BACKGROUND:Childhood obesity has become a public health challenge globally. Existing studies have indicated a potential link between maternal dietary macronutrient compositions and subsequent weight changes in their offspring during early childhood, although few studies have been conducted through early adulthood. OBJECTIVES:We aimed to investigate the relationship between maternal macronutrient intake before or during pregnancy and offspring body weight from late childhood till early adulthood. METHODS:We included 5715 children from the Growing Up Today Study 2 (GUTS2) (mean 11.8 y old at baseline in 2004) born to 4731 mothers who participated in the Nurses' Health Study II (NHSII) during 1989-1995. Diet during or before pregnancy was assessed using a validated food frequency questionnaire (FFQ) in 1991 and 1995. Age- and sex-specific body mass index (BMI) were used to define overweight and obesity in childhood and adolescence. Multivariable linear and log-binomial regression models with generalized estimating equations were used to evaluate the associations of interest. RESULTS:The mean (SD) maternal macronutrient percent energy intake during pregnancy was 19.3% (3.1) for protein, 51.2% (6.6) for carbohydrates, and 30.8% (5.0) for total fat. For diet during pregnancy, after multivariate adjustment for maternal and offspring risk factors, compared with the lowest quartile, the highest quartile of trans fatty acid consumption was associated with a 0.20 unit (95% confidence interval [CI]: 0.00, 0.40) increase in BMI z-score without a significant linear trend (P-trend = 0.06). A positive association with BMI z-score was also observed for total fat intake (β: 0.21; 95% CI: 0.05, 0.36; P-trend = 0.02) when replacing total carbohydrate, and vice versa (β: -0.24; 95% CI: -0.40, -0.08; P-trend = 0.02 for total carbohydrate intake). For diet before pregnancy, none of the macronutrients were associated with offspring BMI z-score or the risk of overweight or obesity. CONCLUSIONS:Higher fat, especially trans fat intake, during pregnancy was positively associated with higher body weight among offspring. Other macronutrients from various food sources were not associated with the offspring weight. Overall, these data suggest that, apart from trans fatty acids, other macronutrient composition of maternal diet may have minimal impact on offspring body weight in this well-nourished population.

BACKGROUND:Lignans are polyphenolic compounds abundant in plant-based foods such as seeds, whole grains, and certain fruits and vegetables and may lead to favorable metabolic health. It remains to be elucidated regarding the role of lignan consumption in the etiology of premature deaths among individuals with diabetes. OBJECTIVES:To prospectively examine the association between postdiagnosis lignan intake and mortality among individuals with type 2 diabetes (T2D). METHODS:We analyzed data from 2 prospective United States cohorts, the Nurses' Health Study (1984-2020) and Health Professionals Follow-up Study (1986-2022). Mean daily consumption of total and individual lignans was calculated, and postdiagnosis lignan intakes were cumulatively averaged. Multivariable-adjusted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between lignan intake and mortality. RESULTS:Among 8465 incident T2D cases contributing 116,026 person-years of follow-up, 4372 deaths were documented, including 1318 from cardiovascular disease (CVD) and 752 from cancer. The pooled multivariable-adjusted HRs (95% CIs) of all-cause mortality comparing the highest compared with the lowest quintiles of postdiagnosis lignan intake were 0.83 (0.74, 0.94) for total lignans, 0.89 (0.80, 0.99) for matairesinol (MAT), 0.78 (0.69, 0.87) for secoisolariciresinol (SECO), 0.91 (0.81, 1.01) for pinoresinol (PINO), and 0.92 (0.82, 1.03) for lariciresinol (LARIC). Higher postdiagnosis SECO intake was also significantly associated with lower CVD and cancer mortality. Changes in lignan intake from pre- to postdiagnosis showed similar favorable associations: 0.83 (0.75, 0.93) for total lignans, 0.86 (0.77, 0.96) for MAT, and 0.81 (0.72, 0.90) for SECO. The associations of lignan intake were significantly stronger among nonwhite individuals. CONCLUSIONS:Among individuals with T2D, a higher intake of lignans, particularly SECO, was significantly associated with reduced overall CVD and cancer mortality. Minority groups may particularly benefit from lignan intake, although further studies are warranted to substantiate this observation.

Aims/hypothesisExisting evidence on the relationship between intake of monounsaturated fatty acids (MUFAs) and type 2 diabetes is conflicting. Few studies have examined whether MUFAs from plant or animal sources (MUFA-Ps and MUFA-As, respectively) exhibit differential associations with type 2 diabetes. We examined associations of intakes of total MUFAs, MUFA-Ps and MUFA-As with type 2 diabetes risk.MethodsWe used data from 51,290 women in the Nurses' Health Study (1990-2016), 61,703 women in the Nurses' Health Study II (1991-2017) and 29,497 men in the Health Professionals Follow-up Study (1990-2016). Using food frequency questionnaires and food composition tables, we calculated MUFA-P and MUFA-A intakes every 4 years and modelled their associations with type 2 diabetes using Cox regression models.ResultsDuring 3,268,512 person-years of follow-up, we documented 13,211 incident type 2 diabetes cases. After multivariate adjustment, total MUFA intake was associated with higher type 2 diabetes risk, with HR for Q5 vs Q1 of 1.10 (95% CI 1.01, 1.22). MUFA-Ps and MUFA-As demonstrated divergent associations, with HRs of 0.87 (95% CI 0.81, 0.94) and 1.34 (1.23, 1.45), respectively. In substitution analyses, HRs were 0.92 (95% CI 0.86, 0.99) for replacing 2% of energy from trans fatty acids or 0.72 (0.66, 0.78) and 0.82 (0.77, 0.88) for replacing 5% from MUFA-As and 5% from the sum of saturated fatty acids and MUFA-As with MUFA-Ps, respectively. Substituting MUFA-As for saturated fatty acids and refined carbohydrates was associated with a 43% and 33% higher risk, respectively.Conclusions/interpretationHigher intake of MUFA-Ps was associated with lower type 2 diabetes risk, whereas increased intake of MUFA-As was associated with higher risk. Replacing saturated fatty acids, trans fatty acids and MUFA-As with MUFA-Ps may be beneficial for type 2 diabetes prevention.

Existing evidence for associations of per- and polyfluoroalkyl substances (PFASs) with blood lipids, lipoproteins and apolipoproteins (apo), and coronary heart disease (CHD) risk is limited and inconsistent. This study aims to explore associations between plasma PFASs, blood lipoprotein subspecies defined by apolipoproteins, and CHD risk. A case–control study of CHD was conducted in the Health Professionals Follow-Up Study (HPFS) and Nurses' Health Study (NHS). Among participants initially free of cardiovascular disease at blood collection in 1994 (HPFS) or 1990 (NHS), 101 participants who developed non-fatal myocardial infarction or fatal CHD were identified and confirmed. A healthy control was matched to each case for age, smoking status, and date of blood draw. Plasma levels of perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), linear PFOS (nPFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured. Conditional logistic regression and cubic spline regression models were used to examine associations between baseline PFASs and CHD risk. Linear regression models were applied to study PFAS associations with lipids and their subfractions. After multivariate adjustments, total PFOS, brPFOS and nPFOS were significantly associated with increased risk of developing CHD, and HRs (95

Abstract Background: While prostate cancer is the second leading cause of cancer death in U.S. males, most men with prostate cancer die from other causes. We prospectively examined the potential benefits of adhering to established healthy dietary patterns on overall and cause-specific mortality among men living with prostate cancer. Methods: We studied men with incident prostate cancer in the Health Professionals Follow-up Study from 1986-2022. Five dietary indices-Alternative Healthy Eating Index (AHEI), the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), anti-insulinemic, and anti-inflammatory diet scores-were derived from validated food frequency questionnaires administered every 4 years. Post-diagnosis scores were cumulatively averaged, and time-varying changes in scores from pre- to post-diagnosis were calculated. We used multivariable-adjusted Cox models to estimate hazard ratios (HRs, 95% CI) for associations between adherence to dietary patterns with overall and cause-specific survival adjusting for demographics, dietary and lifestyle factors. Results: Among 6,086 prostate cancer patients with 71,783 person-years of follow-up, 3,406 deaths occurred: 578 from prostate cancer, 918 from cardiovascular disease (CVD), and 1910 from other causes. When comparing extreme quintiles of post-diagnosis diet scores, a healthy diet was associated with lower overall mortality for AHEI (0.76, 0.66-0.88) and the Mediterranean diet (0.84, 0.73-0.97). Moreover, comparing extreme quintiles of score change, patients who increased their adherence to these diets after diagnosis had better overall survival with HRs (95% CI) that ranged from 0.79 (0.70-0.89) for AHEI to 0.89 (0.79- <1.00) for the anti-inflammatory diet. No significant associations were observed for DASH. Regarding cause-specific survival, increased adherence to anti-insulinemic diet was associated with better CVD-specific survival (0.78, 0.61-0.99). No significant associations were found between these diet scores and prostate cancer survival. Stronger associations of post-diagnosis diet scores with overall survival were seen in men diagnosed before age 70, those classified as obese at diagnosis (BMI≥30 kg/m2), consuming less alcohol (<7.8 g/d), and with lower grade (Gleason Score ≤7) or stage (T1/T2) tumors. Conclusions: For men diagnosed with prostate cancer, adhering to a healthy dietary pattern after cancer diagnosis, such as the AHEI and Mediterranean Diet, was associated with better overall survival. Increasing adherence to these diets after cancer diagnosis was also associated with improved overall and CVD-specific survival. Citation Format: Binkai Liu, Jane B. Vaselkiv, Caroline Himbert, Colleen B. McGrath, LeeAnn Lucas, Edward Giovannucci, Meir J. Stampfer, Konrad H. Stopsack, Qi Sun, Lorelei A. Mucci. Healthy dietary patterns and survival among men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2210.

Introduction: Lignans are polyphenolic compounds abundant in plant-based foods such as seeds, whole grains, and certain fruits and vegetables and may lead to better metabolic health. It remains elucidated regarding the role of lignan consumption in the etiology of premature deaths among diabetes patients. Hypothesis: We hypothesize that a higher intake of post-diagnosis lignans is associated with lower risk of mortality among individuals with incident type 2 diabetes (T2D). Design: Data from two prospective U.S. cohorts were analyzed, including the Nurses' Health Study (1984-2020) and Health Professionals Follow-up Study (1986-2022). Average daily consumption of total and individual lignans were calculated, and post-diagnosis lignan intakes were cumulatively averaged. Multivariable-adjusted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between post-diagnosis lignan intake and mortality. Results: Among 8,691 incident T2D cases contributing 119,065 person-years of follow-up, 4,502 deaths were documented, among which 1,379 cases were attributed to cardiovascular disease (CVD) and 777 to cancer. The pooled multivariable-adjusted HRs (95% CIs) of all-cause mortality comparing extreme quintiles of post-diagnosis lignan intake were 0.83 (0.74, 0.94) for total lignans, 0.87 (0.78, 0.96) for matairesinol (MAT), 0.77 (0.69, 0.86) for secoisolariciresinol (SECO), 0.92 (0.82, 1.03) for pinoresinol (PINO), and 0.92 (0.82, 1.03) for lariciresinol (LARIC). Higher post-diagnosis intakes of SECO were also significantly associated with lower CVD and cancer mortality. The HRs (95% CIs) of total mortality comparing extreme quintiles of changes in lignan intake from pre- to post-diagnosis were 0.84 (0.75, 0.93) for total lignans, 0.85 (0.76, 0.94) for MAT, and 0.79 (0.71, 0.89) for SECO. No significant associations were observed for PINO and LARIC. Stratified analyses showed that the associations of lignans were significantly stronger among non-white individuals. Conclusions: In conclusion, among individuals diagnosed with T2D, a higher intake of lignans, particularly SECO, was significantly associated with reduced overall, cardiovascular, and cancer mortality. Minority groups may particularly benefit from lignan intake, although further studies are warranted to substantiate this observation.

Background: Childhood obesity has become a public health challenge globally, with increasing prevalence worldwide. Existing studies have indicated a potential link between maternal macronutrients intake and subsequent weight changes in their offspring during childhood. However, the long-term relationship between maternal macronutrient consumption at pregnancy and the growth trajectory of offspring into adulthood remains unclear. Objectives: We aim to investigate the relationship between maternal macronutrients intake at pregnancy and the trajectory of the offspring BMI z-score, as well as the risk of becoming overweight or obese before adulthood. Method: We included 5,700 children from the Growing Up Today Study 2 born to 4,697 mothers who participated in the Nurses’ Health Study II . Diet was assessed using a validated food frequency questionnaire in 1991 approximately during or before the pregnancy at issue. Age- and gender-specific BMI thresholds described by the International Obesity Task Force were used to define overweight and obesity in childhood and adolescence. Multivariable linear and log-binomial regression models with generalized estimating equations were used to evaluate the association between maternal macronutrients intake at pregnancy and offspring BMI z-score trajectory and the risk of overweight or obesity. Results: During follow-up, 2145 (37.6%) GUTS2 participants met the criteria of overweight or obesity.After multivariate adjustment for maternal, offspring risk factors, total maternal total energy and carbohydrate percent energy, comparing to the 1 st quartile, the highest quartile of total protein consumption at pregnancy was associated with 0.14-unit [β: 0.14 (95% CI: 0.02, 0.26; P-trend = 0.03)] increase in BMI z-score, while no significant association was observed for the risk of offspring overweight or obesity [RR: 1.17 (95% CI: 0.94, 1.46; P-trend = 0.12)]. The relationship persisted for the top quartile of animal protein energy intake [β: 0.14 (95% CI: 0.01, 0.27; P-trend = 0.03)], but not for vegetable protein consumption. Intakes of dietary fats and carbohydrates were not associated with BMI z-score or risk of overweight or obesity. Furthermore, individual macronutrient subgroups, such as saturated fats, mono- and poly-unsaturated fats, or whole grains and refined grains, were not associated with the outcomes of interest, either. Conclusion: Maternal animal protein intake at pregnancy is positively associated with higher offspring BMI z-score before adulthood, but not the risk of developing overweight or obesity during childhood. Other macronutrients are not significantly associated with these childhood body weight outcomes. Overall, these data suggest that the macronutrient composition of maternal diet at peri-pregnancy period has minimal impact on offspring body weight in this well-nourished population.

Importance:Lignans are phytoestrogens abundant in Western diets and may be associated with type 2 diabetes (T2D) risk. Objective:To prospectively investigate associations between lignan intake and T2D incidence. Design, Setting, and Participants:Population-based cohort study of US men and women enrolled in the Nurses' Health Study (NHS, 1984-2018), NHSII (1991-2019), and Health Professionals Follow-Up Study (HPFS, 1986-2020), as well as 496 participants from the Men's Lifestyle Validation Study (MLVS). Participants were free of T2D, cardiovascular disease, and cancer at baseline. Data were analyzed from November 2022 to July 2023. Exposures:Total and individual lignans were assessed using a validated food frequency questionnaire, which was updated every 2 to 4 years. In the MLVS, lignan intake was measured using 2 sets of 7-day diet records (7DDRs). Main Outcomes and Measures:Incident T2D cases were confirmed using American Diabetes Association diagnostic criteria. Cox proportional hazards models were used to assess multivariable-adjusted associations. Results:The current study included 201 111 participants (mean [SD] age, 44.7 [10.1] years; 161 169 female participants [80.2%]; 2614 African American participants [1.3%], 1609 Asian participants [0.8%], 2414 Hispanic and other race or ethnicity participants [1.2%], and 194 474 White participants [96.7%]) from the HPFS, NHS, and NHSII studies. The median (IQR) total lignan intake of the highest quintile ranged from 355.1 (330.2-396.9) μg/d in NHS to 459.9 (422.2-519.5) μg/d in HPFS at the median follow-up time. Over 5 068 689 person-years, 20 291 incident cases of T2D were identified. Higher lignan intake was inversely associated with T2D incidence, except for lariciresinol. The multivariable-adjusted pooled hazard ratios (HRs) for the highest vs lowest quintiles were 0.87 (95% CI, 0.83-0.91) for total lignans, 0.72 (95% CI, 0.69-0.76) for secoisolariciresinol, 0.92 (95% CI, 0.87-0.96) for pinoresinol, 0.93 (95% CI, 0.89-0.98) for matairesinol, and 0.99 (95% CI, 0.94-1.04) for lariciresinol. Secoisolariciresinol intake exhibited a significant inverse association with T2D risk among individuals with obesity (HR, 0.75 for body mass index [BMI] ≥30; 95% CI, 0.71-0.79 vs HR, 0.82 for BMI <25; 95% CI, 0.81-0.83; P < .001 for interaction) and premenopausal women (HR, 0.67 for premenopausal women; 95% CI, 0.65-0.69 vs HR, 0.82 for the past use of hormones; 95% CI, 0.76-0.88; P = .003 for interaction). Dietary lignan assessed with 7DDRs was associated with lower HbA1c levels (percentage change range from -0.92% to 1.50%), as well as lower C-reactive protein levels and better lipid profiles. Conclusions and Relevance:This cohort study found that long-term lignan consumption was associated with a lower T2D risk, particularly among individuals with obesity and premenopausal women.

Plant-based dietary patterns are gaining more attention due to their potential in reducing the risk of developing major chronic diseases, including type 2 diabetes (T2D), cardiovascular disease (CVD), cancer, and mortality, while an up-to-date comprehensive quantitative review is lacking. This study aimed to summarize the existing prospective observational evidence on associations between adherence to plant-based dietary patterns and chronic disease outcomes. We conducted a systematic review and meta-analysis of evidence across prospective observational studies. The data sources used were PubMed and MEDLINE, Embase, Web of Science, and screening of references. We included all prospective observational studies that evaluated the association between adherence to plant-based dietary patterns and incidence of T2D, CVD, cancer, and mortality among adults (≥ 18 years). A total of 76 publications were identified, including 2,230,443 participants with 60,718 cases of incident T2D, 157,335 CVD cases, 57,759 cancer cases, and 174,435 deaths. An inverse association was observed between higher adherence to a plant-based dietary pattern and risks of T2D (RR, 0.82 [95 https://www.crd.york.ac.uk/PROSPERO/ ) with the registration number CRD42022290202.

OBJECTIVE:To prospectively investigate the associations between dark, milk, and total chocolate consumption and risk of type 2 diabetes (T2D) in three US cohorts. DESIGN:Prospective cohort studies. SETTING:Nurses' Health Study (NHS; 1986-2018), Nurses' Health Study II (NHSII; 1991-2021), and Health Professionals Follow-Up Study (HPFS; 1986-2020). PARTICIPANTS:At study baseline for total chocolate analyses (1986 for NHS and HPFS; 1991 for NHSII), 192 208 participants without T2D, cardiovascular disease, or cancer were included. 111 654 participants were included in the analysis for risk of T2D by intake of chocolate subtypes, assessed from 2006 in NHS and HPFS and from 2007 in NHSII. MAIN OUTCOME MEASURE:Self-reported incident T2D, with patients identified by follow-up questionnaires and confirmed through a validated supplementary questionnaire. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals (CIs) for T2D according to chocolate consumption. RESULTS:In the primary analyses for total chocolate, 18 862 people with incident T2D were identified during 4 829 175 person years of follow-up. After adjusting for personal, lifestyle, and dietary risk factors, participants consuming ≥5 servings/week of any chocolate showed a significant 10% (95% CI 2% to 17%; P trend=0.07) lower rate of T2D compared with those who never or rarely consumed chocolate. In analyses by chocolate subtypes, 4771 people with incident T2D were identified. Participants who consumed ≥5 servings/week of dark chocolate showed a significant 21% (5% to 34%; P trend=0.006) lower risk of T2D. No significant associations were found for milk chocolate intake. Spline regression showed a linear dose-response association between dark chocolate intake and risk of T2D (P for linearity=0.003), with a significant risk reduction of 3% (1% to 5%) observed for each serving/week of dark chocolate consumption. Intake of milk, but not dark, chocolate was positively associated with weight gain. CONCLUSIONS:Increased consumption of dark, but not milk, chocolate was associated with lower risk of T2D. Increased consumption of milk, but not dark, chocolate was associated with long term weight gain. Further randomized controlled trials are needed to replicate these findings and further explore the mechanisms.

Prostate cancer has high heritability. Healthy lifestyle has been associated with lower lethal prostate cancer risk among men at increased genetic susceptibility, but the role of healthy dietary patterns remains unknown. We prospectively followed 10,269 genotyped men in the Health Professionals Follow-up Study (1993-2019). Genetic risk was quantified using an established polygenic risk score (PRS). Five dietary patterns were investigated: healthy eating index, Mediterranean, diabetes risk-reducing, hyperinsulinemic and inflammatory diet. Overall and lethal prostate cancer rates (metastatic disease/prostate cancer-specific death) were analyzed using multivariable Cox proportional hazards models. During 26 years of follow-up, 2133 overall and 253 lethal prostate cancer events were documented. In the highest PRS quartile, higher adherence to a diabetes risk-reducing diet was associated with lower rates of overall (top vs. bottom quintile HR [95% CI], 0.74 [0.58-0.94]) and lethal prostate cancer (0.43 [0.21-0.88]). A low insulinemic diet was associated with similar lower rates (overall, 0.76 [0.60-0.95]; lethal, 0.46 [0.23-0.94]). Other dietary patterns showed weaker, but similar associations. In the highest PRS quartile, men with healthy lifestyles based on body weight, physical activity, and low insulinemic diet had a substantially lower rate (0.26 [0.13-0.49]) of lethal prostate cancer compared with men with unhealthy lifestyles, translating to a lifetime risk of 3.4% (95% CI, 2.3%-5.0%) among those with healthy lifestyles and 9.5% (5.3%-16.7%) among those with unhealthy lifestyles. Our findings indicate that lifestyle modifications lowering insulin resistance and chronic hyperinsulinemia could be relevant in preventing aggressive prostate cancer among men genetically predisposed to prostate cancer.

BACKGROUND:Associations between per- and polyfluoroalkyl substances (PFAS) and blood lipid levels in humans were mixed. OBJECTIVES:The objective of this meta-analysis was to summarize associations between PFAS and blood lipids in adults. METHODS:A literature search was conducted on PubMed and Web of Science for articles published through 13 May 2022 that examined associations between PFAS and blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triacylglycerols (TGs). Inclusion criteria included the presence of associations between five PFAS (PFOA, PFOS, PFHxS, PFDA, and PFNA) and four blood lipid measures (TC, HDL-C, LDL-C, and TGs) in adults. Data on study characteristics and PFAS-lipid associations were extracted. Assessments of individual study quality were performed. Associations of changes of blood lipid levels corresponding to 1 interquartile range (IQR)-unit increase of blood PFAS levels were pooled using random effects models. Dose-response relationships were examined. RESULTS:Twenty-nine publications were included in the present analyses. Every IQR increase of PFOA was significantly associated with a 2.1-mg/dL increase in TC (95% CI: 1.2, 3.0), a 1.3-mg/dL increase in TGs (95% CI: 0.1, 2.4), and a 1.4-mg/dL increase in LDL-C (95% CI: 0.6, 2.2). PFOS was also significantly associated with TC and LDL-C levels, and the corresponding values were 2.6 (95% CI: 1.5, 3.6) and 1.9 (95% CI: 0.9, 3.0), respectively. Associations of PFOS and PFOA with HDL-C levels were largely null. For minor PFAS species, PFHxS was significantly associated with higher levels of HDL-C [0.8 (95% CI: 0.5, 1.2)]. Inverse associations were observed between PFDA and TGs [-5.0 (95% CI: -8.1, -1.9)] and between PFNA and TGs [-1.7 (95% CI: -3.5, -0.02)], whereas a positive association was observed between PFDA and HDL-C [1.4 (95% CI: 0.1, 2.7)]. Nonsignificant nonlinear dose-response relationships were identified for associations of PFOA and PFOS with certain blood lipids. DISCUSSION:PFOA and PFOS were significantly associated with TC and LDL-C levels in adults. Whether these findings may translate into an elevated cardiovascular disease risk associated with PFAS exposure warrants further investigation. https://doi.org/10.1289/EHP11840.

BACKGROUND:Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary artery disease (CAD) risk remains to be elucidated. OBJECTIVES:This study aimed to prospectively assess the associations between total and individual phytosterol intake and CAD risk in United States health professionals. METHODS:The analysis included 213,992 participants from 3 prospective cohorts-the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study-without cardiovascular disease or cancer at baseline. Diet was assessed using a validated food frequency questionnaire every 2-4 y since baseline. Associations between phytosterol intake and the risk of CAD, such as nonfatal myocardial infarction and fatal CAD, were evaluated using Cox proportional hazards regression models. RESULTS:More than 5,517,993 person-years, 8725 cases with CAD were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CAD were 0.93 (0.86, 1.01; P-trend = 0.16) for total phytosterols, 0.89 (0.82, 0.96; P-trend = 0.05) for campesterol, 0.95 (0.88, 1.02; P-trend = 0.10) for stigmasterol, and 0.92 (0.85, 1.00; P-trend = 0.09) for β-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and β-sitosterol: the risk reduction plateaued at intakes above ∼180, 30, and 130 mg/d, respectively (P-nonlinearity < 0.001). In a subset of participants (N range between 11,983 and 22,039), phytosterol intake was inversely associated with plasma concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and IL-6 and positively associated with adiponectin, whereas no significant associations were observed for low-density lipoprotein cholesterol or C-reactive protein concentrations. CONCLUSIONS:Higher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CAD risk, displaying a nonlinear relationship that plateau at moderate intake levels. The role of phytosterols in preventing CAD warrants further investigation.

Backgrounds: Cocoa and cocoa flavonoids may exert health benefits including improving insulin sensitivity and lowering type 2 diabetes (T2D) risk. Previous studies have reported inverse associations between chocolate consumption and T2D risk, although it is largely unknown regarding whether the associations differ between dark chocolate and milk chocolate. The objective of this study is to prospectively examine the associations between the consumption of dark chocolate, milk chocolate, and total chocolate, and the risk of T2D, in three large cohort studies with repeat dietary measurements over 10 years of follow-up. Methods: Data from three prospective cohorts in the United States were used, including Nurses’ Health Study (2006-2020), Nurses’ Health Study II (2007-2019), and Health Professionals Follow-Up Study (2006-2020). Dark and milk chocolate consumption information was assessed at baseline and updated every 4 years through a validated food frequency questionnaire. Chocolate consumption was categorized into 4 groups: never or <1 serving/month, 1 serving/month to 1 serving/week, 1-4 servings/week, and ≥5 servings/week. Self-reported T2D cases were confirmed using a supplementary questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between total, dark, and milk chocolate intake, and the risk of T2D. Results: After adjusting for lifestyle and dietary risk factors for diabetes, compared to participants who never or rarely eat chocolate, those who consumed any chocolate ≥5 servings/week had a 22% (95% CI: 10% to 32%; p for trend = 0.0003) lower rate of T2D. For dark chocolate, those who consumed ≥5 servings/week had a non-significant 16% (95% CI: -2% to 31%; p for trend = 0.005) lower rate of T2D than those who never or rarely eat dark chocolate. The associations between milk chocolate intake and T2D risk are largely null. Spline regression shows an L-shaped non-linear dose-response relationship between total chocolate intake and the risk of T2D (p=0.02 for curvature). The risk reduction plateaus when the total chocolate intake is higher than 5 servings/week. There is a linear dose-response association between dark chocolate intake with the risk of T2D (p=0.006 for linearity). Conclusion: Higher consumption of total chocolate and especially dark chocolate was significantly associated with a lower risk of type 2 diabetes. These findings support the potential cardiometabolic benefits of consuming chocolates that are rich in flavonoids.

Importance:The associations of low-carbohydrate diets (LCDs) with long-term weight management remains unclear, and the source and quality of macronutrients within LCDs are less explored. Objectives:To prospectively examine associations between changes in LCD indices and weight change among US adults. Design, Setting, and Participants:This prospective cohort study included initially healthy participants at baseline from the Nurses' Health Study (NHS; 1986-2010), Nurses' Health Study II (NHSII; 1991-2015), and Health Professionals Follow-up Study (HPFS; 1986-2018). Data analysis was performed between November 2022 and April 2023. Exposures:Five LCD indices were examined: (1) a total LCD (TLCD) emphasizing overall lower carbohydrate intake; (2) an animal-based LCD (ALCD) that emphasized animal-sourced protein and fat; (3) a vegetable-based LCD (VLCD) that emphasized plant-sourced protein and fat; (4) a healthy LCD (HLCD) emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) an unhealthy LCD (ULCD) emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat. Main Outcomes and Measures:The outcome of interest was 4-year changes in self-reported body weight. Results:A total of 123 332 participants (mean [SD] age, 45.0 [9.7] years; 103 320 [83.8%] female) were included in this study. The median carbohydrate intake (as a percentage of energy) of the highest quintiles of TLCD score at baseline ranged from 38.3% in HPFS to 40.9% in NHSII. Mean weight gain over 4-year intervals among participants varied from 0.8 kg in the HPFS to 1.8 kg in the NHSII. After adjusting for demographics and baseline and concomitant changes of selected lifestyle factors, each 1-SD increase in TLCD score was associated with 0.06 (95% CI, 0.04-0.08) kg more weight gain over the 4-year periods. Similarly, participants gained 0.13 (95% CI, 0.11 to 0.14) kg per each 1-SD increase in ALCD score and 0.39 (95% CI, 0.37 to 0.40) kg per each 1-SD change in ULCD score. In contrast, each 1-SD increase in VLCD score was associated with 0.03 (95% CI, 0.01 to 0.04) kg less weight gain, and each 1-SD increase in HLCD score was associated with 0.36 (95% CI, 0.35 to 0.38) kg less weight gain. The associations were more pronounced among obese individuals (per 1-SD increase in HLCD score: BMI ≥30, 0.88 [95% CI, 0.80, 0.97] kg less weight gain; BMI <25, 0.23 [95% CI, 0.20, 0.26] kg less weight gain; P for interaction < .001). Conclusions and Relevance:These findings suggest that the quality of LCDs may play a critical role in modulating long-term weight change. Only LCDs that emphasized high-quality protein, fat, and carbohydrates from whole grains and other plant-based foods were associated with less weight gain.

Low diet quality is a significant public health problem in the United States, especially among low-income populations. The food environment influences dietary choices. When applied to eating behavior, behavioral economics (BE) recognizes that decision biases instigated by a food environment saturated with unhealthy foods may lead people to purchase such foods, even when they possess the necessary information and skills to make healthy dietary choices. Choice architecture, a BE concept that involves modifying the appeal or availability of choices to "nudge" people toward a certain choice, retains freedom of choice but makes unhealthy options less convenient or visible. Choice architecture has been demonstrated to influence food choices in various settings, including supermarkets, convenience stores, and food pantries. These modifications are low-cost and feasible to implement, making them a viable strategy to help "nudge" patrons toward healthier choices in food establishments serving low-income populations, including food pantries and retailers accepting the Supplemental Nutrition Assistance Program. This narrative review searched, appraised, and underscored the strengths and limitations of extant research studies that used choice architecture adaptations to influence food choices among low-income populations in the United States. Findings from studies in food pantry settings suggest the potential of BE strategies to improve the healthfulness of food choices and dietary intake in low-income populations. In food retail settings, research suggests that BE strategies increase sales of healthy foods, like fruits and vegetables. We identify new areas of research needed to determine if BE-based modifications in low-income settings have sustained impacts on diet quality.