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

J Intern Med. 2018 Jun;283(6):544-557. doi: 10.1111/joim.12737. Epub 2018 Mar 15.


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.

Keywords: biomarkers; caffeine; coffee; metabolomics; trial.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / metabolism
  • Biomarkers / metabolism*
  • Coffee / metabolism*
  • Endocannabinoids
  • Fasting / blood
  • Fatty Acids / metabolism
  • Humans
  • Metabolic Networks and Pathways / physiology
  • Metabolomics*
  • Microbiota
  • Single-Blind Method
  • Steroids / metabolism
  • Xanthine / metabolism


  • Benzoates
  • Biomarkers
  • Coffee
  • Endocannabinoids
  • Fatty Acids
  • Steroids
  • Xanthine