Showing papers by "Frank B. Hu published in 2021"

2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association.

Abstract: Poor diet quality is strongly associated with elevated risk of cardiovascular disease morbidity and mortality. This scientific statement emphasizes the importance of dietary patterns beyond individual foods or nutrients, underscores the critical role of nutrition early in life, presents elements of heart-healthy dietary patterns, and highlights structural challenges that impede adherence to heart-healthy dietary patterns. Evidence-based dietary pattern guidance to promote cardiometabolic health includes the following: (1) adjust energy intake and expenditure to achieve and maintain a healthy body weight; (2) eat plenty and a variety of fruits and vegetables; (3) choose whole grain foods and products; (4) choose healthy sources of protein (mostly plants; regular intake of fish and seafood; low-fat or fat-free dairy products; and if meat or poultry is desired, choose lean cuts and unprocessed forms); (5) use liquid plant oils rather than tropical oils and partially hydrogenated fats; (6) choose minimally processed foods instead of ultra-processed foods; (7) minimize the intake of beverages and foods with added sugars; (8) choose and prepare foods with little or no salt; (9) if you do not drink alcohol, do not start; if you choose to drink alcohol, limit intake; and (10) adhere to this guidance regardless of where food is prepared or consumed. Challenges that impede adherence to heart-healthy dietary patterns include targeted marketing of unhealthy foods, neighborhood segregation, food and nutrition insecurity, and structural racism. Creating an environment that facilitates, rather than impedes, adherence to heart-healthy dietary patterns among all individuals is a public health imperative.

The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk.

Abstract: To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome. The beneficial effects of a Mediterranean diet on cardiometabolic health are associated with specific changes in the gut microbiome, suggesting a personalized approach towards cardiometabolic disease prevention.

Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies

Abstract: Background: The optimal intake levels of fruit and vegetables for maintaining long-term health are uncertain. Methods: We followed 66 719 women from the Nurses’ Health Study (1984–2014) and 42 016 ...

Genetic insights into biological mechanisms governing human ovarian ageing.

Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

Abstract: The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death. Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Abstract: Objective To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p Conclusion The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half. Trial registration number NCT03020186.

Incident Type 2 Diabetes Duration and Cancer Risk: A Prospective Study in Two US Cohorts

Abstract: Background The influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood. Methods We prospectively followed for cancer incidence 113 429 women in the Nurses' Health Study (1978-2014) and 45 604 men in the Health Professionals Follow-up Study (1988-2014) who were free of diabetes and cancer at baseline. Cancer incidences were ascertained by review of medical records. Results In the multivariable-adjusted model incident, T2D was associated with higher risk of cancers in the colorectum, lung, pancreas, esophagus, liver, thyroid, breast, and endometrium. The pooled hazard ratios (HRs) ranged from 1.21 (95% confidence interval [CI] = 1.06 to 1.38) for colorectal cancer to 3.39 (95% CI = 2.24 to 5.12) for liver cancer. For both composite cancer outcomes and individual cancers, the elevated risks did not further increase after 8 years of T2D duration. The hazard ratio for total cancer was 1.28 (95% CI = 1.17 to 1.40) for T2D duration of 4.1-6.0 years, 1.37 (95% CI = 1.25 to 1.50) for 6.1-8.0 years, 1.21 (95% CI = 1.09 to 1.35) for 8.1-10.0 years, and 1.04 (95% CI = 0.95 to 1.14) after 15.0 years. In a cross-sectional analysis, a higher level of plasma C-peptide was found among participants with prevalent T2D of up to 8 years than those without T2D, whereas a higher level of HbA1c was found for those with prevalent T2D of up to 15 years. Conclusions Incident T2D was associated with higher cancer risk, which peaked at approximately 8 years after diabetes diagnosis. Similar duration-dependent pattern was observed for plasma C-peptide. Our findings support a role of hyperinsulinemia in cancer development.

Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies

Abstract: Objective Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota. Method We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites. Results Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals. Conclusion Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host–microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.

Changes in Plant-Based Diet Indices and Subsequent Risk of Type 2 Diabetes in Women and Men: Three U.S. Prospective Cohorts.

Abstract: OBJECTIVE We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We prospectively followed 76,530 women in the Nurses’ Health Study (NHS) (1986–2012), 81,569 women in NHS II (1991–2017), and 34,468 men in the Health Professionals Follow-up Study (1986–2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis. RESULTS We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12–23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7–9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0–35.6% of the associations between changes in PDI and hPDI and diabetes risk. CONCLUSIONS Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.

A framework for microbiome science in public health.

Abstract: Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.

Lipid Profiles and Heart Failure Risk: Results from Two Prospective Studies

Abstract: Rationale: Altered lipid metabolism has been implicated in heart failure (HF) development, but no prospective studies have examined comprehensive lipidomics data and subsequent risk of HF. Objectiv...

Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study.

Abstract: Background Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. Methods Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvencion con DIeta MEDiterranea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. Results After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. Conclusions Our findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF.

Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men.

Abstract: Objectives Gut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals. Design We collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features. Results TMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO concentrations (false discovery rate Conclusion We identified microbial taxa that were associated with TMAO concentrations and modified the associations of red meat intake with TMAO concentrations and cardiometabolic risk markers. Our data underscore the interplay between diet and gut microbiome in producing potentially bioactive metabolites that may modulate cardiometabolic health.

Quality of Plant-Based Diet and Risk of Total, Ischemic, and Hemorrhagic Stroke.

Abstract: Objective To determine whether a healthful plant-based diet is related to lower stroke risk, we examined the associations of plant-based diet quality with risk of total, ischemic, and hemorrhagic stroke. Methods The participants were 73,890 women in Nurses9 Health Study (NHS; 1984–2016), 92,352 women in NHSII (1991–2017), and 43,266 men in Health Professionals Follow-Up Study (1986–2012) without cardiovascular disease and cancer at baseline. Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Participants who reported that their meat and/or fish intakes were 0 or Results During the follow-up, 6,241 total stroke cases (including 3,015 ischemic and 853 hemorrhagic strokes) were documented. Compared to participants with the lowest PDIs, among participants with the highest PDIs, the hazard ratios (HRs) for total stroke were 0.94 (95% confidence interval 0.86–1.03) for PDI, 0.90 (0.83–0.98) for hPDI, and 1.05 (0.96–1.15) for uPDI. Participants in the highest hPDI showed marginally lower HR for ischemic stroke (0.92 [0.82–1.04]) and no consistent associations for hemorrhagic stroke. We observed no association between a vegetarian diet and total stroke (1.00 [0.76–1.32]), although the number of cases was small. Conclusion Lower risk of total stroke was observed by those who adhered to a healthful plant-based diet.

Walnut Consumption, Plasma Metabolomics, and Risk of Type 2 Diabetes and Cardiovascular Disease.

Abstract: Background Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. Objectives The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. Methods The discovery population included 1833 participants at high cardiovascular risk from the PREvencion con DIeta MEDiterranea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training-validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. Results A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P Conclusions A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.

The associations between major dietary patterns and risk of periodontitis.

Abstract: Aim To prospectively investigate the associations between major dietary patterns and incidence of periodontitis. Methods We included 34,940 men from the Health Professionals Follow-Up Study, free of periodontal disease and major illnesses at baseline. Detailed medical and dental history was collected through biennial mailed questionnaires, and dietary information was provided through quadrennial food frequency questionnaires. Using principal component analysis, we identified two major dietary patterns ("prudent" and "Western"). We used Cox proportional hazard models to examine the associations between the two dietary patterns and self-reported incidence of periodontitis over a 24-year follow-up period. We investigated each pattern separately. Results There was no overall association between Western or prudent dietary patterns and periodontitis. Among obese, however, the Western dietary pattern was significantly associated with incident periodontitis. The hazard ratio for those in the highest quintile of Western diet versus those in the lowest (reference) was 1.83 (95% confidence interval: 1.21-2.76). Conclusions There was no overall association between Western or prudent dietary patterns and periodontitis; however, in subgroups analysis, the Western diet was significantly associated with higher periodontitis risk only among obese men, a finding that requires replication and biological explication.

Plant-Based Diet Index and Metabolic Risk in Men: Exploring the Role of the Gut Microbiome.

Abstract: Background Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated. Objectives We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers. Methods hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray-Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin. Results After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associated with a higher relative abundance of Bacteroides cellulosilyticus and Eubacterium eligens, amino acid biosynthesis pathways (l-isoleucine biosynthesis I and III and l-valine biosynthesis), and the pathway of pyruvate fermentation to isobutanol. A favorable association between hPDI and the metabolic risk score was more pronounced among men with a higher PCo characterized by higher abundance of Bacteroides uniformis and lower abundance of Prevotella copri. At the individual species level, a similar interaction was also observed between hPDI and P. copri, as well as with Clostridium clostridioforme or Blautia hydrogenotrophica (all P-interaction Conclusion A greater adherence to a healthy plant-based diet by older men was associated with a microbial profile characterized by a higher abundance of multiple species, including B. cellulosilyticus and E. eligens, as well as pathways in amino acid metabolism and pyruvate fermentation. In addition, inverse associations between healthy plant-based diet and human metabolic risk may partially depend on microbial compositions.

Metabolomics Meets Nutritional Epidemiology: Harnessing the Potential in Metabolomics Data

Abstract: Traditionally, nutritional epidemiology is the study of the relationship between diet and health and disease in humans at the population level. Commonly, the exposure of interest is food intake. In recent years, nutritional epidemiology has moved from a “black box” approach to a systems approach where genomics, metabolomics and proteomics are providing novel insights into the interplay between diet and health. In this context, metabolomics is emerging as a key tool in nutritional epidemiology. The present review explores the use of metabolomics in nutritional epidemiology. In particular, it examines the role that food-intake biomarkers play in addressing the limitations of self-reported dietary intake data and the potential of using metabolite measurements in assessing the impact of diet on metabolic pathways and physiological processes. However, for full realisation of the potential of metabolomics in nutritional epidemiology, key challenges such as robust biomarker validation and novel methods for new metabolite identification need to be addressed. The synergy between traditional epidemiologic approaches and metabolomics will facilitate the translation of nutritional epidemiologic evidence to effective precision nutrition.

Mediterranean diet - promotion and dissemination of healthy eating: proceedings of an exploratory seminar at the Radcliffe institute for advanced study.

Abstract: The traditional Mediterranean diet is considered the world's most evidence-based eating pattern for promoting health and longevity. However, institutional food environments and their busy consumers often sacrifice health benefits for the convenience of faster and cheaper foods that generally are of lower quality and are more processed, and thus, contribute to the current epidemics of obesity and diabetes. Expert consensus has even identified the Mediterranean diet as the easiest to follow among healthy eating patterns. Nonetheless, fewer American families cook at home and many food services have been slow to implement healthier food options compatible with the Mediterranean diet. In September 2019, we convened a group of thought leaders at an exploratory seminar entitled: "Mediterranean Diet: Promotion and Dissemination of Healthy Eating", hosted by the Radcliffe Institute for Advanced Studies at Harvard University. The multidisciplinary faculty discussed best practices for translating traditional Mediterranean lifestyle principles to modern society.

Healthful and unhealthful plant-based diets and risk of breast cancer in U.S. women: results from the Nurses' Health Studies

Abstract: Background: Plant-based diets have been associated with lower risk of various diseases, including type 2 diabetes, cardiovascular disease, and other cardiometabolic risk factors. However, the association between plant-based diet quality and breast cancer remains unclear. Methods: We prospectively followed 76,690 women from the Nurses9 Health Study (NHS, 1984–2016) and 93,295 women from the NHSII (1991–2017). Adherence to an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI) was assessed using previously developed indices. Cox proportional hazards models were used to estimate HR and 95% confidence intervals (CI) for incident invasive breast cancer. Results: Over 4,841,083 person-years of follow-up, we documented 12,482 incident invasive breast cancer cases. Women with greater adherence to PDI and hPDI were at modestly lower risk of breast cancer [(HRQ5 vs. Q1, 0.89; 95% CI, 0.84–0.95); (HRQ5 vs. Q1, 0.89; 95% CI, 0.83–0.94)]. We observed significant heterogeneity by estrogen receptor (ER) status, with the strongest inverse association between hPDI and breast cancer observed with ER-negative tumors [HRQ5 vs. Q1, 0.77; 95% CI, 0.65–0.90; Ptrend Conclusions: This study provides evidence that adherence to a healthful plant-based diet may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors. Impact: This is the first prospective study investigating the relation between healthful and unhealthful plant-based dietary indices and risk of total and subtype-specific breast cancer.

Cord Blood Metabolome and BMI Trajectory from Birth to Adolescence: A Prospective Birth Cohort Study on Early Life Biomarkers of Persistent Obesity.

Abstract: There is increasing recognition on the role of early life metabolic programming in childhood obesity. This study sought to investigate whether newborn cord blood metabolome can predict future BMI. It included 946 children in the Boston Birth Cohort, a sample of high-risk yet understudied US urban, low-income, predominantly Black and Hispanic children, who were enrolled at birth and followed prospectively up to age 18 years. A total of 376 metabolites were measured in cord blood plasma. Longitudinal BMI trajectories were defined and categorized into three distinct patterns: early onset overweight and obesity (early-OWO), late onset OWO (late-OWO), and normal weight trajectory (NW). Multinomial logistic regression models were used to identify metabolites individually or as network modules associated with BMI trajectories. Of the 946 children, 388, 254, and 304 were classified as early-OWO, late-OWO, and NW, respectively. Of the seven co-metabolomic network modules defined, two were inversely correlated with early-OWO. Among the 68 metabolites within the two modules, 22 triacylglycerols and diacylglycerols were negatively associated with early-OWO; 5 cholesterol esters were positively associated with early-OWO. In this prospective birth cohort, we demonstrated distinctive longitudinal BMI trajectories and identified multiple cord plasma metabolites in relevant biological pathways that were associated with early-OWO.