Plasma Proteins Associated with Whole Grains and Fiber Intake in the Cardiovascular Health Study (CHS) and the...

Limited biomarkers exist for whole grains and fiber intake. Large-scale proteomics can be used to identify objective biomarkers of whole grains and fiber intake.

We identified plasma proteins of whole grains and fiber intake in the Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities (ARIC) Study.

Whole grains and fiber intake were quantified from food frequency questionnaire responses in CHS (1989-1990, N = 2411). An aptamer-based technology (SomaLogic) quantified 4979 proteins in stored specimens collected in 1992-1993. Multivariable linear regression identified individual proteins significantly associated with whole grains or fiber intake at a false discovery rate of <0.05. Findings were externally replicated in the ARIC Study. Pathway overrepresentation analysis was conducted for diet-related proteins. Least absolute shrinkage and selection operator (LASSO) regression was used to select a set of proteins associated with whole grains or fiber intake. Prediction statistics assessed the ability of diet-related proteins to predict whole grains and fiber intake beyond participant characteristics.

A total of 68 and 26 proteins were associated with whole grains and fiber intake, respectively, in CHS, with 17 and 20 proteins for whole grains and fiber, respectively, replicated in the ARIC Study. Of these, 5 proteins (beta-glucuronidase, neuropeptide W, inhibin beta C chain, transcobalamin 1, and toll-like receptor 5) were associated with both whole grains and fiber intake. Ascorbate and aldarate metabolism were overrepresented for both whole grains and fiber-related proteins. A total of 13 proteins for whole grains and 19 proteins for fiber intake were selected from LASSO to improve the prediction of these dietary exposures beyond participant characteristics (range of differences in AUCs: 0.022-0.041, P for all tests < 0.05).

We identified proteins and pathways that are robustly associated with whole grains and fiber intake in 2 studies. These proteins may serve as candidate biomarkers if validated in controlled feeding studies.