Plasma protein biomarkers of healthy dietary patterns: results from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study

Authors: DU, SHUTONG - Johns Hopkins University; CHEN, JINGSHA - Johns Hopkins University; KIM, HYUNJU - Johns Hopkins University; WALKER, MAURA - Boston University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CHATTERJEE, NILANJAN - Johns Hopkins University; GANZ, PETER - University Of California San Francisco (UCSF); YU, BING - University Of Texas Health Science Center; RAMACHANDRAN, VASAN - Boston University; CORESH, JOSEF - Johns Hopkins University; REBHOLZ, CASEY - Johns Hopkins University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/2022
Publication Date: 12/21/2022
Citation: Du, S., Chen, J., Kim, H., Walker, M.E., Lichtenstein, A.H., Chatterjee, N., Ganz, P., Yu, B., Ramachandran, V., Coresh, J., Rebholz, C.M. 2022. Plasma protein biomarkers of healthy dietary patterns: results from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2022.11.008.
DOI: https://doi.org/10.1016/j.tjnut.2022.11.008

Interpretive Summary: Adhering to a healthy dietary pattern is a key component of lifestyles associated with chronic disease prevention, including metabolic syndrome, cardiovascular disease, diabetes and some cancers. Most of what we know about dietary patterns and chronic disease risk depends on self-reported subjective food intake data, which may have inherent biases. Identifying plasma biomarkers of food intake, such as diet-related proteins, could provide an objective assessment of individuals' diet quality as related to chronic disease risk. The aim of this study was to use dietary data and blood samples from a large group of individuals to identify plasma proteins uniquely associated with four different healthy dietary patterns and then determine if these plasma proteins were associated with the same dietary patterns in a second group of individuals (replication). Two hundred and eighty-two proteins out of almost 5,000 were associated with at least one dietary pattern in the first group of individuals. Of those, 20 were associated with similar healthy dietary patterns in the second group of individuals. These proteins identified may serve as objective markers of healthy dietary pattern adherence and in the future be valuable in identifying diet related health outcomes.

Technical Abstract: Background: Molecular mechanisms underlying the benefits of healthy dietary patterns are poorly understood. Identifying protein biomarkers of dietary patterns can contribute to characterizing biological pathways influenced by food intake. Objective: To identify protein biomarkers associated with 4 healthy dietary patterns: Healthy Eating Index-2015 (HEI-2015); Alternative Healthy Eating Index-2010 (HEI-2010); Dietary Approaches to Stop Hypertension (DASH) diet; and Alternate Mediterranean Diet (aMED). Design: Analyses were conducted on 10,490 black and white men and women aged 49-73 years from the Atherosclerosis Risk in Communities (ARIC) study at visit 3 (1993-1995). Dietary data were collected using a food frequency questionnaire, and plasma proteins were quantified using an aptamer-based proteomics assay. Multivariable linear regression models were used to examine the association between 4,955 proteins and dietary patterns. We performed pathway over-representation analysis for diet-related proteins. An independent study population, the Framingham Heart Study, was used for replication analyses. Results: In the multivariable-adjusted models, 282 out of 4,955 proteins (5.7%) were significantly associated with at least one dietary pattern (HEI-2015: 137; AHEI-2010: 72; DASH: 254; aMED: 35; p-value <0.05/4,955=1.01x10-5). There were 148 proteins that were associated with a single dietary pattern (HEI-2015: 22; AHEI-2010: 5; DASH: 121; aMED: 0), and 20 proteins were associated with all four dietary patterns. Five unique biological pathways were significantly enriched by diet-related proteins. Seven out of 20 proteins associated with all dietary patterns in the ARIC study were available for replication analyses, and six out of seven were consistent in direction and significantly associated with at least one dietary pattern in the Framingham Heart Study (HEI-2015: 2; AHEI-2010: 4; DASH: 6; aMED: 4; p-value <0.05/7=7.14x10-3). Conclusions: A large-scale proteomic analysis identified plasma protein biomarkers that are representative of healthy dietary patterns among middle-aged and older US adults. These protein biomarkers may be useful objective indicators of healthy dietary patterns.