Metabolomic response to coffee consumption: application to a three-stage clinical trial

M. C. Cornelis*, I. Erlund, G. A. Michelotti, C. Herder, J. A. Westerhuis, J. Tuomilehto

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Background: Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Objective: To identify individual metabolite changes in response to coffee. Methods: We profiled the metabolome of fasting serum samples collected from a previously reported single-blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed four cups of coffee/day in the second month and eight cups/day in the third month. Samples collected after each coffee stage were subject to nontargeted metabolomic profiling using UPLC-ESI-MS/MS. A total of 733 metabolites were included for univariate and multivariate analyses. Results: A total of 115 metabolites were significantly associated with coffee intake (P < 0.05 and Q < 0.05). Eighty-two were of known identity and mapped to one of 33 predefined biological pathways. We observed a significant enrichment of metabolite members of five pathways (P < 0.05): (i) xanthine metabolism: includes caffeine metabolites, (ii) benzoate metabolism: reflects polyphenol metabolite products of gut microbiota metabolism, (iii) steroid: novel but may reflect phytosterol content of coffee, (iv) fatty acid metabolism (acylcholine): novel link to coffee and (v) endocannabinoid: novel link to coffee. Conclusions: The novel metabolites and candidate pathways we have identified may provide new insight into the mechanisms by which coffee may be exerting its health effects.

Original languageEnglish
Pages (from-to)544-557
Number of pages14
JournalJournal of Internal Medicine
Issue number6
Publication statusPublished - 1 Jun 2018
Externally publishedYes


MATLAB computations in this study were run on the Quest cluster supported in part through the computational resources and staff contributions provided for the Quest high-performance computing facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research and Northwestern University Information Technology. This work was supported by the American Diabetes Association (ADA, 7-13-JF-15 to MCC). The German Diabetes Center was supported by the Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW), the German Federal Ministry of Health (BMG) and in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD).

FundersFunder number
German Federal Ministry of Health
Ministry of Science and Research of the State of North Rhine-Westphalia
Northwestern University Information Technology
American Diabetes Association7-13-JF-15
Office of the Provost, University of South Carolina
Office of Research-Wichita, School of Medicine, University of Kansas
Bundesministerium für Bildung und Forschung
Bundesministerium für Gesundheit
Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen


    • biomarkers
    • caffeine
    • coffee
    • metabolomics
    • trial


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