Publications by authors named "Meir J Stampfer"

580 Publications

A Metabolomics Analysis of Circulating Carotenoids and Breast Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2021 Oct 25. Epub 2021 Oct 25.

Channing Division of Network Medicine, Brigham and Women's Hospital.

Background: Higher circulating carotenoids are associated with lower breast cancer risk. The underlying biology remains under-explored.

Methods: We profiled 293 pre-diagnostic plasma metabolites in a nested case-control study (n=887 cases) within the Nurses' Health Studies. Associations between circulating carotenoids and metabolites were identified using linear-mixed models (FDR less/equal to 0.05), and we further selected metabolites most predictive of carotenoids with LASSO. Metabolic signatures for carotenoids were calculated as weighted sums of LASSO selected metabolites. We further evaluated the metabolic signatures in relation to breast cancer risk using conditional logistic-regression.

Results: We identified 48-110 metabolites associated with plasma levels of α-carotene, β-carotene, β-cryptoxanthin, estimated-vitamin-A-potential, lutein/zeaxanthin, and lycopene, which included primarily positively associated metabolites implicated in immune regulation (tryptophan), redox balance (plasmalogens, glutamine), epigenetic regulations (acetylated-/methylated-metabolites), and primarily inversely associated metabolites involved in β-oxidation (carnitines). The metabolomic signatures derived for β-carotene (Q4 vs. Q1 relative risk RR=0.74, p-trend=0.02), and estimated-vitamin-A-potential (Q4 vs. Q1 RR=0.74, p-trend=0.02)-measured greater than 10 years before diagnosis-were associated with lower breast cancer risk. Modest attenuations of RR for measured levels of β-carotene and estimated-vitamin-A-potential were seen when we adjusted for their corresponding metabolic signatures.

Conclusions: Metabolites involved in immune regulation, redox balance, membrane signaling and β-oxidation were associated with plasma carotenoids. While some metabolites may reflect shared common food sources or compartmental co-localization with carotenoids, others may signal the underlying pathways of carotenoids-associated lowered breast cancer risk.

Impact: Consumption of carotenoid-rich diet is associated with a wide-range of metabolic changes which may help to reduce breast cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0837DOI Listing
October 2021

Development and Validation of a Novel Food-Based Global Diet Quality Score (GDQS).

J Nutr 2021 Oct;151(Supplement_2):75S-92S

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Poor diet quality is a major driver of both classical malnutrition and noncommunicable disease (NCD) and was responsible for 22% of adult deaths in 2017. Most countries face dual burdens of undernutrition and NCDs, yet no simple global standard metric exists for monitoring diet quality in populations and population subgroups.

Objectives: We aimed to develop an easy-to-use metric for nutrient adequacy and diet related NCD risk in diverse settings.

Methods: Using cross-sectional and cohort data from nonpregnant, nonlactating women of reproductive age in 10 African countries as well as China, India, Mexico, and the United States, we undertook secondary analyses to develop novel metrics of diet quality and to evaluate associations between metrics and nutrient intakes and adequacy, anthropometry, biomarkers, type 2 diabetes, and iteratively modified metric design to improve performance and to compare novel metric performance to that of existing metrics.

Results: We developed the Global Diet Quality Score (GDQS), a food-based metric incorporating a more comprehensive list of food groups than most existing diet metrics, and a simple means of scoring consumed amounts. In secondary analyses, the GDQS performed comparably with the Minimum Dietary Diversity - Women indicator in predicting an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B12 adequacy and with anthropometric and biochemical indicators of undernutrition (including underweight, anemia, and serum folate deficiency), and the GDQS also performed comparably or better than the Alternative Healthy Eating Index - 2010 in capturing NCD-related outcomes (including metabolic syndrome, change in weight and waist circumference, and incident type 2 diabetes).

Conclusions: The simplicity of the GDQS and its ability to capture both nutrient adequacy and diet-related NCD risk render it a promising candidate for global monitoring platforms. Research is warranted to validate methods to operationalize GDQS assessment in population surveys, including a novel application-based 24-h recall system developed as part of this project.
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http://dx.doi.org/10.1093/jn/nxab244DOI Listing
October 2021

Application of the Global Diet Quality Score in Chinese Adults to Evaluate the Double Burden of Nutrient Inadequacy and Metabolic Syndrome.

J Nutr 2021 Oct;151(Supplement_2):93S-100S

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: The double burdens of under- and overnutrition are changing the health of individuals and the economic and disease burdens in China. Poor diet plays an important role; however, a valid and easily operationalized metric that could capture the full range of characteristics of the diet that are relevant to both under- and overnutrition is lacking in China.

Objectives: We aimed to examine the application of the Global Diet Quality Score (GDQS) to evaluate nutrient inadequacy and metabolic syndrome in different demographic groups of Chinese adults.

Methods: A total of 35,146 individuals (men 14,978, women 20,168) aged >18 y from the 2010-2012 China National Nutrition and Health Survey were included. We scored the GDQS using average intakes of 25 food groups from 3 d of 24-h dietary recalls. Double burden was defined as coexisting metabolic syndrome and nutrient inadequacy.

Results: Diet quality assessed by GDQS was significantly higher in urban than in rural residents (20.8 compared with 18.7), and increased with both educational level and household income (P-trends < 0.0001). A higher GDQS score was inversely associated with metabolic syndrome and nutrient inadequacy, or both (P-trends < 0.0001): multivariate adjusted ORs comparing extreme quintiles of GDQS were 0.79 (95% CI: 0.69, 0.91) for metabolic syndrome, 0.17 (95% CI: 0.14, 0.20) for nutrient inadequacy, and 0.59 (95% CI: 0.50, 0.69) for the double burden. These associations were consistent across different household income levels (P-interaction = 0.26), suggestively stronger in younger (<50 y), females, urban residents, and the more highly educated (P-interaction < 0.05) compared with their counterparts.

Conclusions: A higher GDQS was inversely associated with a double burden of nutrient inadequacy and metabolic syndrome across various subgroups of Chinese adults. The finding supports the use of the GDQS in different demographic groups of Chinese adults to assess diet quality and nutritional status.
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http://dx.doi.org/10.1093/jn/nxab162DOI Listing
October 2021

The Global Diet Quality Score is Associated with Higher Nutrient Adequacy, Midupper Arm Circumference, Venous Hemoglobin, and Serum Folate Among Urban and Rural Ethiopian Adults.

J Nutr 2021 Oct;151(Supplement_2):130S-142S

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Nutritionally inadequate diets in Ethiopia contribute to a persisting national burden of adult undernutrition, while the prevalence of noncommunicable diseases (NCDs) is rising.

Objectives: To evaluate performance of a novel Global Diet Quality Score (GDQS) in capturing diet quality outcomes among Ethiopian adults.

Methods: We scored the GDQS and a suite of comparison metrics in secondary analyses of FFQ and 24-hour recall (24HR) data from a population-based cross-sectional survey of nonpregnant, nonlactating women of reproductive age and men (15-49 years) in Addis Ababa and 5 predominately rural regions. We evaluated Spearman correlations between metrics and energy-adjusted nutrient adequacy, and associations between metrics and anthropometric/biomarker outcomes in covariate-adjusted regression models.

Results: In the FFQ analysis, correlations between the GDQS and an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B12 adequacy were 0.32 in men and 0.26 in women. GDQS scores were inversely associated with folate deficiency in men and women (GDQS Quintile 5 compared with Quintile 1 OR in women, 0.50; 95% CI: 0.31-0.79); inversely associated with underweight (OR, 0.63; 95% CI: 0.44-0.90), low midupper arm circumference (OR, 0.61; 95% CI: 0.45-0.84), and anemia (OR, 0.59; 95% CI: 0.38-0.91) in women; and positively associated with hypertension in men (OR: 1.77, 95% CI: 1.12-2.80). For comparison, the Minimum Dietary Diversity-Women (MDD-W) was associated more positively (P < 0.05) with overall nutrient adequacy in men and women, but also associated with low ferritin in men, overweight/obesity in women, and hypertension in men and women. In the 24HR analysis (restricted to women), the MDD-W was associated more positively (P < 0.05) with nutrient adequacy than the GDQS, but also associated with low ferritin, while the GDQS was associated inversely with anemia.

Conclusions: The GDQS performed capably in capturing nutrient adequacy-related outcomes in Ethiopian adults. Prospective studies are warranted to assess the GDQS' performance in capturing NCD outcomes in sub-Saharan Africa.
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http://dx.doi.org/10.1093/jn/nxab264DOI Listing
October 2021

The Global Diet Quality Score Is Inversely Associated with Nutrient Inadequacy, Low Midupper Arm Circumference, and Anemia in Rural Adults in Ten Sub-Saharan African Countries.

J Nutr 2021 Oct;151(Supplement_2):119S-129S

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Key nutrient deficits remain widespread throughout sub-Saharan Africa (SSA) whereas noncommunicable diseases (NCDs) now cause one-third of deaths. Easy-to-use metrics are needed to track contributions of diet quality to this double burden.

Objectives: We evaluated comparative performance of a novel food-based Global Diet Quality Score (GDQS) against other diet metrics in capturing nutrient adequacy and undernutrition in rural SSA adults.

Methods: We scored the GDQS, Minimum Dietary Diversity-Women (MDD-W), and Alternative Healthy Eating Index-2010 (AHEI-2010) using FFQ data from rural men and nonpregnant, nonlactating women of reproductive age (15-49 y) in 10 SSA countries. We evaluated Spearman correlations between metrics and energy-adjusted nutrient intakes, and age-adjusted associations with BMI, midupper arm circumference (MUAC), and hemoglobin in regression models.

Results: Correlations between the GDQS and an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B-12 adequacy were 0.34 (95% CI: 0.30, 0.38) in men and 0.37 (95% CI: 0.32, 0.41) in women. The GDQS was associated (P < 0.05) with lower odds of low MUAC [GDQS quintile (Q) 5 compared with Q1 OR in men: 0.44, 95% CI: 0.22, 0.85; women: 0.57, 95% CI: 0.31, 1.03] and anemia (Q5/Q1 OR in men: 0.56, 95% CI: 0.32, 0.98; women: 0.60, 95% CI: 0.35, 1.01). The MDD-W correlated better with some nutrient intakes, though associated marginally with low MUAC in men (P = 0.07). The AHEI-2010 correlated better with fatty acid intakes, though associated marginally with low MUAC (P = 0.06) and anemia (P = 0.14) in women. Overweight/obesity prevalence was low, and neither the GDQS, MDD-W, nor AHEI-2010 were predictive.

Conclusions: The GDQS performed comparably with the MDD-W in capturing nutrient adequacy-related outcomes in rural SSA. Given limited data on NCD outcomes and the cross-sectional study design, prospective studies are warranted to assess GDQS performance in capturing NCD outcomes in SSA.
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http://dx.doi.org/10.1093/jn/nxab161DOI Listing
October 2021

Validation of Global Diet Quality Score Among Nonpregnant Women of Reproductive Age in India: Findings from the Andhra Pradesh Children and Parents Study (APCAPS) and the Indian Migration Study (IMS).

J Nutr 2021 Oct;151(Supplement_2):101S-109S

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: In India, there is a need to monitor population-level trends in changes in diet quality in relation to both undernutrition and noncommunicable diseases.

Objectives: We conducted a study to validate a novel diet quality score in southern India.

Methods: We included data from 3041 nonpregnant women of reproductive age (15-49 years) from 2 studies in India. Diet was assessed using a validated food frequency questionnaire (FFQ). The Global Diet Quality Score (GDQS) was calculated from 25 food groups (16 healthy; 9 unhealthy), with points for each group based on the frequency and quantity of items consumed in each group. We used Spearman correlations to examine correlations between the GDQS and several nutrient intakes of concern. We examined associations between the GDQS [overall, healthy (GDQS+), and unhealthy (GDQS-) submetrics] and overall nutrient adequacy, micro- and macronutrients, body mass index (BMI), midupper arm circumference, hemoglobin, blood pressure, high density lipoprotein (HDL), and total cholesterol (TC).

Results: The mean GDQS was 23 points (SD, 3.6; maximum, 46.5). In energy-adjusted models, positive associations were found between the overall GDQS and GDQS+ and intakes of calcium, fiber, folate, iron, monounsaturated fatty acid (MUFA), protein, polyunsaturated fatty acid (PUFA), saturated fatty acid (SFA), total fat, and zinc (ρ = 0.12-0.39; P < 0.001). Quintile analyses showed that the GDQS was associated with better nutrient adequacy. At the same time, the GDQS was associated with higher TC, lower HDL, and higher BMI. We found no associations between the GDQS and hypertension.

Conclusions: The GDQS was a useful tool for reflecting overall nutrient adequacy and some lipid measures. Future studies are needed to refine the GDQS for populations who consume large amounts of unhealthy foods, like refined grains, along with healthy foods included in the GDQS.
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http://dx.doi.org/10.1093/jn/nxab217DOI Listing
October 2021

Exploration of Machine Learning and Statistical Techniques in Development of a Low-Cost Screening Method Featuring the Global Diet Quality Score for Detecting Prediabetes in Rural India.

J Nutr 2021 Oct;151(Supplement_2):110S-118S

Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: The prevalence of type 2 diabetes has increased substantially in India over the past 3 decades. Undiagnosed diabetes presents a public health challenge, especially in rural areas, where access to laboratory testing for diagnosis may not be readily available.

Objectives: The present work explores the use of several machine learning and statistical methods in the development of a predictive tool to screen for prediabetes using survey data from an FFQ to compute the Global Diet Quality Score (GDQS).

Methods: The outcome variable prediabetes status (yes/no) used throughout this study was determined based upon a fasting blood glucose measurement ≥100 mg/dL. The algorithms utilized included the generalized linear model (GLM), random forest, least absolute shrinkage and selection operator (LASSO), elastic net (EN), and generalized linear mixed model (GLMM) with family unit as a (cluster) random (intercept) effect to account for intrafamily correlation. Model performance was assessed on held-out test data, and comparisons made with respect to area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

Results: The GLMM, GLM, LASSO, and random forest modeling techniques each performed quite well (AUCs >0.70) and included the GDQS food groups and age, among other predictors. The fully adjusted GLMM, which included a random intercept for family unit, achieved slightly superior results (AUC of 0.72) in classifying the prediabetes outcome in these cluster-correlated data.

Conclusions: The models presented in the current work show promise in identifying individuals at risk of developing diabetes, although further studies are necessary to assess other potentially impactful predictors, as well as the consistency and generalizability of model performance. In addition, future studies to examine the utility of the GDQS in screening for other noncommunicable diseases are recommended.
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http://dx.doi.org/10.1093/jn/nxab281DOI Listing
October 2021

Unrestrained eating behavior and risk of mortality: A prospective cohort study.

Clin Nutr 2021 Sep 17;40(11):5419-5429. Epub 2021 Sep 17.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Background & Aims: Unrestrained eating behavior has been thought to be a proxy for diet frequency, timing, and caloric intake. We investigated the association of unrestrained eating with mortality risk in the Nurses' Health Study prospectively.

Methods: During follow-up (1994-2016), 21,953 deaths were documented among 63,999 eligible participants in analyses of eating anything at any time, 22,120 deaths were documented among 65,839 participants in analyses of no concern with figure change. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.

Results: Eating anything at any time was associated with an increased mortality from cancer (overall HR, 95%CI: 1.07, 1.00-1.13; driven by gastrointestinal tract cancer: 1.30, 1.10-1.54) and respiratory disease (1.16, 1.05-1.29), and decreased cardiovascular disease-specific mortality (0.92, 0.86-0.99), compared to those without this behavior; however, no association was observed between this behavior and all-cause mortality (1.02, 0.99-1.05). Women who reported having no concern with figure change experienced higher risk of mortality from all-cause (1.08, 1.05-1.11), cancer (1.08, 1.02-1.14), and respiratory disease (1.18, 1.08-1.30), compared to those not reporting this behavior. Their combined effect was associated with a higher all-cause (1.09, 1.04-1.14), cancer-specific (overall: 1.18, 1.09-1.28; gastrointestinal tract cancer: 1.36, 1.08-1.71; lung cancer: 1.09; 1.04-1.14), and respiratory disease-specific (1.30, 1.13-1.50) mortality, and was inversely associated with cardiovascular disease-specific mortality (0.88, 0.80-0.98), compared to those exhibiting the opposite.

Conclusions: Unrestrained eating was associated with increased risk of all-cause, cancer-specific (particularly for gastrointestinal tract cancer and lung cancer), and respiratory disease-specific mortality, and decreased risk of cardiovascular disease-specific mortality.
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http://dx.doi.org/10.1016/j.clnu.2021.09.014DOI Listing
September 2021

Diet-induced fasting ghrelin elevation reflects the recovery of insulin sensitivity and visceral adiposity regression.

J Clin Endocrinol Metab 2021 Oct 13. Epub 2021 Oct 13.

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Aims: Lower fasting-ghrelin-levels (FGL) are associated with obesity and metabolic syndrome. We aimed to explore the dynamics of FGL during weight-loss and its metabolic and adiposity-related manifestations beyond weight-loss.

Methods: A secondary analysis of a clinical trial where we randomized participants with abdominal-obesity/dyslipidemia to one of three diets: healthy-dietary-guidelines (HDG), Mediterranean diet (MED), or green-MED diet, all combined with physical activity (PA). Both MED diets were similarly hypocaloric and included 28g/day walnuts. The green-MED group further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai) plant green-shake. We measured FGL and quantified body fat depots by Magnetic-Resonance-Imaging at baseline and after 18-months.

Results: Among 294 participants [body-mass-index=31.3kg/m 2;FGL=504±208pg/mL; retention rate=89.8%], lower FGL were associated with unfavorable cardiometabolic parameters as higher visceral-adipose-tissue (VAT), intra-hepatic fat, leptin, and blood pressure (p<0.05 for all; multivariate models). ∆FGL18-month differed between men (+7.3+26.6%) and women (-9.2+21.3%,p=0.001). After 18-months of moderate and similar weight loss among the MED-groups, FGL increased by 1.3%, 5.4%, and 10.5% in HDG, MED, and green-MED groups, respectively (p=0.03 for green-MED vs. HDG), sex-stratified analysis revealed similar changes in men only. Among men, FGL18-month elevation was associated with favorable changes in insulin resistance profile and VAT regression, after adjusting for relative weight-loss (HbA1c:r=-0.216; homeostatic-model-of insulin-resistance:r=-0.154; HDL-c:r=0.147;VAT:r=-0.221;p<0.05 for all). , Insulin resistance and VAT remained inversely related with FGL elevation, beyond which was explained by weight-loss (residual regression analyses;p<0.05).

Conclusions: Diet-induced FGL elevation may reflect insulin sensitivity recovery and VAT regression beyond weight-loss, specifically among men. Green-MED diet is associated with greater FGL elevation.
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http://dx.doi.org/10.1210/clinem/dgab681DOI Listing
October 2021

A prospective study of inflammatory biomarkers and growth factors and risk of glioma in the UK Biobank.

Cancer Epidemiol 2021 Sep 24;75:102043. Epub 2021 Sep 24.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States.

Purpose: The role of growth factors and inflammation in the onset of glioma is poorly understood, and conflicting reports of associations of circulating IGF-1 and inflammatory biomarkers with glioma risk exist in the literature. We examined associations between C-reactive protein (CRP), white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and insulin-like growth factor-1 (IGF-1) and glioma risk in the UK Biobank cohort.

Methods: Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to circulating biomarkers concentrations were calculated using Cox proportional hazards regression, adjusted for age, sex, race, and education. Analyses were conducted separately for glioma overall and by glioma subtype.

Results: We identified 417 incident glioma cases among 428,537 participants with 3,255,815 person-years of follow up. Weak, non-significant associations were observed with increasing levels of these biomarkers for risk of glioma overall or by glioma subtype. Among women only, IGF-1 in the highest quartile was positively associated with glioma risk compared to the lowest quartile (HR=1.64, 95%CI: 1.03-2.60, p-trend=0.08), as was NLR (HR=1.54, 95%CI: 1.00-2.39, p-trend=0.05).

Conclusion: In this prospective cohort, we found no significant associations between the inflammatory biomarkers CRP and WBC and the development of glioma. NLR and IGF-1 were associated with risk in women, but not men. When considered with previous studies, further investigation of NLR and IGF-1 as markers of glioma risk appears warranted, particularly in women.
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http://dx.doi.org/10.1016/j.canep.2021.102043DOI Listing
September 2021

Alcohol intake and risk of glioma: results from three prospective cohort studies.

Eur J Epidemiol 2021 Sep 4;36(9):965-974. Epub 2021 Sep 4.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Purpose: The association between alcohol intake and glioma remains unclear. We evaluated the association between alcohol intake and incidence of glioma in three large, prospective cohort studies with repeated alcohol assessments.

Methods: We harnessed data from three studies with repeat alcohol assessment to compute hazard ratios (HR) and 95% confidence intervals (CI) for glioma by overall alcohol intake and intake from specific beverages using Cox proportional hazards regression, adjusted for age, cohort, body mass index, smoking status, and caloric intake. Analyses were conducted separately for glioma overall and for glioblastoma (GBM).

Results: We confirmed 554 incident glioma cases (362 GBM) among 237,505 participants with 6,216,378 person-years of follow up. Cumulative average alcohol intake was associated with reduced risk of glioma (HR = 0.75, 95%CI:0.56-0.99 comparing > 8-15 to ≤ 0.5 g/d; HR = 0.71, 95%CI:0.53-0.96 comparing > 15 g/d to ≤ 0.5 g/d). When stratified by sex, for the same comparisons, the HRs for men were 0.57 (95%CI:0.36-0.89) and 0.79 (0.53-1.16), and for women 0.90 (95%CI:0.62-1.30) and 0.62, 95%CI:0.39-0.97. Results were consistent when examining cumulative average, baseline, and recent intake, and with a 4 year lag.

Conclusion: These results provide evidence against a positive association between alcohol intake and glioma risk. Alcohol intake was associated with reduced risk of glioma in both men and women.
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http://dx.doi.org/10.1007/s10654-021-00800-1DOI Listing
September 2021

Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent.

BMJ Open Diabetes Res Care 2021 08;9(1)

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Introduction: We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults.

Research Design And Methods: We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40-75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates.

Results: Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS.

Conclusions: Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.
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http://dx.doi.org/10.1136/bmjdrc-2021-002298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378385PMC
August 2021

Unrestrained eating behavior and risk of digestive system cancers: a prospective cohort study.

Am J Clin Nutr 2021 Jul 22. Epub 2021 Jul 22.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Background: Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse.

Objectives: We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk.

Methods: Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers.

Results: During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non-statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite.

Conclusions: Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted.
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http://dx.doi.org/10.1093/ajcn/nqab235DOI Listing
July 2021

Physical activity, sedentary behavior, and incidence of obstructive sleep apnea in three prospective US cohorts.

Eur Respir J 2021 Jul 21. Epub 2021 Jul 21.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Reduced physical activity and increased sedentary behavior may independently contribute to development of obstructive sleep apnea (OSA) through increased adiposity, inflammation, insulin resistance and body fluid retention. However, epidemiologic evidence remains sparse, and is primarily limited to cross-sectional studies.We prospectively followed 50 332 women from the Nurses' Health Study (2002-2012), 68 265 women from the Nurses' Health Study II (1995-2013), and 19 320 men from the Health Professionals Follow-up Study (1996-2012). Recreational physical activity (quantified by metabolic equivalent of task [MET]-hours/week) and sitting time spent watching TV and at work/away from home were assessed by questionnaires every 2-4 years. Physician-diagnosed OSA was identified by validated self-report. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for OSA incidence associated with physical activity and sedentary behavior.During 2 004 663 person-years of follow-up, we documented 8733 incident OSA cases. After adjusting for potential confounders, the pooled HR for OSA comparing participants with ≥36.0 <6.0 MET-hours/week of physical activity was 0.46 (95% CI: 0.43, 0.50; p<0.001). Compared with participants spending <4.0 h/week sitting watching TV, the multivariable-adjusted HR (95% CI) was 1.78 (1.60, 1.98) for participants spending ≥28.0 h/week (p<0.001). The comparable HR (95% CI) was 1.49 (1.38, 1.62) for sitting hours at work/away from home (p<0.001). With additional adjustment for several metabolic factors including BMI and waist circumference, the associations with physical activity and sitting hours at work/away from home were attenuated but remained significant (p<0.001), whereas the association with sitting hours watching TV was no longer statistically significant (p=0.18).Higher levels of physical activity and fewer sedentary hours were associated with lower OSA incidence. The potential mediating role of metabolic factors in the association between sedentary behavior and OSA incidence may depend on type of sedentary behavior. Our results suggest that promoting an active lifestyle may reduce OSA incidence.
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http://dx.doi.org/10.1183/13993003.00606-2021DOI Listing
July 2021

Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival.

Br J Cancer 2021 Sep 15;125(7):1016-1024. Epub 2021 Jul 15.

Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Background: The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear.

Methods: Among 1463 stage I-III CRC patients from the Nurses' Health Study and Health Professionals Follow-up Study, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars.

Results: Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87-1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95-1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06-2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26-0.75 and 0.70, 95% CI: 0.55-0.89, respectively).

Conclusions: Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.
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http://dx.doi.org/10.1038/s41416-021-01487-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476625PMC
September 2021

A prospective study of dietary flavonoid intake and risk of glioma in US men and women.

Am J Clin Nutr 2021 10;114(4):1314-1327

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Background: Flavonoids are a diverse group of plant constituents with demonstrated neuroprotective and anti-tumor effects. Flavonoid intake may decrease the risk of glioma, but the possibility of an association has not yet been investigated in humans.

Objectives: We evaluated the association between dietary flavonoid consumption and the risk of glioma.

Methods: We followed participants in the female Nurses' Health Study (1984-2014; n = 81,688) and Nurses' Health Study II (1991-2017; n = 95,228) and the male Health Professionals Follow-Up Study (1986-2014; n = 49,885). We used multivariable-adjusted Cox proportional hazards regression models to evaluate the associations between average long-term (up to 30 years) or recent (up to 12 years) dietary flavonoid intake (total flavonoids and each of 6 subclasses) and risks of incident glioma. Flavonoid intake was derived from validated quadrennial FFQs. Incident glioma was self-reported and confirmed by a medical record review or was determined by a medical record review after death.

Results: We documented 536 incident cases of glioma across 5,936,386 person-years of follow-up. Long-term total flavonoid, flavan-3-ol, and polymeric flavonoid (polymer) intakes were associated with decreased glioma risks in pooled analyses comparing the highest to lowest quintiles of consumption [HR, 0.79 (95% CI, 0.59-1.05; P-trend = 0.04) for total flavonoids; 0.76 (95% CI, 0.57-1.01; P-trend = 0.04) for flavan-3-ols; and 0.82 (95% CI, 0.61-1.09; P-trend = 0.05) for polymers]. Associations with recent intake were weaker. There were no associations with other flavonoid subclasses. After additional adjustment for tea consumption, there were no associations between flavan-3-ol or polymer consumption and glioma.

Conclusions: Increased dietary intakes of flavan-3-ol and polymeric flavonoids, especially those predominant in tea, were associated with decreased glioma risks in a prospective cohort of men and women.
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http://dx.doi.org/10.1093/ajcn/nqab178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488865PMC
October 2021

Prospective study of sleep duration and glioma risk.

Cancer Causes Control 2021 Sep 20;32(9):1039-1042. Epub 2021 May 20.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.

Purpose: Both long and short sleep duration have been linked with risk of some cancers, but evidence for glioma is lacking.

Methods: Using prospective data from the UK Biobank (UKB), the Nurses' Health Study (NHS), and the Health Professionals Follow-Up Study (HPFS), we examined the association between self-reported hours of sleep and incident glioma in multivariable-adjusted Cox proportional hazards models.

Results: In the UKB, compared to 7 h, sleep durations of < 7 h (HR = 0.90; 95% CI 0.70-1.16) or > 7 h (HR = 1.05; 95% CI 0.85-1.30) were not significantly associated with glioma risk. Likewise, no significant associations were found between sleep duration and glioma risk in the NHS/HPFS for either < 7 h (HR = 0.93; 95% CI 0.69-1.26) or > 7 h (HR = 1.22; 95% CI 0.94-1.57), compared to 7 h. Results were similar for low-grade and high-grade glioma, did not materially change after lagging 2 years, or after accounting for factors known to disrupt sleep.

Conclusion: Sleep duration was not associated with incident glioma in either the UKB or the NHS/HPFS cohorts.
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http://dx.doi.org/10.1007/s10552-021-01447-9DOI Listing
September 2021

Pre-diagnostic circulating concentrations of fat-soluble vitamins and risk of glioma in three cohort studies.

Sci Rep 2021 04 29;11(1):9318. Epub 2021 Apr 29.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Few prospective studies have evaluated the relation between fat-soluble vitamins and glioma risk. Using three cohorts-UK Biobank (UKB), Nurses' Health Study (NHS), and Health Professionals Follow-Up Study (HPFS), we investigated associations of pre-diagnostic concentrations of fat-soluble vitamins D, A, and E with incident glioma. In 346,785 participants (444 cases) in UKB, associations with vitamin D (25-hydroxyvitamin D [25(OH)D]) were evaluated by Cox proportional hazards regression. In NHS (52 cases, 104 controls) and HPFS (32 cases, 64 controls), associations with 25(OH)D, vitamin A (retinol), and vitamin E (α- and γ-tocopherol) were assessed using conditional logistic regression. Our results suggested plasma concentrations of 25(OH)D and retinol were not associated with glioma risk. Comparing the highest to lowest tertile, the multivariable hazard ratio (MVHR) for 25(OH)D was 0.87 (95% confidence interval [CI] 0.68-1.11) in UKB and the multivariable risk ratio (MVRR) was 0.97 (95% CI 0.51-1.85) in NHS and HPFS. In NHS and HPFS, the MVRR for the same comparison for retinol was 1.16 (95% CI 0.56-2.38). Nonsignificant associations were observed for α-tocopherol (MVRR = 0.61, 95% CI 0.29-1.32) and γ-tocopherol (MVRR  = 1.30, 95% CI 0.63-2.69) that became stronger in 4-year lagged analyses. Further investigation is warranted on a potential association between α- and γ-tocopherol and glioma risk.
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http://dx.doi.org/10.1038/s41598-021-88485-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084971PMC
April 2021

Body Mass Index and Mortality Among Adults With Incident Myocardial Infarction.

Am J Epidemiol 2021 10;190(10):2019-2028

The relationship between body mass index (BMI; weight (kg)/height (m)2) and mortality among survivors of myocardial infarction (MI) remains controversial. We examined the relationships of BMI before and after MI and change in weight with all-cause mortality among participants in the Nurses' Health Study (1980-2016) and Health Professionals Follow-up Study (1988-2016) cohorts. During a follow-up period of up to 36 years, we documented 4,856 participants with incident nonfatal MI, among whom 2,407 died during follow-up. For pre-MI and post-MI BMI, overweight was not associated with lower mortality. Obesity (BMI ≥30) was associated with higher risk of mortality. Compared with participants with post-MI BMI of 22.5-24.9, hazard ratios were 1.16 (95% confidence interval (CI): 1.01, 1.34) for BMI 30.0-34.9 and 1.52 (95% CI: 1.27, 1.83) for BMI ≥35.0 (P for trend < 0.001). Compared with stable weight from before MI to after MI, a reduction of more than 4 BMI units was associated with increased mortality (hazard ratio = 1.53, 95%: CI: 1.28, 1.83). This increase was seen only among participants who lost weight without improving their physical activity or diet. Our findings showed no survival benefit of excess adiposity in relation to risk of mortality. Weight loss from before to after MI without lifestyle improvement may reflect reverse causation and disease severity.
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http://dx.doi.org/10.1093/aje/kwab126DOI Listing
October 2021

Building better guidelines for healthy and sustainable diets.

Am J Clin Nutr 2021 08;114(2):401-404

Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1093/ajcn/nqab079DOI Listing
August 2021

Prediagnostic Inflammation and Pancreatic Cancer Survival.

J Natl Cancer Inst 2021 Sep;113(9):1186-1193

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Background: Chronic inflammation may promote initiation and progression of pancreatic cancer, but no studies have examined the association between inflammation in the period before diagnosis and pancreatic cancer survival.

Methods: We prospectively examined the association of prediagnostic plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 with survival among 492 participants from 5 large US prospective cohort studies who developed pancreatic cancer. Using an empirical dietary inflammatory pattern (EDIP) score, we evaluated whether long-term proinflammatory diets were associated with survival among 1153 patients from 2 of the 5 cohorts. Cox proportional hazards regression was used to estimate hazard ratios for death with adjustment for potential confounders. All statistical tests were 2-sided.

Results: Higher prediagnostic levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 were individually associated with reduced survival (Ptrend = .03, .01, and .04, respectively). Compared with patients with a combined inflammatory biomarker score of 0 (all 3 marker levels below medians), those with a score of 3 (all 3 marker levels above medians) had a hazard ratio for death of 1.57 (95% confidence interval = 1.16 to 2.12; Ptrend = .003), corresponding to median overall survival times of 8 vs 5 months. Patients consuming the most proinflammatory diets (EDIP quartile 4) in the prediagnostic period had a hazard ratio for death of 1.34 (95% confidence interval = 1.13 to 1.59; Ptrend = .01), compared with those consuming the least proinflammatory diets (EDIP quartile 1).

Conclusion: Prediagnostic levels of inflammatory biomarkers and long-term proinflammatory diets were inversely associated with pancreatic cancer survival.
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http://dx.doi.org/10.1093/jnci/djab040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522350PMC
September 2021

Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial.

Clin Epigenetics 2021 03 4;13(1):48. Epub 2021 Mar 4.

Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel.

Background: DNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. We evaluated the role of multiple factors, including fat deposition, cardiometabolic risk factors and lifestyle weight-loss intervention, on the deviation of mAge from chronological age (mAge deviation) or 18-month change in mAge (∆mAge). In this sub-study of the CENTRAL magnetic resonance imaging weight-loss trial, we evaluated mAge by a validated 240-CpG-based prediction formula at baseline and after 18-month intervention of either low fat (LF) or mediterranean/low carbohydrate (MED/LC) diets.

Results: Among 120 CENTRAL participants with abdominal obesity or dyslipidemia, mAge (mean ± SD: 60.3 ± 7.5 years) was higher than the chronological age (48.6 ± 9.3 years) but strongly correlated (r = 0.93; p = 3.1 × 10). Participants in the lowest tertile of mAge deviation from their chronological age had significantly lower waist-circumference, visceral adipose tissue, intrahepatic fat (IHF) content, fasting-glucose and HOMA-IR, as compared with participants in the highest sex-specific residual tertile (p < 0.05 for all). IHF% remained associated with greater mAge deviation after further adjustments (β = 0.23; p = 0.02). After 18-month weight-loss lifestyle intervention, mAge remained significantly correlated with chronological age (r = 0.94, p = 1.5 × 10). mAging occurred, with no difference between lifestyle intervention groups (∆ = 0.9 ± 1.9 years in MED/LC vs. ∆ = 1.3 ± 1.9 years in LF; p = 0.2); however, we observed a mAging attenuation in successful weight losers (> 5% weight loss) vs. weight-loss failures ( ∆ = 0.6 years vs. ∆ = 1.1 years; p = 0.04), and in participants who completed the trial with healthy liver fat content (< 5% IHF) vs. participants with fatty liver (∆ = 0.6 years vs. ∆ = 1.8 years; p = 0.003). Overall, 18 months of weight-loss lifestyle intervention attenuated the mAging of the men, mainly the older, by 7.1 months than the expected (p < 0.05).

Conclusions: Lifestyle weight-loss intervention may attenuate mAging. Deviation of mAge from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases.

Trial Registration: ClinicalTrials.gov NCT01530724. Registered 10 February 2012, https://clinicaltrials.gov/ct2/show/study/NCT01530724 .
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http://dx.doi.org/10.1186/s13148-021-01038-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934393PMC
March 2021

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.

Circulation 2021 Apr 1;143(17):1642-1654. Epub 2021 Mar 1.

Channing Division for Network Medicine (D.D.W., S.N.B., B.A.R., Q.S., E.L.G., E.B.R., J.E.M., W.C.W., M.J.S., F.B.H.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

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 men from the Health Professionals Follow-up Study (1986-2014) who were free from cardiovascular disease (CVD), cancer, and diabetes at baseline. Diet was assessed using a validated semiquantitative food frequency questionnaire at baseline and updated every 2 to 4 years. We also conducted a dose-response meta-analysis, including results from our 2 cohorts and 24 other prospective cohort studies.

Results: We documented 33 898 deaths during the follow-up. After adjustment for known and suspected confounding variables and risk factors, we observed nonlinear inverse associations of fruit and vegetable intake with total mortality and cause-specific mortality attributable to cancer, CVD, and respiratory disease (all <0.001). Intake of ≈5 servings per day of fruit and vegetables, or 2 servings of fruit and 3 servings of vegetables, was associated with the lowest mortality, and above that level, higher intake was not associated with additional risk reduction. In comparison with the reference level (2 servings/d), daily intake of 5 servings of fruit and vegetables was associated with hazard ratios (95% CI) of 0.87 (0.85-0.90) for total mortality, 0.88 (0.83-0.94) for CVD mortality, 0.90 (0.86-0.95) for cancer mortality, and 0.65 (0.59-0.72) for respiratory disease mortality. The dose-response meta-analysis that included 145 015 deaths accrued in 1 892 885 participants yielded similar results (summary risk ratio of mortality for 5 servings/d=0.87 [95% CI, 0.85-0.88]; <0.001). Higher intakes of most subgroups of fruits and vegetables were associated with lower mortality, with the exception of starchy vegetables such as peas and corn. Intakes of fruit juices and potatoes were not associated with total and cause-specific mortality.

Conclusions: Higher intakes of fruit and vegetables were associated with lower mortality; the risk reduction plateaued at ≈5 servings of fruit and vegetables per day. These findings support current dietary recommendations to increase intake of fruits and vegetables, but not fruit juices and potatoes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084888PMC
April 2021

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

Nat Med 2021 02 11;27(2):333-343. Epub 2021 Feb 11.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

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.
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http://dx.doi.org/10.1038/s41591-020-01223-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186452PMC
February 2021

C-reactive Protein and Risk of OSA in Four US Cohorts.

Chest 2021 06 30;159(6):2439-2448. Epub 2021 Jan 30.

Division of Sleep Medicine, Harvard Medical School, Boston, MA; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background: Individuals with OSA have elevated levels of inflammatory markers, but no prospective study has examined the role of inflammation in the development of OSA.

Research Question: Is C-reactive protein (CRP) prospectively associated with risk of developing OSA?

Study Design And Methods: We followed 1,882 women from the Nurses' Health Study (NHS) (2002-2012), 3,854 women from Nurses' Health Study II (NHSII) (1995-2013), 3,075 men from the Health Professionals Follow-up Study (HPFS) (1996-2012), and 1,919 women and men from the Multi-Ethnic Study of Atherosclerosis (MESA) (2000-2012) who did not have diagnosed OSA at baseline and for whom CRP levels were available. In NHS/NHSII/HPFS, physician-diagnosed OSA was self-reported. In MESA, at-home polysomnography was performed and OSA was identified as an apnea-hypopnea index ≥ 30. Logistic regression was used to estimate the OR for OSA risk according to baseline CRP level, adjusted for multiple inflammation-related factors.

Results: After multivariable adjustment not including BMI, the pooled OR for OSA risk per doubling of baseline CRP level was 1.24 (95% CI, 1.18-1.30). Additional adjustment for BMI substantially attenuated the association (pooled OR, 1.07; 95% CI, 1.01-1.12). The fully adjusted association was consistently stronger in individuals < 55 vs ≥ 55 years of age (P interaction = .01), in individuals with BMI < 25 vs ≥ 25 kg/m (P interaction = .02), and in pre- vs postmenopausal women (P interaction = .002). CRP was more strongly associated with risk of OSA associated with excessive daytime sleepiness, high airway collapsibility, and low arousal threshold (P heterogeneity < .05).

Interpretation: Higher CRP was prospectively associated with increased OSA risk, particularly among younger individuals, underweight/normal-weight individuals, or premenopausal women. The differential associations by OSA phenotype/endotype suggest possible mechanisms through which inflammation operates to modulate OSA risk. Given our reliance on a single CRP level measured a decade before OSA assessment, future studies with repeated CRP measurements are warranted to confirm these prospective associations.
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http://dx.doi.org/10.1016/j.chest.2021.01.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213962PMC
June 2021

Circulating lipids and glioma risk: results from the UK Biobank, Nurses' Health Study, and Health Professionals Follow-Up Study.

Cancer Causes Control 2021 Apr 23;32(4):347-355. Epub 2021 Jan 23.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Purpose: Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts.

Methods: Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models. Within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we carried out a matched, nested case-control study to examine these same associations.

Results: In the UK Biobank, 490 gliomas accrued over 2,358,964 person-years. TC was not significantly associated with glioma risk (MV HR = 1.20, 95% CI 0.89-1.61 for highest quartile vs. lowest, p-trend = 0.24). In 4-year lagged analyses (n = 229), higher TC was associated with significantly higher risk of glioma in men (MV HR = 2.26, 95% CI 1.32-3.89, p-trend = 0.002) but not women (MV HR = 1.28, 95% CI 0.61-2.68, p-trend = 0.72); similar findings emerged for HDL-C and, to a lesser extent, LDL-C. In the NHS/HPFS, no significant associations were found between cholesterol and glioma risk. No significant associations were identified for TG.

Conclusion: In the UK Biobank, higher prediagnostic TC and HDL-C levels were associated with higher risk of glioma in 4-year lagged analyses, but not in non-lagged analyses, in men only. These findings merit further investigation, given that there are few risk factors and no reliable biomarkers of risk identified for glioma.
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http://dx.doi.org/10.1007/s10552-021-01391-8DOI Listing
April 2021

Body Habitus Across the Lifespan and Risk of Pituitary Adenoma.

J Clin Endocrinol Metab 2021 03;106(4):e1591-e1602

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Context: No studies have examined the association between body habitus and incidence of pituitary adenoma.

Objective: To determine if body mass index (BMI), waist circumference, body somatotype, or height are associated with risk of pituitary adenoma.

Design: Pooled analysis of 3 prospective cohort studies.

Setting: Population-based study.

Participants: Participants of the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS), totaling 284 946 American health professionals.

Exposures: BMI, waist circumference, body somatotype, and height.

Outcome Measures: Self-reported incident pituitary adenoma. Multivariable (MV)-adjusted hazard ratios (HRs) of pituitary adenoma were estimated using Cox proportional hazards models.

Results: During 7 350 156 person-years of follow-up, 387 incident pituitary adenomas were reported. Comparing BMI of ≥30 to <25 kg/m2, higher adult BMI was associated with higher risk of pituitary adenoma (MV HR = 1.74; 95% CI, 1.33-2.28), as was higher maximum adult BMI (MV HR = 1.76; 95% CI, 1.34-2.30), higher waist circumference (MV HR = 1.06; 95% CI, 1.04-1.09 per inch), and higher BMI during early adulthood (at age 18 to 21, MV HR = 2.65; 95% CI, 1.56-4.49). Taller adult height was associated with pituitary adenoma (MV HR = 1.05; 95% CI, 1.01-1.09 per inch). Overall findings were similar in women and men, although power was limited in men (n = 62 cases). Sensitivity analyses demonstrated that the association between adult BMI and pituitary adenoma extended to at least 14 years prior to diagnosis and that the results were not affected when analyses were restricted to participants with similar healthcare utilization.

Conclusion: Higher BMI and waist circumference, from early adulthood to the time of diagnosis, were associated with higher risk of pituitary adenoma.
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http://dx.doi.org/10.1210/clinem/dgaa987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993593PMC
March 2021

Reproducibility and Validity of a Semiquantitative Food Frequency Questionnaire in Men Assessed by Multiple Methods.

Am J Epidemiol 2021 06;190(6):1122-1132

Among 626 participants of the Men's Lifestyle Validation Study (2011-2013), we evaluated the validity and reproducibility of a self-administered 152-item semiquantitative food frequency questionnaire (SFFQ) using two 7-day dietary records (7DDRs), 4 Automated Self-Administered 24-hour dietary recalls (ASA24s), four 24-hour urine samples, 1 doubly labeled water measurement (repeated in 104 participants), and 2 fasting blood samples, collected over 15 months. Compared with 7DDRs, SFFQs underestimated energy intake, macronutrients, and sodium intake but overestimated some micronutrients. The mean of the Spearman correlation coefficients was 0.66 (range, 0.38-0.88) between 46 energy-adjusted nutrients estimated from 7DDRs and the final SFFQ, deattenuated for within-person variation in the 7DDRs. These deattenuated correlations were similar using ASA24s as the comparison. Relative to biomarkers, SFFQs underestimated energy, sodium, and protein intakes, as well as the sodium:potassium ratio. The energy-adjusted correlations between the final SFFQ and the biomarkers were slightly lower than the correlations between the SFFQ and 7DDRs. Using the method of triads to calculate validity coefficients, the median validity coefficient between SFFQ and true intake was 0.65 and 0.69 using 7DDRs and ASA24s, respectively, as the third method. These data indicate that this SFFQ provided reasonably valid estimates for a wide range of nutrients when evaluated by multiple comparison methods.
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http://dx.doi.org/10.1093/aje/kwaa280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168140PMC
June 2021

Red meat intake and risk of coronary heart disease among US men: prospective cohort study.

BMJ 2020 12 2;371:m4141. Epub 2020 Dec 2.

Department of Nutrition, Harvard TH Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA

Objectives: To study total, processed, and unprocessed red meat in relation to risk of coronary heart disease (CHD) and to estimate the effects of substituting other protein sources for red meat with CHD risk.

Design: Prospective cohort study with repeated measures of diet and lifestyle factors.

Setting: Health Professionals Follow-Up Study cohort, United States, 1986-2016.

Participants: 43 272 men without cardiovascular disease or cancer at baseline.

Main Outcome Measures: The primary outcome was total CHD, comprised of acute non-fatal myocardial infarction or fatal CHD. Cox models were used to estimate hazard ratios and 95% confidence intervals across categories of red meat consumption. Substitution analyses were conducted by comparing coefficients for red meat and the alternative food in models, including red meat and alternative foods as continuous variables.

Results: During 1 023 872 person years of follow-up, 4456 incident CHD events were documented of which 1860 were fatal. After multivariate adjustment for dietary and non-dietary risk factors, total, unprocessed, and processed red meat intake were each associated with a modestly higher risk of CHD (hazard ratio for one serving per day increment: 1.12 (95% confidence interval 1.06 to 1.18) for total red meat, 1.11 (1.02 to 1.21) for unprocessed red meat, and 1.15 (1.06 to 1.25) for processed red meat). Compared with red meat, the intake of one serving per day of combined plant protein sources (nuts, legumes, and soy) was associated with a lower risk of CHD (0.86 (0.80 to 0.93) compared with total red meat, 0.87 (0.79 to 0.95) compared with unprocessed red meat, and 0.83 (0.76 to 0.91) compared with processed red meat). Substitutions of whole grains and dairy products for total red meat and eggs for processed red meat were also associated with lower CHD risk.

Conclusions: Substituting high quality plant foods such as legumes, nuts, or soy for red meat might reduce the risk of CHD. Substituting whole grains and dairy products for total red meat, and eggs for processed red meat, might also reduce this risk.
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http://dx.doi.org/10.1136/bmj.m4141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030119PMC
December 2020

The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.

Heart 2020 Nov 23. Epub 2020 Nov 23.

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

Background: A Mediterranean diet is favourable for cardiometabolic risk.

Objective: To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk.

Methods: For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3-4 cups/day) and a (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state.

Results: Participants (n=294; age 51 years; body mass index 31.3 kg/m; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean -6.2 kg; Mediterranean -5.4 kg) vs the HDG group -1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (-8.6 cm) than the Mediterranean (-6.8 cm; p=0.033) and HDG (-4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean -6.1 mg/dL (-3.7%), -2.3 (-0.8%), HDG -0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean -7.2 mm Hg, Mediterranean -5.2 mm Hg, HDG -3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean -0.77, Mediterranean -0.46, HDG -0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (-0.38) than in the Mediterranean (-0.21; p=0.021) and HDG (-0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (-0.52 mg/L) than in the Mediterranean (-0.24 mg/L; p=0.023) and HDG (-0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (-3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean-2.3%; p0.073, HDG-1.4%; p<0.001).

Conclusions: The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.

Trial Registration Number: This study is registered under ClinicalTrials.gov Identifier no NCT03020186.
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November 2020
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