Tea Consumption, Milk or Sweeteners Addition, Genetic Variation in Caffeine Metabolism, and Incident Venous Thromboembolism

Abstract

Objective The association between tea consumption and venous thromboembolism (VTE) remains unknown. We aimed to evaluate the association between tea consumption with different additives (milk and/or sweeteners) and incident VTE, and the modifying effects of genetic variation in caffeine metabolism on the association.

Methods A total of 190,189 participants with complete dietary information and free of VTE at baseline in the UK Biobank were included. The primary outcome was incident VTE, including incident deep vein thrombosis and pulmonary embolism.

Results During a median follow-up of 12.1 years, 4,485 (2.4%) participants developed incident VTE. Compared with non-tea drinkers, tea drinkers who added neither milk nor sweeteners (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.76–0.94), only milk (HR: 0.86; 95% CI: 0.80–0.93), and both milk and sweeteners to their tea (HR: 0.90; 95% CI: 0.81–0.99) had a lower risk of VTE, while those who added only sweeteners to their tea did not (HR: 0.94; 95% CI: 0.75–1.17). Moreover, there was an L-shaped relationship between tea consumption and incident VTE among tea drinkers who added neither milk nor sweeteners, only milk, and both milk and sweeteners to their tea, respectively. However, a nonsignificant association was found among tea drinkers who added only sweeteners to their tea. Genetic variation in caffeine metabolism did not significantly modify the association (p-interaction = 0.659).

Conclusion Drinking unsweetened tea, with or without added milk, was associated with a lower risk of VTE. However, there was no significant association between drinking tea with sweeteners and incident VTE.

Keywords

tea consumption - venous thromboembolism - milk - sweeteners - caffeine metabolism

Data Availability Statement

The UK Biobank data are available on application to the UK Biobank, and the analytic methods and study materials that support the findings of this study will be available from the corresponding authors on request.

Authors' Contribution

H.X. and X.Q. designed and conducted the research; H.X. and C.Z., Z.Y., and X.Q. performed the data management and statistical analyses; H.X., C.Z., and X.Q. wrote the manuscript. All authors reviewed/edited the manuscript for important intellectual content. All authors read and approved the final manuscript.

Publication History

Received: 07 December 2023

Accepted: 11 April 2024

Article published online:
10 May 2024

• References

• 1 Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE. The economic burden of incident venous thromboembolism in the United States: a review of estimated attributable healthcare costs. Thromb Res 2016; 137: 3-10
• 2 Barco S, Woersching AL, Spyropoulos AC, Piovella F, Mahan CE. European Union-28: an annualised cost-of-illness model for venous thromboembolism. Thromb Haemost 2016; 115 (04) 800-808
• 3 Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet 2016; 388 (10063): 3060-3073
• 4 Pan Y, Feng X, Zhou S. et al. Hydroxyls on the B ring and gallic acyl are essential for catechins to restrain ADP-induced thrombosis. Food Funct 2023; 14 (02) 1037-1047
• 5 Xing L, Zhang H, Qi R, Tsao R, Mine Y. Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols. J Agric Food Chem 2019; 67 (04) 1029-1043
• 6 Lutsey PL, Zakai NA. Epidemiology and prevention of venous thromboembolism. Nat Rev Cardiol 2023; 20 (04) 248-262
• 7 Wang Q, Zennadi R. Oxidative stress and thrombosis during aging: the roles of oxidative stress in RBCs in venous thrombosis. Int J Mol Sci 2020; 21 (12) 4259
• 8 Montoro-García S, Schindewolf M, Stanford S, Larsen OH, Thiele T. The role of platelets in venous thromboembolism. Semin Thromb Hemost 2016; 42 (03) 242-251
• 9 Reyes CM, Cornelis MC. Caffeine in the diet: country-level consumption and guidelines. Nutrients 2018; 10 (11) 1772
• 10 Mahdavi S, Palatini P, El-Sohemy A. CYP1A2 genetic variation, coffee intake, and kidney dysfunction. JAMA Netw Open 2023; 6 (01) e2247868
• 11 Inoue-Choi M, Ramirez Y, Cornelis MC, Berrington de González A, Freedman ND, Loftfield E. Tea consumption and all-cause and cause-specific mortality in the UK Biobank : a prospective cohort study. Ann Intern Med 2022; 175 (09) 1201-1211
• 12 Wu H, Gu Y, Meng G. et al. Quality of plant-based diet and the risk of dementia and depression among middle-aged and older population. Age Ageing 2023; 52 (05) afad070
• 13 Liu B, Young H, Crowe FL. et al. Development and evaluation of the Oxford WebQ, a low-cost, web-based method for assessment of previous 24 h dietary intakes in large-scale prospective studies. Public Health Nutr 2011; 14 (11) 1998-2005
• 14 Bycroft C, Freeman C, Petkova D. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 2018; 562 (7726) 203-209
• 15 Cornelis MC, Kacprowski T, Menni C. et al; Swiss Kidney Project on Genes in Hypertension (SKIPOGH) team. Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior. Hum Mol Genet 2016; 25 (24) 5472-5482
• 16 Malik R, Georgakis MK, Neitzel J. et al. Midlife vascular risk factors and risk of incident dementia: longitudinal cohort and Mendelian randomization analyses in the UK Biobank. Alzheimers Dement 2021; 17 (09) 1422-1431
• 17 Lichtenstein AH, Appel LJ, Brands M. et al; American Heart Association Nutrition Committee. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006; 114 (01) 82-96
• 18 Lloyd-Jones DM, Hong Y, Labarthe D. et al; American Heart Association Strategic Planning Task Force and Statistics Committee. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond. Circulation 2010; 121 (04) 586-613
• 19 Eastwood SV, Mathur R, Atkinson M. et al. Algorithms for the capture and adjudication of prevalent and incident diabetes in UK Biobank. PLoS One 2016; 11 (09) e0162388
• 20 Nazarzadeh M, Bidel Z, Mohseni H. et al; INVENT Consortium. Blood pressure and risk of venous thromboembolism: a cohort analysis of 5.5 million UK adults and Mendelian randomization studies. Cardiovasc Res 2023; 119 (03) 835-842
• 21 Jørgensen H, Horváth-Puhó E, Laugesen K, Braekkan S, Hansen JB, Sørensen HT. Socioeconomic status and risk of incident venous thromboembolism. J Thromb Haemost 2021; 19 (12) 3051-3061
• 22 Becattini C, Agnelli G. Aspirin for prevention and treatment of venous thromboembolism. Blood Rev 2014; 28 (03) 103-108
• 23 Liu D, Li ZH, Shen D. et al. Association of sugar-sweetened, artificially sweetened, and unsweetened coffee consumption with all-cause and cause-specific mortality : a large prospective cohort study. Ann Intern Med 2022; 175 (07) 909-917
• 24 Austin PC. Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis. Stat Med 2016; 35 (30) 5642-5655
• 25 VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med 2017; 167 (04) 268-274
• 26 Kang WS, Lim IH, Yuk DY. et al. Antithrombotic activities of green tea catechins and (-)-epigallocatechin gallate. Thromb Res 1999; 96 (03) 229-237
• 27 Deana R, Turetta L, Donella-Deana A. et al. Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists. Thromb Haemost 2003; 89 (05) 866-874
• 28 Donà M, Dell'Aica I, Calabrese F. et al. Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. J Immunol 2003; 170 (08) 4335-4341
• 29 Vita JA. Polyphenols and cardiovascular disease: effects on endothelial and platelet function. Am J Clin Nutr 2005; 81 (1, Suppl): 292S-297S
• 30 Tang GY, Meng X, Gan RY. et al. Health functions and related molecular mechanisms of tea components: an update review. Int J Mol Sci 2019; 20 (24) 6196
• 31 Keller A, Wallace TC. Tea intake and cardiovascular disease: an umbrella review. Ann Med 2021; 53 (01) 929-944
• 32 Ras RT, Zock PL, Draijer R. Tea consumption enhances endothelial-dependent vasodilation; a meta-analysis. PLoS One 2011; 6 (03) e16974
• 33 Korir MW, Wachira FN, Wanyoko JK, Ngure RM, Khalid R. The fortification of tea with sweeteners and milk and its effect on in vitro antioxidant potential of tea product and glutathione levels in an animal model. Food Chem 2014; 145: 145-153
• 34 Yang B, Glenn AJ, Liu Q. et al. Added sugar, sugar-sweetened beverages, and artificially sweetened beverages and risk of cardiovascular disease: findings from the women's health initiative and a network meta-analysis of prospective studies. Nutrients 2022; 14 (20) 4226
• 35 Choi HJ, Jeon SY, Hong WK. et al. Effect of glucose ingestion in plasma markers of inflammation and oxidative stress: analysis of 16 plasma markers from oral glucose tolerance test samples of normal and diabetic patients. Diabetes Res Clin Pract 2013; 99 (02) e27-e31
• 36 Lutsey PL, Steffen LM, Virnig BA, Folsom AR. Diet and incident venous thromboembolism: the Iowa Women's Health Study. Am Heart J 2009; 157 (06) 1081-1087
• 37 Nardini M, Natella F, Scaccini C. Role of dietary polyphenols in platelet aggregation. A review of the supplementation studies. Platelets 2007; 18 (03) 224-243
• 38 Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet 2021; 398 (10294): 64-77
• 39 Natella F, Nardini M, Belelli F. et al. Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation. Br J Nutr 2008; 100 (06) 1276-1282
• 40 Lawrenson R, Todd JC, Leydon GM, Williams TJ, Farmer RD. Validation of the diagnosis of venous thromboembolism in general practice database studies. Br J Clin Pharmacol 2000; 49 (06) 591-596
• 41 Cornelis MC, van Dam RM. Habitual coffee and tea consumption and cardiometabolic biomarkers in the UK Biobank: the role of beverage types and genetic variation. J Nutr 2020; 150 (10) 2772-2788