Targeted proteomic response to coffee consumption

  • Alan Kuang
  • Iris Erlund
  • Christian Herder
  • Johan A. Westerhuis
  • Jaakko Tuomilehto
  • Marilyn C. CornelisEmail author
Original Contribution



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.

Clinical trial registry


Coffee Caffeine Proteomics Biomarkers Trial 



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.

Author contributions

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.


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).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Supplementary material

394_2019_2009_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1693 kb)


  1. 1.
    Reyes CM, Cornelis MC (2018) Caffeine in the diet: country-level consumption and guidelines. Nutrients. PubMedPubMedCentralGoogle Scholar
  2. 2.
    Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J (2017) Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ 359:j5024CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gilbert RM (1984) Caffeine consumption. In: Spiller GA (ed) The methylxanthine beverages and foods: chemistry, consumption, and health effects. Alan R. Liss Inc, New York, pp 185–213Google Scholar
  4. 4.
    Cornelis MC, Hu FB (2013) Systems epidemiology: a new direction in nutrition and metabolic disease research. Curr Nutr Rep. PubMedPubMedCentralGoogle Scholar
  5. 5.
    Kempf K, Herder C, Erlund I, Kolb H, Martin S, Carstensen M, Koenig W, Sundvall J, Bidel S, Kuha S, Tuomilehto J (2010) Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr 91(4):950–957. CrossRefPubMedGoogle Scholar
  6. 6.
    Cornelis MC, Erlund I, Michelotti GA, Herder C, Westerhuis JA, Tuomilehto J (2018) Metabolomic response to coffee consumption: application to a three-stage clinical trial. J Intern Med. PubMedGoogle Scholar
  7. 7.
    Kuang A, Erlund I, Herder C, Westerhuis J, Tuomilehto J, Cornelis M (2018) Lipidomic response to coffee consumption. Nutrients 10(12):1851CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Schubert OT, Rost HL, Collins BC, Rosenberger G, Aebersold R (2017) Quantitative proteomics: challenges and opportunities in basic and applied research. Nat Protoc 12(7):1289–1294. CrossRefPubMedGoogle Scholar
  9. 9.
    Assarsson E, Lundberg M, Holmquist G, Bjorkesten J, Thorsen SB, Ekman D, Eriksson A, Rennel Dickens E, Ohlsson S, Edfeldt G, Andersson AC, Lindstedt P, Stenvang J, Gullberg M, Fredriksson S (2014) Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One 9(4):e95192. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lundberg M, Eriksson A, Tran B, Assarsson E, Fredriksson S (2011) Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood. Nucleic Acids Res 39(15):e102. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bijlsma S, Bobeldijk I, Verheij ER, Ramaker R, Kochhar S, Macdonald IA, van Ommen B, Smilde AK (2006) Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation. Anal Chem 78(2):567–574. CrossRefPubMedGoogle Scholar
  12. 12.
    Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol) 57(1):289–300Google Scholar
  13. 13.
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Human Protein Atlas. Accessed Nov 2018
  15. 15.
    Zhang X, Skidgel RA (2013) Carboxypeptidase M. Handbook of proteolytic enzymes, 3rd edn. Elsevier, Amsterdam, pp 1357–1366CrossRefGoogle Scholar
  16. 16.
    Deiteren K, Hendriks D, Scharpé S, Lambeir AM (2009) Carboxypeptidase M: multiple alliances and unknown partners. Clin Chim Acta 399(1–2):24–39CrossRefPubMedGoogle Scholar
  17. 17.
    Magnan J, Paterson SJ, Kosterlitz HW (1982) The interaction of [Met5] enkephalin and [Leu5] enkephalin sequences, extended at the C-terminus, with the μ-, δ-and κ-binding sites in the guinea-pig brain. Life Sci 31(12–13):1359–1361CrossRefPubMedGoogle Scholar
  18. 18.
    Rao R, Koldovský O, Korc M, Pollack P, Wright S, Davis T (1990) Processing and transfer of epidermal growth factor in developing rat jejunum and ileum. Peptides 11(6):1093–1102CrossRefPubMedGoogle Scholar
  19. 19.
    Hollenberg MD, Gregory H (1980) Epidermal growth factor-urogastrone: biological activity and receptor binding of derivatives. Mol Pharmacol 17(3):314–320PubMedGoogle Scholar
  20. 20.
    Skidgel RA, Erdös EG (1998) Cellular carboxypeptidases. Immunol Rev 161(1):129–141CrossRefPubMedGoogle Scholar
  21. 21.
    Skidgel R, Davis R, Tan F (1989) Human carboxypeptidase M. Purification and characterization of a membrane-bound carboxypeptidase that cleaves peptide hormones. J Biol Chem 264(4):2236–2241PubMedGoogle Scholar
  22. 22.
    Bhoola K, Figueroa C, Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 44(1):1–80PubMedGoogle Scholar
  23. 23.
    Muller L-LLMF (2005) Classification of the kinin receptor family: from molecular mechanisms to pathophysiologica consequences. Pharmacol Rev 57:27–77CrossRefGoogle Scholar
  24. 24.
    Paiva C, Beserra B, Reis C, Dorea JG, Da Costa T, Amato AA (2017) Consumption of coffee or caffeine and serum concentration of inflammatory markers: a systematic review. Crit Rev Food Sci Nutr. PubMedGoogle Scholar
  25. 25.
    Baratloo A, Rouhipour A, Forouzanfar MM, Safari S, Amiri M, Negida A (2016) The role of caffeine in pain management: a brief literature review. Anesth Pain Med 6(3):e33193. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Derry CJ, Derry S, Moore RA (2014) Caffeine as an analgesic adjuvant for acute pain in adults. Cochrane Database Syst Rev 12:CD009281. Google Scholar
  27. 27.
    Saied EM, Arenz C (2016) Inhibitors of ceramidases. Chem Phys Lipid 197:60–68CrossRefGoogle Scholar
  28. 28.
    Kono M, Dreier JL, Ellis JM, Allende ML, Kalkofen DN, Sanders KM, Bielawski J, Bielawska A, Hannun YA, Proia RL (2006) Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids. J Biol Chem 281(11):7324–7331CrossRefPubMedGoogle Scholar
  29. 29.
    El Bawab S, Roddy P, Qian T, Bielawska A, Lemasters JJ, Hannun YA (2000) Molecular cloning and characterization of a human mitochondrial ceramidase. J Biol Chem 275(28):21508–21513. CrossRefPubMedGoogle Scholar
  30. 30.
    Airola MV, Allen WJ, Pulkoski-Gross MJ, Obeid LM, Rizzo RC, Hannun YA (2015) Structural basis for ceramide recognition and hydrolysis by human neutral ceramidase. Structure 23(8):1482–1491. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tani M, Sano T, Ito M, Igarashi Y (2005) Mechanisms of sphingosine and sphingosine 1-phosphate generation in human platelets. J Lipid Res 46(11):2458–2467. CrossRefPubMedGoogle Scholar
  32. 32.
    Tani M, Ito M (2018) Neutral ceramidase. In: Choi S (ed) Encyclopedia of Signaling molecules. Springer, ChamGoogle Scholar
  33. 33.
    Ito M, Okino N, Tani M (2014) New insight into the structure, reaction mechanism, and biological functions of neutral ceramidase. Biochim Biophys Acta (BBA) Mol Cell Biol Lipids 1841(5):682–691CrossRefGoogle Scholar
  34. 34.
    Vesper H, Schmelz E-M, Nikolova-Karakashian MN, Dillehay DL, Lynch DV, Merrill AH Jr (1999) Sphingolipids in food and the emerging importance of sphingolipids to nutrition. J Nutr 129(7):1239–1250CrossRefPubMedGoogle Scholar
  35. 35.
    Norris GH, Blesso CN (2017) Dietary sphingolipids: potential for management of dyslipidemia and nonalcoholic fatty liver disease. Nutr Rev 75(4):274–285CrossRefPubMedGoogle Scholar
  36. 36.
    Altmaier E, Kastenmuller G, Romisch-Margl W, Thorand B, Weinberger KM, Adamski J, Illig T, Doring A, Suhre K (2009) Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics. Mol Nutr Food Res 53(11):1357–1365CrossRefPubMedGoogle Scholar
  37. 37.
    Floegel A, Wientzek A, Bachlechner U, Jacobs S, Drogan D, Prehn C, Adamski J, Krumsiek J, Schulze MB, Pischon T, Boeing H (2014) Linking diet, physical activity, cardiorespiratory fitness and obesity to serum metabolite networks: findings from a population-based study. Int J Obes (Lond) 38(11):1388–1396. CrossRefGoogle Scholar
  38. 38.
    Hannun YA, Obeid LM (2018) Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol 19(3):175–191. CrossRefPubMedGoogle Scholar
  39. 39.
    Hao WR, Sung LC, Chen CC, Chen PY, Cheng TH, Chao HH, Liu JC, Chen JJ (2018) Cafestol inhibits cyclic-strain-induced interleukin-8, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 production in vascular endothelial cells. Oxid Med Cell Longev 2018:7861518. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Zheng Z, Sheng Y, Lu B, Ji L (2015) The therapeutic detoxification of chlorogenic acid against acetaminophen-induced liver injury by ameliorating hepatic inflammation. Chem Biol Interact 238:93–101. CrossRefPubMedGoogle Scholar
  41. 41.
    Iris M, Tsou PS, Sawalha AH (2018) Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity. Clin Immunol 192:68–77. CrossRefPubMedGoogle Scholar
  42. 42.
    Liu CW, Tsai HC, Huang CC, Tsai CY, Su YB, Lin MW, Lee KC, Hsieh YC, Li TH, Huang SF, Yang YY, Hou MC, Lin HC, Lee FY, Lee SD (2018) Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats. Am J Physiol Endocrinol Metab 314(5):E433–E447. CrossRefPubMedGoogle Scholar
  43. 43.
    Matsuda Y, Kobayashi M, Yamauchi R, Ojika M, Hiramitsu M, Inoue T, Katagiri T, Murai A, Horio F (2011) Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J mice fed a high-fat diet. Biosci Biotechnol Biochem 75(12):2309–2315. CrossRefPubMedGoogle Scholar
  44. 44.
    Shi H, Dong L, Dang X, Liu Y, Jiang J, Wang Y, Lu X, Guo X (2013) Effect of chlorogenic acid on LPS-induced proinflammatory signaling in hepatic stellate cells. Inflamm Res 62(6):581–587. CrossRefPubMedGoogle Scholar
  45. 45.
    Yamauchi R, Kobayashi M, Matsuda Y, Ojika M, Shigeoka S, Yamamoto Y, Tou Y, Inoue T, Katagiri T, Murai A, Horio F (2010) Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. J Agric Food Chem 58(9):5597–5603. CrossRefPubMedGoogle Scholar
  46. 46.
    Martinez-Lopez S, Sarria B, Mateos R, Bravo-Clemente L (2018) Moderate consumption of a soluble green/roasted coffee rich in caffeoylquinic acids reduces cardiovascular risk markers: results from a randomized, cross-over, controlled trial in healthy and hypercholesterolemic subjects. Eur J Nutr. PubMedGoogle Scholar
  47. 47.
    Anwar J, Spanevello RM, Pimentel VC, Gutierres J, Thome G, Cardoso A, Zanini D, Martins C, Palma HE, Bagatini MD, Baldissarelli J, Schmatz R, Leal CA, da Costa P, Morsch VM, Schetinger MR (2013) Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats. Food Chem Toxicol 56:459–466. CrossRefPubMedGoogle Scholar
  48. 48.
    Schmatz R, Mann TR, Spanevello R, Machado MM, Zanini D, Pimentel VC, Stefanello N, Martins CC, Cardoso AM, Bagatini M, Gutierres J, Leal CA, Pereira LB, Mazzanti C, Schetinger MR, Morsch VM (2013) Moderate red wine and grape juice consumption modulates the hydrolysis of the adenine nucleotides and decreases platelet aggregation in streptozotocin-induced diabetic rats. Cell Biochem Biophys 65(2):129–143. CrossRefPubMedGoogle Scholar
  49. 49.
    Rybakowska IM, Milczarek R, Slominska EM, Smolenski RT (2018) Effect of decaffeinated coffee on function and nucleotide metabolism in kidney. Mol Cell Biochem 439(1–2):11–18. CrossRefPubMedGoogle Scholar
  50. 50.
    De Bona KS, Bonfanti G, Bitencourt PE, Cargnelutti LO, da Silva PS, da Silva TP, Zanette RA, Pigatto AS, Moretto MB (2014) Syzygium cumini is more effective in preventing the increase of erythrocytic ADA activity than phenolic compounds under hyperglycemic conditions in vitro. J Physiol Biochem 70(2):321–330PubMedGoogle Scholar
  51. 51.
    Bandyopadhyay B, Poddar M (1994) Caffeine-induced increase of adenosine deaminase activity in mammalian lymphoid organs. Methods Find Exp Clin Pharmacol 16(10):731–733PubMedGoogle Scholar
  52. 52.
    Minana M, Portoles M, Jorda A, Grisolia S (1984) Lesch-Nyhan syndrome, caffeine model: increase of purine and pyrimidine enzymes in rat brain. J Neurochem 43(6):1556–1560CrossRefPubMedGoogle Scholar
  53. 53.
    Adeniyi PA, Omatsuli EP, Akinyemi AJ, Ishola AO (2016) Caffeine plus nicotine improves motor function, spatial and non-spatial working memory and functional indices in BALB/c male mice. Pathophysiology 23(4):251–258. CrossRefPubMedGoogle Scholar
  54. 54.
    Akomolafe SF (2017) The effects of caffeine, caffeic acid, and their combination on acetylcholinesterase, adenosine deaminase and arginase activities linked with brain function. J Food Biochem 41(5):e12401CrossRefGoogle Scholar
  55. 55.
    Mahinpour R, Ghasemi M, Moosavi-Nejad Z, Zahraie Z (2016) Caffeine effect on adenosine deaminase catalysis: a new look at the effect of caffeine on adenosine deaminase activity. Iran J Catal 6(5):475–480Google Scholar
  56. 56.
    Saboury AA, Divsalar A, Ataie G, Amanlou M, Moosavi-Movahedi AA, Hakimelahi GH (2003) Inhibition study of adenosine deaminase by caffeine using spectroscopy and isothermal titration calorimetry. Acta Biochim Pol 50(3):849–855 (doi: 035003849) PubMedGoogle Scholar
  57. 57.
    Xu Y, Venton BJ (2010) Rapid determination of adenosine deaminase kinetics using fast-scan cyclic voltammetry. Phys Chem Chem Phys 12(34):10027–10032. CrossRefPubMedGoogle Scholar
  58. 58.
    Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L (2011) Signal transduction by vascular endothelial growth factor receptors. Biochem J 437(2):169–183CrossRefPubMedGoogle Scholar
  59. 59.
    Alitalo K (2011) The lymphatic vasculature in disease. Nat Med 17(11):1371CrossRefPubMedGoogle Scholar
  60. 60.
    Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, Saggini A, Potalivo G, Caraffa A, Antinolfi P, Tete S, Tripodi D, Conti F, Cianchetti E, Toniato E, Rosati M, Conti P, Speranza L, Pantalone A, Saggini R, Theoharides TC, Pandolfi F (2013) Vascular endothelial growth factor (VEGF), mast cells and inflammation. Int J Immunopathol Pharmacol 26(2):327–335. CrossRefPubMedGoogle Scholar
  61. 61.
    Wu D, Bao C, Li L, Fu M, Wang D, Xie J, Gong X (2015) Chlorogenic acid protects against cholestatic liver injury in rats. J Pharmacol Sci 129(3):177–182. CrossRefPubMedGoogle Scholar
  62. 62.
    Zhao X, Sun P, Li G, Yi R, Qian Y, Park K-Y (2018) Polyphenols in Kuding tea help prevent HCl/ethanol-induced gastric injury in mice. Food Funct 9(3):1713–1725CrossRefPubMedGoogle Scholar
  63. 63.
    Park JJ, Hwang SJ, Park JH, Lee HJ (2015) Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1alpha/AKT pathway. Cell Oncol (Dordr) 38(2):111–118. CrossRefGoogle Scholar
  64. 64.
    Shi H, Dong L, Zhang Y, Bai Y, Zhao J, Zhang L (2010) Protective effect of a coffee preparation (Nescafe pure) against carbon tetrachloride-induced liver fibrosis in rats. Clin Nutr (Edinburgh, Scotland) 29(3):399–405. CrossRefGoogle Scholar
  65. 65.
    Shi H, Dong L, Bai Y, Zhao J, Zhang Y, Zhang L (2009) Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats. Eur J Pharmacol 623(1–3):119–124. CrossRefPubMedGoogle Scholar
  66. 66.
    Merighi S, Benini A, Mirandola P, Gessi S, Varani K, Simioni C, Leung E, Maclennan S, Baraldi PG, Borea PA (2007) Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Mol Pharmacol 72(2):395–406. CrossRefPubMedGoogle Scholar
  67. 67.
    Kakio S, Funakoshi-Tago M, Kobata K, Tamura H (2017) Coffee induces vascular endothelial growth factor (VEGF) expression in human neuroblastama SH-SY5Y cells. Nutr Neurosci 20(6):336–342. CrossRefPubMedGoogle Scholar
  68. 68.
    Lushnikova I, Orlovsky M, Dosenko V, Maistrenko A, Skibo G (2011) Brief anoxia preconditioning and HIF prolyl-hydroxylase inhibition enhances neuronal resistance in organotypic hippocampal slices on model of ischemic damage. Brain Res 1386:175–183CrossRefPubMedGoogle Scholar
  69. 69.
    Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci 99(18):11946–11950CrossRefPubMedGoogle Scholar
  70. 70.
    Zachary I (2005) Neuroprotective role of vascular endothelial growth factor: signalling mechanisms, biological function, and therapeutic potential. Neurosignals 14(5):207–221CrossRefPubMedGoogle Scholar
  71. 71.
    Storkebaum E, Carmeliet P (2004) VEGF: a critical player in neurodegeneration. J Clin Investig 113(1):14–18CrossRefPubMedGoogle Scholar
  72. 72.
    Vijayalakshmi K, Ostwal P, Sumitha R, Shruthi S, Varghese AM, Mishra P, Manohari SG, Sagar B, Sathyaprabha T, Nalini A (2015) Role of VEGF and VEGFR2 receptor in reversal of ALS-CSF induced degeneration of NSC-34 motor neuron cell line. Mol Neurobiol 51(3):995–1007CrossRefPubMedGoogle Scholar
  73. 73.
    Torres-Rêgo M, Furtado AA, Bitencourt MAO, de Souza Lima MCJ, de Andrade RCLC, de Azevedo EP, da Cunha Soares T, Tomaz JC, Lopes NP, da Silva-Júnior AA (2016) Anti-inflammatory activity of aqueous extract and bioactive compounds identified from the fruits of Hancornia speciosa Gomes (Apocynaceae). BMC Complement Altern Med 16(1):275CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Link AA, Kino T, Worth JA, McGuire JL, Crane ML, Chrousos GP, Wilder RL, Elenkov IJ (2000) Ligand-activation of the adenosine A2a receptors inhibits IL-12 production by human monocytes. J Immunol 164(1):436–442CrossRefPubMedGoogle Scholar
  75. 75.
    Sakurai T (2012) The role of NrCAM in neural development and disorders—beyond a simple glue in the brain. Mol Cell Neurosci 49(3):351–363CrossRefPubMedGoogle Scholar
  76. 76.
    Amin N, Byrne E, Johnson J, Chenevix-Trench G, Walter S, Nolte IM, kConFab I, Vink JM, Rawal R, Mangino M, Teumer A, Keers JC, Verwoert G, Baumeister S, Biffar R, Petersmann A, Dahmen N, Doering A, Isaacs A, Broer L, Wray NR, Montgomery GW, Levy D, Psaty BM, Gudnason V, Chakravarti A, Sulem P, Gudbjartsson DF, Kiemeney LA, Thorsteinsdottir U, Stefansson K, van Rooij FJ, Aulchenko YS, Hottenga JJ, Rivadeneira FR, Hofman A, Uitterlinden AG, Hammond CJ, Shin SY, Ikram A, Witteman JC, Janssens AC, Snieder H, Tiemeier H, Wolfenbuttel BH, Oostra BA, Heath AC, Wichmann E, Spector TD, Grabe HJ, Boomsma DI, Martin NG, van Duijn CM (2012) Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Mol Psychiatry 17(11):1116–1129. CrossRefPubMedGoogle Scholar
  77. 77.
    Lee NK (2010) Molecular understanding of osteoclast differentiation and physiology. Endocrinol Metab 25(4):264–269CrossRefGoogle Scholar
  78. 78.
    Heaney RP (2002) Effects of caffeine on bone and the calcium economy. Food Chem Toxicol 40(9):1263–1270CrossRefPubMedGoogle Scholar
  79. 79.
    Choi J, Choi SY, Lee SY, Lee JY, Kim HS, Lee SY, Lee NK (2013) Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway. Cell Signal 25(5):1222–1227CrossRefPubMedGoogle Scholar
  80. 80.
    Loftfield E, Shiels MS, Graubard BI, Katki HA, Chaturvedi AK, Trabert B, Pinto LA, Kemp TJ, Shebl FM, Mayne ST, Wentzensen N, Purdue MP, Hildesheim A, Sinha R, Freedman ND (2015) Associations of coffee drinking with systemic immune and inflammatory markers. Cancer Epidemiol Biomark Prev 24(7):1052–1060. CrossRefGoogle Scholar
  81. 81.
    Cornelis MC, Gustafsson S, Arnlov J, Elmstahl S, Soderberg S, Sundstrom J, Michaelsson K, Lind L, Ingelsson E (2018) Targeted proteomic analysis of habitual coffee consumption. J Intern Med 283(2):200–211. CrossRefPubMedGoogle Scholar
  82. 82.
    Tian O, Josse AR, Borchers C, El-Sohemy A (2013) Association between caffeine intake and the plasma proteome in humans. J Caffeine Res 3(4):175–181CrossRefGoogle Scholar
  83. 83.
    von Karstedt S, Montinaro A, Walczak H (2017) Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy. Nat Rev Cancer 17(6):352CrossRefGoogle Scholar
  84. 84.
    Karmakar UK, Toume K, Ishikawa N, Arai MA, Sadhu SK, Ahmed F, Ishibashi M (2016) Bioassay-guided isolation of compounds from datura stramonium with TRAIL-resistance overcoming activity. Nat Prod Commun 11(2):185–187PubMedGoogle Scholar
  85. 85.
    Um HJ, Oh JH, Kim YN, Choi YH, Kim SH, Park JW, Kwon TK (2010) The coffee diterpene kahweol sensitizes TRAIL-induced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP. Chem Biol Interact 186(1):36–42. CrossRefPubMedGoogle Scholar
  86. 86.
    Di Bartolo B, Chan J, Bennett M, Cartland S, Bao S, Tuch BE, Kavurma MM (2011) TNF-related apoptosis-inducing ligand (TRAIL) protects against diabetes and atherosclerosis in Apoe−/− mice. Diabetologia 54(12):3157–3167CrossRefPubMedGoogle Scholar
  87. 87.
    Bernardi S, Zauli G, Tikellis C, Candido R, Fabris B, Secchiero P, Cooper ME, Thomas MC (2012) TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation. Clin Sci 123(9):547–555CrossRefPubMedGoogle Scholar
  88. 88.
    Zoller V, Funcke J-B, Keuper M, El Hay MA, Debatin K-M, Wabitsch M, Fischer-Posovszky P (2016) TRAIL (TNF-related apoptosis-inducing ligand) inhibits human adipocyte differentiation via caspase-mediated downregulation of adipogenic transcription factors. Cell Death Dis 7(10):e2412CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Harith HH, Morris MJ, Kavurma MM (2013) On the TRAIL of obesity and diabetes. Trends Endocrinol Metab 24(11):578–587CrossRefPubMedGoogle Scholar
  90. 90.
    Ni Y, Zhang F, An M, Yin W, Gao Y (2017) Acute effect of coffee consumption on urinary proteome in young healthy individuals. MOJ Proteom Bioinform 5(2):45–50Google Scholar
  91. 91.
    Peerapen P, Ausakunpipat N, Sutthimethakorn S, Aluksanasuwan S, Vinaiphat A, Thongboonkerd V (2017) Physiologic changes of urinary proteome by caffeine and excessive water intake. Clin Chem Lab Med 55(7):993–1002. CrossRefPubMedGoogle Scholar
  92. 92.
    Zyba SJ, Shenvi SV, Killilea DW, Holland TC, Kim E, Moy A, Sutherland B, Gildengorin V, Shigenaga MK, King JC (2017) A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations. Am J Clin Nutr 105(2):343–351. CrossRefPubMedGoogle Scholar
  93. 93.
    Grider A, Wickwire K, Ho E, Chung CS, King J (2013) Dietary zinc depletion and repletion affects plasma proteins: an analysis of the plasma proteome. Biometals 26(1):133–140. CrossRefPubMedGoogle Scholar
  94. 94.
    Sinha I, Karagoz K, Fogle RL, Hollenbeak CS, Zea AH, Arga KY, Stanley AE, Hawkes WC, Sinha R (2016) “Omics” of selenium biology: a prospective study of plasma proteome network before and after selenized-yeast supplementation in healthy men. OMICS 20(4):202–213. CrossRefPubMedGoogle Scholar
  95. 95.
    de Roos B, Wanders AJ, Wood S, Horgan G, Rucklige G, Reid M, Siebelink E, Brouwer IA (2011) A high intake of industrial or ruminant trans fatty acids does not affect the plasma proteome in healthy men. Proteomics 11(19):3928–3934. CrossRefPubMedGoogle Scholar
  96. 96.
    Al-Daghri NM, Alokail MS, Manousopoulou A, Heinson A, Al-Attas O, Al-Saleh Y, Sabico S, Yakout S, Woelk CH, Chrousos GP, Garbis SD (2016) Sex-specific vitamin D effects on blood coagulation among overweight adults. Eur J Clin Investig 46(12):1031–1040. CrossRefGoogle Scholar
  97. 97.
    Rentsch ML, Lametsch R, Bugel S, Jessen F, Lauritzen L (2015) The effects of eating marine- or vegetable-fed farmed trout on the human plasma proteome profiles of healthy men. Br J Nutr 113(4):699–707. CrossRefPubMedGoogle Scholar
  98. 98.
    Brauer HA, Libby TE, Mitchell BL, Li L, Chen C, Randolph TW, Yasui YY, Lampe JW, Lampe PD (2011) Cruciferous vegetable supplementation in a controlled diet study alters the serum peptidome in a GSTM1-genotype dependent manner. Nutr J 10:11. CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Duthie SJ, Horgan G, de Roos B, Rucklidge G, Reid M, Duncan G, Pirie L, Basten GP, Powers HJ (2010) Blood folate status and expression of proteins involved in immune function, inflammation, and coagulation: biochemical and proteomic changes in the plasma of humans in response to long-term synthetic folic acid supplementation. J Proteome Res 9(4):1941–1950. CrossRefPubMedGoogle Scholar
  100. 100.
    Fuchs D, Piller R, Linseisen J, Daniel H, Wenzel U (2007) The human peripheral blood mononuclear cell proteome responds to a dietary flaxseed-intervention and proteins identified suggest a protective effect in atherosclerosis. Proteomics 7(18):3278–3288. CrossRefPubMedGoogle Scholar
  101. 101.
    de Roos B, Geelen A, Ross K, Rucklidge G, Reid M, Duncan G, Caslake M, Horgan G, Brouwer IA (2008) Identification of potential serum biomarkers of inflammation and lipid modulation that are altered by fish oil supplementation in healthy volunteers. Proteomics 8(10):1965–1974CrossRefPubMedGoogle Scholar
  102. 102.
    Fuchs D, Vafeiadou K, Hall WL, Daniel H, Williams CM, Schroot JH, Wenzel U (2007) Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones. Am J Clin Nutr 86(5):1369–1375. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alan Kuang
    • 1
  • Iris Erlund
    • 2
  • Christian Herder
    • 3
    • 4
    • 5
  • Johan A. Westerhuis
    • 6
    • 7
  • Jaakko Tuomilehto
    • 8
    • 9
    • 10
  • Marilyn C. Cornelis
    • 1
    Email author
  1. 1.Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Genomics and Biomarkers UnitNational Institute for Health and WelfareHelsinkiFinland
  3. 3.Institute for Clinical Diabetology, German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany
  4. 4.German Center for Diabetes Research (DZD), Partner DüsseldorfDüsseldorfGermany
  5. 5.Division of Endocrinology and Diabetology, Medical FacultyHeinrich Heine University DüsseldorfDüsseldorfGermany
  6. 6.Biosystems Data Analysis, Swammerdam Institute for Life SciencesUniversity of AmsterdamAmsterdamThe Netherlands
  7. 7.Centre for Human Metabolomics, Faculty of Natural SciencesNorth-West University (Potchefstroom Campus)PotchefstroomSouth Africa
  8. 8.Disease Risk UnitNational Institute for Health and WelfareHelsinkiFinland
  9. 9.Department of Public HealthUniversity of HelsinkiHelsinkiFinland
  10. 10.Saudi Diabetes Research GroupKing Abdulaziz UniversityJiddaSaudi Arabia

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