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 journalArticlepeer-review

35 Scopus citations


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 (US)
Pages (from-to)544-557
Number of pages14
JournalJournal of Internal Medicine
Issue number6
StatePublished - Jun 2018


  • biomarkers
  • caffeine
  • coffee
  • metabolomics
  • trial

ASJC Scopus subject areas

  • Internal Medicine


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