Search

Background: Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and colorectal cancer. However, it is unclear if this dietary pattern is associated with other tumors in which the mechanisms are not totally understood such as breast cancer. Methods: We prospectively followed 76,295 women from the Nurses’ Health Study (NHS, 1984-2016) and 91,078 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires (FFQs) every 4 years. The inflammatory potential of diet was evaluated using the previously established EDIP based on plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha receptor 2 (TNF-αR2). Higher scores indicate higher inflammatory potential of the diet. Results: During 4,153,676 person-years of follow-up, we documented 10,632 invasive breast cancer cases (6,807 NHS; 3,825 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIP quintile were at higher breast cancer risk (HRQ5vsQ1=1.12; 95% CI 1.05, 1.20; P-trend< 0.001). This association was attenuated after adjusting for weight change since age 18 y, although it remained significant (HRQ5vsQ1=1.07; 95% CI 1.00, 1.14; P-trend=0.01). In subtype analyses, we found evidence that the inflammatory potential of diet influenced breast cancer risk differentially by ER status (P-heterogeneity=0.038) and by molecular phenotype (P-heterogeneity=0.007), with the association between EDIP and breast cancer limited to ER-negative tumors (HRQ5vsQ1=1.31; 95% CI: 1.11, 1.55; P-trend=0.002; for ER-positive tumors, HR Q5vsQ1=1.03; 95% CI, 0.96, 1.12;P-trend=0.10) and basal-like tumors (HRQ5vsQ1=1.78; 95% CI: 1.19, 2.65; P-trend=0.004). Further adjustment for weight change since age 18 y did not materially alter the association for these subtypes. Conclusions: Dietary patterns with high potential to contribute to chronic systemic inflammation, based on higher EDIP scores, were associated with a modestly increased risk of breast cancer, which was more pronounced for ER-negative and basal-like breast tumors. Citation Format: Andrea Romanos-Nanclares, Walter C Willett, Bernard A Rosner, Daniel G Stover, Sarah Asad, Sagar Sardesai, Michelle D Holmes, Wendy Y Chen, Rulla M. Tamimi, Fred K Tabung, A Heather Eliassen. Proinflammatory Dietary Patterns and Risk of Total and Subtypes of Breast Cancer Among US Women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-14.

ImportanceThe current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality.ObjectiveTo examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality.Design, Setting, and ParticipantsThis prospective cohort study included initially healthy women from the Nurses’ Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020).ExposuresHealthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI).Main Outcomes and MeasuresThe main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors.ResultsThe final study sample included 75 230 women from the NHS (mean [SD] baseline age, 50.2 [7.2] years) and 44 085 men from the HPFS (mean [SD] baseline age, 53.3 [9.6] years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P Conclusions and RelevanceIn this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose–response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6–7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively—and nonlinearly—associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18–20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18–20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC. Electronic supplementary material The online version of this article (10.1007/s10654-020-00688-3) contains supplementary material, which is available to authorized users.

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50- 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations ( 20 nmol/L, 3% of controls) or high concentrations (100- 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95-1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

BackgroundPoor diet is a major risk factor of cardiovascular and chronic diseases, particularly for low-income women. However, the pathways by which race/ethnicity plays a role in this risk factor have not been fully explored.ObjectiveThis observational study aims to identify dietary consumption differences by race/ethnicity of US women living at or below the 130% poverty income level from 2011-2018.DesignA total of 3005 adult women aged 20-80 years from the National Health and Nutrition Examination Survey (2011-2018) living at or below the 130% poverty-income level with at least one complete 24-hr dietary recall were classified into 5 self-identified racial/ethnic subgroups (Mexican, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian). Dietary consumption patterns were defined by 29 major food groups summarized from the Food Pattern Equivalents Database and derived via a robust profile clustering model which identifies foods that share consumption patterns across all low-income adult women, and foods that differ in consumption patterns based on race/ethnic subgroups.ResultsLegumes (protein and vegetable) were the most differentiating foods identified across all racial/ethnic subgroups and were primarily consumed by Mexican and Other Hispanic women. Non-Hispanic Asian women were most likely to favor a high consumption of prudent foods (fruits, vegetables, whole grains). Non-Hispanic White and Black women shared the most similarities in consumption patterns but differed in foods such as milk, poultry, and eggs.ConclusionsDifferences among consumption behaviors of low-income women were found along racial/ethnic lines. Efforts to improve nutritional health of low-income adult women should consider racial/ethnic differences in diet to appropriately focus interventions.DisclaimersN/A.Sources of SupportStudy supported in part by National Heart Lung and Blood Institute (NHLBI) grant R25 (HL105400) to Victor G. Davila-Roman and DC Rao.

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake ("eat less") and increase energy expenditure ("move more"). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intakeexpenditure) the primary cause of obesity, incorporating an emphasis on "complex endocrine, metabolic, and nervous system signals" that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, "ultra-processed" foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body's metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

Objective:To examine the association between adherence to plant-based diets and mortality.Design:Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods.Setting:The VA Million Veteran Program.Participants:315 919 men and women aged 19–104 years who completed a FFQ at the baseline.Results:We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, Ptrend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, Ptrend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, Ptrend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.Conclusions:A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99–1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79–0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14–1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06–1.19) for MI and 1.11 (1.03–1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.

Background To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. Methods Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5 Results Overall, 41.8% of DO-HEALTH participants were healthy agers with significant variability by country: Austria (Innsbruck) 58.3%, Switzerland (Zurich, Basel, Geneva) 51.2%, Germany (Berlin) 37.6%, France (Toulouse) 36.7% and Portugal (Coimbra) 8.8% (p Conclusions Despite the same inclusion and exclusion criteria preselecting relatively healthy adults age 70 years and older, HA prevalence in DO-HEALTH varied significantly between countries and was highest in participants from Austria and Switzerland, lowest in participants from Portugal. Independent of country, younger age, female gender, lower BMI and better physical function were associated with HA. Trial registration DO-HEALTH was registered under the protocol NCT01745263 at the International Trials Registry (clinicaltrials.gov), and under the protocol number 2012–001249-41 at the Registration at the European Community Clinical Trial System (EudraCT).

Introduction: The relationship between artificially sweetened beverage (ASB) intake and type 2 diabetes (T2D) risk remains inconclusive. Few studies have evaluated whether circulating metabolites that reflect ASB consumption may unveil potential mechanisms underlying the association between ASB consumption and T2D risk. Hypothesis: We hypothesized that a novel metabolomic profile reflecting habitual ASB consumption would positively associate with incident T2D among US adults. Methods: We quantified 120 plasma metabolites with liquid chromatography-mass spectroscopy in N=3,424 Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-up Study (HPFS) discovery cohort participants, and N=1,870 Framingham Heart Study (FHS) replication cohort participants. Habitual ASB consumption (servings/day; low-calorie cola or other carbonated beverages) was estimated from food frequency questionnaires at the time of blood draw. We used elastic net regression with 10-fold-cross-validation to age- and body mass index- adjusted metabolite levels to identify a metabolite profile associated with higher ASB consumption (ln-transformed). We then derived the continuous ASB metabolomic score as the weighted sum of these metabolites and replicated the analysis in an internal testing set and FHS. Finally, we evaluated the association of quartiles (Q) of the ASB-derived metabolomic score in NHS/NHSII/HPFS and FHS cohorts with incident T2D risk after blood draw (baseline for analysis) using Cox regression models to estimate hazard ratios (HR) and 95% confidence interval (CI), adjusted for demographics, lifestyle, diet, and body mass index at blood draw. Results: The ASB-derived metabolomic profile included 61 metabolites, primarily lipids and amino acids (Pearson correlation coefficients [ r ] between ASB self-reported intake and metabolomic score: r=0.08 [95% CI: 0.05, 0.11; p p =0.001], for discovery and replication, respectively). Mean follow-up was 20 and 16 years from blood draw, including 359 and 241 confirmed incident T2D cases for NHS/NHSII/HPFS and FHS, respectively. Compared with participants in the lowest quartile of the ASB-derived metabolomic profile, higher quartiles were incrementally and significantly at higher T2D risk in NHS/NHSII/HPFS (HR [CI] for Q2, Q3, Q4 vs. Q1: 1.45 [1.04, 2.02], 1.83 [1.33, 2.52], 1.62 [1.18, 2.22], respectively; p-trend =0.003) and FHS (1.76 [1.24, 2.48], 1.82 [1.28, 2.58], 2.45 [1.77, 3.40], respectively; p-trend Conclusions: A robust metabolomic profile of ASB intake was not identified, yet the objective and replicable ASB-derived metabolomic profile was associated with higher incident T2D risk. The identified metabolites may reflect ASB intake, western dietary patterns, underlying metabolic health, and/or T2D-related pathophysiology.

Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45–86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for energy were 0.07, 0.07, and 0.19 for a single FFQ, 24HR, and FR, respectively. Correlation coefficients for energy were 0.24, 0.23, and 0.40, respectively. Excluding energy, the average attenuation factors across nutrients and studies were 0.22 for a single FFQ, 0.22 for a single 24HR, and 0.51 for a single FR. Corresponding correlation coefficients were 0.31, 0.34, and 0.53, respectively. For densities (nutrient expressed relative to energy), the average attenuation factors across studies were 0.37, 0.17, and 0.50, respectively. The findings support prior research suggesting different instruments have unique strengths that should be leveraged in epidemiologic research.

Background Evidence on the comprehensive role of lifestyle in frailty risk is scarce. To assess the association between a lifestyle-based Healthy Heart Score (HHS), which estimates the 20-year risk of cardiovascular disease (CVD), and risk of frailty among older women. Methods Prospective cohort study in 121,700 nurses from the USA participating at the Nurses’ Health Study. This study included 68,416 women aged ≥60 year with a follow-up from 1990 to 2014. The HHS was computed using the gender-specific beta-coefficients of the nine lifestyle factors, including current smoking, high body mass index, low physical activity, lack of moderate alcohol intake and unhealthy diet. Frailty incidence was assessed every 4 years from 1992 to 2014 as having ≥3 of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses and weight loss ≥5%. Results During 22 years of follow-up, 11,041 total incident cases of frailty were ascertained. Compared to women in the lowest quintile of the HHS (lowest estimated CVD risk), the multivariable-adjusted hazard ratio of frailty across quintiles was: Q2:1.67 (95% confidence interval 1.53, 1.82); Q3: 2.34 (2.15, 2.53); Q4: 3.54 (3.28, 3.83) and Q5: 5.92 (5.48, 6.38); P-trend > 0.001. Results were consistent for each frailty criterion, among participants with 0 frailty criteria at baseline, when using only baseline exposure or in 6-year-, 10-year- and 14-year-exposure lagged analyses, and after excluding participants with diabetes and CVD at baseline. Conclusions The HHS, based on a set of modifiable-lifestyle factors, is strongly associated with risk of frailty in older women.

Sustainable development of India’s food system must ensure a growing population is fed while minimizing both widespread malnutrition and the environmental impacts of food production. After assessing current adequacy of nutrient supplies at the national level, associated natural resource use (land, fresh water) and greenhouse gas (GHG) emissions, we apply an integrated subnational environmental and nutritional optimization approach to explore resource constraints that might limit the achievement of national food self-sufficiency goals. We find that India currently has the capacity to produce sufficient amounts of nutritious foods, supplying vitamins and minerals that would mostly exceed requirements. Regional cropland use could be reduced by up to 50%, water demand by up to 65% and combined resource inputs by up to 40% while still supporting adequate nutrition. Associated GHG emissions would decline by 26–34% and could possibly be sequestered in agroforestry systems. Such dietary shifts could lower the number of diet-related premature deaths by 14–30%. Achieving these potential gains, however, would require a major transition from current production and consumption patterns, particularly of refined cereals, to free-up resources for more traditional and nutritious foods. An integrated subnational environmental and nutritional optimization approach indicates that, with a transition from current production and consumption patterns, India has the capacity to achieve national food self-sufficiency goals while reducing regional cropland use, water demand and GHG emissions.

Background Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. Objectives We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. Methods We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. Results During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2 = 69.8%). There were, however, significant differences by geographic region (P for interaction = 0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2 = 51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2 = 73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2 = 59.1%) studies. Conclusions Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.

Background Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. Objective The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. Methods This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. Results Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n = 123) and 800 IU (n = 127) groups was not statistically significant (-2.75 mm Hg vs. -3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: -0.68, 3.05; P = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: -0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: -0.48 mm Hg; 95% CI: -0.94, -0.01; P = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. Conclusions While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP.This trial was registered at www.clinicaltrials.gov as NCT00599807.

Identifying the susceptible period when environmental factors affect disease risk is essential for understanding disease etiology. Most existing epidemiologic studies use oversimplified summaries of time-dependent exposures such as baseline or most current exposure, or the cumulative average of exposure over available follow-up periods. In this paper, we introduce a damped exponential weighting model for estimating optimal exposure weights for different time intervals. This model can accommodate flexible patterns of weights and can be fit using standard software. We applied the model to assess the latency of BMI and alcohol for post-menopausal breast cancer based on 30-year exposure history in the Nurses’ Health Study. We have also performed a simulation study to assess the validity of the proposed hypothesis testing and estimation procedures in realistic conditions. We found that the type I error is close to 0.05; the bias in our parameter estimates is low and the coverage probability of interval estimates is close to 0.95. For ER+/PR+ breast cancer we found that recent BMI was a more important predictor of risk than more distant BMI; for ER-/PR- breast cancer, no latency was found and risk was characterized by cumulative high levels of BMI over a long period of time. For alcohol intake, we saw a strong positive association with cumulative intake for ER+/PR+ breast cancer; no significant association was found for cumulative intake or for any latency measure of risk for ER-/PR- breast cancer. Our results underscore the value of an easy-to-implement approach to latency analysis of exposure profiles for chronic disease.

Coffee, Caffeine, and Health In many countries, a large majority of adults consume caffeine daily. This review summarizes the evidence about the varied physiological effects of caffeine and coffee ...

BACKGROUND: A protective association of dietary carotenoids with cognitive function has been suggested, but most studies have been relatively small with limited periods of follow-up. OBJECTIVES: We examined prospectively long-term intakes of carotenoids in relation to subjective cognitive function (SCF), a self-reported, validated indicator of cognitive dysfunction. METHODS: Among 49,493 female registered nurses with a mean age of 48 y in 1984, we used multinomial logistic regression to estimate the ORs and 95% CIs relating intakes of carotenoids to self-reported SCF in 2012 and 2014. Mean intakes of carotenoids were calculated from 7 repeated FFQs collected in 1984, 1986, and every 4 y afterwards until 2006. Self-reported SCF was assessed by a 7-item questionnaire on changes in memory and cognition; validity was supported by strong associations with Apolipoprotein E (APOE) ε4 genotype and concurrent cognitive function and cognitive decline measured by telephone-based neuropsychological tests. The mean values of scores assessed in 2012 and 2014 were categorized as “good” (0 points, 40.8%), “moderate” (0.5–2.5 points, 46.9%), and “poor” (3–7 points, 12.3%). RESULTS: Higher intake of total carotenoids was associated with substantially lower odds of moderate or poor cognitive function after controlling for other dietary and nondietary risk factors and total energy intake. Comparing the top with the bottom quintile of total carotenoids, the multivariable ORs were 0.86 (95% CI: 0.80, 0.93; P-trend

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Salivary amylase, encoded by the AMY1 gene, is responsible for the digestion of carbohydrates. We investigated associations of AMY1 genetic variations with general and central adiposity changes considering dietary carbohydrate intake among 32,054 adults from four prospective cohort studies. A genetic risk score (GRS) was calculated based on nine AMY1 single-nucleotide polymorphisms, with higher AMY1-GRS indicating higher activity of salivary amylase. We meta-analyzed interactions between AMY1-GRS and dietary intake for changes in general and central adiposity over 5.5–10 years. We found that carbohydrate food intake significantly altered associations of AMY1-GRS with changes in BMI (Pinteraction = 0.001) and waist circumference (Pinteraction < 0.001). Results were consistent and significant in female cohorts rather than in male cohorts. Among women, higher AMY1-GRS was associated with more increases in adiposity if dietary carbohydrate food intake was high, while higher AMY1-GRS was associated with less gains in adiposity when the dietary intake was low. Also, in a 2-year randomized dietary intervention trial, associations of AMY1-GRS with changes in weight (Pinteraction = 0.023) and waist circumference (Pinteraction = 0.037) were significantly modified by carbohydrate intake. Our results suggest the importance of precision nutrition strategies considering participants’ genetic adaptation to carbohydrate-rich diets in regulating general and central adiposity.

The association of dietary fat intake with ovarian cancer risk has been inconsistent across populations. We examined dietary fat intake, overall and by type and ovarian cancer risk in two prospective cohort studies. We assessed long-term dietary fat intake among Nurses' Health Study (NHS) and NHSII participants using food frequency questionnaires administered every 2-4 years beginning in 1984 and 1991, respectively. We examined cumulative energy-adjusted intake of total fat, specific types of fat (animal, vegetable, saturated, monounsaturated, polyunsaturated and trans fat) and cholesterol. We identified 700 ovarian cancer cases in NHS and 196 in NHSII with dietary information. Cox proportional hazards regression was used to estimate associations between intake and ovarian cancer risk. Dietary fat intake changed over time in both cohorts and was lower in NHS than NHSII. Higher cumulative average intakes of animal fat and cholesterol were significantly positively associated with risk of ovarian cancer in NHS (relative risk [RR] comparing extreme quartiles = 1.57, 95% CI: 1.20, 2.06 and 1.35, 95% CI: 1.08, 1.69, respectively), but not in NHSII. Other dietary fat sources were not clearly associated with risk in either population. We did not observe clear associations between dietary fat and ovarian cancer risk in two large prospective cohort studies.

Introduction We investigated the relation between self-reported hearing loss and risk of subjective cognitive function (SCF) decline among women. Methods We conducted a longitudinal study of 20,193 women in the Nurses' Health Study aged ≥66 years who reported their hearing status and had no subjective cognitive concerns in 2012. SCF scores were assessed by a 7-item questionnaire in 2012 and 2014. SCF decline was defined as a new report of at least one cognitive concern during follow-up. Results Self-reported hearing loss was associated with higher risk of SCF decline. Compared with women with no hearing loss, the multivariable-adjusted odds ratios (95% confidence interval) for incident SCF score ≥1 were 1.35 (1.25, 1.47), 1.39 (1.24, 1.56), and 1.40 (1.21, 1.75) among women with mild, moderate, and severe hearing loss, respectively. Recent progression of hearing loss was associated with even higher risk. Discussion Self-reported hearing loss was associated with higher risk of incident subjective cognitive function decline in women.

Background Olive oil intake has been associated with lower risk of cardiovascular disease (CVD) in Mediterranean populations, but little is known about these associations in the U.S population. Objectives This study sought to examine whether olive oil intake is associated with total CVD, coronary heart disease (CHD), and stroke risk. Methods This study included 61,181 women from the Nurses’ Health Study (1990 to 2014) and 31,797 men from the Health Professionals Follow-up Study (1990 to 2014) who were free of cancer, heart disease, and stroke at baseline. Diet was assessed using food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During 24 years of follow-up, this study documented 9,797 incident cases of CVD, including 6,034 CHD cases and 3,802 stroke cases. After adjusting for major diet and lifestyle factors, compared with nonconsumers, those with higher olive oil intake (>0.5 tablespoon/day or >7 g/day) had 14% lower risk of CVD (pooled HR: 0.86; 95% CI: 0.79 to 0.94) and 18% lower risk of CHD (pooled HR: 0.82; 95% CI: 0.73 to 0.91). No significant associations were observed for total or ischemic stroke. Replacing 5 g/day of margarine, butter, mayonnaise, or dairy fat with the equivalent amount of olive oil was associated with 5% to 7% lower risk of total CVD and CHD. No significant associations were observed when olive oil was compared with other plant oils combined. In a subset of participants, higher olive oil intake was associated with lower levels of circulating inflammatory biomarkers and a better lipid profile. Conclusions Higher olive oil intake was associated with lower risk of CHD and total CVD in 2 large prospective cohorts of U.S. men and women. The substitution of margarine, butter, mayonnaise, and dairy fat with olive oil could lead to lower risk of CHD and CVD.

Background/objectives To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis. Subjects/methods We followed 185,638 participants of three large US prospective cohorts biennially (1976–2016, 1986–2016 and 1991–2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). Results There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91–1.39; Ptrend = 0.40) for the overall score; 1.10 (95% CI, 0.89–1.35; Ptrend = 0.38) for the animal score and 0.96 (95% CI, 0.79–1.18; Ptrend = 0.88) for the vegetable score. No differential associations by IOP level was found (Pheterogeneity ≥ 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55–1.10]; Ptrend = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83–1.44]; Ptrend = 0.14; Pheterogeneity = 0.03). Conclusions Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.

Background Although a link between regular yogurt consumption and mortality appears plausible, data are sparse and have yielded inconsistent results. Objectives We examined the association between regular yogurt consumption and risk of all-cause and cause-specific mortality among US women and men. Methods A total of 82,348 women in the Nurses' Health Study and 40,278 men in the Health Professionals Follow-Up Study without a history of cardiovascular disease (CVD) and cancer in 1980 (women) or 1986 (men) were followed up until 2012. Yogurt consumption was assessed by updated validated FFQs. Results During 3,354,957 person-years of follow-up, 20,831 women and 12,397 men died. Compared with no yogurt consumption, the multivariable-adjusted HRs (95% CIs) of mortality were 0.89 (0.86, 0.93), 0.85 (0.81, 0.89), 0.88 (0.84, 0.91), and 0.91 (0.85, 0.98) for ≤1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and >4 servings/wk in women (P-trend = 0.34), respectively. For men, the corresponding HRs (95% CIs) were 0.99 (0.94, 1.03), 0.98 (0.91, 1.05), 1.04 (0.98, 1.10), and 1.05 (0.95, 1.16), respectively. We further noted inverse associations for cancer mortality (multivariable-adjusted HR comparing extreme categories: 0.87; 95% CI: 0.78, 0.98; P-trend = 0.04) and CVD mortality (HR: 0.92; 95% CI: 0.79, 1.08; P-trend = 0.41) in women, although the latter was attenuated in the multivariable-adjusted model. Replacement of 1 serving/d of yogurt with 1 serving/d of nuts (women and men) or whole grains (women) was associated with a lower risk of all-cause mortality, whereas replacement of yogurt with red meat, processed meat (women and men), and milk or other dairy foods (women) was associated with a greater mortality. Conclusions In our study, regular yogurt consumption was related to lower mortality risk among women. Given that no clear dose-response relation was apparent, this result must be interpreted with caution.

Background The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method. Methods We included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis. Results Among 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94). Conclusions Higher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).

Background Evidence regarding the role of diet quality, especially its change, in subjective cognitive decline (SCD) is scarce. Objectives To examine associations of long-term diet qualities, including Alternate Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and Alternate Healthy Eating Index 2010 (AHEI-2010) with SCD in the Nurses' Health Study. Methods We followed 49,493 female registered nurses averaged 48 years from 1984 to 2014. Diet scores were derived from seven repeated food frequency questionnaires in 1984, 1986, and every four years afterward until 2006. Self-reported SCD was assessed in 2012 and 2014 by a 7-item questionnaire on memory and cognition changes. Categorical SCD score was classified as "none" (0 points, 40.8%), "moderate" (0.5-2.5 points, 46.9%), and "severe" (3-7 points, 12.3%). Results Multinomial and linear regression models were adjusted for total calorie, demographic characteristics, major lifestyle, and clinical factors. Comparing top vs. bottom quintiles of AMED, DASH, and AHEI-2010, multivariable-adjusted odds ratios (ORs) (95% confidence intervals, CIs) for severe vs. none SCD were 0.57 (0.51, 0.64), 0.61 (0.55, 0.68), and 0.81 (0.73, 0.90), respectively. Similar associations remained for three diet indices evaluated 28 years before SCD assessment. Compared to participants with lowest diet quality tertiles in both remote and recent years, the lowest odds of severe SCD was observed among those who maintained highest diet quality tertiles over time, with a 40%, 32%, and 20% lower odds of severe SCD for AMED, DASH, and AHEI-2010, respectively. Moreover, the odds of severe SCD was lower among those with improved diets over time; for each standard deviation higher in diet quality change, reduced risks were 11% for AMED, 5% for DASH, and 3% for AHEI-2010, respectively. Conclusion Our findings support beneficial roles of long-term adherence to, and improvement in healthy dietary patterns for maintenance of subjective cognition in women.

Background Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Methods Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Results Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2–4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5– Conclusions These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.

Background Whether changes in dairy product consumption are related to subsequent risk of type 2 diabetes (T2D) remains unknown. Objective We evaluated the association of long-term changes in dairy product consumption with subsequent risk of T2D among US men and women. Methods We followed up 34,224 men in the Health Professionals Follow-Up Study (1986-2012), 76,531 women in the Nurses' Health Study (1986-2012), and 81,597 women in the Nurses' Health Study II (1991-2013). Changes in dairy consumption were calculated from consecutive quadrennial FFQs. Multivariable Cox proportional regression models were used to calculate HRs for T2D associated with changes in dairy product consumption. Results of the 3 cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. Results During 2,783,210 person-years, we documented 11,906 incident T2D cases. After adjustment for initial and changes in diet and lifestyle covariates, decreasing total dairy intake by >1.0 serving/d over a 4-y period was associated with an 11% (95% CI: 3%, 19%) higher risk of T2D in the subsequent 4 y compared with maintaining a relatively stable consumption (i.e., change in intake of ±1.0 serving/wk). Increasing yogurt consumption by >0.5 serving/d was associated with an 11% (95% CI: 4%, 18%) lower T2D risk, whereas increasing cheese consumption by >0.5 serving/d was associated with a 9% (95% CI: 2%, 16%) higher risk compared with maintaining stable intakes. Substituting 1 serving/d of yogurt or reduced-fat milk for cheese was associated with a 16% (95% CI: 10%, 22%) or 12% (95% CI: 8%, 16%) lower T2D risk, respectively. Conclusions Increasing yogurt consumption was associated with a moderately lower risk of T2D, whereas increasing cheese consumption was associated with a moderately higher risk among US men and women. Our study suggests that substituting yogurt or reduced-fat milk for cheese is associated with a lower risk of T2D.

Evidence supports a carcinogenic role of Escherichia coli carrying the pks island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of the Western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pksWestern diet score was calculated using food frequency questionnaire data obtained every 4 years during follow-up of 134,775 participants in 2 United States-wide prospective cohort studies. Using quantitative polymerase chain reaction, we measured pksThe association of the Western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pksThe Western-style diet is associated with a higher incidence of colorectal cancer containing abundant pks

Objective: Insulin response is related to overall health. Diet modulates insulin response. We aimed to investigate whether insulinemic potential of diet are associated with risk of all-cause and cause-specific mortality. Research Design and Methods: We prospectively followed 63,464 women from the Nurses’ Health Study (1986-2016) and 42,880 men from the Health Professionals Follow-up Study (1986-2016). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using a food-based empirical dietary index for hyperinsulinemia (EDIH), which was pre-defined based on predicting circulating C-peptide concentrations. Results: During 2,792,550 person-years of follow-up, 38,329 deaths occurred. In the pooled multivariable-adjusted analyses, a higher dietary insulinemic potential was associated with an increased risk of mortality from all-cause (hazard ratio [HR] comparing extreme quintiles: 1.33; 95% confidence interval [CI]: 1.29, 1.38; P-trendThese associations were independent of body mass index and remained significant after further adjustment for other well-known dietary indices. Furthermore, compared with participants whose EDIH scores were stable over an 8-year period, those with the greatest increases had a higher subsequent risk of all-cause (HR: 1.13; 95%CI: 1.09, 1.18; P-trend and CVD (HR: 1.10; 95% CI: 1.01, 1.21; P-trend=0.006) mortality. Conclusions: Higher insulinemic potential of diet was associated with increased risk of all-cause, CVD, and cancer mortality. Adopting a diet with low insulinemic potential might be an effective approach to improve overall health and prevent premature death.

Background Epidemiological studies have demonstrated a favorable association of whole grain intake with coronary heart disease (CHD) risk, although whether such an inverse association holds true for individual whole grain foods that have various nutritional profiles has not been examined. Methods We followed 74,244 women from Nurses’ Health Study since 1986, 91,430 women from Nurses’ Health Study II since 1991, and 39,455 men from the Health Professionals Follow-Up Study since 1984, who did not have a history of cardiovascular disease or cancer at baseline. Intake of seven individual whole grain foods was repeatedly assessed using a validated semi-quantitative food frequency questionnaire every 2–4 years since baseline. CHD diagnoses were ascertained through review of medical records or death certificates. Results We documented 9461 CHD cases during an average of 25.8 years’ follow-up. In the multivariable-adjusted model, the pooled hazard ratio (HR) (95% CI) of CHD risk corresponding to each one serving/day consumption of total whole grains was 0.93 (0.90–0.95; p trend p for non-linearity Conclusions These data suggest that higher consumption of total whole grains, as well as individual whole grain foods except popcorn, were significantly associated with lower CHD risk. The inverse associations may plateau at various intake levels for total whole grain and individual whole grain foods. This study provides further evidence in support of increasing whole grain intake for the prevention of CHD in US populations.

BACKGROUND Diet quality scores (DQSs) are frequently used to study diet-disease relationships but the validity of these scores derived from food frequency questionnaires (FFQs) has rarely been evaluated. OBJECTIVE To evaluate the validity and reproducibility of six commonly used DQSs derived from the FFQ, including the Alternate Healthy Eating Index-2010 (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH) score, alternative Mediterranean Diet score (AMED), and three plant-based diet indices (overall, healthful, and unhealthful). DESIGN This analysis included 1,394 participants from the Men's (n = 652) and Women's (n = 742) Lifestyle Validation Studies. Participants completed a 152-item FFQ at the beginning of the study and one year later, and completed two weighed 7-day dietary records (7DDRs) and donated two blood samples six-month apart between FFQ assessments. The reproducibility of the FFQs was evaluated by rank intraclass correlation coefficients (ICC). The validity was assessed by comparing FFQ-derived DQSs to those from the average of two 7DDRs using Spearman rank correlation coefficients deattenuated for random measurement error in the 7DDRs (rs). Further, we calculated the correlations between DQSs and plasma biomarkers of diet including fatty acids, folate, carotenoids, retinol, and alpha-and gamma-tocopherol. RESULTS Six FFQ derived DQSs demonstrated moderate to high reproducibility (energy-adjusted ICCs = 0.61 to 0.84) and validity (energy-adjusted, deattenuated rs = 0.56 to 0.80) in both men and women. We consistently observed expected correlations between FFQ derived DQSs with plasma fatty acids, including long chain N-3 and trans fatty acids, most carotenoids, and gamma-tocopherol (rs>0.2). CONCLUSIONS Our study demonstrates the validity of the FFQ to evaluate overall diet quality using six commonly used DQSs. In addition, these DQSs have qualitatively demonstrated biological relevance as indicated by their correlations with circulating biomarkers.

ObjectivePoor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation.DesignWe used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively.ResultsOver 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation.ConclusionsA diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

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

BACKGROUND: The associations between nut consumption and cancer risk have not been extensively investigated. OBJECTIVES: We aimed to examine the associations between nut consumption, especially specific types of nuts (peanut, tree nut, walnut, and tree nut other than walnut), and cancer risk. METHODS: Nut consumption was assessed by FFQ at baseline and updated every 2–4 y in the Nurses’ Health Study (1980–2014), the Nurses’ Health Study II (1991–2015), and the Health Professionals Follow-up Study (1986–2018). We examined the associations between the intake of total and specific types of nuts and risk of total cancer and common cancers, including lung, colorectal, breast, bladder, and aggressive prostate cancer. Cox proportional-hazards models were used to obtain the HRs and 95% CIs in each cohort as well as pooled. RESULTS: During 5,873,671 person-years of follow-up in 180,832 women and 45,560 men, we documented 44,561 incident cancer cases. As compared with nonconsumers, the pooled multivariable HRs of total nut consumption for ≥5 times/wk were 0.99 (95% CI: 0.94, 1.04; P-trend = 0.54) for total cancer, 0.88 (95% CI: 0.74, 1.04; P-trend = 0.18) for lung cancer, 1.07 (95% CI: 0.92, 1.26; P-trend = 0.89) for colorectal cancer, 0.90 (95% CI: 0.71, 1.14; P-trend = 0.65) for bladder cancer, 0.96 (95% CI: 0.85, 1.08; P-trend = 0.36) for breast cancer, and 1.18 (95% CI: 0.92, 1.51; P-trend = 0.52) for aggressive prostate cancer CONCLUSIONS: In 3 large prospective cohorts, frequent nut consumption was not associated with risk of total cancer and common individual cancers.

Although insufficient or prolonged sleep duration is associated with cardiovascular disease, sleep duration is not included in most lifestyle scores. This study evaluates the relationship between a lifestyle score, including sleep duration and cardiovascular disease risk.A prospective analysis among 67,250 women in the Nurses' Health Study and 29,114 men in Health Professionals Follow-up Study (1986-2016) was conducted in 2021. Lifestyle factors were updated every 2-4 years using self-reported questionnaires. The traditional lifestyle score was defined as not smoking, having a normal BMI, being physically active (≥30 minutes/day of moderate physical activity), eating a healthy diet, and drinking alcohol in moderation. Low-risk sleep duration, defined as sleeping ≥6 to8 hours/day, was included as an additional component in the updated lifestyle score. Cox proportional hazard regression models were used to estimate cardiovascular disease risk. The likelihood-ratio test and C-statistics were used to compare both scores.A total of 11,710 incident cardiovascular disease cases during follow-up were documented. The multivariable-adjusted hazard ratios comparing 6 with 0 low-risk factors in the healthy lifestyle score including sleep duration were 0.17 (95% CI=0.12, 0.23) for cardiovascular disease, 0.14 (95% CI=0.10, 0.21) for coronary heart disease, and 0.20 (95% CI=0.12, 0.33) for stroke. Approximately 66% (95% CI=56%, 75%) of cardiovascular disease, 67% (95% CI=54%, 77%) of coronary heart disease, and 62% (95% CI=42%, 76%) of stroke cases were attributable to poor adherence to a healthy lifestyle including sleep. Adding sleep duration to the score slightly increased the C-statistics from 0.64 (95% CI=0.63, 0.64) to 0.65 (95% CI=0.64, 0.65) (p0.001).Adopting a healthy lifestyle including sleep recommendations could substantially reduce the risk of cardiovascular disease in U.S. adults.

Background Several plant foods have been associated with a lower risk of colorectal cancer (CRC). However, not all plant foods are healthy, and little is known about the association between plant-based diets and specific molecular subtypes of CRC. We aimed to examine the association of healthy and unhealthy plant-based diets and the risk of CRC overall and by molecular subtypes. Methods We followed 76,386 women in the Nurses’ Health Study (1984-2014) and 47,387 men in the Health Professionals Follow-up Study (1986-2014) for up to 30 years. Plant-based diets were assessed using two indices derived from the food frequency questionnaires: a healthy plant-based diet index (hPDI) and an unhealthy plant-based diet index (uPDI). Colorectal tumor tissues were collected to measure the status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. Results During 3,143,205 person-years of follow-up, we documented 3077 incident CRC cases, including 1244 cases with available molecular marker data. A higher hPDI was associated with lower CRC incidence (hazard ratio [HR] comparing extreme quartiles=0.86, 95% CI: 0.77, 0.96; P-trend=0.04), whereas a higher uPDI was associated with higher CRC incidence (HR comparing extreme quartiles=1.16, 95% CI: 1.04, 1.29; P-trend=0.005). The association of hPDI significantly differed by KRAS status (P-heterogeneity=0.003) but not by other tumor markers. The hPDI was associated with lower incidence of KRAS-wildtype CRC (HR comparing extreme quartiles=0.74, 95% CI: 0.57, 0.96; P-trend=0.004) but not KRAS-mutant CRC (P-trend=0.22). Conclusions A plant-based diet rich in whole grains, fruits, and vegetables was associated with a lower incidence of CRC, especially KRAS-wildtype CRC, whereas a plant-based diet emphasizing unhealthy plant foods such as refined grains might be associated with higher CRC incidence. These data emphasize the importance of differentiating healthy and unhealthy plant foods when promoting plant-based diets for the primary prevention of CRC. The differential association of hPDI by KRAS status suggests the interplay of diet and specific tumor pathways.

Food systems are at the center of a brewing storm consisting of a rapidly changing climate, rising hunger and malnutrition, and significant social inequities. At the same time, there are vast opportunities to ensure that food systems produce healthy and safe food in equitable ways that promote environmental sustainability, especially if the world can come together at the UN Food Systems Summit in late 2021 and make strong and binding commitments toward food system transformation. The NIH-funded Nutrition Obesity Research Center at Harvard and the Harvard Medical School Division of Nutrition held their 22nd annual Harvard Nutrition Obesity Symposium entitled “Global Food Systems and Sustainable Nutrition in the 21st Century” in June 2021. This article presents a synthesis of this symposium and highlights the importance of food systems to addressing the burden of malnutrition and noncommunicable diseases, climate change, and the related economic and social inequities. Transformation of food systems is possible, and the nutrition and health communities have a significant role to play in this transformative process.

Scientific collaboration has been a critical aspect of the development of all fields of science, particularly clinical medicine. It is well understood that myriads of benefits can be yielded by interdisciplinary and international collaboration. For instance, our rapidly growing knowledge on COVID-19 and vaccine development could not be attained without expanded collaborative activities. However, achieving fruitful results requires mastering specific tactics in collaborative efforts. These activities can enhance our knowledge, which ultimately benefits society. In addition to tackling the issue of the invisible border between different countries, institutes, and disciplines, the border between the scientific community and society needs to be addressed as well. International and transdisciplinary approaches can potentially be the best solution for bridging science and society. The Universal Scientific Education and Research Network (USERN) is a non-governmental, non-profit organization and network to promote professional, scientific research and education worldwide. The fifth annual congress of USERN was held in Tehran, Iran, in a hybrid manner on November 7-10, 2020, with key aims of bridging science to society and facilitating borderless science. Among speakers of the congress, a group of top scientists unanimously agreed on The USERN 2020 consensus, which is drafted with the goal of connecting society with scientific scholars and facilitating international and interdisciplinary scientific activities in all fields, including clinical medicine.

ObjectivesTo evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes.DesignProspective cohort study.SettingNurses’ Health Study II, US.Participants4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009.Main outcome measureSelf-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index of the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372).ResultsOver a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (PtrendtrendConclusionsAmong women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.

Background & Aims In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease. Methods We leveraged longitudinal data from three prospective cohorts, Nurses’ Health Study (1984-2018, 73,166 women aged 65.1±10.8 years), Nurses’ Health Study II (1991-2017, 90,423 women aged 49.1±8.2 years), and Health Professionals Follow-Up Study (1986-2016, 42,617 men aged 64.8±10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires. Results During 4,801,513 person-years of follow-up, we documented 6,231 incident digestive system cancer cases among three cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a HR (95% CI) of 0.94 (0.87, 1.02) comparing the highest to the lowest quintile of gluten intake (p-trend=0.05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer. Conclusions Gluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population.

OBJECTIVE Insulin response is related to overall health. Diet modulates insulin response. We investigated whether insulinemic potential of diet is associated with risk of all-cause and cause-specific mortality. RESEARCH DESIGN AND METHODS We prospectively followed 63,464 women from the Nurses’ Health Study (1986–2016) and 42,880 men from the Health Professionals Follow-up Study (1986–2016). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using a food-based empirical dietary index for hyperinsulinemia (EDIH), which was predefined based on predicting circulating C-peptide concentrations. RESULTS During 2,792,550 person-years of follow-up, 38,329 deaths occurred. In the pooled multivariable-adjusted analyses, a higher dietary insulinemic potential was associated with an increased risk of mortality from all-cause (hazard ratio [HR] comparing extreme quintiles: 1.33; 95% CI 1.29, 1.38; P-trend CONCLUSIONS Higher insulinemic potential of diet was associated with increased risk of all-cause, CVD, and cancer mortality. Adopting a diet with low insulinemic potential might be an effective approach to improve overall health and prevent premature death.

PURPOSE Metabolomic and preclinical studies suggest that branched-chain amino acids (BCAA) may be inversely associated with neurodegenerative diseases including glaucoma. We therefore assessed the long-term association between dietary intake of BCAA and incident primary open-angle glaucoma (POAG) and POAG subtypes. METHODS We followed biennially participants of the Nurses' Health Study (NHS; 65 531 women: 1984-2016), Health Professionals Follow-up Study (42 254 men: 1986-2016) and NHSII (66 904 women; 1991-2017). Eligible participants were 40+ years old and reported eye examinations. Repeated validated food frequency questionnaires were used to assess dietary intake of BCAA. Incident cases of POAG and POAG subtypes defined by visual field (VF) loss and untreated intraocular pressure (IOP) were confirmed by medical record review. Multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS We identified 1946 incident POAG cases. The pooled MVRRs of POAG for the highest quintile (Q5 = 17.1 g/day) versus lowest quintile (Q1 = 11.2 g/day) of total BCAA intake was 0.93 (95% CI, 0.73-1.19; ptrend = 0.45; pheterogeneity by sex = 0.24). For subtypes of POAG defined by IOP level or POAG with only peripheral VF loss, no associations were observed for men or women (ptrend ≥ 0.20); however, for the POAG subtype with early paracentral VF loss, there was a suggestion of an inverse association in women (MVRRQ5versusQ1 = 0.80 [95% CI, 0.57-1.12; ptrend = 0.12]) but not in men (MVRRQ5versusQ1 = 1.38 [95% CI, 0.81-2.34; ptrend = 0.28; pheterogeneity by sex = 0.06]). CONCLUSION Higher dietary intake of BCAA was not associated with POAG risk.

Emerging data suggest that exposures in early life may affect ovarian development and contribute to ovarian cancer risk. We evaluated the association between early life physical activity and risk of ovarian cancer in adulthood in two large prospective cohorts, the Nurses’ Health Study (NHS) and NHSII. In total, analyses included 28 232 NHS participants (followed from 2004 to 2016) and 56 553 NHSII participants (followed from 1997 to 2017). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of ovarian cancer overall and by early life body mass index (BMI). Neither physical activity at ages 12–13, 14–17 or 18–22 years nor average physical activity across these three periods was associated with ovarian cancer risk overall (≥78 vs

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.