings imply that higher long-term dietary intakes of flavonoids are associated with lower risks of ADRD and AD in US adults.
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http://dx.doi.org/10.1093/ajcn/nqaa079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398772PMC
August 2020

Epigenomic Assessment of Cardiovascular Disease Risk and Interactions With Traditional Risk Metrics.

J Am Heart Assoc 2020 04 20;9(8):e015299. Epub 2020 Apr 20.

JM-USDA Human Nutrition Research Center on Aging at Tufts University Boston MA.

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.
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http://dx.doi.org/10.1161/JAHA.119.015299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428544PMC
April 2020

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

J Nutr 2020 06;150(6):1545-1553

Nutritional Epidemiology Program, Jean Mayer US Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/jn/nxaa068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269753PMC
June 2020

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

Crit Rev Food Sci Nutr 2021 19;61(3):450-461. Epub 2020 Mar 19.

Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1080/10408398.2020.1736509DOI Listing
January 2021

Diet Indices Reflecting Changes to Dietary Guidelines for Americans from 1990 to 2015 Are More Strongly Associated with Risk of Coronary Artery Disease Than the 1990 Diet Index.

Curr Dev Nutr 2019 Dec 5;3(12):nzz123. Epub 2019 Nov 5.

Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.

Background: The Dietary Guidelines for Americans (DGAs) provide dietary recommendations for the general population with the intent of preventing chronic disease such as cardiovascular disease. An evaluation of whether updated versions of the DGAs accomplish this goal is lacking.

Objective: The objective of this project was to determine whether updates to DGAs over time, reflected in subsequent versions of diet quality indices, strengthened the associations between diet quality and risk of cardiovascular disease outcomes.

Methods: Dietary data collected using an FFQ in the Framingham Heart Study Offspring cohort were used to assess adherence to sequential versions of the Healthy Eating Index (HEI) (1990, 2005, 2010, and 2015) and Alternative HEI (2000 and 2010) ( = 3267). We conducted prospective analyses using Cox regression to estimate the associations between diet indices and incident cardiovascular disease outcomes.

Results: Among the 3267 study participants, 54% were female, mean age was 55 y, and BMI was 27 kg/m. There were a total of 544 events for the composite outcome of cardiovascular diseases (324 coronary artery disease events, 153 stroke events, and 187 heart failure events). Adherence to any dietary index was inversely associated with risk of cardiovascular disease, coronary artery disease, and heart failure, but not stroke. Compared with HEI-1990, scores for the more recent diet indices were more strongly associated with coronary artery disease risk, but not cardiovascular disease, heart failure, or stroke.

Conclusions: More recent iterations of diet indices, reflecting updates to the DGAs over time, are more strongly associated with risk of incident coronary artery disease than the original diet index (HEI-1990).
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http://dx.doi.org/10.1093/cdn/nzz123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053570PMC
December 2019

A gene-diet interaction-based score predicts response to dietary fat in the Women's Health Initiative.

Am J Clin Nutr 2020 04;111(4):893-902

Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging, Boston, MA, USA.

Background: Although diet response prediction for cardiometabolic risk factors (CRFs) has been demonstrated using single genetic variants and main-effect genetic risk scores, little investigation has gone into the development of genome-wide diet response scores.

Objective: We sought to leverage the multistudy setup of the Women's Health Initiative cohort to generate and test genetic scores for the response of 6 CRFs (BMI, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and fasting glucose) to dietary fat.

Methods: A genome-wide interaction study was undertaken for each CRF in women (n ∼ 9000) not participating in the dietary modification (DM) trial, which focused on the reduction of dietary fat. Genetic scores based on these analyses were developed using a pruning-and-thresholding approach and tested for the prediction of 1-y CRF changes as well as long-term chronic disease development in DM trial participants (n ∼ 5000).

Results: Only 1 of these genetic scores, for LDL cholesterol, predicted changes in the associated CRF. This 1760-variant score explained 3.7% (95% CI: 0.09, 11.9) of the variance in 1-y LDL cholesterol changes in the intervention arm but was unassociated with changes in the control arm. In contrast, a main-effect genetic risk score for LDL cholesterol was not useful for predicting dietary fat response. Further investigation of this score with respect to downstream disease outcomes revealed suggestive differential associations across DM trial arms, especially with respect to coronary heart disease and stroke subtypes.

Conclusions: These results lay the foundation for the combination of many genome-wide gene-diet interactions for diet response prediction while highlighting the need for further research and larger samples in order to achieve robust biomarkers for use in personalized nutrition.
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http://dx.doi.org/10.1093/ajcn/nqaa037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138684PMC
April 2020

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

Public Health Nutr 2020 06 24;23(9):1576-1588. Epub 2020 Feb 24.

Nutritional Epidemiology Program, The Jean Mayer U.S.D.A. Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1017/S136898001900394XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196005PMC
June 2020

Dose-Response Relation between Tea Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Population-Based Studies.

Adv Nutr 2020 07;11(4):790-814

Department of Nutrition and Food Studies, George Mason University, Fairfax, VA, USA.

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 (I2 = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I2 = 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.
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http://dx.doi.org/10.1093/advances/nmaa010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360449PMC
July 2020

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

J Nutr 2020 05;150(5):1272-1283

Nutritional Epidemiology, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/jn/nxaa021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198289PMC
May 2020

Cumulative sugar-sweetened beverage consumption is associated with higher concentrations of circulating ceramides in the Framingham Offspring Cohort.

Am J Clin Nutr 2020 02;111(2):420-428

Nutritional Epidemiology, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

Background: Ceramides have been implicated in the pathogenesis of type 2 diabetes and cardiovascular disease. Limited data exist on how habitual dietary intake of foods that can alter hepatic lipid metabolism may influence circulating ceramide concentrations.

Objectives: We investigated the cross-sectional association of cumulative sugar-sweetened beverage (SSB) consumption with concentrations of 3 circulating ceramides and ceramide ratios.

Methods: We examined participants from the Framingham Heart Study's Offspring Cohort who had 3 ceramides measured (n  = 1561, mean age 66 y, 59% women). SSB consumption was measured 4 times over ∼14 y. Participants were categorized by cumulative SSB intake as nonconsumers (0 to <1 SSB serving/mo) and occasional (1 SSB serving/mo to <1 serving/wk), frequent (1 SSB serving/wk to <1 serving/d), and daily (≥1 SSB serving/d) consumers. Multivariable linear regression models were used to relate cumulative SSB consumption (independent variable) to blood concentrations of ceramides (C16:0, C22:0, and C24:0) and ceramide ratios (C22:0/C16:0 and C24:0/C16:0).

Results: In adjusted models, more frequent cumulative SSB consumption was positively associated with concentrations of the C16:0 and C22:0 ceramides (Ptrend < 0.05). Compared with nonconsumers, daily consumers had 0.01 μg/mL (95% CI: 0.002, 0.017 µg/mL) and 0.06 µg/mL (95% CI: 0.018, 0.092 µg/mL) higher mean concentrations of the C16:0 and C22:0 ceramides, respectively. Results were consistent when modeling continuous cumulative SSB consumption per 1 serving/d. We observed effect modification by diabetes status in the relation between cumulative SSB consumption and concentrations of the C24:0 ceramide (Pinteraction = 0.014). In a stratified analysis, more frequent cumulative SSB consumption was positively associated with concentrations of the C24:0 ceramide only in individuals with prediabetes or diabetes (Ptrend = 0.001).

Conclusions: Our study raises the possibility that higher concentrations of distinct ceramide species, previously associated with adverse metabolic health, may be one mechanism by which SSB consumption contributes to higher risk of cardiometabolic diseases.
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http://dx.doi.org/10.1093/ajcn/nqz257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997085PMC
February 2020

Reply to MF Rolland-Cachera and KF Michaelsen.

Am J Clin Nutr 2019 11;110(5):1261-1262

From the Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

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http://dx.doi.org/10.1093/ajcn/nqz194DOI Listing
November 2019

DNA methylation modules associate with incident cardiovascular disease and cumulative risk factor exposure.

Clin Epigenetics 2019 10 15;11(1):142. Epub 2019 Oct 15.

JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

Background: Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associations is not always clear, and investigations to-date have often failed to replicate at the level of individual loci.

Methods: Here, we undertook module- and region-based DNA methylation analyses of incident CVD in the Women's Health Initiative (WHI) and Framingham Heart Study Offspring Cohort (FHS) in order to find more robust epigenetic biomarkers for cardiovascular risk. We applied weighted gene correlation network analysis (WGCNA) and the Comb-p algorithm to find methylation modules and regions associated with incident CVD in the WHI dataset.

Results: We discovered two modules whose activation correlated with CVD risk and replicated across cohorts. One of these modules was enriched for development-related processes and overlaps strongly with epigenetic aging sites. For the other, we showed preliminary evidence for monocyte-specific effects and statistical links to cumulative exposure to traditional cardiovascular risk factors. Additionally, we found three regions (associated with the genes SLC9A1, SLC1A5, and TNRC6C) whose methylation associates with CVD risk.

Conclusions: In sum, we present several epigenetic associations with incident CVD which reveal disease mechanisms related to development and monocyte biology. Furthermore, we show that epigenetic modules may act as a molecular readout of cumulative cardiovascular risk factor exposure, with implications for the improvement of clinical risk prediction.
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http://dx.doi.org/10.1186/s13148-019-0705-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792327PMC
October 2019

Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3 Years After a 1-Year Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial.

J Am Heart Assoc 2019 10 9;8(20):e010951. Epub 2019 Oct 9.

Friedman School of Nutrition Science and Policy Tufts University Boston MA.

Background Weight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established. Methods and Results Publicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1-year intensive lifestyle intervention and with year 4 follow-up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1-4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with <10% and ≥10% initial weight loss, and women and men. Maintainers exhibited significant improvements to the cardiometabolic risk factors assessed compared with regainers. No weight regain cut point maximized risk difference between maintainers and regainers across risk factors or sex/initial weight loss subgroups. For many risk factors, allowing more regain as part of maintenance (increasing cut point) diminished the cardiometabolic benefit among maintainers. Conclusions Maintaining weight loss was better than regain for all risk factors. No single cut point maximized the risk difference between maintainers and regainers. Maintainers who kept off ≥75% of weight lost had the greatest benefit. These findings emphasize the importance of intervention programs focusing not only on weight loss but weight loss maintenance, given the adverse consequences of the latter. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00017953.
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http://dx.doi.org/10.1161/JAHA.118.010951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818027PMC
October 2019