Protein Biomarkers of Ultra-Processed Food Consumption and Risk of Coronary Heart Disease, Chronic Kidney Disease, and All-Cause Mortality

Background: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health.

Objectives: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk.

Methods: A total of 9361 participants from the Atherosclerosis Risk in Communities visit 3 (1993-1995) were included. Dietary intake was assessed using a 66-item food-frequency questionnaire and the processing levels were categorized on the basis of the Nova classification. Plasma proteins were detected using an aptamer-based proteomic assay. We used multivariable linear regressions to examine the association between ultra-processed food and proteins, and Cox proportional hazard models to identify associations between ultra-processed food-related proteins and health outcomes. Models extensively controlled for sociodemographic characteristics, health behaviors, and clinical factors.

Results: Eight proteins (6 positive, 2 negative) were identified as significantly associated with ultra-processed food consumption. Over a median follow-up of 22 y, there were 1276, 3084, and 5127 cases of CHD, CKD, and death, respectively. Three, 5, and 3 ultra-processed food-related proteins were associated with each outcome, respectively. One protein (β-glucuronidase) was significantly associated with a higher risk of all 3 outcomes, and 3 proteins (receptor-type tyrosine-protein phosphatase U, C-C motif chemokine 25, and twisted gastrulation protein homolog 1) were associated with a higher risk of 2 outcomes.

Conclusions: We identified a panel of protein biomarkers that were significantly associated with ultra-processed food consumption. These proteins may be considered potential biomarkers for ultra-processed food intake and may elucidate the biological processes through which ultra-processed foods impact health outcomes.