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Background and Aims: Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD)., Methods: This prospective nested case-control study included 762 incident cases of CHD and 762 controls from the Nurses' Health Study. Plasma concentrations of polyols were measured at baseline (1989-90 or 2000-02). Associations of erythritol with cardiometabolic risk factors were also analyzed in the Women's Lifestyle Validation Study (n=728; blood collected in 2010-12)., Results: Higher erythritol levels were related to more adverse cardiometabolic risk factor status. The relative risk (RR) for CHD per 1-SD increment was 1.15 [95% CI: 1.04, 1.28] for erythritol and 1.16 [1.05, 1.28] for mannitol/sorbitol, after adjusting for diet quality, lifestyles, and adiposity. Compared with women in the lowest quartile, those in the highest quartile (Q4) of erythritol had a RR 1.55 [1.13, 2.14] for CHD. The RR in Q4 of erythritol was 1.61 [1.15, 2.24; p=0.006] when hypertension and dyslipidemia were further added to the model; the RR was 1.21 [0.86, 1.70] after adjustment for diabetes. For mannitol/sorbitol, the RR in the Q4 was 1.42 [1.05, 1.91; p=0.022] for CHD in the multivariable-adjusted model including diabetes., Conclusions: Higher plasma erythritol and mannitol/sorbitol were related to elevated risks of CHD even after adjustment for diet, lifestyles, adiposity, and other risk factors. The unfavorable association of mannitol/sorbitol, but not erythritol, with CHD risk remained significant independently of diabetes/hyperglycemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: In 2019, the EAT-Lancet Commission on healthy diets from sustainable food systems proposed a Planetary Health Diet that seeks to optimise both chronic disease prevention as well as global environmental health. In this study, we aimed to examine the association between a dietary index based on the Planetary Health Diet and risk of cardiovascular disease., Methods: We included women from the Nurses' Health Study (NHS I; 1986-2016), women from the Nurses' Health Study II (NHS II; 1991-2017), and men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of cardiovascular disease, cancer, and diabetes at baseline. Dietary data were collected every 4 years using a validated, semi-quantitative food frequency questionnaire. The Planetary Health Diet Index (PHDI) was based on 15 food groups: whole grains, vegetables, fruit, fish and shellfish, nuts and seeds, non-soy legumes, soy foods, and unsaturated oils were scored positively; starchy vegetables, dairy, red or processed meat, poultry, eggs, saturated fats and trans fat, and added sugar received negative scores. Scores for each food group were summed to get a total score of 0-140. Higher scores indicated greater adherence to the PHDI. We used Cox proportional hazards regression with time-varying covariates to evaluate the association between PHDI score, cumulatively averaged, and incident cardiovascular disease (defined as fatal and non-fatal myocardial infarction and stroke), adjusting for demographic, health, and lifestyle confounders in all participants with available data. Cohort-specific estimates were combined using inverse variance-weighted fixed effects meta-analyses., Findings: Of the 62 919 women included from the NHS I, 88 535 women included from the NHS II, and 42 164 men included from the HPFS, a total of 9831 cases of cardiovascular disease were confirmed over 4 541 980 person-years of follow-up. Mean PHDI scores ranged from 60·7 (SD 5·1) to 90·6 (5·3) in the lowest versus highest quintile in NHS I, 55·6 (4·9) to 86·3 (6·3) in NHS II, and 59·6 (5·9) to 94 (5·9) in HPFS. In the multivariable-adjusted meta-analysis, participants in the highest quintile of PHDI score had a lower risk of incident cardiovascular disease than did those in the lowest quintile (hazard ratio [HR] 0·83 [95% CI 0·78-0·89]; p-trend <0·0001). When we examined cardiovascular disease subtypes, the highest quintile of PHDI was also associated with a lower risk of coronary heart disease (HR 0·81 [95% CI 0·74-0·88]; p-trend <0·0001) and total stroke (HR 0·86 [0·78-0·95]; p-trend=0·0004) compared with the lowest quintile., Interpretation: We found that adherence to the Planetary Health Diet, designed to be a more environmentally sustainable dietary pattern, was associated with a lower risk of cardiovascular disease in three large cohorts of men and women in the USA. These observations support the Planetary Health Diet as a promising strategy to promote both human and planetary health., Funding: National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: For over 45 y increasingly comprehensive food tables of glycemic index (GI) and glycemic load (GL) have been published in the American Journal of Clinical Nutrition to determine the GI and GL values of diets. Recently the WHO based on a 2019 series of meta-analyses concluded that increases in dietary fiber and whole grains but not reduction in GI or GL warranted recommendations for chronic disease reduction., Methods and Results: We therefore provide a perspective on the current evidence that indicates that GI and GL are also determinants of risk of chronic disease outcomes. We are also concerned with the term dietary fiber used in the singular when there are many dietary fibers that may differ in their physiological effects. Furthermore, the term "whole grains" that refers to "whole grain flour" limits the exploration of "intact" grains that are low GI and have useful physiological effects., Conclusion: We conclude that all these determinants of the health values of carbohydrate-rich foods should be used in combination to assess the health value of carbohydrate-rich foods., Competing Interests: Conflict of interest DJAJ’s wife has previously been a director of INQUIS, which is responsible for clinical studies and GI testing. WCW declares that he has no conflict of interest to declare for this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches., Methods: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity., Findings: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I 2 =61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I 2 =59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I 2 =68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes., Interpretation: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines., Funding: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre., Competing Interests: Declaration of interests J-PD-C received research grants and consulting fees from the Dairy Farmers of Canada, research grants from The Weston Family Foundation, and travel support from the International Dairy Federation in the past 5 years, unrelated to the submitted work. SS-M received research funding (2019 and 2023 unrestricted grants) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation, and funds from Nutrimedes (Affligem, Belgium)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy., Methods: We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality., Conclusion: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Background: Alcohol use is associated with a wide spectrum of neurological disorders, including cognitive dysfunction and dementia. Likewise, the high prevalence of cognitive dysfunction and dementia specifies the urgent need to identify modifiable risk factors. Because findings on alcohol and cognitive dysfunction and dementia have been inconsistent, the present dose-response meta-analysis of cohort and case control studies was conducted to evaluate the available evidence., Method and Materials: A systematic search was conducted on PubMed/MEDLINE, Scopus, Embase, and PsychInfo databases and Google Scholar up to April, 2023. In the dose-response meta-analysis, a restricted cubic spline regression model was conducted to evaluate a possible non-linear relation between alcohol intake and the outcomes. Random-effects model was used to perform the meta-analysis and evaluate heterogeneity. Egger's test and a funnel plot were used to assess small study effects. Subgroup analyses were carried out to explore possible sources of heterogeneity., Results: Seventeen eligible studies comprising 80,680 total persons with 4929 cases for dementia and 13,530 total persons with 1579 cases for cognitive dysfunction were included for dose-response analysis. When compared to the reference group of 0 g/day of alcohol intake, the dose-response meta-analysis revealed a significant non-linear (J-shaped) association between alcohol intake and the risk of each of cognitive dysfunction, (lower dose range: 1-30.5 g/day, RR: 0.97; 95 % CI 0.95-0.99; higher dose range: >30.5 g/day, RR: 1.07; 95 % CI 1.01-1.15) and dementia (lower dose range: 1-17.5 g/day, RR: 0.92; 95 % CI 0.88-0.96, higher dose range: >17.5 g/day, RR: 1.23; 95 % CI 1.09-1.35). The lowest risk was achieved at approximately 30 g/day of alcohol for cognitive dysfunction and 15 g/day for dementia. The J-shape association remained with subgroups defined by age (≤65; >65 years) or study duration (<10; ≥10 years) for dementia, and within age >65 and duration <10 years for cognitive dysfunction., Conclusion: We observed a J-shape association between alcohol consumption and both cognitive dysfunction and dementia, with light-to-moderate alcohol intake being associated with a reduced risk in adults. Further studies are needed to clarify more specifically the association between alcohol consumption and six domains of cognitive dysfunction based on diagnostic and statistical manual of mental disorders (DSM) criteria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Herpes zoster (HZ), commonly known as "shingles," may contribute to cognitive decline through mechanisms such as neuroinflammation or direct neuronal injury. However, evidence on the longitudinal association between HZ and cognitive decline is conflicting and whether the risk differs by APOE ε4-carrier status has not been studied; prospective cohort studies on the association between HZ vaccination and cognitive decline are also lacking., Methods: We included 149,327 participants from three large cohorts-the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS)-to prospectively examine the association between HZ and subsequent subjective cognitive decline (SCD). Poisson regression was used to estimate the multivariable-adjusted relative risk (MVRR) of a 3-unit increment in SCD score according to years since HZ compared with participants with no history of HZ., Results: Compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was significantly and independently higher among individuals with a history of HZ, but the duration of time since HZ when the elevated risk of SCD was statistically significant differed among the cohorts. In NHS, HZ was associated with higher long-term risk of SCD; compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was 1.14 (1.01, 1.32) for ≥ 13 years since HZ. In NHS II, HZ was associated with higher risk of SCD in both the short-term [MVRR 1.34 (1.18, 1.53) for 1-4 years] and long-term [MVRR 1.20 (1.08, 1.34) for ≥ 13 years since HZ]. In HPFS, an elevated risk of SCD was suggested across all time points. Among the subset of participants with information on APOE ε4, there was a suggestion that the association differed by APOE ε4 carrier status, but the results were not consistent between women and men. Among the subset of women with information on HZ vaccination, there was a suggestion that the long-term risk of SCD may be greater among women who were not vaccinated against HZ., Conclusions: Data from three large independent cohorts of women and men showed that HZ was associated with higher long-term risk of SCD, and the risk may differ by APOE ε4-carrier status., (© 2024. The Author(s).)

Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomarkers and metabolomic profiles in subsets of 37,544 (82% females) and 9,024 (84% females) participants, respectively. Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk, with a multivariable-adjusted hazard ratio of 1.26 (95% confidence interval 1.20-1.33; P for trend <0.001) comparing the highest to the lowest quintiles. Haem iron accounts for significant proportions of the T2D risk linked to unprocessed red meat and specific dietary patterns. Increased haem iron intake correlates with unfavourable plasma profiles of insulinaemia, lipids, inflammation and T2D-linked metabolites. We also identify metabolites, including L-valine and uric acid, potentially mediating the haem iron-T2D relationship, highlighting their pivotal role in T2D pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: An adequate magnesium intake might lower the risk of frailty through its role in muscle function., Methods: We analysed data from 81 524 women aged ≥60 years participating in the Nurses' Health Study. Total magnesium intake was obtained from repeated food frequency questionnaires administered between 1984 and 2010 and self-reported information on supplementation. Frailty was defined as having at least three of the following five FRAIL scale criteria: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses and weight loss ≥ 5%. The occurrence of frailty was assessed every 4 years from 1992 to 2018. Cox proportional hazards models adjusted for lifestyle factors, medication use and dietary factors were used to assess the association between magnesium intake and frailty., Results: During a median follow-up of 16 years, we identified 15 477 incident cases of frailty. Women with a higher intake of total energy-adjusted magnesium had a decreased risk of frailty after adjustment for lifestyle factors, medication use and dietary factors. The relative risk (95% confidence interval) for Quintile 5 (Q5) versus Quintile 1 (Q1) was 0.88 (0.82, 0.94) (P-trend < 0.001). When only energy-adjusted magnesium from the diet was considered, the inverse association was stronger (Q5 vs. Q1: 0.68 [0.56, 0.82]; P-trend < 0.001). Those reaching the recommended daily allowance (RDA) of magnesium through diet had a 14% (9%, 19%) lower risk of frailty compared with those not meeting the RDA., Conclusions: Increased intake of foods rich in magnesium was associated with a decreased risk of frailty., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Plant-based diets (PBDs) and planetary-health diets (PHDs) are recommended for their potential health and environmental benefits, but population-based evidence in diverse cultures is scarce., Methods: We included 9364 adults aged 45 years and older (52·3% female, 47·7% male) from the open cohort of the China Health and Nutrition Survey. Dietary intake was assessed using 3-day 24 h dietary recalls combined with weighing methods from 1997 to 2011, and mortality was documented from 1997 to 2015. We calculated the overall PBD index (PDI), healthful PBD index (hPDI), and unhealthful PBD index (uPDI; ranges 18-90), and the PHD score (range 0-140). We also estimated the related greenhouse gas emissions, land appropriation, and total water footprint and examined their associations with mortality., Findings: PBD indices were inversely related to greenhouse gas emissions, land appropriation, and total water footprint, whereas higher PHD score was related to higher environmental burdens (p<0·0001). During follow-up (mean 9·2 years), 792 (8·5%) death cases were documented. PDI (HR 1·08 [95% CI 0·88-1·32]) and hPDI (0·98 [0·80-1·21]) were not significantly associated with mortality, whereas higher uPDI was related to a higher mortality risk (1·55 [1·26-1·91]). In contrast, higher PHD score was associated with lower mortality risk (0·79 [0·63-0·99])., Interpretation: The PBDs showed environmental benefits, but are not necessarily associated with lower mortality risk. The PHD, developed mainly in western populations, was related to lower mortality risk but higher environmental burdens in the Chinese population., Funding: Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and National Natural Science Foundation of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosures: The authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3391.

Competing Interests: DJAJ reports research grants from the Soy Nutrition Institute and the Canadian Institutes of Health Research (CIHR); in-kind supplies for trials as a research support from the Almond Board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, and WhiteWave Foods; payment or honoraria for lectures or presentations from Nutritional Fundamentals for Health–Nutramedica, Saint Barnabas Medical Center Rutgers New Jersey Medical School, The University of Chicago, 2020 China Glycemic Index International Conference, Atlantic Pain Conference, Academy of Life Long Learning; and travel support from NUTS 2022 and the 40th International Symposium on Diabetes and Nutrition. DJAJ is a co-chair of the International Carbohydrate Quality Consortium (ICQC) and has been invited by the International Diabetes Federation to join the committee on diabetes treatment and to take the lead in writing the dietary guidelines for the treatment of diabetes. His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry; his two daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the foods described here (Jenkins WM, Jenkins AE, Jenkins AL, Brydson C. The portfolio diet for cardiovascular disease risk reduction. London: Elsevier, 2019); and his sister, Caroline Brydson, received funding through a grant from the St Michael's Hospital Foundation to develop a cookbook for one of his studies. JLS reports research grants from the CIHR, Canada Foundation for Innovation, Ontario Research Fund, American Society for Nutrition, International Nut and Dried Fruit Council Foundation, National Honey Board, Institute for the Advancement of Food and Nutrition Sciences, Pulse Canada, The United Soybean Board, The Tate and Lyle Nutritional Research Fund (University of Toronto), The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund established by the Alberta Pulse Growers (University of Toronto), Nutrition Trialists Network Fund established by an inaugural donation from the Calorie Control Council (University of Toronto), Diabetes Canada, and Quaker Oats Center of Excellence; in-kind research support from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever–Upfield, Unico–Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods–Danone, Nutrartis, and Dairy Farmers of Canada; and speaker fees, honoraria, or both from Dairy Farmers of Canada, FoodMinds, International Sweeteners Association, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council, Calorie Control Council, International Glutamate Technical Committee, Arab Beverages Assocation, and Phynova. JLS reports ad hoc consulting arrangements with Perkins Coie, Tate & Lyle, Danone, Inquis Clinical Research, and Brightseed; has served as a scientific board member of the European Fruit Juice Association and the Soy Nutrition Institute; is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the Study of Diabetes, Canadian Cardiovascular Society, and Obesity Canada–Canadian Association of Bariatric Physicians and Surgeons; is a member of the ICQC, Institute for the Advancement of Food and Nutrition Sciences, Canadian Nutrition Society; is executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes; and is director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of AB InBev. WCW, KS, and TAK declare no competing interests.

The association of gut microbial features with type 2 diabetes (T2D) has been inconsistent due in part to the complexity of this disease and variation in study design. Even in cases in which individual microbial species have been associated with T2D, mechanisms have been unable to be attributed to these associations based on specific microbial strains. We conducted a comprehensive study of the T2D microbiome, analyzing 8,117 shotgun metagenomes from 10 cohorts of individuals with T2D, prediabetes, and normoglycemic status in the United States, Europe, Israel and China. Dysbiosis in 19 phylogenetically diverse species was associated with T2D (false discovery rate < 0.10), for example, enriched Clostridium bolteae and depleted Butyrivibrio crossotus. These microorganisms also contributed to community-level functional changes potentially underlying T2D pathogenesis, for example, perturbations in glucose metabolism. Our study identifies within-species phylogenetic diversity for strains of 27 species that explain inter-individual differences in T2D risk, such as Eubacterium rectale. In some cases, these were explained by strain-specific gene carriage, including loci involved in various mechanisms of horizontal gene transfer and novel biological processes underlying metabolic risk, for example, quorum sensing. In summary, our study provides robust cross-cohort microbial signatures in a strain-resolved manner and offers new mechanistic insights into T2D., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications., (© 2024. The Author(s).)

Background: Whether observational study can be employed to establish calibration equations for self-reported dietary intake using food biomarkers is unknown., Objectives: This study aims to demonstrate the feasibility of obtaining calibration equations based on food biomarkers and 7-d diet records (7DDRs) to correct measurement errors of food frequency questionnaires (FFQs) in an observational study setting., Methods: The study population consisted of 669 males and 749 females from the Women's and Men's Lifestyle Validation Studies. In the training set, the biomarker-predicted intake derived by regressing 7DDR-assessed intake on urinary proline betaine concentration 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, FFQs, and calibrated FFQs were 62.5, 75.3, and 63.2 g/d for total citrus; 41.6, 42.5, and 41.9 g/d for orange juice; 11.8, 24.3, and 12.3 g/d for oranges; and 8.3, 9.3, and 8.6 g/d for grapefruit, respectively. 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., Conclusions: Our 2-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., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals., Objectives: We aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study., Methods: In 1028 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 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then 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 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., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet., Objectives: We aimed to assess associations between PHDI and total and cause-specific mortality in 3 prospective cohorts of males and females in the United States., Methods: We followed 66,692 females from the Nurses' Health Study (1986-2019), 92,438 females from the Nurses' Health Study II (1989-2019), and 47,274 males from the Health Professionals Follow-up Study (1986-2018) who were free of cancer, diabetes, and major cardiovascular diseases at baseline. The PHDI was calculated every 4 y using a semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models., Results: During follow-up, we documented 31,330 deaths among females and 23,206 among males. When comparing the highest with the lowest quintile of PHDI, the pooled multivariable-adjusted HRs were 0.77 [95% confidence interval (CI): 0.75, 0.80] for all-cause mortality (P-trend < 0.0001). The PHDI was associated with lower risk of deaths from cardiovascular diseases (HR: 0.86; 95% CI: 0.81, 0.91), cancer (HR: 0.90; 95% CI: 0.85, 0.95), respiratory diseases (HR: 0.53; 95% CI: 0.48, 0.59), and neurodegenerative diseases (HR: 0.72; 95% CI: 0.67, 0.78). In females, but not males, the PHDI was also significantly associated with a lower risk of deaths from infectious diseases (HR: 0.62; 95% CI: 0.51, 0.76). PHDI scores were also associated inversely with greenhouse gas emissions and other environmental impacts., Conclusions: In 3 large United States-based prospective cohorts of males and females with up to 34 y of follow-up, a higher PHDI was associated with lower risk of total and cause-specific mortality and environment impacts., (Copyright © 2024 American Society for Nutrition. All rights reserved.)

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., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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); p heterogeneity  = 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); p heterogeneity  = 0.99). In analyses of moderate-vigorous activity and breast cancer risk, no heterogeneity by menopausal status was observed (p het  ≥ 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., (© 2024. The Author(s).)

Objective: We assessed ultraprocessed food (UPF) intake and systemic lupus erythematosus (SLE) incidence within the prospective Nurses' Health Study (NHS) cohorts., Methods: A total of 204,175 women were observed (NHS 1984-2016; NHSII 1991-2017). Semiquantitative food frequency questionnaires were completed every two to four years. UPF intake was determined as per the Nova classification. Nurses self-reported new doctor-diagnosed SLE, confirmed by medical records. Time-varying Cox regressions estimated hazard ratios (HRs; 95% confidence intervals [CIs]) for patients with incident SLE and SLE by anti-double-stranded DNA (dsDNA) antibody at diagnosis, according to cumulatively updated daily (a) UPF servings, (b) total intake (in grams and milliliters), and (c) percentage of total intake. Analyses adjusted for age, race, cohort, caloric and alcohol intakes, household income, smoking, body mass index (BMI), physical activity, menarchal age, and oral contraceptive use. We tested for interaction with BMI and examined UPF categories., Results: Mean baseline age was ~50 years (NHS) and ~36 years (NHSII); 93% self-reported White race. A total of 212 patients with incident SLE were identified. SLE risk was higher in the third versus first UPF tertile (servings per day pooled multivariable [MV] HR 1.56, 95% CI 1.04-2.32; P = 0.03). Results were stronger for dsDNA antibody in patients with SLE (servings per day pooled MV HR 2.05, 95% CI 1.15-3.65; P = 0.01) and for absolute (servings or total) than percentage of total intake. Sugar-sweetened/artificially sweetened beverages were associated with SLE risk (third vs first tertile MV HR 1.45, 95% CI 1.01-2.09). No BMI interactions were observed., Conclusion: Higher cumulative average daily UPF intake was associated with >50% increased SLE risk and with doubled risk for anti-dsDNA antibody in patients with SLE. Many deleterious effects on systemic inflammation and immunity are postulated., (© 2024 American College of Rheumatology.)

Background: Few cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service ("SMS-program") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement., Methods and Findings: We conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 ("non-SMS group") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations of the study were that DNBC participants, though derived from the general population, tend to have higher socioeconomic status than average, and that outcome measures were self-reported., Conclusions: In this study, a chatbot health education program delivered through an SMS program had no effect on dietary habits or weight trajectories in ITT analyses. However, IPW-PP-analyses, based on those 63% who had joined the offered SMS program, suggested modest improvements in weight development at 6 m, which had faded at 18 m. Future research should focus on developing gender-specific messaging programs including "booster" messages to obtain sustained engagement., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02809196 https://clinicaltrials.gov/study/NCT02809196., Competing Interests: ELD and DEZ are co-inventors of the Epidemic Health chatbot technology platform. There are no other competing interests. JVH was employed by Statens Serum Institut at the time this study was conducted and data analyzed, but has been employed by Novo Nordisk A/S, Søborg, Denmark since June 1st 2023. Novo Nordisk A/S played no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript., (Copyright: © 2024 Bjerregaard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Sleep duration and moderate-to-vigorous physical activity (MVPA) are associated with healthy aging, but the associations of sedentary behaviors and light-intensity physical activity (LPA) with healthy aging are still unclear., Objective: To examine the independent association of sedentary behaviors and LPA with healthy aging, and to estimate the theoretical association of replacing sedentary behavior with LPA, MVPA, or sleep with healthy aging., Design, Setting, and Participants: In this cohort study using data from the Nurses' Health Study, participants aged 50 years or older and free of major chronic diseases in 1992 were prospectively followed up for 20 years. Data were analyzed from January to May 2022., Exposures: Three measures for sedentary behaviors (hours watching television, sitting at work, and other sitting at home) and 2 measures for LPA (hours of standing or walking around at home [LPA-Home] and at work [LPA-Work])., Main Outcomes and Measures: Healthy aging was defined as survival to at least age 70 years with maintenance of 4 health domains (ie, no major chronic diseases and no impairment in subjective memory, physical function, or mental health). The isotemporal substitution model was used to evaluate the potential impact on healthy aging of replacing 1 hour of 1 behavior with equivalent duration of another., Results: Among 45 176 participants (mean [SD] age, 59.2 [6.0] years), 3873 (8.6%) women achieved healthy aging. After adjustment for covariates including MVPA, each increment of 2 hours per day in sitting watching television was associated with a 12% (95% CI, 7%-17%) reduction in the odds of healthy aging. In contrast, each increase of 2 hours per day in LPA-Work was associated with a 6% (95% CI, 3%-9%) increase in the odds of healthy aging. Replacing 1 hour of sitting watching television with LPA-Home (OR, 1.08; 95% CI, 1.05-1.12), LPA-Work (OR, 1.10; 95% CI, 1.07-1.14), or MVPA (OR, 1.28; 95% CI, 1.23-1.34) was associated with increased odds of healthy aging. Among participants who slept 7 hours per day or less, replacing television time with sleep was also associated with increased odds of healthy aging., Conclusions and Relevance: In this cohort study, longer television watching time decreased odds of healthy aging, whereas LPA and MVPA increased odds of healthy aging and replacing sitting watching television with LPA or MVPA, or with sleep in those who slept 7 hours per day or less, was associated with increased odds of healthy aging, providing evidence for rearranging 24-hour behavior to promote overall health.

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., (© 2024. Springer Nature B.V.)

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 (p interaction =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., Competing Interests: Declaration of interests SR received consulting fees from Eli Lilly, Apnimed, and Jazz Pharma, and was on the board for Alliance for Sleep Apnea Partners (no support), the US National Sleep Foundation (no support), and the US National Heart, Lung, and Blood Institute Council. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

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.

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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health for the submitted work; NK received a consulting fee from the Pan American Health Organization for three months on the topic of nutrition disclosure initiatives and nutrient profiling models; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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.

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: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC., Design: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study., Participants/setting: There were 842 149 men followed for up to 9 to 22 years between 1985 and 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), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality., Statistical Analysis Performed: 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 = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% 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 ≤ .03), and 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 = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366)., 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., (Copyright © 2024. Published by Elsevier Inc.)

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 (β=-5.39 [95% CI, -8.91, -1.87]) and nicotine exposure (β=-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.

Background: Food insecurity is a pivotal determinant of health outcomes. Little evidence exists on the association between food insecurity and health behaviors and outcomes, including diet quality, among graduate students or postdoctoral trainees., Objectives: This study aimed to examine the association between food insecurity and diet quality among graduate students and postdoctoral trainees at 3 health-focused graduate schools (public health, medical, and dental medicine) within Harvard University., Methods: Between April and June 2023, 1287 graduate students and 458 postdoctoral trainees at the health-focused schools within Harvard University completed a web-based survey. The primary exposure was food security status, assessed using the United States Household Food Security Survey Module. The primary outcome was diet quality, measured using the 30-day Prime Diet Quality Score screener (ranges from 0 to 126, with higher scores indicating healthier diets). The associations between food insecurity and diet quality were examined using multivariable regression models, adjusting for sociodemographic covariates., Results: Among graduate students, compared with those with high food security, diet quality was significantly lower among those experiencing marginal food security [β: -4.7; 95% confidence interval (CI): -6.5, -2.9], low food security (β: -5.4; 95% CI: -7.6, -3.3), and very low food security (β: -4.4; 95% CI: -7.4, -1.4). Poor diet quality included lower intake frequencies of vegetables, fruits, beans/peas/soy products, nuts/seeds, poultry, fish, low-fat dairy, and liquid oils, and higher intake frequencies of refined grains/baked products, sugar-sweetened beverages, and fried foods. Among postdoctoral trainees, compared with those with high food security, diet quality was significantly lower among those experiencing low food security (β: -5.1; 95% CI: -8.8, -1.4), and very low food security (β: -5.2; 95% CI: -10.2, -0.2). Poor diet quality included lower intake frequencies of dark green leafy vegetables, other fruits, and whole grains., Conclusions: Graduate students and postdoctoral trainees who experienced degrees of food insecurity reported lower diet quality. These observations underscore the need for policies and interventions to simultaneously reduce food insecurity and improve diet quality., (© 2024 The Author(s).)

Background: A high body mass index (BMI, kg/m 2 ) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology., Methods: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy., Results: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO., Conclusion: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55., Competing Interests: Declaration of Competing Interest none., (Published by Elsevier Ltd.)

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., (© 2024. The Author(s).)

Purpose: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer., Methods: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity., Results: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship ( P nonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; P het = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity., Conclusion: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Introduction: The Department of Veterans Affairs (VA) Million Veteran Program (MVP) nutrition data is derived from dietary food/beverage intake information collected through a semiquantitative food frequency questionnaire (SFFQ)., Methods: Estimates of dietary energy, nutrient, and non-nutritive food components intakes data were derived from an extensively validated SFFQ, which assessed the habitual frequency of consumption of 61 food items, added sugar, fried food frequency, and 21 nutritional supplements over the 12 months preceding questionnaire administration., Results: Complete nutrition data was available for 353,418 MVP participants as of 30 th September 2021. Overall, 91.5% of MVP participants with nutrition data were male with an average age of 65.7 years at enrollment. Participants who completed the SFFQ were primarily White (82.5%), and Blacks accounted for 13.2% of the responders. Mean ± SD energy intake for 353, 418 MVP participants was 1428 ± 616 kcal/day, which was 1434 ± 617 kcal/day for males and 1364 ± 601 kcal/day for females. Energy intake and information on 322 nutrients and non-nutritive food components is available through contact with MVP for research collaborations at www.research.va.gov/mvp., Conclusions: The energy and nutrient data derived from MVP SFFQ are an invaluable resource for Veteran health and research. In conjunction with the MVP Lifestyle Survey, electronic health records, and genomic data, MVP nutrition data may be used to assess nutritional status and related risk factors, disease prevalence, and determinants of health that can provide scientific support for the development of evidence-based public health policy and health promotion programs and services for Veterans and general population., Competing Interests: Conflict of interest statement: None to declare.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet., Objective: To examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years., Methods: Adherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI 26 ), or <24 (MCI 24 ). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done., Results: We included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94-1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96-1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6., Conclusion: Adherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Whether physical activity could mitigate the adverse impacts of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) on incident cardiovascular disease (CVD) remains uncertain., Objectives: This study aimed to examine the independent and joint associations between SSB or ASB consumption and physical activity and risk of CVD, defined as fatal and nonfatal coronary artery disease and stroke, in adults from 2 United States-based prospective cohort studies., Methods: Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs between SSB or ASB intake and physical activity with incident CVD among 65,730 females in the Nurses' Health Study (1980-2016) and 39,418 males in the Health Professional's Follow-up Study (1986-2016), who were free from chronic diseases at baseline. SSBs and ASBs were assessed every 4-y and physical activity biannually., Results: A total of 13,269 CVD events were ascertained during 3,001,213 person-years of follow-up. Compared with those who never/rarely consumed SSBs or ASBs, the HR for CVD for participants consuming ≥2 servings/d was 1.21 (95% CI: 1.12, 1.32; P-trend < 0.001) for SSBs and 1.03 (95% CI: 0.97, 1.09; P-trend = 0.06) for those consuming ≥2 servings/d of ASBs. The HR for CVD per 1 serving increment of SSB per day was 1.18 (95% CI: 1.10, 1.26) and 1.12 (95% CI: 1.04, 1.20) for participants meeting and not meeting physical activity guidelines (≥7.5 compared with <7.5 MET h/wk), respectively. Compared with participants who met physical activity guidelines and never/rarely consumed SSBs, the HR for CVD was 1.47 (95% CI: 1.37, 1.57) for participants not meeting physical activity guidelines and consuming ≥2 servings/wk of SSBs. No significant associations were observed for ASB when stratified by physical activity., Conclusions: Higher SSB intake was associated with CVD risk regardless of physical activity levels. These results support current recommendations to limit the intake of SSBs even for physically active individuals., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Red meat consumption was associated with an increased risk of cardiovascular disease (CVD) in prospective cohort studies and a profile of biomarkers favoring high CVD risk in short-term controlled trials. However, several recent systematic reviews and meta-analyses concluded with no or weak evidence for limiting red meat intake., Objectives: To prospectively examine the associations between red meat intake and incident CVD in an ongoing cohort study with diverse socioeconomic and racial or ethnic backgrounds., Methods: Our study included 148,506 participants [17,804 female (12.0%)] who were free of cancer, diabetes, and CVD at baseline from the Million Veteran Program. A food frequency questionnaire measured red meat intakes at baseline. Nonfatal myocardial infarction and acute ischemic stroke were identified through a high-throughput phenotyping algorithm, and fatal CVD events were identified by searching the National Death Index., Results: Comparing the extreme categories of intake, the multivariate-adjusted relative risks of CVD was 1.18 (95% CI: 1.01, 1.38; P-trend < 0.0001) for total red meat, 1.14 (95% CI: 0.96, 1.36; P-trend = 0.01) for unprocessed red meat, and 1.29 (95% CI: 1.04, 1.60; P-trend = 0.003) for processed red meat. We observed a more pronounced positive association between red meat intake and CVD in African American participants than in White participants (P-interaction = 0.01). Replacing 0.5 servings/d of red meat with 0.5 servings/d of nuts, whole grains, and skimmed milk was associated with 14% (RR: 0.86; 95% CI: 0.83, 0.90), 7% (RR: 0.93; 95% CI: 0.89, 0.96), and 4% (RR: 0.96; 95% CI: 0.94, 0.99) lower risks of CVD, respectively., Conclusions: Red meat consumption is associated with an increased risk of CVD. Our findings support lowering red meat intake and replacing red meat with plant-based protein sources or low-fat dairy foods as a key dietary recommendation for the prevention of CVD., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Importance: Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials., Objective: To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults., Data Sources: MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023., Study Selection: Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls., Data Extraction and Synthesis: Data were pooled using random-effects models and presented as β coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs., Main Outcomes and Measures: Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults., Results: A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45 851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268 095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg)., Conclusion and Relevance: Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.

Background: Dairy contains a complex mixture of lipids, proteins, and micronutrients. Whether habitual dairy consumption is associated with health benefits is not well established. Since dairy is high in nutrients that are potentially protective against frailty, the association between dairy products and the risk of frailty is of interest., Methods: We analyzed data from 85,280 women aged ≥ 60 years participating in the Nurses' Health Study. Consumption of milk, yogurt, and cheese was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥ 5 chronic illnesses, and a weight loss of ≥ 5%. The occurrence of frailty was assessed every four years from 1992 to 2018. Cox proportional hazard models were used to examine the association between the intake of dairy foods and frailty., Results: During follow-up we identified 15,912 incident cases of frailty. Consumption of milk or yogurt was not associated with the risk of frailty after adjustment for lifestyle factors, medication use, and overall diet quality. Cheese consumption was positively associated with risk of frailty [relative risk (95% confidence interval) for one serving/day increment in consumption: 1.10 (1.05, 1.16)]. Replacing one serving/day of milk, yogurt, or cheese with one serving/day of whole grains, nuts, or legumes was associated with a significant lower risk of frailty, while replacing milk, yogurt, or cheese with red meat or eggs was associated with an increased risk. When milk was replaced with a sugar-sweetened or artificially sweetened beverage, a greater risk of frailty was observed, while replacing milk with orange juice was associated with a lower risk of frailty., Conclusions: The results suggest that the association between milk, yogurt, and cheese and frailty partly depends on the replacement product. Habitual consumption of milk or yogurt was not associated with risk of frailty, whereas cheese consumption may be associated with an increased risk., (© 2024. The Author(s).)

Importance: Previous research has found that vegetarian diets are associated with lower bone mineral density and higher risk of fractures, but these studies did not differentiate the quality of the plant-based foods., Objective: To examine the association between the quality of plant-based diets (not necessarily vegan but also omnivorous) and hip fracture risk among postmenopausal women in the Nurses' Health Study., Design, Setting, and Participants: This cohort study analyzed data from 70 285 postmenopausal women who participated in the US Nurses' Health Study from 1984 through 2014. Data were analyzed from January 1 to July 31, 2023., Main Outcomes and Measures: Hip fractures were self-reported on biennial questionnaires. Diet was assessed every 4 years using a validated semiquantitative food frequency questionnaire. Plant-based diet quality was assessed using 2 previously established indices: the healthful Plant-Based Diet Index (hPDI), for which healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee) received positive scores, whereas less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, and sweets or desserts) and animal foods received reversed scores; and the unhealthful Plant-Based Diet Index (uPDI), for which positive scores were given to less healthy plant foods and reversed scores to healthy plant and animal foods. Quintile scores of 18 food groups were summed, with a theoretical range for both indices of 18 to 90 (highest adherence). Cox proportional hazards regression with time-varying covariates was used to compute hazard ratios (HRs) and 95% CIs for hip fracture., Results: In total, 70 285 participants (mean [SD] age, 54.92 [4.48] years; 100% White women) were included, and 2038 cases of hip fracture were ascertained during the study and for up to 30 years of follow-up. Neither the hPDI (HR for highest vs lowest quintile, 0.97 [95% CI, 0.83-1.14]) nor the uPDI (HR for highest vs lowest quintile, 1.02 [95% CI, 0.87-1.20]) for long-term diet adherence was associated with hip fracture risk. However, when examining recent intake for the highest vs lowest quintiles, the hPDI was associated with 21% lower risk of hip fracture (HR, 0.79 [95% CI, 0.68-0.92]; P = .02 for trend), and the uPDI was associated with 28% higher risk (1.28 [95% CI, 1.09-1.51]; P = .008 for trend)., Conclusions and Relevance: Findings of this cohort study indicated that long-term adherence to healthful or unhealthful plant-based diets as assessed by hPDI and uPDI scores was not associated with hip fracture risk. Future research should clarify whether the associations observed with recent dietary intake are due to short-term effects of these dietary patterns, reverse causality, or both.

Background: The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D 3 , omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE)., Methods: The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years., Results: Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D 3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control., Conclusion: Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D 3 , and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS., Gov Identifier: NCT01745263., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Protein intake plays an important role in maintaining the health status of older adults. However, few epidemiologic studies examined midlife protein intake in relation to healthy aging., Objectives: The objective of this study was to evaluate the long-term role of dietary protein intake in healthy aging among female participants in the prospective Nurses' Health Study (NHS) cohort., Methods: We included 48,762 NHS participants aged <60 y in 1984. Total protein, animal protein, dairy protein (a subset of animal protein), and plant protein were derived from validated food frequency questionnaires. Healthy aging was defined as being free from 11 major chronic diseases, having good mental health, and not having impairments in either cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. We used multivariate logistic regression adjusted for lifestyle, demographics, and health status to estimate the odds ratios (ORs) and 95% confidence intervals for protein intake in relation to healthy aging., Results: A total of 3721 (7.6%) NHS participants met our healthy aging definition. Protein intake was significantly associated with higher odds of healthy aging. The ORs (95% confidence intervals) per 3%-energy increment with healthy aging were 1.05 (1.01, 1.10) for total protein, 1.07 (1.02, 1.11) for animal protein, 1.14 (1.06, 1.23) for dairy protein, and 1.38 (1.24, 1.54) for plant protein. Plant protein was also associated with higher odds of absence of physical function limitations and good mental status. In substitution analyses, we observed significant positive associations for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein (ORs for healthy aging: 1.22-1.58 for 3% energy replacement with plant protein)., Conclusions: Dietary protein intake, especially plant protein, in midlife, is associated with higher odds of healthy aging and with several domains of positive health status in a large cohort of female nurses., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous literature on dairy products and risk of breast cancer is inconsistent, and the relationship may depend on the life-period of dietary assessment., Objective: We examined dairy consumption from adolescence through later adulthood and incidence of breast cancer by menopausal status and tumor molecular subtypes in the Nurses' Health Study (NHS), a prospective cohort study., Methods: We analyzed data from 63,847 females in the NHS collected from 1980 to 2018. Average intake of dairy products during adulthood was assessed by validated semiquantitative food frequency questionnaires throughout follow-up. Participants recalled adolescent dietary intake in 1986. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) relating dairy product consumption to breast cancer risk overall, by menopausal status, and by subtypes., Results: We documented 5733 incident cases of invasive breast cancer during 32 y of follow-up (n = 5298 postmenopausal). Lifetime, adolescent, adulthood, and postmenopausal total dairy and milk intakes were not associated with overall breast cancer risk (nonsignificant HRs comparing highest with lowest quintile range = 0.97-1.08), although there was a suggestive positive association between adolescent milk intake and breast cancer risk (HR: 1.09; 95% CI: 1.00, 1.18). Higher lifetime and premenopausal cheese intakes were associated with modestly lower risks of breast cancer (comparing highest with lowest quintile, HR for lifetime cheese intake: 0.90; 95% CI: 0.82, 0.98; HR for premenopausal cheese intake: 0.89; 95% CI: 0.79, 1.00). Results varied by tumor subtype and some evidence for heterogeneity was observed for an association between premenopausal milk intake and breast cancer (HR for estrogen receptor [ER]-positive: 0.84; 95% CI: 0.72, 0.99; ER-negative: 1.36; 95% CI: 1.00, 1.84; P heterogeneity = 0.04)., Conclusions: These findings suggest that overall dairy consumption was not associated with risk of breast cancer. However, heterogeneity was observed for type of dairy food, period of life, and tumor subtypes., Competing Interests: Conflicts of interest ER is a Technical Editor for the American Journal for Clinical Nutrition (AJCN) and did not contribute to the decision-making or reviewing of this manuscript at AJCN. All other authors have declared no conflicts of interest., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)