Biomarkers for Whole Grain Intake and Cardiometabolic Health - SUMMARY/ABSTRACT Growing evidence suggests that whole grain (WG) intake may play an important role in cardiometabolic disease prevention. However, numerous individual human studies have failed to support clear-cut conclusions on the topic. This inconsistency may be because the prevailing nutrition research relies heavily on self-reported measures of diet that are often prone to measurement error. In addition, these instruments cannot reflect the complexity of the chemical compositions of each WG, the impact of varieties, environment, cooking, and food processing on WG chemical compositions, and the interindividual variations on the absorption and metabolisms of WG phytochemicals. The molecular signatures of WG intake remain largely undefined. The major dietary cereals - wheat, rye, oat, barley, rice and corn- contain different unique phytochemicals, which can be used to reflect the intake of each individual WG. We recently found that the combination of targeted and non-targeted metabolomics approaches can effectively identify biomarkers of WG wheat and oat intake. However, the biomarkers of WG barley, rice, and corn have not been identified and these biomarkers have not been validated and associated with coronary heart disease (CHD) in an epidemiological setting. This application is aimed to test the hypothesis that bioactive WG phytochemicals, and their metabolites, are objective biomarkers of WG intake, integrate inter-individual differences, affect endogenous metabolome, and are likely more intimately associated with cardiometabolic diseases than traditional dietary assessments. This hypothesis will be tested in two aims. Aim 1 is to identify biomarkers of WG barley, rice, and corn intake following an acute exposure in a pharmacokinetic feeding study. In this aim, we will conduct a randomized crossover acute pharmacokinetic study of WG barley, rice, and corn, respectively. We will then use a targeted metabolomics approach to identify the exposure markers of WG barley, rice, and corn intake, further develop analytical methods to study their pharmacokinetics, and build our in-house WG metabolite database, and an untargeted metabolomics approach to investigate post-prandial biomarkers of WG barley, rice, and corn intake. The goals of Aim 2 are to determine 1) whether biomarkers of WG intake identified can represent habitual intake from two well phenotyped observational studies – the Men’s Lifestyle Validation Study (MLVS) and the Women’s Lifestyle Validation Study (WLVS), which have detailed and repeated measurements of diet using multiple 7-day diet records (7DDRs); and 2) whether biomarkers of WG intake are prospectively associated with risk of CHD in a cohort of female nurses. At the completion of these studies, our expectation is that we will identify WG phytochemicals and their metabolites as objective biomarkers of total and individual WGs that are commonly consumed by Americans. We also expect that the markers are robustly associated with WG intake and a lower CHD risk in free-living individuals.
