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The American Journal of Clinical Nutrition
Available online 1 September 2023
In Press, Journal Pre-proof
Original Research Article


Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake and Markers of Inflammation


https://doi.org/10.1016/j.ajcnut.2023.08.018

Abstract
Background
Whether red meat consumption is associated with higher inflammation, or confounded by increased adiposity, remains unclear. Plasma metabolites both capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so can help clarify diet-health relationships.

Objective
To identify whether any metabolites associated with red meat intake are also associated with inflammation.

Design
A cross-sectional analysis of observational data from older adults (52.84% female, mean age 63±0.3 years), participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, homocysteine, and tumor necrosis factor alpha, and untargeted proton nuclear magnetic resonance 1H NMR metabolomic features. Associations between these variables were examined using linear regression models, adjusted for demographic factors lifestyle behaviors, and BMI.

Results
Neither processed not unprocessed forms of red meat were associated with any markers of inflammation (all P>.01). However, again in analyses which adjust for BMI, unprocessed red meat was inversely associated with inversely associated with spectral features representing the metabolite glutamine (sentinel hit: β=-0.09 ± 0.02, P=2.0*10-5), an amino acid which was also inversely associated with CRP level (β=-0.11 ± 0.01, P=3.3*10-10).

Conclusions
Our analyses were unable to support a relationship between either processed or unprocessed red meat and inflammation, over and above any confounding by BMI. Glutamine, a plasma correlate of lower unprocessed red meat intake, was associated with lower CRP levels. The differences in diet-inflammation associations vs. diet metabolite-inflammation associations warrants further investigation to understand the extent that these arise from (1) a reduction in measurement error with metabolite measures; (2) the extent that factors other than unprocessed red meat intake contribute to glutamine levels; (3) the ability of plasma metabolites to capture individual differences in how food intake is metabolized.