Introduction/Intent

In addition to analysis and reporting activities arising from data collected in the current project period, the major thrust of the RO1 competitive renewal will be the conduct of a controlled feeding study among 150 women in the Seattle components of the WHI OS and DM comparison group. The data generated will be used to develop biomarkers based on blood or urine for various nutrients, and will examine the potential of ActivPAL^TM monitors for the objective assessment of physical activity. Calibration equations will be obtained by regressing the new biomarkers on corresponding self-report measures and study subject characteristics for use in association studies with cardiovascular disease, cancer and diabetes, among other clinical outcomes, in WHI cohorts. This competitive renewal application to NCI will be submitted in response to PAR-07-259 “Improving Diet and Physical Activity Assessment.” 

Specific Aims

Primary Aims:

1. To develop nutritional biomarkers through the conduct of a novel controlled feeding study. WHI participants will complete a two-week controlled feeding study. Feeding study diets will be highly individualized and designed to approximate participant usual diets, thus enabling an accurate evaluation of the relationship between intake of specific nutrients or specified quantities of foods and the biomarkers of interest. Biomarkers will be developed by regressing provided nutrient consumption on corresponding blood or urine measures for the nutrient under study as well as other nutrients, and other objectively measured study subject characteristics (e.g., BMI).

2. To use the biomarkers developed from the feeding study in Aim 1 to calibrate nutrient consumption and activity-related energy expenditure with application to a wide range of disease association studies in the WHI cohorts (i.e., cancer, cardiovascular disease, diabetes). Calibration equations will be developed by regressing the new biomarkers on corresponding self-report measures and other study subject characteristics for the 450 women who participated in the current phase of NPAAS.

Secondary Aims:

1. To quantitatively estimate urine-derived nutritional biomarkers after two weeks on a controlled feeding study diet. The measures will include: nitrogen (protein), fructose, sucrose (sugars), alkylresorcinols (whole grains) and 1- and 3-methylhistidine (meat).
2. To quantitatively estimate blood-derived nutritional measures after two weeks on a controlled feeding study diet. The measures will include: carotenoids (fruits and vegetables), α- and γ-tocopherols (fats and oils), phospholipid fatty acids (fats and oils) and folate (fruits and vegetables).
3. To objectively measure total energy expenditure (TEE) using a doubly-labeled water protocol.
4. To objectively measure physical activity during the same two-week period as the controlled feeding study using an ActivPAL™ (PAL Technologies, Glasgow, Scotland) worn for 14 days, and resting energy expenditure (REE) from indirect calorimetry. We will compare the properties of [TEE-REE] vs. ActivPAL™ as biomarkers of activity-related energy expenditure (AREE).
5. To measure the reliability of nutrient consumption physical activity biomarkers. A subset of 50 women will repeat all study procedures six months after the first application of the protocol.
6. To combine the biomarker-calibrated estimates of nutrient consumption and activity-related energy expenditure in this study with that obtained from previous biomarker studies in the WHI in a wide-range of disease association studies in the WHI cohorts.

To meet these aims, 150 women from the WHI Extension Study (Seattle Field Center) will be recruited to participate in a two-week controlled feeding study. All foods and most beverages during the feeding period will be prepared under highly controlled conditions in the Human Nutrition Laboratory at the Fred Hutchinson Cancer Research Center in Seattle.  A subset of 50 women will repeat all procedures six months later.​