Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Benefits and risks of caffeine and caffeinated beverages

Bryan Bordeaux, DO, MPH
Harris R Lieberman, PhD
Section Editor
Timothy O Lipman, MD
Deputy Editor
Daniel J Sullivan, MD, MPH


Caffeinated coffee and tea are the most consumed, socially accepted stimulants in the world. Approximately 90 percent of all adults in the world consume caffeine daily. In their natural forms, coffee and tea contain several chemical components that may confer both beneficial and adverse health effects, including caffeine and antioxidants (eg, polyphenols, catechins, and flavonoids).

Most of the data on the health benefits and risks of caffeine are from observational studies in which self-reported consumption of beverages and foods are associated with health outcomes. Such studies make it difficult to identify caffeine itself as the causative agent and to exclude residual confounding. Based on available data, there is insufficient evidence for promoting or discouraging regular coffee and/or tea consumption. Caffeine has multiple systemic effects on the neuropsychiatric, cardiovascular, endocrine, and gastrointestinal systems. The impact on health may be modified by genetic factors, age, sex, medications, and other environmental exposures.

This review will focus on the effects of caffeine and caffeinated beverages on specific disease processes, including insulin resistance, cancer, and all-cause mortality. The specific effects of caffeine on the cardiovascular system, as well as the effects of caffeine on pregnancy, are discussed separately. (See "Cardiovascular effects of caffeine and caffeinated beverages" and "Nutrition in pregnancy".)


Safe levels — For most adults, consumption of up to 400 mg of caffeine a day appears to be safe [1,2]. A list of commonly consumed caffeinated beverages and average caffeine content is shown in the table (table 1).

Safe levels of caffeine consumption for adolescents have not been established but are presumed to be lower than for adults. Young adults need to be cautioned about using caffeinated energy drinks in excess and not mixing them with other substances. (See 'Dependence and abuse' below.)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 13, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Heckman MA, Weil J, Gonzalez de Mejia E. Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci 2010; 75:R77.
  2. Poole R, Kennedy OJ, Roderick P, et al. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ 2017; 359:j5024.
  3. Grigg D. The worlds of tea and coffee: Patterns of consumption. Geojournal 2002; 57:283.
  4. Liu J, Sui X, Lavie CJ, et al. Association of coffee consumption with all-cause and cardiovascular disease mortality. Mayo Clin Proc 2013; 88:1066.
  5. Lieberman HR, Stavinoha T, McGraw S, et al. Caffeine use among active duty US Army soldiers. J Acad Nutr Diet 2012; 112:902.
  6. Ettinger B, Sidney S, Cummings SR, et al. Racial differences in bone density between young adult black and white subjects persist after adjustment for anthropometric, lifestyle, and biochemical differences. J Clin Endocrinol Metab 1997; 82:429.
  7. Tea Fact Sheet. Tea association of the USA, Inc. Available at: www.teausa.com/general/teafactsheet-updated2-10-06.pdf (Accessed on October 11, 2011).
  8. Lorenz M, Jochmann N, von Krosigk A, et al. Addition of milk prevents vascular protective effects of tea. Eur Heart J 2007; 28:219.
  9. Arnlöv J, Vessby B, Risérus U. Coffee consumption and insulin sensitivity. JAMA 2004; 291:1199.
  10. Renouf M, Marmet C, Guy P, et al. Nondairy creamer, but not milk, delays the appearance of coffee phenolic acid equivalents in human plasma. J Nutr 2010; 140:259.
  11. Gunja N, Brown JA. Energy drinks: health risks and toxicity. Med J Aust 2012; 196:46.
  12. Reissig CJ, Strain EC, Griffiths RR. Caffeinated energy drinks--a growing problem. Drug Alcohol Depend 2009; 99:1.
  13. Wolk BJ, Ganetsky M, Babu KM. Toxicity of energy drinks. Curr Opin Pediatr 2012; 24:243.
  14. US Food and Drug Administration. FDA Consumer Advice on Powdered Pure Caffeine. www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm405787.htm (Accessed on July 28, 2014).
  15. Olthof MR, Hollman PC, Katan MB. Chlorogenic acid and caffeic acid are absorbed in humans. J Nutr 2001; 131:66.
  16. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 2006; 295:1135.
  17. Fredholm BB, Bättig K, Holmén J, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 1999; 51:83.
  18. Carvey CE, Thompson LA, Lieberman HR. Caffeine: Mechanism of action, genetics and behavioral studies conducted in simulators and in the field. In: Sleep Deprivation, Stimulant Mmedications, and Cognition, Wesensten NJ (Ed), Cambridge University Press, Cambridge, United Kingdom 2012. p.93.
  19. Olthof MR, Hollman PC, Zock PL, Katan MB. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am J Clin Nutr 2001; 73:532.
  20. Saw SM. Homocysteine and atherosclerotic disease: the epidemiologic evidence. Ann Acad Med Singapore 1999; 28:565.
  21. Lee WJ, Zhu BT. Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. Carcinogenesis 2006; 27:269.
  22. Jayasuriya H, Herath KB, Ondeyka JG, et al. Diterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources. J Nat Prod 2005; 68:1247.
  23. Cavin C, Marin-Kuan M, Langouët S, et al. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver. Food Chem Toxicol 2008; 46:1239.
  24. Corti R, Binggeli C, Sudano I, et al. Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation 2002; 106:2935.
  25. Richelle M, Tavazzi I, Offord E. Comparison of the antioxidant activity of commonly consumed polyphenolic beverages (coffee, cocoa, and tea) prepared per cup serving. J Agric Food Chem 2001; 49:3438.
  26. Yen WJ, Wang BS, Chang LW, Duh PD. Antioxidant properties of roasted coffee residues. J Agric Food Chem 2005; 53:2658.
  27. Benvenga S, Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 2008; 18:293.
  28. Gertz BJ, Holland SD, Kline WF, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 1995; 58:288.
  29. Hurrell RF, Reddy M, Cook JD. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr 1999; 81:289.
  30. Mascitelli L, Goldstein MR. Does inhibition of iron absorption by coffee reduce the risk of gout? Int J Clin Pract 2011; 65:713.
  31. Lieberman HR, Wurtman RJ, Emde GG, Coviella IL. The effects of caffeine and aspirin on mood and performance. J Clin Psychopharmacol 1987; 7:315.
  32. Amendola CA, Gabrieli JD, Lieberman HR. Caffeine's Effects on Performance and Mood are Independent of Age and Gender. Nutr Neurosci 1998; 1:269.
  33. Smith A, SturgessW, Gallagher J. Effects of a low dose of caffeine given in different drinks on mood and performance. Hum Psychopharmacol Clin Exp 1999; 14:473.
  34. Smith A, Sutherland D, Christopher G. Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers. J Psychopharmacol 2005; 19:620.
  35. Childs E, de Wit H. Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. Psychopharmacology (Berl) 2006; 185:514.
  36. Lieberman HR, Tharion WJ, Shukitt-Hale B, et al. Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land. Psychopharmacology (Berl) 2002; 164:250.
  37. Magill RA, Waters WF, Bray GA, et al. Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation. Nutr Neurosci 2003; 6:237.
  38. Kamimori GH, Johnson D, Thorne D, Belenky G. Multiple caffeine doses maintain vigilance during early morning operations. Aviat Space Environ Med 2005; 76:1046.
  39. Doan BK, Hickey PA, Lieberman HR, Fischer JR. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat Space Environ Med 2006; 77:1034.
  40. Jarvis MJ. Does caffeine intake enhance absolute levels of cognitive performance? Psychopharmacology (Berl) 1993; 110:45.
  41. Smith A. Effects of caffeine on human behavior. Food Chem Toxicol 2002; 40:1243.
  42. Lorist MM, Snel J, Kok A, Mulder G. Influence of caffeine on selective attention in well-rested and fatigued subjects. Psychophysiology 1994; 31:525.
  43. Lieberman HR. Foods and Food Constituents, Effects on Human Behavior. In: The Encyclopedia of Neuroscience, 3rd ed, Adelman G, Smith B (Eds), Elsevier Science, The Netherlands 2004.
  44. Lieberman HR, Carvey CE, Thompson LA. Caffeine. In: Encyclopedia of Dietary Supplements, Coates PM (Ed), Informa Health Care, New York 2010. p.90.
  45. Ker K, Edwards PJ, Felix LM, et al. Caffeine for the prevention of injuries and errors in shift workers. Cochrane Database Syst Rev 2010; :CD008508.
  46. Goldstein J, Silberstein SD, Saper JR, et al. Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study. Headache 2006; 46:444.
  47. Diener HC, Gold M, Hagen M. Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies. J Headache Pain 2014; 15:76.
  48. Bigal ME, Sheftell FD, Rapoport AM, et al. Chronic daily headache: identification of factors associated with induction and transformation. Headache 2002; 42:575.
  49. Ragonese P, Salemi G, Morgante L, et al. A case-control study on cigarette, alcohol, and coffee consumption preceding Parkinson's disease. Neuroepidemiology 2003; 22:297.
  50. Abbott RD, Ross GW, White LR, et al. Environmental, life-style, and physical precursors of clinical Parkinson's disease: recent findings from the Honolulu-Asia Aging Study. J Neurol 2003; 250 Suppl 3:III30.
  51. Hernán MA, Takkouche B, Caamaño-Isorna F, Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann Neurol 2002; 52:276.
  52. Ascherio A, Weisskopf MG, O'Reilly EJ, et al. Coffee consumption, gender, and Parkinson's disease mortality in the cancer prevention study II cohort: the modifying effects of estrogen. Am J Epidemiol 2004; 160:977.
  53. Ascherio A, Chen H, Schwarzschild MA, et al. Caffeine, postmenopausal estrogen, and risk of Parkinson's disease. Neurology 2003; 60:790.
  54. Barranco Quintana JL, Allam MF, Serrano Del Castillo A, Fernández-Crehuet Navajas R. Alzheimer's disease and coffee: a quantitative review. Neurol Res 2007; 29:91.
  55. Arendash GW, Schleif W, Rezai-Zadeh K, et al. Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience 2006; 142:941.
  56. Griffiths RR. Principles of Addiction Medicine, Graham AW (Ed), 2003. p.193.
  57. Uhde TW. Neurobiology of Panic Disorder, Ballenger JC (Ed), p.219.
  58. Bruce M, Scott N, Shine P, Lader M. Anxiogenic effects of caffeine in patients with anxiety disorders. Arch Gen Psychiatry 1992; 49:867.
  59. Kendler KS, Myers J, O Gardner C. Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and substance use disorders: an epidemiologic and co-twin control analysis. Psychol Med 2006; 36:1717.
  60. Lucas M, Mirzaei F, Pan A, et al. Coffee, caffeine, and risk of depression among women. Arch Intern Med 2011; 171:1571.
  61. van Dam RM, Pasman WJ, Verhoef P. Effects of coffee consumption on fasting blood glucose and insulin concentrations: randomized controlled trials in healthy volunteers. Diabetes Care 2004; 27:2990.
  62. Keijzers GB, De Galan BE, Tack CJ, Smits P. Caffeine can decrease insulin sensitivity in humans. Diabetes Care 2002; 25:364.
  63. Lane JD, Feinglos MN, Surwit RS. Caffeine increases ambulatory glucose and postprandial responses in coffee drinkers with type 2 diabetes. Diabetes Care 2008; 31:221.
  64. van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet 2002; 360:1477.
  65. Rosengren A, Dotevall A, Wilhelmsen L, et al. Coffee and incidence of diabetes in Swedish women: a prospective 18-year follow-up study. J Intern Med 2004; 255:89.
  66. van Dam RM, Willett WC, Manson JE, Hu FB. Coffee, caffeine, and risk of type 2 diabetes: a prospective cohort study in younger and middle-aged U.S. women. Diabetes Care 2006; 29:398.
  67. Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Arch Intern Med 2006; 166:1311.
  68. Iso H, Date C, Wakai K, et al. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006; 144:554.
  69. Salazar-Martinez E, Willett WC, Ascherio A, et al. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med 2004; 140:1.
  70. MacKenzie T, Comi R, Sluss P, et al. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial. Metabolism 2007; 56:1694.
  71. Williams CJ, Fargnoli JL, Hwang JJ, et al. Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study. Diabetes Care 2008; 31:504.
  72. Goto A, Song Y, Chen BH, et al. Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women. Diabetes 2011; 60:269.
  73. Ding EL, Song Y, Manson JE, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med 2009; 361:1152.
  74. Egawa T, Hamada T, Kameda N, et al. Caffeine acutely activates 5'adenosine monophosphate-activated protein kinase and increases insulin-independent glucose transport in rat skeletal muscles. Metabolism 2009; 58:1609.
  75. Park S, Jang JS, Hong SM. Long-term consumption of caffeine improves glucose homeostasis by enhancing insulinotropic action through islet insulin/insulin-like growth factor 1 signaling in diabetic rats. Metabolism 2007; 56:599.
  76. Huxley R, Lee CM, Barzi F, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med 2009; 169:2053.
  77. Zhang WL, Lopez-Garcia E, Li TY, et al. Coffee consumption and risk of cardiovascular events and all-cause mortality among women with type 2 diabetes. Diabetologia 2009; 52:810.
  78. Murakami K, Okubo H, Sasaki S. Dietary intake in relation to self-reported constipation among Japanese women aged 18-20 years. Eur J Clin Nutr 2006; 60:650.
  79. Liu F, Wang X, Wu G, et al. Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis. PLoS One 2015; 10:e0142457.
  80. Nawrot P, Jordan S, Eastwood J, et al. Effects of caffeine on human health. Food Addit Contam 2003; 20:1.
  81. Loomis D, Guyton KZ, Grosse Y, et al. Carcinogenicity of drinking coffee, mate, and very hot beverages. Lancet Oncol 2016; 17:877.
  82. Boehm K, Borrelli F, Ernst E, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev 2009; :CD005004.
  83. Nkondjock A, Ghadirian P, Kotsopoulos J, et al. Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer 2006; 118:103.
  84. Baker JA, Beehler GP, Sawant AC, et al. Consumption of coffee, but not black tea, is associated with decreased risk of premenopausal breast cancer. J Nutr 2006; 136:166.
  85. Hirvonen T, Mennen LI, de Bree A, et al. Consumption of antioxidant-rich beverages and risk for breast cancer in French women. Ann Epidemiol 2006; 16:503.
  86. Ishitani K, Lin J, Manson JE, et al. Caffeine consumption and the risk of breast cancer in a large prospective cohort of women. Arch Intern Med 2008; 168:2022.
  87. Tang N, Wu Y, Ma J, et al. Coffee consumption and risk of lung cancer: a meta-analysis. Lung Cancer 2010; 67:17.
  88. Tang N, Wu Y, Zhou B, et al. Green tea, black tea consumption and risk of lung cancer: a meta-analysis. Lung Cancer 2009; 65:274.
  89. Turati F, Galeone C, La Vecchia C, et al. Coffee and cancers of the upper digestive and respiratory tracts: meta-analyses of observational studies. Ann Oncol 2011; 22:536.
  90. Yang TO, Crowe F, Cairns BJ, et al. Tea and coffee and risk of endometrial cancer: cohort study and meta-analysis. Am J Clin Nutr 2015; 101:570.
  91. Bravi F, Scotti L, Bosetti C, et al. Coffee drinking and endometrial cancer risk: a metaanalysis of observational studies. Am J Obstet Gynecol 2009; 200:130.
  92. Braem MG, Onland-Moret NC, Schouten LJ, et al. Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis. Am J Clin Nutr 2012; 95:1172.
  93. Zeegers MP, Tan FE, Goldbohm RA, van den Brandt PA. Are coffee and tea consumption associated with urinary tract cancer risk? A systematic review and meta-analysis. Int J Epidemiol 2001; 30:353.
  94. Pelucchi C, La Vecchia C. Alcohol, coffee, and bladder cancer risk: a review of epidemiological studies. Eur J Cancer Prev 2009; 18:62.
  95. Villanueva CM, Silverman DT, Murta-Nascimento C, et al. Coffee consumption, genetic susceptibility and bladder cancer risk. Cancer Causes Control 2009; 20:121.
  96. Kurahashi N, Sasazuki S, Iwasaki M, et al. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol 2008; 167:71.
  97. Severson RK, Nomura AM, Grove JS, Stemmermann GN. A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 1989; 49:1857.
  98. Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 2006; 66:1234.
  99. Wilson KM, Kasperzyk JL, Rider JR, et al. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst 2011; 103:876.
  100. Wilson KM, Kasperzyk JL, Rider JR, et al. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst 2011; 103:876.
  101. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001; 74:694.
  102. Harris SS, Dawson-Hughes B. Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr 1994; 60:573.
  103. Korpelainen R, Korpelainen J, Heikkinen J, et al. Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 women. Osteoporos Int 2003; 14:34.
  104. Kanis JA, Johnell O, Oden A, et al. Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies. Bone 2002; 30:251.
  105. Cauley JA, Hochberg MC, Lui LY, et al. Long-term risk of incident vertebral fractures. JAMA 2007; 298:2761.
  106. De Laet CE, Van Hout BA, Burger H, et al. Hip fracture prediction in elderly men and women: validation in the Rotterdam study. J Bone Miner Res 1998; 13:1587.
  107. Hallström H, Wolk A, Glynn A, Michaëlsson K. Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women. Osteoporos Int 2006; 17:1055.
  108. Hegarty VM, May HM, Khaw KT. Tea drinking and bone mineral density in older women. Am J Clin Nutr 2000; 71:1003.
  109. Devine A, Hodgson JM, Dick IM, Prince RL. Tea drinking is associated with benefits on bone density in older women. Am J Clin Nutr 2007; 86:1243.
  110. Chen Z, Pettinger MB, Ritenbaugh C, et al. Habitual tea consumption and risk of osteoporosis: a prospective study in the women's health initiative observational cohort. Am J Epidemiol 2003; 158:772.
  111. Mikuls TR, Cerhan JR, Criswell LA, et al. Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis Rheum 2002; 46:83.
  112. Pedersen M, Stripp C, Klarlund M, et al. Diet and risk of rheumatoid arthritis in a prospective cohort. J Rheumatol 2005; 32:1249.
  113. Karlson EW, Mandl LA, Aweh GN, Grodstein F. Coffee consumption and risk of rheumatoid arthritis. Arthritis Rheum 2003; 48:3055.
  114. Choi HK, Curhan G. Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey. Arthritis Rheum 2007; 57:816.
  115. Choi HK, Willett W, Curhan G. Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum 2007; 56:2049.
  116. Bird ET, Parker BD, Kim HS, Coffield KS. Caffeine ingestion and lower urinary tract symptoms in healthy volunteers. Neurourol Urodyn 2005; 24:611.
  117. Bryant CM, Dowell CJ, Fairbrother G. Caffeine reduction education to improve urinary symptoms. Br J Nurs 2002; 11:560.
  118. Armstrong LE, Pumerantz AC, Roti MW, et al. Fluid, electrolyte, and renal indices of hydration during 11 days of controlled caffeine consumption. Int J Sport Nutr Exerc Metab 2005; 15:252.
  119. Jura YH, Townsend MK, Curhan GC, et al. Caffeine intake, and the risk of stress, urgency and mixed urinary incontinence. J Urol 2011; 185:1775.
  120. Burke LM. Caffeine and sports performance. Appl Physiol Nutr Metab 2008; 33:1319.
  121. Jenkinson DM, Harbert AJ. Supplements and sports. Am Fam Physician 2008; 78:1039.
  122. http://www.ncaa.org/sites/default/files/2016SSI_DrugTestingProgramBooklet_20160728.pdf.
  123. Happonen P, Läärä E, Hiltunen L, Luukinen H. Coffee consumption and mortality in a 14-year follow-up of an elderly northern Finnish population. Br J Nutr 2008; 99:1354.
  124. Paganini-Hill A, Kawas CH, Corrada MM. Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study. Prev Med 2007; 44:305.
  125. Woodward M, Tunstall-Pedoe H. Coffee and tea consumption in the Scottish Heart Health Study follow up: conflicting relations with coronary risk factors, coronary disease, and all cause mortality. J Epidemiol Community Health 1999; 53:481.
  126. Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006; 113:2045.
  127. Freedman ND, Park Y, Abnet CC, et al. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012; 366:1891.
  128. Lopez-Garcia E, van Dam RM, Li TY, et al. The relationship of coffee consumption with mortality. Ann Intern Med 2008; 148:904.
  129. Saito E, Inoue M, Sawada N, et al. Association of coffee intake with total and cause-specific mortality in a Japanese population: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr 2015; 101:1029.
  130. Ding M, Satija A, Bhupathiraju SN, et al. Association of Coffee Consumption With Total and Cause-Specific Mortality in 3 Large Prospective Cohorts. Circulation 2015; 132:2305.
  131. Loftfield E, Freedman ND, Graubard BI, et al. Association of Coffee Consumption With Overall and Cause-Specific Mortality in a Large US Prospective Cohort Study. Am J Epidemiol 2015; 182:1010.
  132. Park SY, Freedman ND, Haiman CA, et al. Association of Coffee Consumption With Total and Cause-Specific Mortality Among Nonwhite Populations. Ann Intern Med 2017; 167:228.
  133. Gunter MJ, Murphy N, Cross AJ, et al. Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study. Ann Intern Med 2017; 167:236.
  134. Crippa A, Discacciati A, Larsson SC, et al. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol 2014; 180:763.
  135. Sugiyama K, Kuriyama S, Akhter M, et al. Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women. J Nutr 2010; 140:1007.
  136. Tsujimoto T, Kajio H, Sugiyama T. Association Between Caffeine Intake and All-Cause and Cause-Specific Mortality: A Population-Based Prospective Cohort Study. Mayo Clin Proc 2017; 92:1190.
  137. Lopez-Garcia E, Rodriguez-Artalejo F, Li TY, et al. Coffee consumption and mortality in women with cardiovascular disease. Am J Clin Nutr 2011; 94:218.
  138. Lieberman HR. Mental energy: Assessing the cognition dimension. Nutr Rev 2006; 64:S10.
  139. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  140. Satel S. Is caffeine addictive?--a review of the literature. Am J Drug Alcohol Abuse 2006; 32:493.
  141. Hughes JR, Oliveto AH, Helzer JE, et al. Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10? Am J Psychiatry 1992; 149:33.
  142. Ogawa N, Ueki H. Clinical importance of caffeine dependence and abuse. Psychiatry Clin Neurosci 2007; 61:263.
  143. McCarthy DM, Mycyk MB, DesLauriers CA. Hospitalization for caffeine abuse is associated with abuse of other pharmaceutical products. Am J Emerg Med 2008; 26:799.
  144. Valjent E, Pagès C, Hervé D, et al. Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain. Eur J Neurosci 2004; 19:1826.
  145. Cornelis MC, El-Sohemy A, Campos H. Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am J Clin Nutr 2007; 86:240.
  146. Pallanti S, Bernardi S, Quercioli L. The Shorter PROMIS Questionnaire and the Internet Addiction Scale in the assessment of multiple addictions in a high-school population: prevalence and related disability. CNS Spectr 2006; 11:966.
  147. Howland J, Rohsenow DJ, Arnedt JT, et al. The acute effects of caffeinated versus non-caffeinated alcoholic beverage on driving performance and attention/reaction time. Addiction 2011; 106:335.
  148. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004; 176:1.
  149. Kendler KS, Prescott CA. Caffeine intake, tolerance, and withdrawal in women: a population-based twin study. Am J Psychiatry 1999; 156:223.