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Development and validation of a metabolite score for red meat intake: an observational cohort study and randomized controlled dietary intervention.

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Li, Chunxiao 
Stewart, Isobel D 
Pietzner, Maik 


BACKGROUND: Self-reported meat consumption is associated with disease risk but objective assessment of different dimensions of this heterogeneous dietary exposure in observational and interventional studies remains challenging. OBJECTIVES: We aimed to derive and validate scores based on plasma metabolites for types of meat consumption. For the most predictive score, we aimed to test whether the included metabolites varied with change in meat consumption, and whether the score was associated with incidence of type 2 diabetes (T2D) and other noncommunicable diseases. METHODS: We derived scores based on 781 plasma metabolites for red meat, processed meat, and poultry consumption assessed with 7-d food records among 11,432 participants in the EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort. The scores were then tested for internal validity in an independent subset (n = 853) of the same cohort. In focused analysis on the red meat metabolite score, we examined whether the metabolites constituting the score were also associated with meat intake in a randomized crossover dietary intervention trial of meat (n = 12, Lyon, France). In the EPIC-Norfolk study, we assessed the association of the red meat metabolite score with T2D incidence (n = 1478) and other health endpoints. RESULTS: The best-performing score was for red meat, comprising 139 metabolites which accounted for 17% of the explained variance of red meat consumption in the validation set. In the intervention, 11 top-ranked metabolites in the red meat metabolite score increased significantly after red meat consumption. In the EPIC-Norfolk study, the red meat metabolite score was associated with T2D incidence (adjusted HR per SD: 1.17; 95% CI: 1.10, 1.24). CONCLUSIONS: The red meat metabolite score derived and validated in this study contains metabolites directly derived from meat consumption and is associated with T2D risk. These findings suggest the potential for objective assessment of dietary components and their application for understanding diet-disease associations.The trial in Lyon, France, was registered at as NCT03354130.



biomarker, diabetes, meat, metabolomics, prediction, Cohort Studies, Diabetes Mellitus, Type 2, Diet, Humans, Meat, Prospective Studies, Red Meat, Risk Factors

Journal Title

Am J Clin Nutr

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Elsevier BV
MRC (MC_UU_00006/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
MRC (MC_UU_00006/3)
Medical Research Council (MR/N003284/1)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (G0401527/1)
The EPIC-Norfolk study ( has received funding from the Medical Research Council (MR/N003284/1 MC-UU_12015/1 and MC_UU_00006/1) and Cancer Research UK (C864/A14136). Metabolite measurements in the EPIC-Norfolk study were supported by the MRC Cambridge Initiative in Metabolic Science (MR/L00002/1) and the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372. N.J.W, N.G.F, F.I, I.D.S, M.P, E.W, and C.L acknowledge funding from the Medical Research Council Epidemiology Unit MC_UU_00006/1 and MC_UU_00006/3; NJW and NGF, from NIHR Cambridge Biomedical Research Centre: nutrition, diet, and lifestyle research theme (IS-BRC-1215-20014). C.Li was supported by a Jardine-Cambridge Graduate Scholarship.