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Background: Various foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger-scale prospective study on postmenopausal women., Objective: The objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women., Design: This was a prospective cohort study as part of the Women's Health Initiative (WHI), with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI)-2015 total score. In addition, intake of food groups and nutrients that align with HEI-2015 components was assessed., Participants/setting: Postmenopausal women (N = 109 591) were included in this study, which was conducted at various clinical centers across the United States with recruitment from 1993 to 1998. Women's Health Initiative participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded., Main Outcome Measures: The primary outcome measure was incident RA. Statistical analyses performed Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI)., Results: During 857 517 person-years of follow-up, 5823 incident RA cases were identified. After adjustment for multiple comparisons, compared with quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with lower RA risks of 1%, 10%, and 19%, respectively (P-trend < .001). Greater consumption of total fruits (P-trend = .014), whole fruits (P-trend < .0002), total vegetables (P-trend = .008), greens and beans (P-trend < .0002), whole grains (P-trend = .008), and dairy (P-trend = .018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (P-trend = .002) was significantly associated with higher rates of incident RA., Conclusion: A higher-quality diet reflected by higher HEI-2015 total scores was inversely associated with incident RA in postmenopausal women., (Copyright © 2024 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to examine the combined impact of diet quality and rheumatoid arthritis (RA) on development of cardiovascular and mortality outcomes among postmenopausal women., Methods: A total of 99,840 women without baseline RA and 10,494 women with baseline RA were prospectively followed for an average of 12.7 years through the Women's Health Initiative. Diet quality was evaluated using food frequency questionnaires and the Healthy Eating Index 2015. Cardiovascular and mortality outcomes were identified through study follow-up. Four patient groups were used: Reference Group (no RA and healthy diet), Group 1 (no RA and unhealthy diet), Group 2 (RA and healthy diet), Group 3 (RA and unhealthy diet). Data was analyzed using multivariable Cox proportional regression models., Results: After adjustment for confounders, Groups 1 and 3 developed significantly more cardiovascular disease (CVD), coronary heart disease, and incident stroke as compared to the reference. All groups developed more CVD-related mortality and all-cause mortality as compared to the reference. Among patients who already have RA, the incidence of these poorer cardiovascular outcomes does not significantly increase based on diet quality., Conclusion: While healthy diet quality is associated with reduced adverse cardiovascular and mortality outcomes, RA overpowers the benefits that may be attained through a healthy diet, resulting in the fact that diet quality does not significantly change cardiovascular and mortality outcome incidence in those who already have RA. Conversely, in those who do not have RA, the benefits of a healthy diet are realized with significant reduction of adverse cardiovascular and mortality outcomes as compared to those with an unhealthy diet. Key Points •Healthy diet quality is associated with reduced adverse cardiovascular and mortality outcomes. •RA is associated with increased adverse cardiovascular and mortality outcomes. •While diet quality does not significantly change cardiovascular and mortality outcomes in those who already have RA, those without RA experience significant reduction of these adverse outcomes by adhering to a healthy diet., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: Test an obesity intervention for families with low incomes., Methods: A total of 208 families were included (a parent with a body mass index [BMI] ≥ 30 and a child aged 6-12 years). A 12-month randomized controlled trial combining family health coaching (motivational interviewing) and connection to community resources. Comparison group: referrals for basic needs, written educational materials. Questionnaires, accelerometry, and anthropometrics. Intention-to-treat analysis of change in outcomes. Two-sided t test with multiple imputation., Results: Parents were 95% female, 31% Black, and 27% Hispanic. Children had a mean BMI-Z score of 1.15. Primary outcomes did not differ between groups at 12 months. Both groups significantly (P < 0.05) improved on the Family Nutrition and Physical Activity Scale for behaviors related to childhood obesity (mean ± SE: comparison, 2.8 ± 1.0; intervention, 2.2 ± 0.9), increased child sedentary activity (comparison, 32.5 ± 12.1; intervention, 39.9 ± 12.4 min/d), and decreased child moderate-vigorous physical activity (comparison, -9.6 ± 3.3; intervention -7.0 ± 3.0 min/d). Parents had no change in BMI., Conclusions and Implications: We successfully embedded screening and referral to address social needs within an obesity intervention. The coaching intervention did not provide additional benefits. Future research could explore ways to make these interventions more accessible, valuable, and effective for families., (Copyright © 2024 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: Folate is the primary methyl donor and B vitamins are cofactors for one-carbon metabolism that maintain DNA integrity and epigenetic signatures implicated in carcinogenesis. Breast tissue is particularly susceptible to stimuli in early life. Only limited data are available on associations of one-carbon metabolism-related vitamin intake during youth and young adulthood with breast density, a strong risk factor for breast cancer., Methods: Over 18 years in the DISC and DISC06 Follow-up Study, diets of 182 young women were assessed by three 24-hour recalls on five occasions at ages 8 to 18 years and once at 25 to 29 years. Multivariable-adjusted linear mixed-effects regression was used to examine associations of intakes of one-carbon metabolism-related vitamins with MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at ages 25 to 29 years., Results: Folate intake in youth was inversely associated with %DBV (Ptrend = 0.006) and ADBV (Ptrend = 0.02). These inverse associations were observed with intake during post-, though not premenarche. In contrast, premenarche vitamin B2 intake was positively associated with ADBV (Ptrend < 0.001). Young adult folate and vitamin B6 intakes were inversely associated with %DBV (all Ptrend ≤ 0.04), whereas vitamins B6 and B12 were inversely associated with ADBV (all Ptrend ≤ 0.04)., Conclusions: Among these DISC participants intakes of one-carbon metabolism-related vitamins were associated with breast density. Larger prospective studies among diverse populations are needed to replicate these findings., Impact: Our results suggest the importance of one-carbon metabolism-related vitamin intakes early in life with development of breast density and thereby potentially breast cancer risk later in life., (©2024 American Association for Cancer Research.)

Inflammation can play a role in the pathophysiology of depression, and specific types of antidepressants may have inflammatory or anti-inflammatory properties. Furthermore, depression and antidepressant use has been linked to white blood cell (WBC) count, a routinely measured inflammatory marker. We examined the cross-sectional and longitudinal relationships of depressive symptoms and/or antidepressant use with WBC count among postmenopausal women. Analyses of cross-sectional data at enrollment were performed on 125,307 participants, 50-79 years of age, from the Women's Health Initiative Clinical Trials and Observational Studies who met eligibility criteria, and a subset of those with 3-year follow-up data were examined for longitudinal relationships. Depressive symptoms were defined using the Burnam Algorithm whereas antidepressant use was defined using therapeutic class codes. WBC count (Kcell/ml) was obtained through laboratory evaluations of fasting blood samples. Multivariable regression modeling was performed taking sociodemographic, lifestyle and health characteristics into consideration. At enrollment, nearly 85% were non-users of antidepressants with no depressive symptoms, 5% were antidepressant users with no depressive symptoms, 9% were non-users of antidepressants with depressive symptoms, and 2% were users of antidepressants with depressive symptoms. In fully-adjusted models, cross-sectional relationships were observed whereby women in the 2 nd (OR = 1.06, 95% CI: 1.01, 1.13), 3 rd (OR = 1.06, 95% CI: 1.00, 1.12) or 4 th (OR = 1.10, 95% CI: 1.05, 1.17) quartiles of WBC count were more likely to exhibit depressive symptoms, and women in the 4 th quartile were more likely to be users of antidepressants (OR = 1.07, 95% CI: 1.00, 1.15), compared to women in the 1 st quartile. Compared to women who exhibited no depressive symptoms at either visit, those with consistent depressive symptoms at enrollment and at 3-year follow-up had faster decline in WBC count (β = -0.73, 95% CI: -1.33, -0.14) over time. No significant bidirectional relationships were observed between changes in depressive symptoms score and WBC count over time. In conclusion, depressive symptoms and/or antidepressant use were cross-sectionally related to higher WBC counts among postmenopausal women. Further evaluation of observed relationships is needed in the context of prospective cohort studies involving older adult men and women, with repeated measures of depression, antidepressant use, and WBC count., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data., Objectives: We aimed to develop biomarkers for saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities, and to study their associations with cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) in Women's Health Initiative (WHI) cohorts., Methods: Biomarker equations were based primarily on serum and urine metabolomics profiles from an embedded WHI human feeding study (n = 153). Calibration equations were based on biomarker values in a WHI nutritional biomarker study (n = 436). Calibrated intakes were assessed in relation to disease incidence in larger WHI cohorts (n = 81,894). Participants were postmenopausal women, aged 50-79 when enrolled at 40 United States Clinical Centers (1993-1998), with a follow-up period of ∼20 y., Results: Biomarker equations meeting criteria were developed for SFA, MUFA, and PUFA densities. That for SFA density depended somewhat weakly on metabolite profiles. On the basis of our metabolomics platforms, biomarkers were insensitive to trans fatty acid intake. Calibration equations meeting criteria were developed for SFA and PUFA density, but not for MUFA density. With or without biomarker calibration, SFA density was associated positively with risk of CVD, cancer, and T2D, but with small hazard ratios, and CVD associations were not statistically significant after controlling for other dietary variables, including trans fatty acid and fiber intake. Following this same control, PUFA density was not significantly associated with CVD risk, but there were positive associations for some cancers and T2D, with or without biomarker calibration., Conclusions: Higher SFA and PUFA diets were associated with null or somewhat higher risk for clinical outcomes considered in this population of postmenopausal United States women. Further research is needed to develop even stronger biomarkers for these fatty acid densities and their major components. This study is registered with clinicaltrials.gov identifier: NCT00000611., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here, we use WHI observational data for further insight into the chronic disease implications of adopting this type of low-fat dietary pattern., Objectives: We aimed to use our earlier work on metabolomics-based biomarkers of carbohydrate and protein to develop a fat intake biomarker by subtraction, to use the resulting biomarker to develop calibration equations that adjusts self-reported fat intake for measurement error, and to study associations of biomarker-calibrated fat intake with chronic disease risk in WHI cohorts. Corresponding studies for specific fatty acids will follow separately., Methods: Prospective disease association results are presented using WHI cohorts of postmenopausal women, aged 50-79 y when enrolled at 40 United States clinical centers. Biomarker equations were developed using an embedded human feeding study (n = 153). Calibration equations were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with cancer, cardiovascular diseases, and diabetes incidence in WHI cohorts (n = 81,954) over an approximate 20-y follow-up period., Results: A biomarker for fat density was developed by subtracting protein, carbohydrate, and alcohol densities from one. A calibration equation was developed for fat density. Hazard ratios (95% confidence intervals) for 20% higher fat density were 1.16 (1.06, 1.27) for breast cancer, 1.13 (1.02, 1.26) for CHD, and 1.19 (1.13, 1.26) for diabetes, in substantial agreement with findings from the DM trial. With control for additional dietary variables, especially fiber, fat density was no longer associated with CHD, with hazard ratio (95% confidence interval) of 1.00 (0.88, 1.13), whereas that for breast cancer was 1.11 (1.00, 1.24)., Conclusions: WHI observational data support prior DM trial findings of low-fat dietary pattern benefits in this population of postmenopausal United States women., Trial Registration Number: This study is registered with clinicaltrials.gov identifier: NCT00000611., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

This perspective article is a product of a workshop of experts convened by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), a nonprofit organization that brings together scientists from government, academia, and industry to catalyze science relevant to food and nutrition for public benefit. An expert group was convened in March 2022 to discuss the current issues surrounding cognitive task selection in nutrition research, with a focus on solutions toward informing dietary guidance for cognitive health, to address a gap identified in the 2020 United States Dietary Guidelines Advisory Committee report, specifically the "considerable variation in testing methods used, [and] inconsistent validity and reliability of cognitive testing methods." To address this issue, we first undertook an umbrella review of relevant reviews already undertaken; these indicate agreement on some of the issues that affect heterogeneity in task selection, and on many of the fundamental principles underlying the selection of cognitive outcome measures. However, resolving the points of disagreement is critical to ensuring a meaningful impact on the issue of heterogeneity in task selection; these issues hamper the evaluation of existing data for informing dietary guidance. This summary of the literature is therefore followed by the expert group's perspective in the form of a discussion of potential solutions to these challenges, with the aim of building on the work of previous reviews in the area and advancing dietary guidance for cognitive health. Registered on PROSPERO: CRD42022348106. Data described in the manuscript, code book, and analytic code will be made publicly and freely available without restriction at doi.org/10.17605/OSF.IO/XRZCK., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aβ 42/40 ) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment., (© 2023. The Author(s).)

Background: Previous dietary studies and current dietary guidelines have mainly focused on dietary intake and food patterns. Little is known about the association between eating behaviors such as meal frequency, skipping and intervals, and mortality., Objective: The objective was to examine the associations of meal frequency, skipping, and intervals with all-cause and cardiovascular disease (CVD) mortality., Design: This was a prospective study., Participants/setting: A total of 24,011 adults (aged ≥40 years) who participated in the National Health and Nutrition Examination Survey 1999-2014 were included in this study. Eating behaviors were assessed using 24-hour recall. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2015., Main Outcome Measures: The outcomes were all-cause and CVD mortality., Statistical Analyses Performed: Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of all-cause and CVD mortality., Results: During 185,398 person-years of follow-up period, 4,175 deaths occurred, including 878 cardiovascular deaths. Most participants ate three meals per day. Compared with participants eating three meals per day, the multivariable-adjusted HRs for participants eating one meal per day were 1.30 (95% CI 1.03 to 1.64) for all-cause mortality, and 1.83 (95% CI 1.26 to 2.65) for CVD mortality. Participants who skipped breakfast have multivariable-adjusted HRs 1.40 (95% CI 1.09 to 1.78) for CVD mortality compared with those who did not. The multivariable-adjusted HRs for all-cause mortality were 1.12 (95% CI 1.01 to 1.24) for skipping lunch and 1.16 (95% CI 1.02 to 1.32) for skipping dinner compared with those who did not. Among participants eating three meals per day, the multivariable-adjusted HR for participants with an average interval of ≤4.5 hours in two adjacent meals was 1.17 (95% CI 1.04 to 1.32) for all-cause mortality, comparing with those having a meal interval of 4.6 to 5.5 hours., Conclusions: In this large, prospective study of US adults aged 40 years or older, eating one meal per day was associated with an increased risk of all-cause and CVD mortality. Skipping breakfast was associated with increased risk of CVD mortality, whereas skipping lunch or dinner was associated with increased risk of all-cause mortality. Among participant with three meals per day, a meal interval of ≤4.5 hours in two adjacent meals was associated with higher all-cause mortality., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the association between the dietary inflammatory index (DII ® ) and incident cardiovascular disease (CVD) in Hispanic women from the Women's Health Initiative (WHI), and to determine if body mass index (BMI) interacted with the DII scores., Methods: Secondary analysis of baseline dietary data and long-term CVD outcomes among 3,469 postmenopausal women who self-identified as Hispanic enrolled in WHI. DII scores were calculated from self-administered food frequency questionnaires. The CVD outcomes included coronary heart disease (CHD) and stroke. Stratified Cox regression models were used to assess the relationship between DII scores and CVD in women with and without obesity. Models were adjusted for age, lifestyle risk factors, known risk factors, and neighborhood socioeconomic status., Results: The incidence of CHD was 3.4 and 2.8% for stroke after a median follow-up of 12.9 years. None of the DIIs were associated with CVD risk in this sample of Hispanic women. BMI interacted with the DII (p < 0.20) and stratified models showed that the associations between the DII and CVD were only significant in women with overweight (p < 0.05). In this group, higher DII scores were associated with a higher risk of CHD (HR 1.27; 95% CI: 1.08, 1.51) and a higher risk of stroke (HR 1.32; 95% CI: 1.07, 1.64)., Conclusion: Among postmenopausal Hispanic women with overweight, greater adherence to pro-inflammatory diets was associated with higher risk of CVD. Additional research is needed to understand how to promote long-term heart-healthy dietary habits to reduce inflammation and prevent CVD in at-risk Hispanic women., (© 2023. The Author(s).)

Introduction: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B 12 , and B 6 ) modified the association between PM 2.5 exposure and incidence of all-cause dementia., Methods: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3-year average PM 2.5 exposure was estimated using a spatiotemporal model., Results: During a mean follow-up of 9 years, 342 participants developed all-cause dementia. We found that residing in locations with PM 2.5 exposure above the regulatory standard (12 μg/m 3 ) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins., Discussion: This is the first study suggesting that the putative neurotoxicity of PM 2.5 exposure may be attenuated by high B vitamin intakes., (© 2021 the Alzheimer's Association.)

Purpose: We investigated the association of coffee and caffeine with breast cancer (BCa) risk, overall and by ER/PR status. We also examined potential interactions of coffee and caffeine with postmenopausal hormone use., Methods: Our study included 77,688 postmenopausal participants from the Women's Health Initiative observational study cohort without a history of any cancer at baseline (except non-melanoma skin) and with valid Food Frequency Questionnaire data and complete data on dietary caffeine. Regular coffee (none, 1, 2-3, 4-5, and ≥ 6 cups/day) and caffeine (tertiles) were assessed at baseline. Information on BCa risk factors was collected at baseline. The associations were examined using survival analysis, accounting for death as a competing risk., Results: The median follow-up time for our cohort was 18.3 years. During the follow-up, 5005 women developed invasive breast cancer. In multivariable analysis, coffee was not associated with the overall invasive BCa risk. Higher caffeine intake was mildly associated with increased BCa risk (2nd vs. 1st tertile SHR = 1.10, 95% CI 1.03-1.18, 3rd vs. 1st tertile SHR-1.05, 95% CI 0.98-1.13, overall p = 0.03). We found no interaction of coffee/caffeine with postmenopausal hormone use (p interaction = 0.44 and 0.42, respectively). In the exploratory analysis by ER/PR status, we found a positive association of caffeine with ER+ /PR+ BCa (2nd vs. 1st tertile SHR = 1.17, 95% CI 1.07-1.28, 3rd vs. 1st tertile SHR = 1.13, 95% CI 1.03-1.24, overall p = 0.002); no associations were observed for ER-/PR- tumors. Coffee was not associated with the risk of ER+ /PR+ or ER-/PR- tumors., Conclusion: We found no associations of coffee with BCa risk, overall and for ER/PR-defined tumor subtypes. The higher caffeine consumption was mildly and positively associated with the overall BCa risk and with ER+ /PR+ tumors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI)., Methods: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking., Results: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR] highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHR highvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR] highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HR highvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (P trend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification., Conclusions: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality., Lay Summary: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers., (© 2022 American Cancer Society.)

Background: The associations of red and processed meat with chronic disease risk remain to be clarified, in part because of measurement error in self-reported diet., Objectives: We sought to develop metabolomics-based biomarkers for red and processed meat, and to evaluate associations of biomarker-calibrated meat intake with chronic disease risk among postmenopausal women., Methods: Study participants were women who were members of the Women's Health Initiative (WHI) study cohorts. These participants were postmenopausal women aged 50-79 y when enrolled during 1993-1998 at 40 US clinical centers with embedded human feeding and nutrition biomarker studies. Literature reports of metabolomics correlates of meat consumption were used to develop meat intake biomarkers from serum and 24-h urine metabolites in a 153-participant feeding study (2010-2014). Resulting biomarkers were used in a 450-participant biomarker study (2007-2009) to develop linear regression calibration equations that adjust FFQ intakes for random and systematic measurement error. Biomarker-calibrated meat intakes were associated with cardiovascular disease, cancer, and diabetes incidence among 81,954 WHI participants (1993-2020)., Results: Biomarkers and calibration equations meeting prespecified criteria were developed for consumption of red meat and red plus processed meat combined, but not for processed meat consumption. Following control for nondietary confounding factors, hazard ratios were calculated for a 40% increment above the red meat median intake for coronary artery disease (HR: 1.10; 95% CI: 1.07, 1.14), heart failure (HR: 1.26; 95% CI: 1.20, 1.33), breast cancer (HR: 1.10; 95% CI: 1.07, 1.13) for, total invasive cancer (HR: 1.07; 95% CI: 1.05, 1.09), and diabetes (HR: 1.37; 95% CI: 1.34, 1.39). HRs for red plus processed meat intake were similar. HRs were close to the null, and mostly nonsignificant following additional control for dietary potential confounding factors, including calibrated total energy consumption., Conclusions: A relatively high-meat dietary pattern is associated with somewhat higher chronic disease risks. These elevations appear to be largely attributable to the dietary pattern, rather than to consumption of red or processed meat per se., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women's Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR = 1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR = 1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR = 1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, whereas protein density associations were mixed., Objectives: To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber., Methods: Prospective disease association analyses were undertaken in Women's Health Initiative (WHI) cohorts of postmenopausal US women, aged 50-79 y when enrolled at 40 US clinical centers. Biomarkers were developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-y (median) follow-up period, using HR regression methods., Results: Previously reported elevations in cardiovascular disease (CVD) with higher-protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had an HR of 1.20 (95% CI: 1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with a 20% increment HR factor of 0.89 (95% CI: 0.83, 0.94). Cancer risk showed little association with fiber density, whereas diabetes risk had a 20% increment HR of 0.93 (95% CI: 0.88, 0.98) relative to the HRs for total carbohydrate density., Conclusions: In a population of postmenopausal US women, CVD risk was associated with high-animal-protein and low-fiber diets, cancer risk was associated with low-carbohydrate diets, and diabetes risk was associated with low-fiber/low-carbohydrate diets., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Aim: To investigate the association between dietary patterns and total and obesity-related cancers risk. Additionally, to examine if acculturation modifies this relationship., Subject and Methods: Dietary intake of postmenopausal Hispanic women (N=5,482) enrolled in the Women's Health Initiative was estimated from a Food Frequency Questionnaire and used to calculate dietary pattern scores; Healthy Eating Index-2015 (HEI-2015), Mexican Diet (MexD) score, alternate Mediterranean Diet Score (aMED), and the energy adjusted-Dietary Inflammatory Index (E-DII™). Associations were evaluated using Cox proportional hazards regression models., Results: 631 cancers and 396 obesity-related cancers were diagnosed over a mean-follow up of 12 years. Across dietary scores, there were no significant associations with cancer risk or mortality. Trend analysis suggest a potentially lower risk for total cancer related to the highest MexD score (HR 0.68, 95% CI 0.45-1.04, P -trend=0.03), and lower risk for obesity-related cancer mortality related to the highest score category for MexD (HR 0.65, 95% CI 0.37-1.16, P -trend=0.02), and aMED (HR 0.87, 95% CI 0.45-1.67, P -trend=0.04). Further analysis suggests less acculturated women with higher MexD scores had 56% lower risk for any cancer (HR 0.44, 95% CI 0.22-0.88, P- trend=0.03) and 83% lower risk for cancer mortality (HR 0.17, 95% CI 0.04-0.76, P- trend=0.01) compared to more acculturated Hispanic women., Conclusions: Dietary patterns were not associated with cancer risk and mortality in postmenopausal Hispanic women. Less-acculturated, Spanish-preferred speakers, who reported consuming a more traditional Mexican diet may experience a lower risk for cancer and cancer mortality., Competing Interests: Competing Interests: Authors declare no potential conflicts of interest.

Interval breast cancers (IBCs) emerge after a non-suspicious mammogram and before the patient's next scheduled screen. Risk factors associated with IBC have not been identified. This study evaluated if the empirical dietary inflammatory pattern (EDIP) or empirical dietary index for hyperinsulinemia (EDIH) scores are associated with IBC compared to screen-detected breast cancer. Data were from women 50-79 years-old in the Women's Health Initiative cohort who completed food frequency questionnaires at baseline (1993-98) and were followed through March 31, 2019 for breast cancer detection. Women were identified as having either IBC diagnosed within 1-year after their last negative screening mammogram ( N  = 317) or screen-detected breast cancer ( N  = 1,928). Multivariable-adjusted logistic regression analyses were used to estimate odds ratios for risk of IBC compared to screen-detected cancer in dietary index tertiles. No associations were observed between EDIP or EDIH and IBC. Odds ratios comparing the highest to the lowest dietary index tertile were 1.08; 95%CI, 0.78-1.48 for EDIP and 0.92; 95%CI, 0.67-1.27 for EDIH. The null associations persisted when stratified by BMI categories. Findings suggest that diet-driven inflammation or insulinemia may not be substantially associated with IBC risk among postmenopausal women. Future studies are warranted to identify modifiable factors for IBC prevention.

Background: Maternal nutrition during pregnancy and lactation has profound effects on the development and lifelong health of the child. Long-chain PUFAs are particularly important for myelination and the development of vision during the perinatal period., Objectives: We conducted a systematic review to examine the relationship between supplementation with omega-3 fatty acids during pregnancy and/or lactation and neurodevelopment in children, to inform the Scientific Report of the 2020 Dietary Guidelines Advisory Committee., Methods: We identified articles on omega-3 fatty acid supplementation in pregnant and lactating women that included measures of neurodevelopment in their children (0-18 y) by searching PubMed, CENTRAL, Embase, and CINAHL Plus. After dual screening articles for inclusion, we qualitatively synthesized and graded the strength of evidence using pre-established criteria for assessing risk of bias, consistency, directness, precision, and generalizability., Results: We included 33 articles from 15 randomized controlled trials (RCTs) and 1 prospective cohort study. Of the 8 RCTs that delivered omega-3 fatty acid dietary supplements during pregnancy alone (200-2200 mg/d DHA and 0-1100 mg/d EPA for approximately 20 wk), 5 studies reported ≥1 finding that supplementation improved measures of cognitive development in the infant or child by 6%-11% (P < 0.05), but all 8 studies also reported ≥1 nonsignificant (P > 0.05) result. There was inconsistent or insufficient evidence for other outcomes (language, social-emotional, physical, motor, or visual development; academic performance; risks of attention deficit disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, anxiety, or depression) and for supplementation during lactation or both pregnancy and lactation. Populations with a lower socioeconomic status and adolescents were underrepresented and studies lacked racial and ethnic diversity., Conclusions: Limited evidence suggests that omega-3 fatty acid supplementation during pregnancy may result in favorable cognitive development in the child. There was insufficient evidence to evaluate the effects of omega-3 fatty acid supplementation during pregnancy and/or lactation on other developmental outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions compared with a spot urine sample, if comparable, could reduce participant burden in epidemiologic and clinical studies., Objectives: In a 2-week controlled-feeding study, Na and K excretions from a 24-h urine collection were compared with a first-void spot urine sample, applying established algorithms and enhanced models to estimate 24-h excretion. Actual and estimated 24-h excretions were evaluated relative to mean daily Na and K intakes in the feeding study., Methods: A total of 153 older postmenopausal women ages 75.4 ± 3.5 y participated in a 2-wk controlled-feeding study with a 4-d repeating menu cycle based on their usual intake (ClinicalTrials.gov Identifier: NCT00000611). Of the 150 participants who provided both a first-void spot urine sample and a 24-h urine collection on the penultimate study day, statistical methods included Pearson correlations for Na and K between intake, 24-h collections, and the 24-h estimated excretions using 4 established algorithms: enhanced biomarker models by regressing ln-transformed intakes on ln-transformed 24-h excretions or ln-transformed 24-h estimated excretions plus participant characteristics and sensitivity analyses for factors potentially influencing Na or K excretion (e.g., possible kidney disease estimated glomerular filtration rate <60 mL/min/1.73 m 2 )., Results: Pearson correlation coefficients between Na and K intakes and actual 24-h excretions were 0.57 and 0.38-0.44 for estimated 24-h excretions, depending on electrolyte and algorithm used. Enhanced biomarker model cross-validated R 2 (CVR 2 ) for 24-h excretions were 38.5% (Na), 40.2% (K), and 42.0% (Na/K). After excluding participants with possible kidney disease, the CVR 2 values were 43.2% (Na), 40.2% (K), and 38.1% (Na/K)., Conclusions: Twenty-four-hour urine excretion measurement performs better than estimated 24-h excretion from a spot urine as a biomarker for Na and K intake among a sample of primarily White postmenopausal women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components., Methods: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score., Results: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01)., Conclusions: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk., Registry: ClinicalTrials.gov (NCT00000611)., (© 2021. The Author(s), under exclusive licence to Cancer Research UK.)

Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia., Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake., Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P <0.0001), but not significantly among the lowest SSB consumers ( P =0.81; P Diff <0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (β, 0.06 [95% CI, 0.02-0.09] ln-mg/dL per allele, P =0.001) but not the lowest SSB consumers ( P =0.84; P Diff =0.0005)., Conclusions: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited., Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR)., Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions., Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk., Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Purpose: Personality traits have been reported to be associated with type 2 diabetes (T2DM) risk. The objective of this study was to examine whether and to what extent the associations between personality traits (dispositional optimism, hostility, and negative emotional expressiveness) and risk of T2DM were mediated by health behaviors and obesity., Methods: Postmenopausal women (n = 110,992) aged 50-79 years without diabetes at enrollment in the Women's Health Initiative study (1993-1998) were followed up to 25 years. Incident diabetes was assessed via a validated self-report of physician-diagnosed diabetes treated with insulin or other hypoglycemic medications. Mediation analyses were performed using approaches under a counterfactual framework., Results: An inverse association of optimism with diabetes was significantly mediated by a factor primarily extracted from physical activity, diet quality, and sleep quality with a mediated proportion of 28%. Positive associations for hostility and negative emotional expressiveness were substantially mediated by a factor primarily composed of body mass index and waist circumference with mediated proportions of 32% and 44%, respectively., Conclusions: Our data revealed that less than half of the associations between personality traits and risk of T2DM were explained by indirect health behavior pathways. Women's personality traits should be considered in prevention of diabetes in addition to promoting health behaviors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The Western dietary pattern (WD) is positively associated with risk of coronary artery disease (CAD) and cancer, whereas the Prudent dietary pattern (PD) may be protective. Foods may influence metabolite concentrations as well as oxidative stress and lipid dysregulation, biological mechanisms associated with CAD and cancer., Objective: The aim was to assess the association of 2 derived dietary pattern scores with serum metabolites and identify metabolic pathways associated with the metabolites., Methods: We evaluated the cross-sectional association between each dietary pattern (WD, PD) and metabolites in 2199 Women's Health Initiative (WHI) participants. With FFQ and factor analysis, we determined 2 dietary patterns consistent with WD and PD. Metabolites were measured with LC-tandem MS. Metabolite discovery among 904 WHI Observational Study (WHI-OS) participants was replicated among 1295 WHI Hormone Therapy Trial (WHI-HT) participants. We analyzed each of 495 metabolites with each dietary score (WD, PD) in linear regression models., Results: The PD included higher vegetables and fruit intake compared with the WD with higher saturated fat and meat intake. Independent of energy intake, BMI, physical activity, and other confounding variables, 45 overlapping metabolites were identified (WHI-OS) and replicated (WHI-HT) with an opposite direction of associations for the WD compared with the PD [false discovery rate (FDR) P < 0.05]. In metabolite set enrichment analyses, phosphatidylethanolamine (PE) plasmalogens were positively enriched for association with WD [normalized enrichment score (NES) = 2.01, P = 0.001, FDR P = 0.005], and cholesteryl esters (NES = -1.77, P = 0.005, FDR P = 0.02), and phosphatidylcholines (NES = -1.72, P = 0.01, P = 0.03) were negatively enriched for WD. PE plasmalogens were positively correlated with saturated fat and red meat. Phosphatidylcholines and cholesteryl esters were positively correlated with fatty fish., Conclusions: Distinct metabolite signatures associated with Western and Prudent dietary patterns highlight the positive association of mitochondrial oxidative stress and lipid dysregulation with a WD and the inverse association with a PD., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Over 23 million Americans have type 2 diabetes (T2D). Eating habits such as breakfast consumption, time-restricted eating, and limiting daily eating occasions have been explored as behaviors for reducing T2D risk, but prior evidence is inconclusive., Objectives: Our objectives were to examine associations between number of daily eating occasions and T2D risk in the Women's Health Initiative Dietary Modification Trial (WHI-DM) and whether associations vary by BMI, age, or race/ethnicity., Methods: Participants were postmenopausal women in the WHI-DM who comprised a 4.6% subsample completing 24-h dietary recalls (24HRs) at years 3 and 6 as part of trial adherence activities ( n  = 2159). Numbers of eating occasions per day were obtained from the year 3 24HRs, and participants were grouped into approximate tertiles as 1-3 ( n  = 795), 4 ( n  = 713), and ≥5 ( n  = 651) daily eating occasions as the exposure. Incident diabetes was self-reported on semiannual questionnaires as the outcome., Results: Approximately 15% (15.4%, n  = 332) of the WHI-DM 24HR cohort reported incident diabetes at follow-up. Cox proportional hazards regression tested associations of eating occasions with T2D adjusted for neighborhood socioeconomic status, BMI, waist circumference, race/ethnicity, family history of T2D, recreational physical activity, Healthy Eating Index-2005, 24HR energy intake, and WHI-DM arm. Compared with women reporting 1-3 meals/d, those consuming 4 meals/d had a T2D HR = 1.38 (95% CI: 1.03, 1.84) without further increases in risk for ≥5 meals/d. In stratified analyses, associations for 4 meals/d compared with 1-3 meals/d were stronger in women with BMI <30.0 kg/m 2 (HR = 1.55; 95% CI: 1.00, 2.39) and women aged ≥60 (HR = 1.61; 95% CI: 1.11, 2.33)., Conclusions: Four meals per day compared with 1-3 meals/d was associated with increased risk of T2D in postmenopausal women, but no dose-response effect was observed for additional eating occasions. Further studies are needed to understand eating occasions in relation to T2D risk., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Objective: To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation., Research Design and Methods: We included 84,285 postmenopausal women without a history of diabetes from the national Women's Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women who participated in the WHI-Clinical Trial (WHI-CT). Additionally, data from a case-control study of 3,749 women nested in the WHI-OS with information on biomarkers of inflammation and endothelial dysfunction were examined using mediation analysis to determine the relative contributions of these known biomarkers by which manganese affects type 2 diabetes risk., Results: Compared with the lowest quintile of energy-adjusted dietary manganese, WHI-OS participants in the highest quintile had a 30% lower risk of type 2 diabetes (hazard ratio [HR] 0.70 [95% CI 0.65, 0.76]). A consistent association was also confirmed in the WHI-CT (HR 0.79 [95% CI 0.73, 0.85]). In the nested case-control study, higher energy-adjusted dietary manganese was associated with lower circulating levels of inflammatory biomarkers that significantly mediated the association between dietary manganese and type 2 diabetes risk. Specifically, 19% and 12% of type 2 diabetes risk due to manganese were mediated through interleukin 6 and hs-CRP, respectively., Conclusions: Higher intake of manganese was directly associated with a lower type 2 diabetes risk independent of known risk factors. This association may be partially mediated by inflammatory biomarkers., (© 2020 by the American Diabetes Association.)

Purpose: Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women's Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence., Methods: In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings., Results: During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02)., Conclusion: Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.

Background: Multiple methods of correcting nutrient intake for misreported energy intake have been proposed but have not been extensively compared. The availability of the Women's Health Initiative (WHI) data set, which includes several objective recovery biomarkers, offers an opportunity to compare these corrections with respect to protein intake., Objective: We compared 5 energy-correction methods for self-reported dietary protein against urinary nitrogen-derived protein intake., Methods: As part of the WHI Nutritional Biomarkers Study (NBS) 544 participants (50- to 80-y-old women) completed a FFQ and biomarker assessments using doubly labeled water (DLW) for total energy expenditure (TEE) and 24-h urinary nitrogen. Correction methods evaluated were as follows: 1) DLW-TEE; 2) the Institute of Medicine's (IOM's) estimated energy requirement (EER) TEE prediction equation based on sex, height, weight, and age; 3) published NBS total energy TEE prediction (WHI-NBS-TEE) using age, BMI, race, and income; 4) reported protein versus reported energy linear regression-based residual method; and 5) a Goldberg cutoff to exclude subjects reporting energy intakes <1.35 times their basal metabolic rate. Efficacy was evaluated using correlations obtained by regressing corrected protein against biomarker protein (6.25 × urinary nitrogen/0.81)., Results: Unadjusted self-reported protein intake from the FFQ (mean = 66.7 g) correlated weakly (r = 0.31) with biomarker protein (mean = 74.9 g). DLW-TEE-corrected self-reported protein intake (mean = 90.7 g) had the strongest correlation with biomarker protein (r = 0.47). Other energy corrections yielded lower, but still significant correlations: EER, r = 0.44 (mean = 92.1 g); WHI-NBS-TEE, r = 0.37 (mean = 90.4 g); Goldberg cutoff, r = 0.36 (mean = 88.4 g); and residual method, r = 0.35 (mean = 66.7 g)., Conclusions: Our data indicate that proportional correction of reported protein intake using a measure of energy requirement from DLW-TEE or IOM-EER performed modestly better than other methods in this cohort. These energy adjustments, however, yielded corrected protein exceeding the biomarker protein, indicating that energy adjustment alone does not eliminate all self-reported protein reporting bias., (Copyright © The Author(s) 2020.)

Objective: To examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS)., Methods: We identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS., Results: There was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], p for trend = 0.054), but in multivariable models the association was only evident in men., Conclusions: The majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies., (© 2019 American Academy of Neurology.)

Background: Previous studies have shown mixed results on the association between carbohydrate intake and insomnia. However, any influence that refined carbohydrates have on risk of insomnia is likely commensurate with their relative contribution to the overall diet, so studies are needed that measure overall dietary glycemic index (GI), glycemic load, and intakes of specific types of carbohydrates., Objective: We hypothesized that higher GI and glycemic load would be associated with greater odds of insomnia prevalence and incidence., Methods: This was a prospective cohort study with postmenopausal women who participated in the Women's Health Initiative Observational Study, investigating the relations of GI, glycemic load, other carbohydrate measures (added sugars, starch, total carbohydrate), dietary fiber, and specific carbohydrate-containing foods (whole grains, nonwhole/refined grains, nonjuice fruits, vegetables, dairy products) with odds of insomnia at baseline (between 1994 and 1998; n = 77,860) and after 3 y of follow-up (between 1997 and 2001; n = 53,069)., Results: In cross-sectional and longitudinal analyses, higher dietary GI was associated with increasing odds of prevalent (fifth compared with first quintile OR: 1.11; CI: 1.05, 1.16; P-trend = 0.0014) and incident (fifth compared with first quintile OR: 1.16; CI: 1.08, 1.25; P-trend < 0.0001) insomnia in fully adjusted models. Higher intakes of dietary added sugars, starch, and nonwhole/refined grains were each associated with higher odds of incident insomnia. By contrast, higher nonjuice fruit and vegetable intakes were significantly associated with lower odds of incident insomnia. Also, higher intakes of dietary fiber, whole grains, nonjuice fruit, and vegetables were significantly associated with lower odds of prevalent insomnia., Conclusions: The results suggest that high-GI diets could be a risk factor for insomnia in postmenopausal women. Substitution of high-GI foods with minimally processed, whole, fiber-rich carbohydrates should be evaluated as potential treatments of, and primary preventive measures for, insomnia in postmenopausal women., (Copyright © The Author(s) 2019.)

Citrus products are rich sources of furocoumarins, a class of photoactive compounds. Certain furocoumarins combined with ultraviolet radiation can induce skin cancer. We examined the relationship between citrus consumption and cutaneous melanoma risk among 56,205 Caucasian postmenopausal women in the Women's Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by citrus intake level. During a mean follow-up of 15.7 years, 956 incident melanoma cases were documented. In multivariable adjusted models, the HR (95% CI) for melanoma was 1.12 (0.91, 1.37) among the highest citrus consumers (1.5+ servings/day of fruit or juice) versus the lowest (<2 servings/week), 0.95 (0.76, 1.20) among the highest citrus fruit consumers (5+ servings/week) versus non-consumers, and was 1.13 (0.96, 1.32) for the highest citrus juice consumers (1+ servings/day) versus the lowest (<1 serving/week). In stratified analyses, an increased melanoma risk associated with citrus juice intake was observed among women who spent the most time outdoors in summer as adults; the HR for the highest versus lowest intake was 1.22 (1.02, 1.46) ( p trend = 0.03). Further research is needed to explore the association of melanoma with citrus juices among women with high sun exposure.

Background: Contemporary energy expenditure data are crucial to inform and guide nutrition policy in older adults to optimize nutrition and health., Objective: The aim was to determine the optimal method of estimating total energy expenditure (TEE) in adults (aged ≥65 y) through 1) establishing which published predictive equations have the closest agreement between measured resting metabolic rate (RMR) and predicted RMR and 2) utilizing the RMR equations with the best agreement to predict TEE against the reference method of doubly labeled water (DLW)., Methods: A database consisting of international participant-level TEE data from DLW studies was developed to enable comparison with energy requirements estimated by 17 commonly used predictive equations. This database included 31 studies comprising 988 participant-level RMR data and 1488 participant-level TEE data. Mean physical activity level (PAL) was determined for men (PAL = 1.69, n = 320) and women (PAL = 1.66, n = 668). Bland-Altman plots assessed agreement of measured RMR and TEE with predicted RMR and TEE in adults aged ≥65 y, and subgroups of 65-79 y and ≥80 y. Linear regression assessed proportional bias., Results: The Ikeda, Livingston, and Mifflin equations most closely agreed with measured RMR and TEE in all adults aged ≥65 y and in the 65-79 y and ≥80 y subgroups. In adults aged ≥65 y, the Ikeda and Livingston equations overestimated TEE by a mean ± SD of 175 ± 1362 kJ/d and 86 ± 1344 kJ/d, respectively. The Mifflin equation underestimated TEE by a mean ± SD of 24 ± 1401 kJ/d. Proportional bias was present as energy expenditure increased., Conclusions: The Ikeda, Livingston, or Mifflin equations are recommended for estimating energy requirements of older adults. Future research should focus on developing predictive equations to meet the requirements of the older population with consideration given to body composition and functional measures., (Copyright © American Society for Nutrition 2019.)

Objective: High consumption of soft drinks has been associated with lower bone mineral density among postmenopausal women. This study explores the association of soft drink consumption, osteoporosis, and incidental fractures in this population., Methods: Cross-sectional (at baseline) and cohort combined designs, over 11.9 years of median follow-up for 72,342 postmenopausal women participating in the Women's Health Initiative Observational Study. Multiple linear regression models were used to examine the cross-sectional associations between soft drink consumption and hip and lumbar spine bone mineral density. Cox proportional hazards regression models were used to examine the association of soft drink consumption with incident hip fractures., Results: There were no associations between soft drink consumption and hip or lumbar spine t scores. During 700,388 person-years of follow-up, 2,578 hip fractures occurred. Adjusted hazard ratios for incident hip fracture for the highest consumption category compared with no consumption were 1.26 (95% confidence interval [CI] 1.01-1.56) for total soda and 1.32 (95% CI 1.00-1.75) for caffeine-free soda. There was no association between caffeinated soda and incident hip fracture (hazard ratio = 1.16; 95% CI 0.86-1.57). There was no apparent linear trend in the risk of hip fracture across categories of soda consumption in the fully adjusted models, suggesting a threshold effect. A sensitivity analysis using adjudicated hip fractures showed significant associations for all three soda exposures in the highest intake groups., Conclusions: Consuming more than two servings of soft drinks per day on average showed potential associations with higher risk of hip fracture among postmenopausal women.

Barriers to following dietary recommendations have been described; however, they remain poorly understood. The purpose of this qualitative study was to explore perceived barriers to adherence to dietary recommendations in a diverse hemodialysis patient population. Participants were eligible to participate in a semi-structured qualitative telephone interview prior to randomization for an ongoing clinical trial to evaluate the efficacy of an intervention designed to reduce dietary sodium intake. Interviews were digitally recorded, transcribed verbatim and coded using an iterative qualitative process. In total, 30 (37% females, 53% Caucasians) participants, 63.2 ± 13.3 years, were interviewed. Time, convenience, and financial constraints hindered dietary adherence. Dietary counseling efforts were rated positively but require individualization. Ability to follow recommended guidelines was challenging. Suggestions for addressing barriers include technology-based interventions that allow patients to improve food choices and real-time decision-making, and permit tailoring to individual barriers and preferences.

Background: Fiber-based prebiotic supplements are marketed for maintaining bowel health and promoting beneficial gut bacteria. However, the association between prebiotic supplement use and colorectal cancer risk and mortality is unknown., Methods: The association between prebiotic use and colorectal cancer risk and mortality was evaluated in postmenopausal women in the Women's Health Initiative study. Self-reported prebiotic use was documented at study enrollment. Adjudicated colorectal cancer cases and mortality were captured using medical and death records. Cox proportional hazards models were used to estimate the HR related to prebiotic use and colorectal cancer risk and mortality., Results: In total, 3,032 colorectal cancer cases were diagnosed during an average 15.4 years of follow-up. Overall, 3.7% of women used a prebiotic with psyllium, the major fiber type. Use of any prebiotic supplement was not associated with colorectal cancer risk or mortality. The type of prebiotic supplement (none vs. insoluble or soluble) was not associated with colorectal cancer risk; however, use of insoluble fiber prebiotics compared with none was associated with higher colorectal cancer mortality [HR, 2.79; 95% confidence interval (CI), 1.32-5.90; P = 0.007]. Likelihood ratio tests indicated no significant interactions between prebiotic use and other colorectal cancer risk factors, including metabolic syndrome., Conclusions: Prebiotic fiber supplement use was not associated with colorectal cancer risk. Insoluble, but not soluble, prebiotic fiber use was associated with higher colorectal cancer mortality. These findings do not support the promotion of prebiotic fiber supplements to reduce colorectal cancer risk or colorectal cancer mortality., Impact: Further investigation is warranted for findings regarding insoluble prebiotic fiber and higher colorectal cancer mortality in postmenopausal women., (©2019 American Association for Cancer Research.)

Background: The preferred macronutrient dietary composition, and the health consequences of dietary fat reduction specifically, have been debated for decades. Here we provide a comprehensive overview of long-term health outcomes in the Women's Health Initiative Dietary Modification (DM) trial., Objective: The DM trial aimed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer, colorectal cancer, and, secondarily, coronary heart disease (CHD), with various other health outcomes also considered., Methods: The DM trial is a randomized controlled trial conducted at 40 centers in the US, among 48,835 postmenopausal women aged 50-79 y with baseline intake of ≥32% energy from fat. Participants were randomly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group, during 1993-1998. Intervention goals were to reduce fat intake from ∼35% to 20% of total energy, in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d., Results: Over an 8.5-y (median) intervention period, intervention and comparison group differences included lower fat by 8-10%, and higher carbohydrate by 8-10%, of total energy, in conjunction with higher consumption of vegetables, fruit, and grains. Time-to-outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer, colorectal cancer, or CHD, either over the intervention period or over longer-term cumulative follow-up. Additional analyses showed significant intervention group benefits related to breast cancer, CHD, and diabetes, without adverse effects. Over a 19.6-y (median) follow-up period, HRs (95% CIs) were 0.84 (0.74, 0.96) for breast cancer followed by death, and 0.87 (0.77, 0.98) for diabetes requiring insulin., Conclusions: Reduction in dietary fat with corresponding increase in vegetables, fruit, and grains led to benefits related to breast cancer, CHD, and diabetes, without adverse effects, among healthy postmenopausal US women., This trial was registered at clinicaltrials.gov as NCT00000611., (Copyright © American Society for Nutrition 2019.)

Background . The gateway behavior hypothesis posits that change in a health behavior targeted for modification may promote positive changes in other untargeted health behaviors; however, previous studies have shown inconsistent results. Aims . To examine the patterns and predictors of change in untargeted health behaviors in a large health behavior change trial. Method . Using repeated-measures latent class analysis, this study explored patterns of change in untargeted physical activity, alcohol consumption, and smoking behavior during the first year of the Women's Health Initiative dietary modification trial that targeted total fat reduction to 20% kcal and targeted increased fruit and vegetable intake. Participants were healthy postmenopausal women who were randomly assigned to either the low-fat dietary change intervention ( n = 8,193) or a control ( n = 12,187) arm. Results . Although there were increases in untargeted physical activity and decreases in alcohol consumption and smoking in the first year, these changes were not consistently associated with study arm. Moreover, although the results of the repeated-measures latent class analysis identified three unique subgroups of participants with similar patterns of untargeted health behaviors, none of the subgroups showed substantial change in the probability of engagement in any of the behaviors over 1 year, and the study arms had nearly identical latent class solutions. Discussion and Conclusion . These findings suggest that the dietary intervention did not act as a gateway behavior for change in the untargeted behaviors and that researchers interested in changing multiple health behaviors may need to deliberately target additional behaviors.

Purpose: To investigate associations between lipid profiles and fatigue in a cohort of progressive multiple sclerosis (MS) patients on a diet-based multimodal intervention., Methods: This pilot study included 18 progressive MS patients who participated in a prospective longitudinal study of fatigue following a diet-based multimodal intervention that included exercise, neuromuscular electrical stimulation and stress reduction. The diet recommended high intake of vegetables and fruits, encouraged consumption of animal and plant protein and excluded foods with gluten-containing grains, dairy and eggs. Fatigue was measured on the Fatigue Severity Scale (FSS) at baseline and every 3 months for 12 months. A lipid profile consisting of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) was obtained on fasting blood samples at baseline and 12 months., Results: FSS scores decreased from a baseline of 5.51 (95% CI: 4.86, 6.16) to a mean of 3.03 (95% CI: 2.23, 3.82) at 12 months (p < 0.001). At 12 months, increases in HDL-C (mean change: +6.0 mg/dl; 95% CI: 0.3, 12.0; p = 0.049) and decreases in BMI (mean change: -2.6 kg/m2; 95% CI: -3.6, -2.5; p < 0.001), LDL-C (mean change: -10.4 mg/dl; 95% CI:-19.7, -1.2; p = 0.029), TG (mean change: -29.2 mg/dl; 95% CI: -44.3, -14.2; p = 0.001), TG to HDL-C ratio (mean change: -0.6; 95% CI: -1.0, -0.3; p = 0.002) and TC to HDL-C ratio (mean change:-0.6; 95% CI: -1.0, -0.3; p = 0.003) were observed compared to baseline. Improvements in FSS were associated with increases in HDL-C (β = -0.05; 95% CI: -0.1, -0.0004; p = 0.048) and changes in TC (p = 0.005) from baseline to 12 months., Conclusions: Lipid profile variables are associated with improvements in fatigue in progressive MS patients on a diet-based multimodal intervention., Competing Interests: DJO Inc. provided in-kind support for the use of electrotherapy devices and electrode. Pinnaclife Inc. provided study vitamins and supplements. TZ Press LLC provided print materials. This does not alter our adherence to PLOS One policies on sharing data and materials. Dr. Terry L Wahls owns the copyrights to the books Minding My Mitochondria, 2nd Edition, The Wahls Protocol: A Radical New Way to Treat All Chronic Autoimmune Conditions Using Paleo Principles, and The Wahls Protocol Cooking for Life: The Revolutionary Modern Paleo Plan to Treat All Chronic Autoimmune Conditions. Dr. Wahls has research funding from the National Multiple Sclerosis Society and has financial relationships with Penguin Random House Inc., Integrative Medicine for Mental Health, Institute for Health and Healing, Suttler Pacific, BioCeuticals, NCURA, MCG Health Inc., Genova Diagnostics and Metagenics Institute. Dr. Wahls has also trademarked the following terms: Wahls™ Diet, Wahls Paleo™ Diet, Wahls Paleo Plus™ Diet, Wahls Protocol® and has equity interest in TZ Press, LLC, Dr. Terry Wahls, LLC, The Wahls Institute, PLC, and the website www.terrywahls.com. Conflict of interest management plans have been completed and are on file with the University of Iowa and the Iowa City Veterans Affairs Health Care System.

Background and Purpose- We examine the association between self-reported consumption of artificially sweetened beverages (ASB) and stroke and its subtypes, coronary heart disease, and all-cause mortality in a cohort of postmenopausal US women. Methods- The analytic cohort included 81 714 women from the Women's Health Initiative Observational Study, a multicenter longitudinal study of the health of 93 676 postmenopausal women of ages 50 to 79 years at baseline who enrolled in 1993 to 1998. This prospective study had a mean follow-up time of 11.9 years (SD of 5.3 years.) Participants who completed a follow-up visit 3 years after baseline were included in the study. Results- Most participants (64.1%) were infrequent consumers (never or <1/week) of ASB, with only 5.1% consuming ≥2 ASBs/day. In multivariate analyses, those consuming the highest level of ASB compared to never or rarely (<1/wk) had significantly greater likelihood of all end points (except hemorrhagic stroke), after controlling for multiple covariates. Adjusted models indicated that hazard ratios and 95% confidence intervals were 1.23 (1.02-1.47) for all stroke; 1.31 (1.06-1.63) for ischemic stroke; 1.29 (1.11-1.51) for coronary heart disease; and 1.16 (1.07-1.26) for all-cause mortality. In women with no prior history of cardiovascular disease or diabetes mellitus, high consumption of ASB was associated with more than a 2-fold increased risk of small artery occlusion ischemic stroke hazard ratio =2.44 (95% confidence interval, 1.47-4.04.) High consumption of ASBs was associated with significantly increased risk of ischemic stroke in women with body mass index ≥30; hazard ratio =2.03 (95% confidence interval, 1.38-2.98). Conclusions- Higher intake of ASB was associated with increased risk of stroke, particularly small artery occlusion subtype, coronary heart disease, and all-cause mortality. Although requiring replication, these new findings add to the potentially harmful association of consuming high quantities of ASB with these health outcomes.

Background: In the Women's Health Initiative Dietary Modification trial, a low-fat dietary pattern reduced deaths after breast cancer. Mortality from other cancer sites has not been reported., Methods: A low-fat dietary pattern influence on deaths from and after site-specific cancers was examined during 8.5 years (median) of dietary intervention and cumulatively during 17.7 years (median) of follow-up. A total 48 835 postmenopausal women, ages 50-79 years, were randomly assigned from 1993 to 1998 at 40 US clinical centers to dietary intervention (40%, n = 19 541 or a usual diet comparison group (60%, n = 29 294). Dietary intervention influence on mortality from protocol-specified cancers (breast, colon and rectum, endometrium and ovary), individually and as a composite, represented the primary analyses., Results: During the dietary intervention period, a reduction in deaths after breast cancer (HR = 0.65 95% CI = 0.45 to 0.94, P  = .02) was the only statistically significant cancer mortality finding. During intervention, the HRs for deaths after the protocol-specified cancer composite were 0.90 (95% CI = 0.73 to 1.10) and 0.95 (95% CI = 0.85 to 1.06) for deaths after all cancers. During 17.7 years of follow-up with 3867 deaths after all cancers, reduction in deaths after breast cancer continued in the dietary intervention group (HR = 0.85, 95% CI = 0.74 to 0.99, P  = .03). However, no dietary intervention influence on deaths from or after any other cancer or cancer composite was seen., Conclusions: A low-fat dietary pattern reduced deaths after breast cancer. No reduction in mortality from or after any other cancer or cancer composite was seen.

Background: The prevalence of arthritis in the United States is substantial and on the rise. Long-chain n-3 polyunsaturated fatty acids, which have anti-inflammatory properties, have been shown to provide therapeutic benefit to arthritis patients; however, to date few have examined these associations with arthritis risk., Objective: The study objective was to examine the associations of long-chain n-3 polyunsaturated fatty acids intake with osteoarthritis (OA) and rheumatoid arthritis (RA) risk among postmenopausal women., Design: This was a prospective cohort study., Participants: The sample for this analysis consisted of 80,551 postmenopausal women, aged 55 to 79 years and with no history of arthritis, recruited into the Women's Health Initiative Observational Study and Clinical Trials cohort between 1993 and 1998. Women completed a 120-item food frequency questionnaire at baseline., Main Outcome Measures: After a median follow-up of 8 years, 22,306 incident OA and 3,348 RA cases were identified., Statistical Analyses Performed: Adjusted Cox regression models were used to estimate hazard ratios and 95% CI for the associations between dietary LCn-3PUFA intake and OA and RA risk., Results: Individual and total long-chain n-3 polyunsaturated fatty acids (Quintile 5 vs Quintile 1: hazard ratio 1.04, 95% CI 0.99 to 1.09 for OA; hazard ratio 1.01, 95% CI 0.90 to 1.13 for RA) were not associated with OA and RA risk. Further, no associations were observed between n-6 polyunsaturated fatty acids intake and either arthritis outcome., Conclusions: This study is the first to examine associations of long-chain n-3 polyunsaturated fatty acids intake with OA risk and the largest to examine associations with RA risk. Despite their therapeutic potential, the study provides no evidence of benefit of these nutrients in relation to arthritis risk., (Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)