Use of melatonin supplements and risk of type 2 diabetes and cardiovascular diseases in the USA: insights from three prospective cohort studies.

BACKGROUND: Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults. METHODS: In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work. FINDINGS: For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses. INTERPRETATION: With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work. FUNDING: US National Institutes of Health.

Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts.

There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities. We therefore aimed to estimate metabolomic differences between Black and White women in the U.S. We leveraged data from two prospective cohorts: the Nurses' Health Study (NHS; n = 2077) and Women's Health Initiative (WHI; n = 2128). The WHI served as the replication cohort. Plasma metabolites (n = 334) were measured via liquid chromatography-tandem mass spectrometry. Observed metabolomic differences were estimated using linear regression and metabolite set enrichment analyses. Residual metabolomic differences in a hypothetical population in which the distributions of 14 risk factors were equalized across racial groups were estimated using inverse odds ratio weighting. In the NHS, Black-White differences were observed for most metabolites (75 metabolites with observed differences ≥ |0.50| standard deviations). Black women had lower average levels than White women for most metabolites (e.g., for N6, N6-dimethlylysine, mean Black-White difference = - 0.98 standard deviations; 95% CI: - 1.11, - 0.84). In metabolite set enrichment analyses, Black women had lower levels of triglycerides, phosphatidylcholines, lysophosphatidylethanolamines, phosphatidylethanolamines, and organoheterocyclic compounds, but higher levels of phosphatidylethanolamine plasmalogens, phosphatidylcholine plasmalogens, cholesteryl esters, and carnitines. In a hypothetical population in which distributions of 14 risk factors were equalized, Black-White metabolomic differences persisted. Most results replicated in the WHI (88% of 272 metabolites available for replication). Substantial differences in metabolomic profiles exist between Black and White women. Future studies should prioritize racial representation.

Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death.

Importance: Age-standardized dementia mortality rates are on the rise. Whether long-term consumption of olive oil and diet quality are associated with dementia-related death is unknown. Objective: To examine the association of olive oil intake with the subsequent risk of dementia-related death and assess the joint association with diet quality and substitution for other fats. Design, Setting, and Participants: This prospective cohort study examined data from the Nurses' Health Study (NHS; 1990-2018) and Health Professionals Follow-Up Study (HPFS; 1990-2018). The population included women from the NHS and men from the HPFS who were free of cardiovascular disease and cancer at baseline. Data were analyzed from May 2022 to July 2023. Exposures: Olive oil intake was assessed every 4 years using a food frequency questionnaire and categorized as (1) never or less than once per month, (2) greater than 0 to less than or equal to 4.5 g/d, (3) greater than 4.5 g/d to less than or equal to 7 g/d, and (4) greater than 7 g/d. Diet quality was based on the Alternative Healthy Eating Index and Mediterranean Diet score. Main Outcome and Measure: Dementia death was ascertained from death records. Multivariable Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs adjusted for confounders including genetic, sociodemographic, and lifestyle factors. Results: Of 92 383 participants, 60 582 (65.6%) were women and the mean (SD) age was 56.4 (8.0) years. During 28 years of follow-up (2 183 095 person-years), 4751 dementia-related deaths occurred. Individuals who were homozygous for the apolipoprotein ε4 (APOE ε4) allele were 5 to 9 times more likely to die with dementia. Consuming at least 7 g/d of olive oil was associated with a 28% lower risk of dementia-related death (adjusted pooled HR, 0.72 [95% CI, 0.64-0.81]) compared with never or rarely consuming olive oil (P for trend < .001); results were consistent after further adjustment for APOE ε4. No interaction by diet quality scores was found. In modeled substitution analyses, replacing 5 g/d of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8% (95% CI, 4%-12%) to 14% (95% CI, 7%-20%) lower risk of dementia mortality. Substitutions for other vegetable oils or butter were not significant. Conclusions and Relevance: In US adults, higher olive oil intake was associated with a lower risk of dementia-related mortality, irrespective of diet quality. Beyond heart health, the findings extend the current dietary recommendations of choosing olive oil and other vegetable oils for cognitive-related health.

Development of the VEGANScreener, a Tool for a Quick Diet Quality Assessment among Vegans in Europe.

BACKGROUND: Plant-based diets are not inherently healthy. Similar to omnivorous diets, they may contain excessive amounts of sugar, sodium, and saturated fats, or lack diversity. Moreover, vegans might be at risk of inadequate intake of certain vitamins and minerals commonly found in foods that they avoid. We developed the VEGANScreener, a tool designed to assess the diet quality of vegans in Europe. METHODS: Our approach combined best practices in developing diet quality metrics with scale development approaches and involved the following: (a) narrative literature synthesis, (b) evidence evaluation by an international panel of experts, and (c) translation of evidence into a diet screener. We employed a modified Delphi technique to gather opinions from an international expert panel. RESULTS: Twenty-five experts in the fields of nutrition, epidemiology, preventive medicine, and diet assessment participated in the first round, and nineteen participated in the subsequent round. Initially, these experts provided feedback on a pool of 38 proposed items from the literature review. Consequently, 35 revised items, with 17 having multiple versions, were suggested for further consideration. In the second round, 29 items were retained, and any residual issues were addressed in the final consensus meeting. The ultimate screener draft encompassed 29 questions, with 17 focusing on foods and nutrients to promote, and 12 addressing foods and nutrients to limit. The screener contained 24 food-based and 5 nutrient-based questions. CONCLUSIONS: We elucidated the development process of the VEGANScreener, a novel diet quality screener for vegans. Future endeavors involve contrasting the VEGANScreener against benchmark diet assessment methodologies and nutritional biomarkers and testing its acceptance. Once validated, this instrument holds potential for deployment as a self-assessment application for vegans and as a preliminary dietary screening and counseling tool in healthcare settings.

Calibration of citrus intake assessed by food frequency questionnaires using urinary proline betaine in an observational study setting.

BACKGROUND: Whether observational study can be employed to establish calibration equations for self-reported dietary intake using food biomarkers is unknown. OBJECTIVE: This study aims to demonstrate the feasibility of obtaining calibration equations based on food biomarkers and 7-day diet records (7DDRs) to correct measurement errors of food frequency questionnaires (FFQ) in an observational study setting. METHODS: The study population consisted of 669 male and 749 female from the Women and Men's Lifestyle Validation Study. In the training set, the biomarker-predicted intake derived by regressing 7DDR-assessed intake on urinary proline betaine level was regressed on the FFQ-assessed intake to obtain the calibration equations. The regression coefficients were applied to the test set to calculate the calibrated FFQ intake. We examined total citrus as well as individual citrus fruits/beverages. RESULTS: Urinary proline betaine was moderately correlated with orange juice intake [Pearson correlation (r): 0.53 for 7DDR and 0.48 for FFQ] but only weakly correlated with intakes of orange (r: 0.12 for 7DDR and 0.15 for FFQ) and grapefruit (r: 0.14 for 7DDR and 0.09 for FFQ). The FFQ-assessed citrus intake was systematically higher than the 7DDR-assessed intake, and after calibrations the mean calibrated FFQ measurements were almost identical to 7DDR assessments. In the test set, the mean intake levels from 7DDRs, FFQ, and calibrated FFQ were 62.5, 75.3, 63.2 g/d for total citrus, 41.6, 42.5, 41.9 g/d for orange juice, 11.8, 24.3, 12.3 g/d for oranges, and 8.3, 9.3, 8.6 g/d for grapefruit. We observed larger differences between calibrated FFQ and 7DDR assessments at the extreme ends of intake, although on average good agreements were observed for all citrus except grapefruit. CONCLUSION: Our two-step calibration approach has the potential to be adapted to correct systematic measurement error for other foods/nutrients with established food biomarkers in a cost-effective way.

24-hour urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in US adults: A cross-sectional study.

BACKGROUND: High sodium and low potassium intakes are associated with a higher risk of hypertension and cardiovascular disease (CVD), but there are limited data on the circulating metabolomics profiles of 24-hour urinary sodium and potassium excretions in free-living individuals. OBJECTIVES: To characterize metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study. METHODS: In 1,028 healthy older adults from the Women's and Men's Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2-4 24-hour urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-hour urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the Doubly Labelled Water method. Then we assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers. RESULTS: Higher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism, and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman's rank correlation coefficient ρ=0.27), C-peptide (ρ=0.30), and triglyceride (ρ=0.46), and negatively with adiponectin (ρ=-0.40), and high-density lipoprotein (HDL) cholesterol (ρ=-0.42). CONCLUSIONS: We discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium-low potassium diet is associated with multiple components of elevated cardiometabolic risk.

Prediction of 24-Hour Urinary Sodium Excretion Using Machine-Learning Algorithms.

BACKGROUND: Accurate quantification of sodium intake based on self-reported dietary assessments has been a persistent challenge. We aimed to apply machine-learning (ML) algorithms to predict 24-hour urinary sodium excretion from self-reported questionnaire information. METHODS AND RESULTS: We analyzed 3454 participants from the NHS (Nurses' Health Study), NHS-II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study), with repeated measures of 24-hour urinary sodium excretion over 1 year. We used an ensemble approach to predict averaged 24-hour urinary sodium excretion using 36 characteristics. The TOHP-I (Trial of Hypertension Prevention I) was used for the external validation. The final ML algorithms were applied to 167 920 nonhypertensive adults with 30-year follow-up to estimate confounder-adjusted hazard ratio (HR) of incident hypertension for predicted sodium. Averaged 24-hour urinary sodium excretion was better predicted and calibrated with ML compared with the food frequency questionnaire (Spearman correlation coefficient, 0.51 [95% CI, 0.49-0.54] with ML; 0.19 [95% CI, 0.16-0.23] with the food frequency questionnaire; 0.46 [95% CI, 0.42-0.50] in the TOHP-I). However, the prediction heavily depended on body size, and the prediction of energy-adjusted 24-hour sodium excretion was modestly better using ML. ML-predicted sodium was modestly more strongly associated than food frequency questionnaire-based sodium in the NHS-II (HR comparing Q5 versus Q1, 1.48 [95% CI, 1.40-1.56] with ML; 1.04 [95% CI, 0.99-1.08] with the food frequency questionnaire), but no material differences were observed in the NHS or HPFS. CONCLUSIONS: The present ML algorithm improved prediction of participants' absolute 24-hour urinary sodium excretion. The present algorithms may be a generalizable approach for predicting absolute sodium intake but do not substantially reduce the bias stemming from measurement error in disease associations.

Association of ultra-processed food consumption with all cause and cause specific mortality: population based cohort study.

OBJECTIVE: To examine the association of ultra-processed food consumption with all cause mortality and cause specific mortality. DESIGN: Population based cohort study. SETTING: Female registered nurses from 11 US states in the Nurses' Health Study (1984-2018) and male health professionals from all 50 US states in the Health Professionals Follow-up Study (1986-2018). PARTICIPANTS: 74 563 women and 39 501 men with no history of cancer, cardiovascular diseases, or diabetes at baseline. MAIN OUTCOME MEASURES: Multivariable Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for the association of ultra-processed food intake measured by semiquantitative food frequency questionnaire every four years with all cause mortality and cause specific mortality due to cancer, cardiovascular, and other causes (including respiratory and neurodegenerative causes). RESULTS: 30 188 deaths of women and 18 005 deaths of men were documented during a median of 34 and 31 years of follow-up, respectively. Compared with those in the lowest quarter of ultra-processed food consumption, participants in the highest quarter had a 4% higher all cause mortality (hazard ratio 1.04, 95% confidence interval 1.01 to 1.07) and 9% higher mortality from causes other than cancer or cardiovascular diseases (1.09, 1.05 to 1.13). The all cause mortality rate among participants in the lowest and highest quarter was 1472 and 1536 per 100 000 person years, respectively. No associations were found for cancer or cardiovascular mortality. Meat/poultry/seafood based ready-to-eat products (for example, processed meat) consistently showed strong associations with mortality outcomes (hazard ratios ranged from 1.06 to 1.43). Sugar sweetened and artificially sweetened beverages (1.09, 1.07 to 1.12), dairy based desserts (1.07, 1.04 to 1.10), and ultra-processed breakfast food (1.04, 1.02 to 1.07) were also associated with higher all cause mortality. No consistent associations between ultra-processed foods and mortality were observed within each quarter of dietary quality assessed by the Alternative Healthy Eating Index-2010 score, whereas better dietary quality showed an inverse association with mortality within each quarter of ultra-processed foods. CONCLUSIONS: This study found that a higher intake of ultra-processed foods was associated with slightly higher all cause mortality, driven by causes other than cancer and cardiovascular diseases. The associations varied across subgroups of ultra-processed foods, with meat/poultry/seafood based ready-to-eat products showing particularly strong associations with mortality.

Ultraprocessed foods, unprocessed or minimally processed foods, and risk of frailty in a cohort of United States females.

BACKGROUND: Ultraprocessed foods (UPFs) and poor diet quality have been associated with frailty but existing studies had relatively short follow-up time. It is also unclear whether the association of UPF was primarily due to its correlation with poorer diet quality. OBJECTIVES: We examined the association between unprocessed or minimally processed foods (UMFs) and UPF and risk of frailty and explored whether the association with UPF was mainly driven by poor diet quality. METHODS: In total, 63,743 nonfrail females aged 60+ y from the Nurses' Health Study (cohort study) were followed up for ≥26 y. Diet was assessed every 4 y by food frequency questionnaires. UPF and UMF intakes were calculated using the Nova classification. Diet quality was estimated using the Alternate Healthy Eating Index (AHEI) 2010. The association of UMF and UPF with risk of frailty was examined using multivariable adjusted Cox proportional hazard model. RESULTS: During the follow-up period, we recorded 15,187 incident cases of frailty. The hazard ratio (HR) of frailty for the highest compared with the lowest quintile of UMFs (servings per day) was 0.86 (95% CI: 0.83, 0.95; P-trend < 0.001). However, this was no longer statistically significant after adjustment for AHEI-2010. UPFs (servings per day) was directly associated with risk of frailty, even after adjustment for AHEI-2010 (1.31; 95% CI: 1.23, 1.39; P-trend < 0.001). Among those at the highest category of the AHEI-2010, UPFs remained directly associated with frailty (HR comparing top with bottom quintile: 1.40; 95% CI:1.24, 1.57; P-trend < 0.001). For UPF components, we found a higher frailty risk with each serving per day of artificial and sugar-sweetened beverages; fat, spreads, and condiments; yogurt and dairy-based desserts; and other UPFs. However, processed whole grains were not associated with frailty. CONCLUSIONS: Higher intake of UPF is associated with a higher risk of frailty in older females. This is not explained by a lower diet quality contributed by UPFs.

The global diet quality score as an indicator of adequate nutrient intake and dietary quality - a nation-wide representative study.

BACKGROUND: The Global Diet Quality Score (GDQS) was developed to be a simple, timely and cost-effective tool to track, simultaneously, nutritional deficiency and non-communicable disease risks from diet in diverse settings. The objective was to investigate the performance of GDQS as an indicator of adequate nutrient intake and dietary quality in a national-representative sample of the Brazilian population. METHODS: Nationally-representative data from 44,744 men and non-pregnant and non-lactating women aging ≥ 10 years, from the Brazilian National Dietary Survey were used. Dietary data were collected through two 24-h recalls (24HR). The GDQS was calculated and compared to a proxy indicator of nutrient adequate intake (the Minimum Dietary Diversity for Women-MDD-W) and to an indicator of high-risk diet for non-communicable diseases (caloric contribution from ultra-processed foods-UPF). To estimate the odds for overall nutrient inadequacy across MDD-W and GDQS quintiles, a multiple logistic regression was applied, and the two metrics' performances were compared using Wald's post-test. RESULTS: The mean GDQS for Brazilians was 14.5 (0-49 possible range), and only 1% of the population had a low-risk diet (GDQS ≥ 23). The GDQS mean was higher in women, elderly individuals and in higher-income households. An inverse correlation was found between the GDQS and UPF (rho (95% CI) = -0.20(-0.21;-0.19)). The odds for nutrient inadequacy were lower as quintiles of GDQS and MDD-W were higher (p-trend < 0.001), and MDD-W had a slightly better performance than GDQS (p-diff < 0.001). Having a low-risk GDQS (≥ 23) lowered the odds for nutrient inadequacy by 74% (95% CI:63%-81%). CONCLUSION: The GDQS is a good indicator of overall nutrient adequacy, and correlates well with UPF in a nationally representative sample of Brazil. Future studies must investigate the relationship between the GDQS and clinical endpoints, strengthening the recommendation to use this metric to surveillance dietary risks.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: To examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: Pooled analysis of the primary data in 15 cohorts in three continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: 842,149 men were followed for up to 9-22 years between 1985-2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), high grade (Gleason score ≥8 or poorly differentiated/undifferentiated) PC, and PC mortality. STATISTICAL ANALYSIS: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n=4,863), advanced restricted (n=2,978), or high-grade PC (n=9,673) or PC mortality (n=3,097). Dietary fiber intake from grains was inversely associated with advanced PC (MVHR comparing the highest vs. lowest quintile=0.84, 95% confidence interval [CI] 0.76-0.93), advanced restricted PC (MVHR=0.85, 95%CI 0.74-0.97), and PC mortality (MVHR=0.78, 95%CI 0.68-0.89); statistically significant trends were noted for each of these associations (p≤0.03), while a null association was observed for high grade PC for the same comparison (MVHR=1.00, 95%CI 0.93-1.07). The comparable results were 1.06 (95%CI 1.01-1.10, p-value, test for trend=0.002) for localized (n=35,199) and 1.05 (95%CI 0.99-1.11, , p-value, test for trend=0.04) for low/intermediate grade (n=34,366) PC. CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

Food Insecurity and Ideal Cardiovascular Health Risk Factors Among US Adolescents.

BACKGROUND: Food insecurity, a social and economic condition of limited availability of healthy food, is a risk factor for adverse cardiovascular health outcomes among adults; few studies have been conducted in adolescents. This study explores the association between food insecurity and cardiovascular health risk factors among a nationally representative sample of US adolescents, adopting the American Heart Association's Life's Essential 8 metric. METHODS AND RESULTS: We analyzed data from 2534 adolescents aged 12 to 19 years from the 2013 to 2018 National Health and Nutrition Examination Surveys. In the sample, 24.8% of adolescents lived in food-insecure households. After multivariable adjustment, food insecurity was associated with a 3.23-unit lower total Life's Essential 8 score (95% CI, -6.32, -0.15) and lower scores on diet quality (ß=-5.39 [95% CI, -8.91, -1.87]) and nicotine exposure (ß=-4.85 [95% CI, -9.24, -0.45]). Regarding diet, food insecurity was associated with 5% lower Healthy Eating Index-2015 scores [95% CI, -7%, -2%], particularly lower intakes of whole grains and seafood/plant proteins and marginally higher intake of added sugar. Regarding nicotine exposure, food insecurity was associated with ever use of a tobacco product among m (odds ratio, 1.74 [95% CI, 1.20-2.53]). Compared with their food-secure counterparts, food-insecure male (odds ratio, 1.98 [95% CI, 1.07-3.65]) and female (odds ratio, 3.22 [95% CI, 1.60-6.45]) adolescents had higher odds of living with a current indoor smoker. CONCLUSIONS: In this nationally representative sample of adolescents, food insecurity was associated with multiple indicators of cardiovascular health risk. These findings underscore the need for public health interventions and policies to reduce food insecurity and improve cardioprotective behaviors during adolescence, with particular efforts targeting diet quality and nicotine exposure.

Recreational physical activity and breast cancer risk by menopausal status and tumor hormone receptor status: results from the Nurses' Health Studies.

PURPOSE: Physical activity is associated with lower breast cancer risk, especially in postmenopausal women. Associations in premenopausal women are less well established. METHODS: We evaluated recreational physical activity and breast cancer risk in the Nurses' Health Study (NHS) and NHSII (187,278 women; n = 12,785 breast cancers; follow-up: NHS = 1986-2016, NHSII = 1989-2017) by menopausal status and estrogen (ER) and progesterone (PR) receptor status. Physical activity was evaluated as updated cumulative average of metabolic equivalent of task (MET)-h/week. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Recreational physical activity was inversely associated with breast cancer risk in pre- and postmenopausal women. Higher activity levels were associated with lower risk of ER+/PR + breast cancer in both pre- and postmenopausal women (e.g., total recreational activity, ≥ 27 vs < 3 MET-h/week, premenopausal HR = 0.83, 95%CI = (0.70-0.99), postmenopausal HR = 0.86 (0.78-0.95); pheterogeneity = 0.97). Results were attenuated with adjustment for current body mass index (BMI) among postmenopausal, but not premenopausal, women (e.g., ≥ 27 vs < 3 MET-h/week, premenopausal HR = 0.83 (0.69-0.98); postmenopausal HR = 0.95 (0.85-1.05); pheterogeneity = 0.99). In analyses of moderate-vigorous activity and breast cancer risk, no heterogeneity by menopausal status was observed (phet ≥ 0.53; e.g., ≥ 27 vs < 3 MET-h/week, ER+/PR+, premenopausal HR = 0.88 (0.69-1.11); postmenopausal HR = 0.71 (0.58-0.88). No associations were observed for ER-/PR- disease. CONCLUSIONS: Recreational physical activity was associated with lower breast cancer risk in both pre- and postmenopausal women, supporting recreational physical activity as an accessible, modifiable exposure associated with reduced breast cancer risk regardless of menopausal status.

Maternal One-Carbon Nutrient Intake and Risk of Being Overweight or Obese in Their Offspring-A Transgenerational Prospective Cohort Study.

We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] p-trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], p-trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], p-trend: 0.46; p-interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.

Dietary inflammatory pattern and risk of hip fracture in the Nurses' Health Study.

Our immune system activity is impacted by what we eat and can influence fracture risk under certain conditions. In this article, we show that postmenopausal women with a pro-inflammatory dietary pattern have an increased risk of hip fracture. PURPOSE: The immune system influences bone homeostasis and can increase the risk of fracture under certain pro-inflammatory conditions. Immune system activity is impacted by dietary patterns. Using the empirical dietary inflammatory pattern (EDIP), we investigated whether postmenopausal women with a pro-inflammatory dietary pattern had an increased risk of hip fracture. METHODS: The study population consisted of postmenopausal women participating in the Nurses' Health Study from 1980 to 2014, who reported information on lifestyle and health, including hip fractures, on biennial questionnaires, while semiquantitative food frequency questionnaires (FFQs) were completed every fourth year. Hazard ratios (HR) for hip fracture were computed using Cox proportional hazards models, adjusting for potential confounders. RESULTS: EDIP was calculated using intake information from the FFQ for 87,955 postmenopausal participants, of whom 2348 sustained a non-traumatic hip fracture during follow-up. After adjustment for confounders, there was a 7% increase in the risk of hip fracture per 1 SD increase in EDIP (HR 1.07, 95% CI 1.02-1.12), and the uppermost quintile had a 22% greater risk compared to the lowest (HR 1.22, 95% CI 1.06-1.40). For the separate components of the EDIP, we found that higher intakes of low-energy beverages (diet sodas) were independently associated with an increased risk of hip fracture, while higher intakes of green leafy vegetables were associated with a reduced risk. CONCLUSION: A pro-inflammatory dietary pattern was associated with an increased risk of hip fracture among postmenopausal women.

Perspective: Beyond the Mediterranean Diet-Exploring Latin American, Asian, and African Heritage Diets as Cultural Models of Healthy Eating.

The Mediterranean diet is a well-studied cultural model of healthy eating, yet research on healthy models from other cultures and cuisines has been limited. This perspective article summarizes the components of traditional Latin American, Asian, and African heritage diets, their association with diet quality and markers of health, and implications for nutrition programs and policy. Though these diets differ in specific foods and flavors, we present a common thread that emphasizes healthful plant foods and that is consistent with high dietary quality and low rates of major causes of disability and deaths. In this perspective, we propose that nutrition interventions that incorporate these cultural models of healthy eating show promise, though further research is needed to determine health outcomes and best practices for implementation.

Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

Validity and reproducibility of the PERSIAN Cohort food frequency questionnaire: assessment of major dietary patterns.

BACKGROUND: Dietary patterns, encompassing an overall view of individuals' dietary intake, are suggested as a suitable means of assessing nutrition's role in chronic disease development. The aim of this study was to evaluate the validity and reproducibility of a food frequency questionnaire (FFQ) designed for use in the Prospective Epidemiological Research Studies in IrAN (PERSIAN), by comparing major dietary patterns assessed by the FFQ with a reference method. METHODS: Study participants included men and women who enrolled in the PERSIAN Cohort Study at seven of the eighteen centers. These centers were chosen to include dietary variations observed among the different Iranian ethnic populations. Two FFQ were completed for each participant over a one-year study period (FFQ1 upon enrollment and FFQ2 at the end of the study), with 24 interviewer-administered 24-hour dietary recalls (24 h) being completed monthly in between. Spearman correlation coefficients (SCC) were used comparing FFQs 1 and 2 to the 24 h to assess validity, while FFQ1 was compared to FFQ2 to assess reproducibility of the questionnaire. RESULTS: Three major dietary patterns-Healthy, Low Protein/High Carb and Unhealthy-were identified, accounting for 70% of variance in the study population. Corrected SCC ranged from 0.31 to 0.61 in the validity and from 0.34 to 0.57 in reproducibility analyses, with the first two patterns, which accounted for over 50% of population variance, correlated at above 0.5 in both parameters, showing acceptable findings. CONCLUSIONS: The PERSIAN Cohort FFQ is suitable for identification of major dietary patterns in the populations it is used for, in order to assess diet-disease relationships.