This competing renewal of CA119171-12 “Nutrition and Physical Activity Assessment Study” (NPAAS)
continues to focus on the development of novel dietary biomarkers and application of these biomarkers to
investigations of diet and cancer, cardiovascular disease and type 2 diabetes risk in the Women’s Health
Initiative (WHI) cohorts of postmenopausal U.S. women. Our work uses objective biomarkers of nutrients,
foods and dietary patterns using blood and urine biospecimens collected in controlled feeding studies where
types and quantities of foods and beverages are known. The dietary biomarkers can be used as stand-alone
assessments of diet or, as emphasized in this proposal, they may be able to be extended to make them
suitable for inexpensive disease association applications using a regression calibration approach. Progress
has been made on the identification of objective measures of some dietary variables for public health
applications, but there is still limited use of high-dimensional platforms (e.g., metabolomics in blood and urine)
for this purpose. Further development is also needed for discovery and evaluation of stable isotope biomarkers
of important dietary components, such as meat, fish and added sugars, where there are likely links to chronic
disease risk. The discovery and validation of objective measures of healthy dietary patterns is another gap that
we will address. In this cycle of funding, we propose to contribute to these research areas and to carry out
generalizability studies toward extending these biomarker-intake results to diverse populations beyond the
WHI. Our specific aims are: 1) To develop further and evaluate candidate biomarkers of foods, nutrients and
other dietary compounds informed by data from the NPAAS feeding study (n=153) and to apply biomarkers
meeting our prespecified NPAAS-derived criteria to examine associations with risk of cancer, cardiovascular
disease and type 2 diabetes in WHI cohorts of postmenopausal women (n=161,808); 2) To measure serum
carbon and nitrogen isotope ratios and amino acid carbon isotope ratios as biomarkers of fish/seafood, animal
protein and added sugars in the NPAAS Observational Study (n=450) and to apply these measures to test
associations with risk of cancer, cardiovascular disease and diabetes in WHI cohorts; 3) To identify and
evaluate candidate dietary biomarkers of healthy eating patterns (e.g., Healthy Eating Index, Alternative
Mediterranean Diet Score) for testing associations between these eating patterns with the same set of chronic
diseases in WHI cohorts; and 4) To test, using blood and urine metabolomics, the generalizability of novel
metabolomic biomarkers identified in the NPAAS feeding study to diverse study populations in two controlled
feeding studies. Our productive research team is expected to make additional, innovative contributions to
nutritional epidemiology research and more broadly to chronic disease prevention research. Our research
builds on the understanding that biomarkers of dietary intake, as stand-alone exposures or as tools to calibrate
self-report, are crucial to the development of reliable information on the effects of diet on chronic disease risk.
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