Untargeted metabolomic analysis investigating links between unprocessed red meat intake and markers of inflammation

Background: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.Objective: To identify whether any metabolites associated with red meat intake are also associated with inflammation.Methods: A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 +/- 0.3 y) 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 (H-1 NMR) metabolomic features. Associations between these variables were examined using linear regression models, adjusted for demographic factors, lifestyle behaviors, and body mass index (BMI).Results: In analyses that adjust for BMI, neither processed nor unprocessed forms of red meat were associated with any markers of inflammation (all P > 0.01). However, when adjusting for BMI, unprocessed red meat was inversely associated with spectral features representing the metabolite glutamine (sentinel hit: beta = -0.09 +/- 0.02, P = 2.0 x 10(-5)), an amino acid which was also inversely associated with CRP level (beta = -0.11 +/- 0.01, P = 3.3 x 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, compared with diet metabolite-inflammation associations, warrant further investigation to understand the extent that these arise from the following: 1) a reduction in measurement error with metabolite measures; 2) the extent that which factors other than unprocessed red meat intake contribute to glutamine levels; and 3) the ability of plasma metabolites to capture individual differences in how food intake is metabolized.