Search

BackgroundEpidemiological studies have been inconsistent regarding the relations between diabetes risk and the consumption of eggs and nutrients in eggs, such as choline, betaine, and cholesterol. There have been few studies among elderly women.ObjectivesThe objective of this study was to examine associations between consumption of eggs, cholesterol, choline, and betaine and the risk of diabetes among elderly US women.MethodsMultivariable Cox regression was used with data from the prospective Women's Health Initiative. Population attributable risks were calculated. Consumption of eggs alone (not mixed in foods) and nutrients were assessed with an FFQ. Diabetes incidence was defined as the first incidence of self-reported diabetes treated with oral diabetes medication or insulin injections.ResultsThere were 46,263 women at follow-up baseline. During 13.3 y and 592,984 person-years of follow-up, there were 5480 incident diabetes cases. Higher egg, cholesterol, and choline consumption were each significantly associated with increases in diabetes risk. The associations for eggs and choline were not significant after adjustment for cholesterol consumption. The association for eggs was attenuated after adjustment for non-egg cholesterol consumption, with 1 significant HR in the top consumption quintile (≥3 eggs/wk) of 1.15 (95% CI: 1.05, 1.27; P for linear trend = 0.0001). The population attributable risks for obesity, overweight, consumption of ≥3 eggs/wk, inadequate exercise, and poor diet were 25.0 (95% CI: 22.3, 27.6), 12.8 (95% CI: 11.1, 14.5), 4.2 (95% CI: 2.3, 6.1), 3.5 (95% CI: 1.2, 5.8), and 3.1 (95% CI: 0.5, 5.7), respectively.ConclusionsAs egg consumption increased to ≥3 eggs/wk, there was a steady increase in diabetes risk that may have been due to the cholesterol in the eggs. The population attributable risk for ≥3 eggs/wk was far lower than that for being obese or overweight.

BackgroundThe effects of dietary protein on bone health are controversial.ObjectiveWe examined the relation between protein intake with fracture and bone mineral density (BMD) within the Women's Health Initiative (WHI).DesignThis prospective analysis included 144,580 women aged 50-79 y at baseline in the WHI clinical trials (CTs) and observational study (OS) that recruited participants in 1993-1998 with follow-up through 2011. Self-reported clinical fractures were collected semiannually through the original end of the trials (WHI CTs) and annually (WHI OS) by questionnaires. Hip fracture was adjudicated by a central review of radiology reports. BMDs for total body, hip, and spine were measured at baseline and 3 and 6 y in 9062 women at 3 WHI clinics by using dual-energy X-ray absorptiometry. Protein intake was assessed via food-frequency questionnaire and calibrated by using biomarkers of energy and protein intakes. Associations between protein intake and fracture were estimated by using Cox proportional hazards regression, and the relation between protein intake and BMD was estimated by using linear regression.ResultsMedian biomarker-calibrated protein intake was 15% of energy intake. Per 20% increase in calibrated protein intake (percentage of energy), there was no significant association with total fracture (HR: 0.99; 95% CI: 0.97, 1.02) or hip fracture (HR: 0.91; 95% CI: 0.84, 1.00), but there was an inverse association with forearm fracture (HR: 0.93; 95% CI: 0.88, 0.98). Each 20% increase in calibrated protein intake was associated with a significantly higher BMD for total body (mean 3-y change: 0.003 g/cm²; 95% CI: 0.001, 0.005 g/cm²) and hip (mean 3-y change: 0.002 g/cm²; 95% CI: 0.001, 0.004 g/cm²).ConclusionsHigher biomarker-calibrated protein intake within the range of usual intake was inversely associated with forearm fracture and was associated with better maintenance of total and hip BMDs. These data suggest higher protein intake is not detrimental to bone health in postmenopausal women.

Background Although older adults commonly take multivitamin-multimineral (MVM) supplements to promote health, evidence on the use of daily MVMs on invasive cancer is limited. Objectives The study objective was to determine if a daily MVM decreases total invasive cancer among older adults. Methods We performed a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of a daily MVM and cocoa extract for prevention of cancer and cardiovascular disease (CVD) among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y) free of major CVD and recently diagnosed cancer. The intervention phase was from June 2015 through December 2020. This article reports on the MVM intervention. Participants were randomly assigned to daily MVM or placebo. The primary outcome was total invasive cancer, excluding nonmelanoma skin cancer. Secondary outcomes included major site-specific cancers, total CVD, all-cause mortality, and total cancer risk among those with a baseline history of cancer. Results During a median follow-up of 3.6 y, invasive cancer occurred in 518 participants in the MVM group and 535 participants in the placebo group (HR: 0.97; 95% CI: 0.86, 1.09; P  = 0.57). We observed no significant effect of a daily MVM on breast cancer (HR: 1.06; 95% CI: 0.79, 1.42) or colorectal cancer (HR: 1.30; 95% CI: 0.80, 2.12). We observed a protective effect of a daily MVM on lung cancer (HR: 0.62; 95% CI: 0.42, 0.92). The composite CVD outcome occurred in 429 participants in the MVM group and 437 participants in the placebo group (HR: 0.98; 95% CI: 0.86, 1.12). MVM use did not significantly affect all-cause mortality (HR: 0.93; 95% CI: 0.81, 1.08). There were no safety concerns. Conclusions A daily MVM supplement, compared with placebo, did not significantly reduce the incidence of total cancer among older men and women. Future studies are needed to determine the effects of MVMs on other aging-related outcomes among older adults. This trial is registered at www.clinicaltrials.gov as NCT02422745. [ABSTRACT FROM AUTHOR]

The dietary modification (DM) clinical trial, within the Women’s Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and chronic disease risk by using self-reported dietary data. In addition to this large trial, which had breast and colorectal cancer as its primary outcomes, a substantial biomarker research effort was initiated midway in the WHI program to contribute to nutritional epidemiology research more broadly. Here we review and update findings from the DM trial and from the WHI nutritional biomarker studies and examine implications for future nutritional epidemiology research. The WHI included the randomized controlled DM trial (n = 48,835) and a prospective cohort observational (OS) study (n = 93,676), both among postmenopausal US women, aged 50–79 y when enrolled during 1993–1998. Also reviewed is a nutrition and physical activity assessment study in a subset of 450 OS participants (2007–2009) and a related controlled feeding study among 153 WHI participants (2010–2014). Long-term follow-up in the DM trial provides evidence for intervention-related reductions in breast cancer mortality, diabetes requiring insulin, and coronary artery disease in the subset of normotensive healthy women, without observed adverse effects or changes in all-cause mortality. Studies of intake biomarkers, and of biomarker-calibrated intake, suggest important associations of total energy intake and macronutrient dietary composition with the risk for major chronic diseases among postmenopausal women. Collectively these studies argue for a nutrition epidemiology research agenda that includes major efforts in nutritional biomarker development, and in the application of biomarkers combined with self-reported dietary data in disease association analyses. We expect such efforts to yield novel disease association findings and to inform disease prevention approaches for potential testing in dietary intervention trials. [ABSTRACT FROM AUTHOR]

Background Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures. Objectives To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes. Methods Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n  = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (<50 mg/dL), hypertension [systolic blood pressure (BP) ≥130 or diastolic BP ≥85 mmHg], elevated serum glucose (>100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity. Results For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15–1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00–1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02–1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95–1.03). No differences were seen when examining metabolic phenotypes. Conclusions We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background We recently presented associations between serum-based biomarkers of carotenoid and tocopherol intake and chronic disease risk in a Women's Health Initiative (WHI) Measurement Precision subcohort (n  = 5488). Questions remain as to whether self-reported dietary data can usefully augment such biomarkers or can be calibrated using biomarkers for reliable disease association estimation in larger WHI cohorts. Objectives The aims were to examine the potential of FFQ data to explain intake variation in a WHI Feeding Study and to compare association parameter estimates and their precision from studies based on biomarker-calibrated FFQ intake in larger WHI cohorts, with those previously presented. Methods Serum-based intake measures were augmented by using FFQ data in a WHI Feeding Study (n  = 153). Corresponding calibration equations were generated, both in a companion Nutritional Biomarker Study (n  = 436) and in the previously mentioned subcohort (n  = 5488), by regressing these intake measures on dietary data and participant characteristics, for α- and β-carotene, lutein plus zeaxanthin, and α-tocopherol. The supplemental value of FFQ data was considered by examining the fraction of feeding study intake variation explained by these regression models. Calibrated intake and disease association analyses were evaluated by comparisons with previously reported subcohort results. Results The inclusion of FFQ data led to some increases in feeding study intake variation explained (total R 2 of ∼50%). Calibrated intake estimates explained 25–75% of serum-based intake variation, whether developed using either of the 2 cohort subsamples. Related disease associations for micronutrients were precisely estimated in larger WHI cohorts (n  = 76,691) but were often closer to the null compared with previously reported associations. Conclusions FFQ data may usefully augment blood concentrations in estimating the intake of carotenoids and tocopherols. Calibrated intake estimates using FFQ, dietary supplement, and participant characteristics only may require further justification to ensure reliable estimation of related disease associations. [ABSTRACT FROM AUTHOR]

Background Biomarkers provide potential to objectively measure the intake of nutrients and foods, and thereby to strengthen nutritional epidemiology association studies. However, there are only a few established intake biomarkers, mostly based on recovery of nutrients or their metabolites in urine. Blood concentration measures provide a potential biomarker source for many additional nutritional variables, but their use in disease-association studies requires further development. Objective The aim of this study was to apply recently proposed serum-based carotenoid and tocopherol intake biomarkers and to examine their association with the incidence of major cardiovascular diseases, cancers, and diabetes in a subset of Women's Health Initiative (WHI) cohorts. Methods Serum concentrations of α- and β-carotene, lutein plus zeaxanthin (L + Z), and α-tocopherol were routinely measured at baseline in a subset of 5488 enrollees in WHI cohorts. Intake biomarkers for these 4 micronutrients, obtained by combining serum concentrations with participant characteristics, were recently proposed using a 153-woman feeding study within WHI. These biomarker equations are augmented here to include pertinent disease risk factors and are associated with subsequent chronic disease incidence in this WHI subset. Results HRs for a doubling of micronutrient intake differed only moderately from the null for the outcomes considered. However, somewhat lower risks of specific cardiovascular outcomes, breast cancer, and diabetes were associated with a higher intake of α- and β-carotene, lower risk of diabetes was associated with higher L + Z intake, and elevated risks of certain cardiovascular outcomes were associated with a higher intake of α-tocopherol. These patterns remained following the exclusion of baseline users of dietary supplements. Conclusions Concentration biomarkers can be calculated from blood specimens obtained in large epidemiologic cohorts and applied directly in disease-association analyses, without relying on self-reported dietary data. Observed associations between carotenoid and tocopherol biomarkers and chronic disease risk could be usefully evaluated further using stored serum specimens on the entire WHI cohort. This study was registered at www.clinicaltrials.gov as NCT00000611. [ABSTRACT FROM AUTHOR]

Background: Biomarkers of macronutrient intake are lacking. Controlled human feeding studies that preserve the normal variation in nutrient and food consumption are necessary for the development and validation of robust nutritional biomarkers. Objective: We aimed to assess the utility of serum phospholipid fatty acids (PLFAs) as biomarkers of dietary intakes of fatty acids, total fat, and carbohydrate. Design: We used an individualized controlled feeding study in which 153 postmenopausal women from the Women's Health Initiative (WHI) were provided with a 2-wk controlled diet that mimicked each individual's habitual food intake. A total of 41 PLFAs were measured with the use of gas chromatography in end-of-feeding-period fasting serum samples and expressed in both relative and absolute concentrations. R² values (percentages of variation explained) from linear regressions of (ln-transformed) consumed fatty acids (individual, groups, and broad categories) on (ln-transformed) corresponding measures of serum PLFAs alone and together with selected participant-related variables (age, race/ethnicity, body mass index, season of study participation, education level, and estimated energy intake from doubly labeled water) were used for evaluation against established urinary recovery biomarkers of energy and protein intake as benchmarks. Models to predict intakes of other nutrients were also explored. Results: Intakes of eicosapentaenoic acid and docosahexaenoic acid achieved the benchmark of R² > 36% with or without covariates. When all 41 serum PLFAs and participant-related covariates were initially included in the model for selection, cross-validated R² achieved >36% for consumed total carbohydrate (grams per day), total saturated fatty acids (SFAs), percentage of energy from SFAs, and total trans fatty acids with serum PLFAs in both relative and absolute concentrations. Conclusions: Serum PLFA biomarkers perform similarly to established energy and protein urinary recovery biomarkers in describing intake variations for several nutrients and, thus, appear suitable for application in this population of postmenopausal women. This approach represents an important methodologic contribution toward the utilization of nutritional biomarkers to assess macronutrient intake. This trial was registered at clinicaltrials.gov as NCT00000611. [ABSTRACT FROM AUTHOR]

Background: Controlled human feeding studies are necessary for robust nutritional biomarker development and validation. Previous feeding studies have typically evaluated single nutrients and tested relatively few diets. Objectives: The objectives were 1) to simultaneously associate dietary intake with a range of potential nutritional biomarkers in postmenopausal women by using a controlled feeding study whereby each participant was provided a diet similar to her usual diet and 2) to evaluate serum concentrations of select nutrients as potential biomarkers with the use of established urinary recovery biomarkers of energy and protein as benchmarks for evaluation. Design: Postmenopausal women from the Women's Health Initiative (n = 153) were provided with a 2-wk controlled diet in which each individual's menu approximated her habitual food intake as estimated from her 4-d food record and adjusted for estimated energy requirements. Serum biomarkers, including carotenoids, tocopherols, folate, vitamin B-12, and phospholipid fatty acids, were collected at the beginning and end of the feeding period. Doubly labeled water and urinary nitrogen biomarkers were used to derive estimates of energy and protein consumption, respectively. Results: Linear regression of (ln-transformed) consumed nutrients on (ln-transformed) potential biomarkers and participant characteristics led to the following regression (R²) values for serum concentration biomarkers: folate, 0.49; vitamin B-12, 0.51; α-carotene, 0.53; β-carotene, 0.39; lutein + zeaxanthin, 0.46; lycopene, 0.32; and α-tocopherol, 0.47. R² values for percentage of energy from polyunsaturated fatty acids and urinary recovery biomarkers of energy and protein intakes were 0.27, 0.53, and 0.43, respectively. Phospholipid saturated fatty acids and monounsaturated fatty acids and serum γ-tocopherol were weakly associated with intake (R², 0.25). Conclusions: Serum concentration biomarkers of several vitamins and carotenoids performed similarly to established energy and protein urinary recovery biomarkers in representing nutrient intake variation in a feeding study, and thus are likely suitable for application in this population of postmenopausal women. Further work is needed to identify objective measures of categories of fatty acid intake. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets are characterized by higher intake of fruit, vegetables, whole grains, and unsaturated fatty acids. All of these foods and nutrients may affect cholesterol, inflammation, the development of atherosclerosis, and, therefore, risk of cardiac death. Objective: Our objective was to examine the association between the Mediterranean and DASH dietary patterns and risk of sudden cardiac death (SCD) in women. Design: We used a prospective cohort of 93,122 postmenopausal women enrolled in the Women's Health Initiative study between 1993 and 1998 and followed for an average of 10.5 y. Women completed a food-frequency questionnaire (FFQ) twice during follow-up. We scored their diets according to how closely the reported diet resembled each dietary pattern. SCD was defined as death that occurred within 1 h of symptom onset. Results: A higher Mediterranean diet score was associated with lower risk of SCD (HR: 0.64; 95% CI: 0.43, 0.94) when women in the highest quintile were compared with women in the lowest quintile after adjustment for age, total energy, race, income, smoking, and physical activity. After adjustment for potential mediators, the association was similar (HR: 0.67; 95% CI: 0.46, 0.99). A higher DASH diet score was not associated with risk of SCD. However, sodium intake, which is a crucial component of the DASH dietary pattern, was not well characterized by the FFQ. Conclusion: The Mediterranean dietary pattern may be associated with lower risk of SCD in women. This trial was registered at clinicaltrials.gov as NCT00000611. [ABSTRACT FROM AUTHOR]

Background: Self-report of dietary energy and protein intakes has been shown to be systematically and differentially underreported. Objective: We assessed and compared the association of diabetes among postmenopausal women with biomarker-calibrated and uncalibrated dietary energy and protein intakes from food-frequency questionnaires (FFQs). Design: The analyses were performed for 74,155 participants of various race-ethnicities from the Women's Health Initiative. Uncalibrated and calibrated energy and protein intakes from FFQs were assessed for associations with incident diabetes by using HR estimates based on Cox regression. Results: A 20% increment in uncalibrated energy consumption was associated with increased diabetes risk (HR) of 1.03 (95% CI: 1.01, 1.05), 2.41 (95% CI: 2.06, 2.82) with biomarker calibration, and 1.30 (95% CI: 0.96, 1.76) after adjustment for BMI. A 20% increment in uncalibrated protein (g/d) resulted in an HR of 1.05 (95% CI: 1.03, 1.07), 1.82 (95% CI: 1.56, 2.12) with calibration, and 1.16 (95% CI: 1.05, 1.28) with adjustment for BMI. A 20% increment in uncalibrated protein density (% of energy from protein) resulted in an HR of 1.13 (95% CI: 1.09, 1.17), 1.01 (95% CI: 0.75, 1.37) with calibration, and 1.19 (95% CI: 1.07, 1.32) with adjustment for BMI. Conclusions: Higher protein and total energy intakes (calibrated) appear to be associated with a substantially increased diabetes risk that may be mediated by an increase in body mass over time. Diet-disease associations without correction of self-reported measurement error should be viewed with caution. [ABSTRACT FROM AUTHOR]

Background: Ulycemic effects of the Women’s Health Initiative (WHI) low-fat dietary intervention are unknown. Objective: Our objective was to analyze the effects of the WHI low-fat dietary intervention on serum glucose and insulin and insulin resistance up to 6 y after random assignment. Design: Postmenopausal WHI Dietary Modification trial intervention (DM-I) and comparison (DM-C) participants with blood measures at least at baseline and year 1 (n = 2263) were included. Anthropometric measures, dietary assessments, serum glucose and insulin concentrations, homeostasis model assessment of insulin resistance (HOMA-IR) measures, and quantitative insulin sensitivity check index (QUICKI) values were obtained at baseline, year 1, year 3, and year 6. Changes in measures were compared between groups at years 1, 3, and 6 overall and within stratified analyses. Results: Mean (± SD) differences in changes at year 1 betwecn the DM-I and DM-C groups were as follows: glucose, —1.7 ± 17.9 mgI dL; insulin, —0.7 ± 5.1 μIU/mL; HOMA-IR, -0.2 ± 1.9; and QUICKI, 0.004 ± 0.019 (all P < 0.05). Similar findings resulted from repeated-measures analyses comparing the intervention and comparison groups over the 6 y. Whereas normoglycemic women at baseline had a decrease in glucose at year 1 that was 1.9 ± 17.2 mg/dL greater in the DM-I than in the DM-C group, diabetic women had an increase in glucose that was 7.9 ± 20.3 mg/dL greater in the DM-I than in the DM-C group (P for interaction <0.001). Conclusions: A low-fat diet was not significantly associated with adverse glycemic effects up to 6 y after random assignment in post- menopausal women. However, diabetic women experienced adverse glycemic effects of the low-fat diet. [ABSTRACT FROM AUTHOR]

Background: The association of total energy intake (EI) with all-cause mortality is uncertain as are the dependencies of this association on age and weight change history., Objectives: To identify an EI biomarker suitable for use in epidemiologic association studies and to study EI associations with total mortality in a Women's Health Initiative (WHI) cohort of postmenopausal United States females (1993-present)., Methods: EI biomarkers were developed based on doubly labeled water (DLW) total energy expenditure (TEE) and weight variation during the 2-wk DLW protocol period using the energy balance method in an embedded feeding study (n = 153). This along with 2 earlier WHI nutrition biomarker studies having TEE assessments (n = 1131 total), with 14.6 y (median) follow-up, constituted a prospective cohort for the study of EI and all-cause mortality., Results: An empirical biomarker for log(EI) was developed that had a correlation of 0.73 with log(feeding study-consumed EI). The overall association between EI and mortality was nonsignificant. The association, however, depended on age (P = 0.009), with lower EI associated with lower mortality at younger ages, and also on preceding weight change history (P = 0.03). Among participants with stable or increasing weight, mortality hazard ratios (95% confidence intervals [CIs]) for a 12% lower EI were 0.66 (95% CI: 0.51, 0.87) at age 60, 0.84 (95% CI: 0.72, 0.98) at age 70, and 1.06 (95% CI: 0.87, 1.29) at age 80. Corresponding values for participants having preceding weight loss were 0.83 (95% CI: 0.61, 1.12) at age 60, 1.05 (95% CI: 0.87, 1.26) at age 70, and 1.33 (95% CI: 1.08, 1.63) at age 80. A previously considered EI biomarker, using a theoretical model for variation in body fat and fat-free mass components over time, gave similar results following rescaling., Conclusions: Lower EI is associated with lower all-cause mortality among younger postmenopausal females with stable or increasing weight and with higher mortality among older females with weight loss. This study was registered with clinicaltrials.gov as NCT00000611., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Metabolomics has the potential to enhance dietary assessment by revealing objective measures of many aspects of human food intake. Although metabolomics studies indicate that hundreds of metabolites are associated with dietary intake, correlations have been modest (e.g., r < 0.50), and few have been evaluated in controlled feeding studies., Objectives: The aim of this study was to evaluate associations between metabolites and weighed food and beverage intake in a controlled feeding study of habitual diet., Methods: Healthy postmenopausal females from the Women's Health Initiative (N = 153) were provided with a customized 2-wk controlled diet designed to emulate their usual diet. Metabolites were measured by liquid chromatography tandem mass spectrometry in end-of-study 24-h urine and fasting serum samples (1293 urine metabolites; 1113 serum metabolites). We calculated partial Pearson correlations between these metabolites and intake of 65 food groups, beverages, and supplements during the feeding study. The threshold for significance was Bonferroni-adjusted to account for multiple testing (5.94 × 10 -07 for urine metabolites; 6.91 × 10 -07 for serum metabolites)., Results: Significant diet-metabolite correlations were identified for 23 distinct foods, beverages, and supplements (171 distinct metabolites). Among foods, strong metabolite correlations (r ≥ 0.60) were evident for citrus (highest r = 0.80), dairy (r = 0.65), and broccoli (r = 0.63). Among beverages and supplements, strong correlations were evident for coffee (r = 0.86), alcohol (r = 0.69), multivitamins (r = 0.69), and vitamin E supplements (r = 0.65). Moderate correlations (r = 0.50-0.60) were also observed for avocado, fish, garlic, grains, onion, poultry, and black tea. Correlations were specific; each metabolite correlated with one food, beverage, or supplement, except for metabolites correlated with juice or multivitamins., Conclusions: Metabolite levels had moderate to strong correlations with weighed intake of habitually consumed foods, beverages, and supplements. These findings exceed in magnitude those previously observed in population studies and exemplify the strong potential of metabolomics to contribute to nutrition research. The Women's Health Initiative is registered at clinicaltrials.gov as NCT00000611., (Copyright © 2023. Published by Elsevier Inc.)

Background: Low diet quality, diabetes, and chronic inflammation are risk factors of liver cancer and chronic liver disease (CLD), but the extent to which insulinemic and inflammatory diets are independently associated with risk of liver cancer and CLD mortality is unknown., Methods: We conducted a prospective cohort analysis among 78,356 postmenopausal women in the Women's Health Initiative Observational Study. Two validated dietary indices, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food-frequency questionnaire. Incident cases of liver cancer and CLD mortality were adjudicated via review of medical records and linkage to National Death Index. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models, adjusted for age, diabetes, body mass index, and other covariates., Results: During a median 22.1 y of follow-up, we documented 176 primary liver cancer cases and 156 CLD mortality cases. EDIH was positively associated with incident liver cancer (HR Quartile 4 vs. Quartile 1 = 1.68; 95% CI: 1.00, 2.83; P-trend = 0.05) and CLD mortality (HR Q4 vs. Q1 = 2.28; 95% CI: 1.25, 4.15; P-trend = 0.02) in the multivariable model. EDIP was also positively associated with liver cancer (HR Q4 vs. Q1 = 1.88; 95% CI: 1.17, 3.03; P-trend = 0.009) and CLD mortality (HR Q4 vs. Q1 = 1.85; 95% CI: 1.09, 3.15; P-trend = 0.007). Estimates remained significant and robust in sensitivity analyses. Further analyses indicated positive associations for refined grains, processed meat, sugary beverages, and eggs, and inverse associations for coffee/tea and poultry., Conclusions: Dietary insulinemic and inflammatory potentials were independently associated with higher risk of liver cancer and CLD mortality in U.S. postmenopausal women. These findings suggest a potential role for diet modification to reduce risk of liver cancer and CLD., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The association of TEE with all-cause mortality is uncertain, as is the dependence of this association on age., Objectives: To examine the association between TEE and all-cause mortality, and its age interaction, in a Women's Health Initiative (WHI) cohort of postmenopausal United States women (1992-present)., Methods: A cohort of 1131 WHI participants having DLW TEE assessment of ∼10.0 y (median) following WHI enrollment with ∼13.7 y (median) of subsequent follow-up, was used to study the EE associations with all-cause mortality. To enhance the comparability of TEE and total EI, key analyses excluded participants having >5% weight change between WHI enrollment and DLW assessment. The influence of participant age on mortality associations was examined, as was the ability of concurrent and earlier weight and height measurements to explain the results., Results: There were 308 deaths following the TEE assessment through 2021. TEE was unrelated to overall mortality (P = 0.83) in this cohort of generally healthy, older (mean 71 y at TEE assessment) United States women. However, this potential association varied with age (P = 0.003). Higher TEE was associated with a higher mortality rate at the age of 60 y and a lower mortality rate at the age of 80 y. Within the weight-stable subset (532 participants, 129 deaths), TEE was weakly positively related to overall mortality (P = 0.08). This association also varied with age (P = 0.03), with mortality HRs (95% CIs) for a 20% increment in TEE of 2.33 (1.24, 4.36) at the age of 60 y, 1.49 (1.10, 2.02) at 70 y of age, and 0.96 (0.66, 1.38) at 80 y of age. This pattern remained, although was somewhat attenuated, following control for baseline weight and weight changes between WHI enrollment and TEE assessment., Conclusions: Higher EE is associated with higher all-cause mortality among younger postmenopausal women, only partially explained by weight and weight change. This study is registered with clinicaltrials.gov identifier: NCT00000611., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Background: Although studies to date have confirmed the association between nutrition and frailty, the impact of dietary intake and dietary patterns on survivorship in those with frailty is yet to be examined in a well-powered cohort with validated frailty status. Moreover, previous studies were limited by measurement error from dietary self-reports. Objective: We derived biomarker-calibrated dietary energy and protein intakes to address dietary self-report error. Using these data, we then evaluated the association of mortality in older women with frailty and dietary intake and healthy diet indexes, such as the alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII). Design: The analytic sample included 10,034 women aged 65-84 y with frailty and complete dietary data from the Women's Health Initiative Observational Study. Frailty was assessed with modified Fried's criteria. Dietary data were collected by food-frequency questionnaire. Results: Over a mean follow-up period of 12.4 y, 3259 (31%) deaths occurred. The HRs showed progressively decreased rates of mortality in women with higher calibrated dietary energy intakes ( P- trend = 0.003), higher calibrated dietary protein intakes ( P- trend = 0.03), higher aMED scores ( P- trend = 0.006), and higher DASH scores ( P- trend = 0.02). Although the adjusted point estimates of HRs (95% CIs) for frail women scoring in the second, third, and fourth quartiles on DII measures were 1.15 (1.03, 1.27), 1.28 (1.15, 1.42), and 1.24 (1.12, 1.38), respectively, compared with women in the first quartile, no overall effect was observed across quartiles ( P- trend = 0.35). Subgroup analyses by chronic morbidity or smoking status or by excluding women with early death did not substantially change these findings. Conclusions: The current study highlights the importance of nutrition in older, frail women. Diet quality and quantity should be considered in managing persons with frailty., (© 2017 American Society for Nutrition.)

Background: Biomarkers of macronutrient intake are lacking. Controlled human feeding studies that preserve the normal variation in nutrient and food consumption are necessary for the development and validation of robust nutritional biomarkers. Objective: We aimed to assess the utility of serum phospholipid fatty acids (PLFAs) as biomarkers of dietary intakes of fatty acids, total fat, and carbohydrate. Design: We used an individualized controlled feeding study in which 153 postmenopausal women from the Women's Health Initiative (WHI) were provided with a 2-wk controlled diet that mimicked each individual's habitual food intake. A total of 41 PLFAs were measured with the use of gas chromatography in end-of-feeding-period fasting serum samples and expressed in both relative and absolute concentrations. R 2 values (percentages of variation explained) from linear regressions of (ln-transformed) consumed fatty acids (individual, groups, and broad categories) on (ln-transformed) corresponding measures of serum PLFAs alone and together with selected participant-related variables (age, race/ethnicity, body mass index, season of study participation, education level, and estimated energy intake from doubly labeled water) were used for evaluation against established urinary recovery biomarkers of energy and protein intake as benchmarks. Models to predict intakes of other nutrients were also explored. Results: Intakes of eicosapentaenoic acid and docosahexaenoic acid achieved the benchmark of R 2 > 36% with or without covariates. When all 41 serum PLFAs and participant-related covariates were initially included in the model for selection, cross-validated R 2 achieved >36% for consumed total carbohydrate (grams per day), total saturated fatty acids (SFAs), percentage of energy from SFAs, and total trans fatty acids with serum PLFAs in both relative and absolute concentrations. Conclusions: Serum PLFA biomarkers perform similarly to established energy and protein urinary recovery biomarkers in describing intake variations for several nutrients and, thus, appear suitable for application in this population of postmenopausal women. This approach represents an important methodologic contribution toward the utilization of nutritional biomarkers to assess macronutrient intake. This trial was registered at clinicaltrials.gov as NCT00000611., (© 2017 American Society for Nutrition.)