Targeted proteomic response to coffee consumption



Coffee is widely consumed and implicated in numerous health outcomes but the mechanisms by which coffee contributes to health is unclear. The purpose of this study was to test the effect of coffee drinking on candidate proteins involved in cardiovascular, immuno-oncological and neurological pathways.


We examined 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 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were analyzed using three multiplex proximity extension assays that, after quality control, measured a total of 247 proteins implicated in cardiovascular, immuno-oncological and neurological pathways and of which 59 were previously linked to coffee exposure. Repeated measures ANOVA was used to test the relationship between coffee treatment and each protein.


Two neurology-related proteins including carboxypeptidase M (CPM) and neutral ceramidase (N-CDase or ASAH2), significantly increased after coffee intake (P < 0.05 and Q < 0.05). An additional 46 proteins were nominally associated with coffee intake (P < 0.05 and Q > 0.05); 9, 8 and 29 of these proteins related to cardiovascular, immuno-oncological and neurological pathways, respectively, and the levels of 41 increased with coffee intake.


CPM and N-CDase levels increased in response to coffee intake. These proteins have not previously been linked to coffee and are thus novel markers of coffee response worthy of further study.

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We thank Paulig Oy, Helsinki, Finland for the donation of coffee for this trial. Matlab computations in this paper 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 original trial was supported by a grant from the Institute of Scientific Information on Coffee, which is a consortium of major European Coffee Companies (JT). The German Diabetes Center was supported by the Ministry of Culture and Science of the State of North Rhine-Westphalia (MKW 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).

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AK analyzed the data. IE, CH and JT lead the coffee trial and provided samples for the current study. MCC and JAW supervised the statistical analysis. MCC acquired the proteomics data and was responsible for the current study concept, study design and final content. MCC wrote the paper. All authors critically revised for important intellectual content and approved the final manuscript.

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Correspondence to Marilyn C. Cornelis.

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Kuang, A., Erlund, I., Herder, C. et al. Targeted proteomic response to coffee consumption. Eur J Nutr 59, 1529–1539 (2020).

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  • Coffee
  • Caffeine
  • Proteomics
  • Biomarkers
  • Trial