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

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