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Effect of coffee, tea and alcohol intake on circulating inflammatory cytokines: a two sample-Mendelian randomization study



Despite the abundance of research examining the effects of coffee, tea, and alcohol on inflammatory diseases, there is a notable absence of conclusive evidence regarding their direct causal influence on circulating inflammatory cytokines. Previous studies have primarily concentrated on established cytokines, neglecting the potential impact of beverage consumption on lesser-studied but equally important cytokines.


Information regarding the consumption of coffee, tea, and alcohol was collected from the UK Biobank, with sample sizes of 428,860, 447,485, and 462,346 individuals, respectively. Data on 41 inflammatory cytokines were obtained from summary statistics of 8293 healthy participants from Finnish cohorts.


The consumption of coffee was found to be potentially associated with decreased levels of Macrophage colony-stimulating factor (β = −0.57, 95% CI −1.06 ~ −0.08; p = 0.022) and Stem cell growth factor beta (β = −0.64, 95% CI −1.16 ~ −0.12; p = 0.016), as well as an increase in TNF-related apoptosis-inducing ligand (β = 0.43, 95% CI 0.06 ~ 0.8; p = 0.023) levels. Conversely, tea intake was potentially correlated with a reduction in Interleukin-8 (β = −0.45, 95% CI −0.9 ~ 0; p = 0.045) levels. Moreover, our results indicated an association between alcohol consumption and decreased levels of Regulated on Activation, Normal T Cell Expressed and Secreted (β = −0.24, 95% CI −0.48 ~ 0; p = 0.047), as well as an increase in Stem cell factor (β = 0.17, 95% CI 0.02 ~ 0.31; p = 0.023) and Stromal cell-derived factor-1 alpha (β = 0.20, 95% CI 0.04 ~ 0.36; p = 0.013).


Revealing the interactions between beverage consumption and various inflammatory cytokines may lead to the discovery of novel therapeutic targets, thereby facilitating dietary interventions to complement clinical disease treatments.

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Fig. 1
Fig. 2
Fig. 3: Scatter plot of nominal significant estimates of coffee, tea and alcohol intake on inflammatory cytokines based on genetic predictions.
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The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.


  1. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and arrhythmias time to grind the data. JACC Clin Electrophysiol. 2018;4:425–32.

    Article  PubMed  Google Scholar 

  2. Liczbinski P, Bukowska B. Tea and coffee polyphenols and their biological properties based on the latest in vitro investigations. Ind Crops Prod 2022; 175.

  3. de Mejia EG, Vinicio Ramirez-Mares M. Impact of caffeine and coffee on our health. Trends Endocrinol Metab. 2014;25:489–92.

    Article  CAS  Google Scholar 

  4. Chieng D, Kistler PM. Coffee and tea on cardiovascular disease (CVD) prevention. Trends Cardiovasc Med. 2022;32:399–405.

    Article  CAS  PubMed  Google Scholar 

  5. Machado F, Coimbra MA, del Castillo MD, Coreta-Gomes F. Mechanisms of action of coffee bioactive compounds - a key to unveil the coffee paradox. Crit Rev Food Sci Nutr 2023.

  6. Saric S, Notay M, Sivamani RK. Green tea and other tea polyphenols: effects on sebum production and acne vulgaris. Antioxidants 2017; 6.

  7. Rana A, Samtiya M, Dhewa T, Mishra V, Aluko RE. Health benefits of polyphenols: a concise review. J Food Biochem 2022; 46.

  8. Zhao X, Zhou R, Li H, Fan Y, Sun Y, Hu X et al. The effects of moderate alcohol consumption on circulating metabolites and gut microbiota in patients with coronary artery disease. Front Cardiovasc Med 2021; 8.

  9. Visontay R, Mewton L, Sunderland M, Bell S, Britton A, Osman B et al. A comprehensive evaluation of the longitudinal association between alcohol consumption and a measure of inflammation: Multiverse and vibration of effects analyses. Drug Alcohol Depend 2023; 247.

  10. Chen X, Kong J, Pan J, Huang K, Zhou W, Diao X et al. Kidney damage causally affects the brain cortical structure: a mendelian randomization study. eBioMedicine 2021; 72.

  11. Richmond RC, Smith GD. Mendelian randomization: concepts and scope. Cold Spring Harbor Perspect Med 2022; 12.

  12. Sekula P, Del Greco FM, Pattaro C, Koettgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27:3253–65.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cai J, Li X, Wu S, Tian Y, Zhang Y, Wei Z, et al. Assessing the causal association between human blood metabolites and the risk of epilepsy. J Transl Med. 2022;20:437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Res Synth Methods. 2019;10:486–96.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Evans DM, Smith GD. Mendelian randomization: new applications in the coming age of hypothesis-free causality. In: Chakravarti A, Green E (eds). Annual Review of Genomics and Human Genetics, Vol 16, vol. 16, 2015, pp 327–50.

  16. Elsworth BL, Lyon MS, Alexander T, Liu Y, Matthews P, Hallett J et al. The MRC IEU OpenGWAS data infrastructure. bioRxiv 2020.

  17. Hemani G, Zhengn J, Elsworth B, Wade KH, Haberland V, Baird D et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife 2018; 7.

  18. Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ahola-Olli AV, Wurtz P, Havulinna AS, Aalto K, Pitkanen N, Lehtimaki T, et al. Genome-wide association study identifies 27 loci influencing concentrations of circulating cytokines and growth factors. Am J Hum Genet. 2017;100:40–50.

    Article  CAS  PubMed  Google Scholar 

  20. Chen X, Hong X, Gao W, Luo S, Cai J, Liu G et al. Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study. J Transl Med 2022; 20.

  21. Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658–65.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Xiang M, Wang Y, Gao Z, Wang J, Chen Q, Sun Z, et al. Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: a mendelian randomization. Front Immunol. 2022;13:985729

    Article  CAS  PubMed  Google Scholar 

  23. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:1196–1196.

    Article  CAS  PubMed  Google Scholar 

  24. Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol. 2011;40:740–52.

    Article  PubMed  Google Scholar 

  25. Li F, Hatano T, Hattori N. Systematic analysis of the molecular mechanisms mediated by coffee in Parkinson’s disease based on network pharmacology approach. J Funct Foods 2021; 87.

  26. Gavrieli A, Yannakoulia M, Fragopoulou E, Margaritopoulos D, Chamberland JP, Kaisari P, et al. Caffeinated coffee does not acutely affect energy intake, appetite, or inflammation but prevents serum cortisol concentrations from falling in healthy men. J Nutr. 2011;141:703–7.

    Article  CAS  PubMed  Google Scholar 

  27. Kempf K, Herder C, Erlund I, Kolb H, Martin S, Carstensen M, et al. Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr. 2010;91:950–7.

    Article  CAS  PubMed  Google Scholar 

  28. Paiva C, Beserra B, Reis C, Dorea JG, Da Costa T, Amato AA. Consumption of coffee or caffeine and serum concentration of inflammatory markers: a systematic review. Crit Rev Food Sci Nutr. 2019;59:652–63.

    Article  CAS  PubMed  Google Scholar 

  29. Xiang C, Li H, Tang W Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases. Pharmacol Res 2023; 187.

  30. Deng X, Yang Q, Wang Y, Yang Y, Pei G, Zhu H et al. Association of plasma macrophage colony-stimulating factor with cardiovascular morbidity and all-cause mortality in chronic hemodialysis patients. BMC Nephrol 2019; 20.

  31. Irvine KM, Andrews MR, Fernandez-Rojo MA, Schroder K, Burns CJ, Su S, et al. Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages. J Leukoc Biol. 2009;85:278–88.

    Article  CAS  PubMed  Google Scholar 

  32. Yoon CS, Keun LS. Concurrent innate immunity activation and anti-inflammation effects of dialyzed coffee extract in RAW 264.7 cells, murine macrophage lineage. Korean J Oral Maxillofac Pathol. 2017;41:121–9.

    Article  Google Scholar 

  33. Sukowati CHC, Patti R, Pascut D, Ladju RB, Tarchi P, Zanotta N, et al. Serum stem cell growth factor beta for the prediction of therapy response in hepatocellular carcinoma. Biomed Res Int. 2018;2018:6435482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tarantino G, Citro V, Balsano C, Capone D. Could SCGF-beta levels be associated with inflammation markers and insulin resistance in male patients suffering from obesity-related NAFLD? Diagnostics 2020; 10.

  35. Schiro A, Wilkinson FL, Weston R, Smyth JV, Serracino-Inglott F, Alexander MY. Elevated levels of endothelialderived microparticles, and serum CXCL9 and SCGF-beta are associated with unstable asymptomatic carotid plaques. Sci Rep 2015; 5.

  36. Chen ZJ, Hu ZL, Hu YQ, Sheng YX, Li Y, Song JP. Novel potential biomarker of adult cardiac surgery-associated acute kidney injury. Front Physiol 2020; 11.

  37. Beyer K, Baukloh AK, Stoyanova A, Kamphues C, Sattler A, Kotsch K. Interactions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the immune system: implications for inflammation and cancer. Cancers 2019; 11.

  38. Rushworth SA, Micheau O. Molecular crosstalk between TRAIL and natural antioxidants in the treatment of cancer. Br J Pharmacol. 2009;157:1186–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jong KXJ, Mohamed EHM, Ibrahim ZA. Escaping cell death via TRAIL decoy receptors: a systematic review of their roles and expressions in colorectal cancer. Apoptosis. 2022;27:787–99.

    Article  PubMed  Google Scholar 

  40. Forde H, Harper E, Rochfort KD, Wallace RG, Davenport C, Smith D, et al. TRAIL inhibits oxidative stress in human aortic endothelial cells exposed to pro-inflammatory stimuli. Physiol Rep. 2020;8:e14612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kang YH, Park MG, Noh KH, Park HR, Lee HW, Son SM, et al. Low serum TNF-related apoptosis-inducing ligand (TRAIL) levels are associated with acute ischemic stroke severity. Atherosclerosis. 2015;240:228–33.

    Article  CAS  PubMed  Google Scholar 

  42. Hu D, Xia SL, Shao XX, Yu LQ, Lin XX, Guo M, et al. Association of ulcerative colitis with TNF-related apoptosis inducing ligand (TRAIL) gene polymorphisms and plasma soluble TRAIL levels in Chinese Han population. Eur Rev Med Pharmacol Sci. 2015;19:467–76.

    CAS  PubMed  Google Scholar 

  43. Um HJ, Oh JH, Kim YN, Choi YH, Kim SH, Park JW, et al. 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. 2010;186:36–42.

    Article  CAS  PubMed  Google Scholar 

  44. El-Elimat T, Qasem WM, Al-Sawalha NA, AbuAlSamen MM, Munaiem RT, Al-Qiam R, et al. A prospective non-randomized open-label comparative study of the effects of matcha tea on overweight and obese individuals: a pilot observational study. Plant Foods Hum Nutr. 2022;77:447–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bogdanski P, Suliburska J, Szulinska M, Stepien M, Pupek-Musialik D, Jablecka A. Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients. Nutr Res. 2012;32:421–7.

    Article  CAS  PubMed  Google Scholar 

  46. Sirotkin AV, Kolesarova A. The anti-obesity and health-promoting effects of tea and coffee. Physiol Res. 2021;70:161–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Iris M, Tsou PS, Sawalha AH. Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity. Clin Immunol. 2018;192:68–77.

    Article  CAS  PubMed  Google Scholar 

  48. Li ZD, Geng MY, Dou SR, Wang X, Zhang ZH, Chang YZ. Caffeine decreases hepcidin expression to alleviate aberrant iron metabolism under inflammation by regulating the IL-6/STAT3 pathway. Life 2022; 12.

  49. Chen L, Wang XJ, Chen JX, Yang JC, Lin L, Cai XB et al. Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism. Diabetol Metabol Syndr 2023; 15.

  50. Karuppagounder SS, Uthaythas S, Govindarajulu M, Ramesh S, Parameshwaran K, Dhanasekaran M. Caffeine, a natural methylxanthine nutraceutical, exerts dopaminergic neuroprotection. Neurochem Int 2021; 148.

  51. Deng MG, Liu F, Wang K, Liang YH, Nie JQ, Chai C. Genetic association between coffee/caffeine consumption and the risk of obstructive sleep apnea in the European population: a two-sample Mendelian randomization study. Eur J Nutr. 2023;62:3423–31.

    Article  CAS  PubMed  Google Scholar 

  52. Chang HP, Chen YF, Du JK. Obstructive sleep apnea treatment in adults. Kaohsiung J Med Sci. 2020;36:7–12.

    Article  PubMed  Google Scholar 

  53. Lotersztajn S, Riva A, Wang S, Dooley S, Chokshi S, Gao B. Inflammation in alcohol-associated liver disease progression. Z Fur Gastroenterol. 2022;60:58–66.

    Article  CAS  Google Scholar 

  54. Huang YY, Li YM, Zheng SC, Yang X, Wang TH, Zeng J. Moderate alcohol consumption and atherosclerosis Meta-analysis of effects on lipids and inflammation. Wien Klinische Wochenschr. 2017;129:835–43.

    Article  CAS  Google Scholar 

  55. Klarich DS, Penprase J, Cintora P, Medrano O, Erwin D, Brasser SM, et al. Effects of moderate alcohol consumption on gene expression related to colonic inflammation and antioxidant enzymes in rats. Alcohol. 2017;61:25–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zeng Z, Lan TX, Wei YQ, Wei XW. CCL5/CCR5 axis in human diseases and related treatments. Genes Dis. 2022;9:12–27.

    Article  CAS  PubMed  Google Scholar 

  57. Aldinucci D, Borghese C, Casagrande N. The CCL5/CCR5 axis in cancer progression. Cancers 2020; 12.

  58. Chatterjee M, Gawaz M. Platelet-derived CXCL12 (SDF-1 alpha): basic mechanisms and clinical implications. J Thromb Haemost. 2013;11:1954–67.

    Article  CAS  PubMed  Google Scholar 

  59. Gil-Bernabe P, Boveda-Ruiz D, D’Alessandro-Gabazza C, Toda M, Miyake Y, Mifuji-Moroka R, et al. Atherosclerosis amelioration by moderate alcohol consumption is associated with increased circulating levels of stromal cell-derived factor-1. Circ J. 2011;75:2269–79.

    Article  CAS  PubMed  Google Scholar 

  60. Garcia-Hernandez V, Raya-Sandino A, Azcutia V, Miranda J, Kelm M, Flemming S, et al. Inhibition of soluble stem cell factor promotes intestinal mucosal repair. Inflamm Bowel Dis. 2023;29:1133–44.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ptaschinski C, Zhu D, Fonseca W, Lukacs NW. Stem cell factor inhibition reduces Th2 inflammation and cellular infiltration in a mouse model of eosinophilic esophagitis. Mucosal Immunol 2023.

  62. Im PK, Millwood IY, Kartsonaki C, Chen Y, Guo Y, Du H, et al. Alcohol drinking and risks of total and site-specific cancers in China: A 10-year prospective study of 0.5 million adults. Int J Cancer. 2021;149:522–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Niemela O, Aalto M, Bloigu A, Bloigu R, Halkola AS, Laatikainen T. Alcohol drinking patterns and laboratory indices of health: does type of alcohol preferred make a difference? Nutrients 2022; 14.

  64. Zhong VW, Kuang A, Danning RD, Kraft P, van Dam RM, Chasman DI, et al. A genome-wide association study of bitter and sweet beverage consumption. Hum Mol Genet. 2019;28:2449–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Said MA, van de Vegte YJ, Verweij N, van der Harst P. Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes mellitus. J Am Heart Assoc. 2020;9:e016808

    Article  PubMed  PubMed Central  Google Scholar 

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This work was supported by the School of Food Science and technology, Jiangnan University.


The work was supported by Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Future Food Technology Innovation Center (bm2020023) and Natural Science Foundation of China (32172136).

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Yuan He, Yong-Jiang Xu and Yuan-Fa Liu: Conceived and designed the experiments; Yuan He and Shuang Zhu: Performed and analyzed the experiments. Yuan He, Yu Zhang and Shuang Zhu: Collecting data; Yuan He, Jian-Bin Zhang, Yong-Jiang Xu and Chin Ping Tan: Wrote and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jianbin Zhang or Yong-Jiang Xu.

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He, Y., Zhu, S., Zhang, Y. et al. Effect of coffee, tea and alcohol intake on circulating inflammatory cytokines: a two sample-Mendelian randomization study. Eur J Clin Nutr (2024).

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