This competing renewal of R01 CA119171, "Nutrition and Physical Activity Assessment Study" (NPAAS), continues to focus on the use of biomarkers to evaluate and compare measurement properties of prominent nutritional and physical activity assessment methods, and on the use of biomarker-calibrated nutrient consumption and activity-related energy expenditure (AREE) estimates in studies in Women's Health Initiative (WHI) cohorts of postmenopausal women.
Our aims are: 1) To conduct a controlled feeding study to develop biomarkers for additional nutrients and foods, and 2) To use biomarkers from the ongoing and proposed NPAAS study phases to develop biomarker-calibrated nutrient consumption and AREE estimates, throughout the WHI cohorts for use in disease-association studies. We will recruit 150 women, in the age range 60-80 y, enrolled in the WHI Seattle Field Center, into a feeding study of a highly individualized controlled diet, with each woman's diet designed to approximate her usual food consumption patterns. Women will receive all foods and beverages during the 2-week feeding period. We will obtain 24-h urine-derived nutritional measures, including nitrogen (protein), fructose, sucrose (sugars), alkylresorcinols (whole grains) and 1- and 3- methylhistidine (meat);and blood-derived nutritional measures, including carotenoids (fruits &vegetables), 1- and 3 -tocopherols (fats &oils), phospholipid fatty acids (fats &oils), and folate (fruits &vegetables) at the beginning and end of the 2-week feeding period. Biomarker evaluation will include an assessment of the ability of urine and blood measures, and study subject characteristics to explain variation in nutrients and foods provided during the feeding study. Total energy expenditure (TEE) will be measured using a doubly-labeled water protocol, as will resting energy expenditure (REE) using indirect calorimetry with 0.9TEE-REE as objective measure of AREE. We will develop calibration equations for each nutrient/food or activity measure having a suitable biomarker, by regression analysis of the biomarker on corresponding self-report measures using specimens and data from the women in both NPAAS project phases. Suitable biomarkers will be available for total energy, protein, percent of energy from protein, and for total activity-related energy expenditure. We will apply these calibration equations in the WHI cohorts using a food-frequency questionnaire and multiple-day food record to produce calibrated consumption estimates and using a WHI activity questionnaire to produce calibrated AREE estimates. These calibrated estimates will be related to the subsequent incidence of a broad range of clinical outcomes (e.g., cancer, cardiovascular disease, diabetes, frailty, obesity, etc) among the 161,808 women in the WHI cohorts. This work addresses fundamental gaps in diet and physical activity epidemiology research, in the context of national and international obesity epidemics, and in much related chronic disease morbidity and mortality.

Public Health Relevance

Dietary and physical activity patterns have an important role in maintaining body weight and overall health (in preventing obesity-related diseases). However, because previous research in this area has been conflicting, public health campaigns and health care provider instructions for diet and physical activity typically lack specificity and force. A major reason for the lack of convincing data to support lifestyle-related disease risk- reduction efforts is that the tools and methods used to gather data on diet and physical activity may incorporate major systematic biases. This study will develop and use biomarkers in blood and urine to calibrate self- reported diet and physical activity and will examine the relationship of calibrated 'exposures'to cancer, cardiovascular disease, and diabetes in postmenopausal women.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-PSE-B (80))
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Subar, Amy
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Fred Hutchinson Cancer Research Center
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Beasley, Jeannette M; Gunter, Marc J; LaCroix, Andrea Z et al. (2014) Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative. Br J Nutr 111:847-53
Tasevska, Natasha; Midthune, Douglas; Tinker, Lesley F et al. (2014) Use of a urinary sugars biomarker to assess measurement error in self-reported sugars intake in the nutrition and physical activity assessment study (NPAAS). Cancer Epidemiol Biomarkers Prev 23:2874-83
Prentice, Ross L (2014) Postmenopausal hormone therapy and the risks of coronary heart disease, breast cancer, and stroke. Semin Reprod Med 32:419-25
Huang, Ying; Van Horn, Linda; Tinker, Lesley F et al. (2014) Measurement error corrected sodium and potassium intake estimation using 24-hour urinary excretion. Hypertension 63:238-44
Zheng, Cheng; Beresford, Shirley A; Van Horn, Linda et al. (2014) Simultaneous association of total energy consumption and activity-related energy expenditure with risks of cardiovascular disease, cancer, and diabetes among postmenopausal women. Am J Epidemiol 180:526-35
Neuhouser, Marian L; Di, Chongzhi; Tinker, Lesley F et al. (2013) Physical activity assessment: biomarkers and self-report of activity-related energy expenditure in the WHI. Am J Epidemiol 177:576-85
Prentice, Ross L; Neuhouser, Marian L; Tinker, Lesley F et al. (2013) An exploratory study of respiratory quotient calibration and association with postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 22:2374-83
Prentice, R L; Pettinger, M B; Jackson, R D et al. (2013) Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study. Osteoporos Int 24:567-80
Prentice, Ross L; Tinker, Lesley F; Huang, Ying et al. (2013) Calibration of self-reported dietary measures using biomarkers: an approach to enhancing nutritional epidemiology reliability. Curr Atheroscler Rep 15:353
Tinker, Lesley F; Sarto, Gloria E; Howard, Barbara V et al. (2011) Biomarker-calibrated dietary energy and protein intake associations with diabetes risk among postmenopausal women from the Women's Health Initiative. Am J Clin Nutr 94:1600-6

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