Demographic and clinical factors influence the metabolome. The discovery and validation of disease biomarkers are often challenged by potential confounding effects from such factors. To address this challenge, we investigated the magnitude of the correlation between serum and urine metabolites and demographic and clinical parameters in a well-characterized observational cohort of 444 post-menopausal women participating in the Women's Health Initiative (WHI). Using LC-MS and lipidomics, we measur...

Background: Although measures of blood and tissue fatty acid (FA) concentrations are available, objective measures of dietary FA densities (grams per kilocalories) are generally lacking. Objectives: We aimed to explore the development of biomarkers for specific and composite dietary FA densities, not including contributions from dietary supplements, using metabolite profiles from serum and 24-h urine, along with separately measured serum phospholipid FA concentrations in the Women's Health Initi...

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 fro...

Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women's Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum...

Addressing systematic measurement errors in self-reported data is a critical challenge in association studies of dietary intake and chronic disease risk. The regression calibration method has been utilized for error correction when an objectively measured biomarker is available; however, biomarkers for only a few dietary components have been developed. This paper proposes to use high-dimensional objective measurements to construct biomarkers for many more dietary components and to estimate the d...

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 ser...

Purpose: Objective biomarkers of dietary exposure are needed to establish reliable diet-disease associations. Unfortunately, robust biomarkers of macronutrient intakes are scarce. We aimed to assess the utility of serum, 24-h urine and spot urine high-dimensional metabolites for the development of biomarkers of daily intake of total energy, protein, carbohydrate and fat, and the percent of energy from these macronutrients (%E). Methods: A 2-week controlled feeding study mimicking the participant...

Systematic measurement error in self-reported data creates important challenges in association studies between dietary intakes and chronic disease risks, especially when multiple dietary components are studied jointly. The joint regression calibration method has been developed for measurement error correction when objectively measured biomarkers are available for all dietary components of interest. Unfortunately, objectively measured biomarkers are only available for very few dietary components,...

The inconsistent findings from epidemiologic studies relating total sugars (TS) consumption to cardiovascular disease (CVD) or type 2 diabetes (T2D) risk may be partly due to measurement error (ME) in self-reported intake. Using regression calibration equations developed based on the predictive biomarker for TS and recovery biomarker for energy, we examined the association of TS with T2D and CVD risk, before and after dietary calibration, in 82,254 postmenopausal women of the Women's Health Init...

Background: Dietary supplement use is common among older adults; however, the association between supplement use and corresponding nutrient biomarkers in this population is less well understood. Objectives: This study aimed to determine whether older women using dietary supplements had higher serum concentrations of corresponding biomarkers and whether those using multiple supplement sources of the nutrient had incrementally higher serum nutrient concentrations. Methods: Participants from the Wo...

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...

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 outco...

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 ...

Studies of sodium and potassium intake and cardiovascular disease incidence often rely on self-reported dietary data. Here self-reported intakes from postmenopausal women at 40 participating U.S. clinical centers are calibrated using 24-hour urinary excretion measures in Women's Health Initiative cohorts, with follow-up over 1993-2010. Hypertension incidence related positively to (calibrated) sodium intake and to the ratio of sodium-to-potassium. The sodium-to-potassium ratio was associated with...

Background: Associations of the macronutrient composition of the diet with total energy intake (EI) are uncertain, as are associations of macronutrient composition with self-reported energy underreporting. Objectives: We aim to estimate associations of biomarker-assessed EI with both biomarker-assessed and self-reported macronutrient component densities in a Women's Health Initiative (WHI) sub-cohort of postmenopausal U.S. females. Secondarily, we examine energy underreporting using food records...

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 U.S. females (1993-present). Design: EI biomarkers were developed based on doubly-labeled water (DLW) total energy expen...

Background: Prior studies examined associations between Healthy Eating Index (HEI) and chronic disease risk based on self-reported diet without measurement error correction. Objectives: Our objective was to test associations between biomarker-calibration of food frequency questionnaire (FFQ)-derived HEI-2010 with incident cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) among Women's Health Initiative (WHI) participants. WHI is registered at clinicaltrials.gov: NCT00000611. Method...

Correction for systematic measurement error in self-reported data is an important challenge in association studies of dietary intake and chronic disease risk. The regression calibration method has been used for this purpose when an objectively measured biomarker is available. However, a big limitation of the regression calibration method is that biomarkers have only been developed for a few dietary components. We propose new methods to use controlled feeding studies to develop valid biomarkers f...

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...

Dietary guidance emphasizes healthy dietary patterns, but supporting evidence comes from measurement-error prone self-reported diet. We explored whether nutritional biomarkers from the Women's Health Initiative Nutrition and Physical Activity Assessment Study Feeding Study (n=153; 2010-2014) and the WHI-NPAAS Observational Study (NPAAS-OS; n=450; 2006-2009) could identify biomarker signatures of dietary patterns for development of corresponding regression calibration equations to help mitigate m...

Abstract 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. OBJECT...

We developed calibration equations using metabolomics from fasting blood and 24-hour urine for Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) to address measurement error from self-reported diet. We examined associations between metabolomic-calibrated dietary patterns and cancer risk in the Women's Health Initiative (WHI, n=108,522). Metabolomic signatures were created from a WHI Feeding (n=153;2010-2014) and WHI Observational Study (n=450;2006-2009). ...