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

Authors: WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); GRACA, GONCALO - Imperial College; GADGIL, MEGHANA - University Of California San Francisco (UCSF); SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC); ALLISON, MATTHEW - University Of California, San Diego; TZOULAKI, IOANNA - University Of Ioannina; GREENLAND, PHILIP - Northwestern University; EBBELS, TIMOTHY - Imperial College; ELLIOTT, PAUL - Imperial College; GOODARZI, MARK - Cedars-Sinai Medical Center; TRACY, RUSSELL - University Of Vermont; ROTTER, JEROME - Harbor-Ucla Medical Center; HERRINGTON, DAVID - Wake Forest School Of Medicine

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/30/2023
Publication Date: 9/1/2023
Citation: Wood, A.C., Graca, G., Gadgil, M., Senn, M.K., Allison, M.A., Tzoulaki, I., Greenland, P., Ebbels, T., Elliott, P., Goodarzi, M.O., Tracy, R., Rotter, J.I., Herrington, D. 2023. Untargeted metabolomic analysis investigating links between unprocessed red meat intake and markers of inflammation. The American Journal of Clinical Nutrition. https://doi.org/10.1016/j.ajcnut.2023.08.018.
DOI: https://doi.org/10.1016/j.ajcnut.2023.08.018

Interpretive Summary: Higher levels of inflammation in the body is a risk factor for many chronic diseases, including type 2 diabetes (T2D) and cardiovascular disease. Red meat consumption was initially associated with higher inflammation, but it is not clear why: the relationship may be attributable to the higher body weight seen in red meat eaters, since excess adiposity causes inflammation. As metabolites in the blood capture the effects of diet after food is processed, digested, and absorbed (i.e., metabolized), incorporating them into scientific investigations can help clarify diet-health relationships. Therefore the current study sought to identify whether any metabolites associated with red meat intake are also associated with inflammation. In an analysis of 4,000 older US adults, neither the intake of processed, nor unprocessed forms of red meat were associated with inflammation, in analyses which adjust for individuals' body mass indexes (BMI). However, unprocessed red meat was associated with lower levels of one metabolite: the amino acid glutamine. Lower levels of glutamine were, in turn, associated with higher inflammation levels. Overall, these 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 inflammation. The differences in diet-inflammation associations vs. diet metabolite-inflammation associations warrants further investigation to understand the extent that these arise the ability of plasma metabolites to capture individual differences in how food intake is metabolized.

Technical Abstract: The objective of our study was to identify whether any metabolites associated with red meat intake are also associated with inflammation. We used 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. We found neither processed nor 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 spectral features representing the metabolite glutamine (sentinel hit: Beta=-0.09+/-0.02, P=2.0x10**-5), an amino acid which was also inversely associated with CRP level (Beta=-0.11+/-0.01, P=3.3x10**-10). 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.