The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled “Caffeine: Friend or Foe?,” which was held during the 2015 ILSI Annual Meeting. The panelists' expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session.


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Literature Cited

  1. Aldridge A, Bailey J, Neims AH. 1981. The disposition of caffeine during and after pregnancy. Semin. Perinatol. 5:310–14 [Google Scholar]
  2. Alford C, Cox H, Wescott R. 2001. The effects of Red Bull energy drink on human performance and mood. Amino Acids 21:139–50 [Google Scholar]
  3. Alsene K, Deckert J, Sand P, de Wit H. 2003. Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 28:1694–702 [Google Scholar]
  4. Am. Coll. Obstet. Gynecol 2010. ACOG Committee Opinion No. 462: moderate caffeine consumption during pregnancy. Obstet. Gynecol. 116:467–68 [Google Scholar]
  5. Andersen LF, Jacobs DR Jr, Carlsen MH, Blomhoff R. 2006. Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women's Health Study. Am. J. Clin. Nutr. 83:1039–46 [Google Scholar]
  6. Arnaud MJ. 1993. Metabolism of caffeine and other components of coffee. Caffeine, Coffee and Health S Garattini 43–96 New York: Raven Press [Google Scholar]
  7. Arnett DK, Baird AE, Barkley RA, Basson CT, Boerwinkle E. et al. 2007. Relevance of genetics and genomics for prevention and treatment of cardiovascular disease: a scientific statement from the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation 115:2878–901 [Google Scholar]
  8. Azagba S, Langille D, Asbridge M. 2014. An emerging adolescent health risk: caffeinated energy drink consumption patterns among high school students. Prev. Med. 62:54–59 [Google Scholar]
  9. Azevedo A, Barros H. 2006. Coffee and myocardial infarction: heterogeneity of an association in Portuguese men. Eur. J. Cardiovasc. Prev. Rehabil. 13:268–73 [Google Scholar]
  10. Barone JJ, Roberts HR. 1996. Caffeine consumption. Food Chem. Toxicol. 34:119–29 [Google Scholar]
  11. Benedum CM, Yazdy MM, Mitchell AA, Werler MM. 2013. Risk of spina bifida and maternal cigarette, alcohol, and coffee use during the first month of pregnancy. Int. J. Environ. Res. Public Health 10:3263–81 [Google Scholar]
  12. Benowitz NL. 1990. Clinical pharmacology of caffeine. Annu. Rev. Med. 41:277–88 [Google Scholar]
  13. Bickford PC, Fredholm BB, Dunwiddie TV, Freedman R. 1985. Inhibition of Purkinje cell firing by systemic administration of phenylisopropyl adenosine: effect of central noradrenaline depletion by DSP4. Life Sci. 37:289–97 [Google Scholar]
  14. Bonnet MH, Balkin TJ, Dinges DF, Roehrs T, Rogers NL, Wesensten NJ. 2005. The use of stimulants to modify performance during sleep loss: a review by the sleep deprivation and Stimulant Task Force of the American Academy of Sleep Medicine. Sleep 28:1163–87 [Google Scholar]
  15. Boylan SM, Cade JE, Kirk SF, Greenwood DC, White KL. et al. 2008. Assessing caffeine exposure in pregnant women. Br. J. Nutr. 100:875–82 [Google Scholar]
  16. Boylan SM, Greenwood DC, Alwan N, Cooke MS, Dolby VA. et al. 2013. Does nausea and vomiting of pregnancy play a role in the association found between maternal caffeine intake and fetal growth restriction?. Matern. Child Health J. 17:601–8 [Google Scholar]
  17. Bracken MB, Triche E, Grosso L, Hellenbrand K, Belanger K, Leaderer BP. 2002. Heterogeneity in assessing self-reports of caffeine exposure: implications for studies of health effects. Epidemiology 13:165–71 [Google Scholar]
  18. Brantsaeter AL, Haugen M, Alexander J, Meltzer HM. 2008. Validity of a new food frequency questionnaire for pregnant women in the Norwegian Mother and Child Cohort Study (MoBa). Matern. Child Nutr. 4:28–43 [Google Scholar]
  19. Breinholt VM, Offord EA, Brouwer C, Nielsen SE, Brosen K, Friedberg T. 2002. In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem. Toxicol. 40:609–16 [Google Scholar]
  20. Brent RL, Christian MS, Diener RM. 2011. Evaluation of the reproductive and developmental risks of caffeine. Birth Defects Res. B 92:152–87 [Google Scholar]
  21. Brice CF, Smith AP. 2002. Factors associated with caffeine consumption. Int. J. Food Sci. Nutr. 53:55–64 [Google Scholar]
  22. Browne ML, Hoyt AT, Feldkamp ML, Rasmussen SA, Marshall EG. et al. 2011. Maternal caffeine intake and risk of selected birth defects in the National Birth Defects Prevention Study. Birth Defects Res. A 91:93–101 [Google Scholar]
  23. Bull S, Brown T, Burnett K, Ashdown L, Rushton L. 2015. External scientific report: extensive literature search as preparatory work for the safety assessment for caffeine. EFSA supporting publication 2015:EN-561. Parma, It.: EFSA http://www.efsa.europa.eu/en/supporting/doc/561e.pdf
  24. CARE Study Group 2008. Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study. BMJ 337:a2332 [Google Scholar]
  25. Carvey CE, Thompson LA, Mahoney CR, Lieberman HR. 2012. Caffeine: mechanism of action, genetics, and behavioral studies conducted in task simulators and the field. Sleep Deprivation, Stimulant Medications, and Cognition NJ Wesensten 93–107 Cambridge, UK: Cambridge Univ. Press [Google Scholar]
  26. Castorena-Torres F, Mendoza-Cantu A, de Leon MB, Cisneros B, Zapata-Perez O. et al. 2005. CYP1A2 phenotype and genotype in a population from the Carboniferous Region of Coahuila, Mexico. Toxicol. Lett. 156:331–39 [Google Scholar]
  27. Childs E, Hohoff C, Deckert J, Xu K, Badner J, de Wit H. 2008. Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 33:2791–800 [Google Scholar]
  28. Cnattingius S, Signorello LB, Anneren G, Clausson B, Ekbom A. et al. 2000. Caffeine intake and the risk of first-trimester spontaneous abortion. N. Engl. J. Med. 343:1839–45 [Google Scholar]
  29. Corella D, Ordovas JM. 2014. Aging and cardiovascular diseases: the role of gene-diet interactions. Ageing Res. Rev. 18:53–73 [Google Scholar]
  30. Cornelis MC, El-Sohemy A. 2007. Coffee, caffeine, and coronary heart disease. Curr. Opin. Lipidol. 18:13–19 [Google Scholar]
  31. Cornelis MC, El-Sohemy A, Campos H. 2007. Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am. J. Clin. Nutr. 86:240–44 [Google Scholar]
  32. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. 2006. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–41 [Google Scholar]
  33. Daly JW, Bruns RF, Snyder SH. 1981. Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. Life Sci. 28:2083–97 [Google Scholar]
  34. de Koning Gans JM, Uiterwaal CS, van der Schouw YT, Boer JM, Grobbee DE. et al. 2010. Tea and coffee consumption and cardiovascular morbidity and mortality. Arterioscler. Thromb. Vasc. Biol. 30:1665–71 [Google Scholar]
  35. Denoeud F, Carretero-Paulet L, Dereeper A, Droc G, Guyot R. et al. 2014. The coffee genome provides insight into the convergent evolution of caffeine biosynthesis. Science 345:1181–84 [Google Scholar]
  36. Dietz PM, Homa D, England LJ, Burley K, Tong VT. et al. 2011. Estimates of nondisclosure of cigarette smoking among pregnant and nonpregnant women of reproductive age in the United States. Am. J. Epidemiol. 173:355–59 [Google Scholar]
  37. Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E. 2008. Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur. J. Clin. Pharmacol. 64:381–85 [Google Scholar]
  38. Djordjevic N, Ghotbi R, Jankovic S, Aklillu E. 2010. Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C > A polymorphism. Eur. J. Clin. Pharmacol. 66:697–703 [Google Scholar]
  39. Durbin RJ. 2012. First letter to FDA Commissioner Dr. Margaret Hamburg regarding health concerns and energy drinks (April 3, 2012) http://www.durbin.senate.gov/newsroom/press-releases/durbin-blumenthal-once-again-ask-fda-to-address-their-energy-drink-concerns [Google Scholar]
  40. Durbin RJ, Blumenthal R. 2012. Second letter to FDA Commissioner Dr. Margaret Hamburg regarding health concerns and energy drinks (September 11, 2012 http://www.durbin.senate.gov/newsroom/press-releases/durbin-blumenthal-once-again-ask-fda-to-address-their-energy-drink-concerns [Google Scholar]
  41. Eur. Food Saf. Auth 2015. Scientific opinion on the safety of caffeine: EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA J. 13:4102 [Google Scholar]
  42. Fernstrom JD, Fernstrom MH. 1984. Effects of caffeine on monoamine neurotransmitters in the central and peripheral nervous system. Caffeine: Perspectives From Recent Research PB Dews 107–18 Heidelberg, Germany: Springer-Verlag [Google Scholar]
  43. Frary CD, Johnson RK, Wang MQ. 2005. Food sources and intakes of caffeine in the diets of persons in the United States. J. Am. Diet. Assoc. 105:110–13 [Google Scholar]
  44. Fredholm BB. 1980. Are methylxanthine effects due to antagonism of endogenous adenosine?. Trends Pharmacol. Sci. 1:129–32 [Google Scholar]
  45. Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE. 1999. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol. Rev. 51:83–133 [Google Scholar]
  46. Fulgoni VL 3rd, Keast DR, Lieberman HR. 2015. Trends in intake and sources of caffeine in the diets of US adults: 2001–2010. Am. J. Clin. Nutr. 101:1081–87 [Google Scholar]
  47. Garrett BE, Griffiths RR. 1997. The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol. Biochem. Behav. 57:533–41 [Google Scholar]
  48. Gillum RF, Makuc DM, Feldman JJ. 1991. Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study. Am. Heart J. 121:172–77 [Google Scholar]
  49. Glade MJ. 2010. Caffeine: not just a stimulant. Nutrition 26:932–38 [Google Scholar]
  50. Greenland S. 1993. A meta-analysis of coffee, myocardial infarction, and coronary death. Epidemiology 4:366–74 [Google Scholar]
  51. Greenland S, Lash TL. 2008. Bias analysis. Modern Epidemiology KJ Rothman, S Greenland, TL Lash 345–80 Philadelphia: Lippincott Williams & Wilkins [Google Scholar]
  52. Greenwood DC, Alwan N, Boylan S, Cade JE, Charvill J. et al. 2010. Caffeine intake during pregnancy, late miscarriage and stillbirth. Eur. J. Epidemiol. 25:275–80 [Google Scholar]
  53. Grosso LM, Bracken MB. 2005. Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure assessment considerations during pregnancy. Ann. Epidemiol. 15:460–66 [Google Scholar]
  54. Gu L, Gonzalez FJ, Kalow W, Tang BK. 1992. Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 2:73–77 [Google Scholar]
  55. Hammar N, Andersson T, Alfredsson L, Reuterwall C, Nilsson T. et al. 2003. Association of boiled and filtered coffee with incidence of first nonfatal myocardial infarction: the SHEEP and the VHEEP study. J. Intern. Med. 253:653–59 [Google Scholar]
  56. Han XM, Ou-Yang DS, Lu PX, Jiang CH, Shu Y. et al. 2001. Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics 11:429–35 [Google Scholar]
  57. Happonen P, Voutilainen S, Salonen JT. 2004. Coffee drinking is dose-dependently related to the risk of acute coronary events in middle-aged men. J. Nutr. 134:2381–86 [Google Scholar]
  58. Harland BF. 2000. Caffeine and nutrition. Nutrition 16:522–26 [Google Scholar]
  59. Hatch EE, Wise LA, Mikkelsen EM, Christensen T, Riis AH. et al. 2012. Caffeinated beverage and soda consumption and time to pregnancy. Epidemiology 23:393–401 [Google Scholar]
  60. Higdon JV, Frei B. 2006. Coffee and health: a review of recent human research. Crit. Rev. Food Sci. Nutr. 46:101–23 [Google Scholar]
  61. Horne JA, Reyner LA. 2001. Beneficial effects of an “energy drink” given to sleepy drivers. Amino Acids 20:83–89 [Google Scholar]
  62. Inst. Med 2013. Correspondence regarding a letter to FDA Commissioner Margaret A. Hamburg regarding the use of caffeine in energy drinks (March 19, 2013) Washington, DC: Institute of Medicine https://www.iom.edu/∼/media/Files/Activity%20Files/Nutrition/PotentialEffectsofCaffeine/Caffeine-Items%20Submitted%20to%20Committee%202.pdf [Google Scholar]
  63. Int. Food Inf. Counc. Found 2008. IFIC Review: Caffeine and Health: Clarifying the Controversies. Washington, DC: IFIC
  64. Jacobsen BK, Thelle DS. 1987. The Tromso Heart Study: Is coffee drinking an indicator of a life style with high risk for ischemic heart disease?. Acta Med. Scand. 222:215–21 [Google Scholar]
  65. James JE, Kristjansson AL, Sigfusdottir ID. 2011. Adolescent substance use, sleep, and academic achievement: evidence of harm due to caffeine. J. Adolesc. 34:665–73 [Google Scholar]
  66. James JE, Rogers PJ. 2005. Effects of caffeine on performance and mood: Withdrawal reversal is the most plausible explanation. Psychopharmacology 182:1–8 [Google Scholar]
  67. Jensen TK, Swan SH, Skakkebaek NE, Rasmussen S, Jorgensen N. 2010. Caffeine intake and semen quality in a population of 2,554 young Danish men. Am. J. Epidemiol. 171:883–91 [Google Scholar]
  68. Johnson CY, Flanders WD, Strickland MJ, Honein MA, Howards PP. 2014. Potential sensitivity of bias analysis results to incorrect assumptions of nondifferential or differential binary exposure misclassification. Epidemiology 25:902–9 [Google Scholar]
  69. Jurek AM, Maldonado G, Greenland S, Church TR. 2006. Exposure-measurement error is frequently ignored when interpreting epidemiologic study results. Eur. J. Epidemiol. 21:871–76 [Google Scholar]
  70. Kawachi I, Colditz GA, Stone CB. 1994. Does coffee drinking increase the risk of coronary heart disease? Results from a meta-analysis. Br. Heart J. 72:269–75 [Google Scholar]
  71. Ker K, Edwards PJ, Felix LM, Blackhall K, Roberts I. 2010. Caffeine for the prevention of injuries and errors in shift workers. Cochrane Database Syst. Rev. 12:CD008508 [Google Scholar]
  72. Kirkinen P, Jouppila P, Koivula A, Vuori J, Puukka M. 1983. The effect of caffeine on placental and fetal blood flow in human pregnancy. Am. J. Obstet. Gynecol. 147:939–42 [Google Scholar]
  73. Kleemola P, Jousilahti P, Pietinen P, Vartiainen E, Tuomilehto J. 2000. Coffee consumption and the risk of coronary heart disease and death. Arch. Intern. Med. 160:3393–400 [Google Scholar]
  74. Knight CA, Knight I, Mitchell DC, Zepp JE. 2004. Beverage caffeine intake in US consumers and subpopulations of interest: estimates from the Share of Intake Panel survey. Food Chem. Toxicol. 42:1923–30 [Google Scholar]
  75. Lara DR. 2010. Caffeine, mental health, and psychiatric disorders. J. Alzheimer's Dis. 20:Suppl. 1S239–48 [Google Scholar]
  76. Lawson CC, LeMasters GK, Wilson KA. 2004. Changes in caffeine consumption as a signal of pregnancy. Reprod. Toxicol. 18:625–33 [Google Scholar]
  77. Lee Y, Moon SJ, Montell C. 2009. Multiple gustatory receptors required for the caffeine response in Drosophila. PNAS 106:4495–500 [Google Scholar]
  78. Le Marchand L, Franke AA, Custer L, Wilkens LR, Cooney RV. 1997. Lifestyle and nutritional correlates of cytochrome CYP1A2 activity: inverse associations with plasma lutein and alpha-tocopherol. Pharmacogenetics 7:11–19 [Google Scholar]
  79. Leviton A, Cowan L. 2002. A review of the literature relating caffeine consumption by women to their risk of reproductive hazards. Food Chem. Toxicol. 40:1271–310 [Google Scholar]
  80. Lieberman H, Marriott B, Judelson D, Glickman E, Geiselman P. et al. 2015. Intake of caffeine from all sources including energy drinks and reasons for use in US college students. FASEB J. 29 (Suppl.):392.1 [Google Scholar]
  81. Lieberman HR. 1992. Caffeine. Handbook of Human Performance, Volume 2: Health and Performance AP Smith, DM Jones 49–72 London: Academic [Google Scholar]
  82. Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R. 2002. Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land. Psychopharmacology 164:250–61 [Google Scholar]
  83. Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE. et al. 2006. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 113:2045–53 [Google Scholar]
  84. Lorist MM, Tops M. 2003. Caffeine, fatigue, and cognition. Brain Cogn. 53:82–94 [Google Scholar]
  85. Mandel HG. 2002. Update on caffeine consumption, disposition and action. Food Chem. Toxicol. 40:1231–34 [Google Scholar]
  86. Marmot M, Elliott P. 2005. Coronary Heart Disease Epidemiology: From Aetiology to Public Health Oxford, UK: Oxford Univ. Press
  87. Mayer B, Erdmann J, Schunkert H. 2007. Genetics and heritability of coronary artery disease and myocardial infarction. Clin. Res. Cardiol. 96:1–7 [Google Scholar]
  88. McCusker RR, Goldberger BA, Cone EJ. 2006. Caffeine content of energy drinks, carbonated sodas, and other beverages. J. Anal. Toxicol. 30:112–14 [Google Scholar]
  89. Mets MA, Ketzer S, Blom C, van Gerven MH, van Willigenburg GM. et al. 2011. Positive effects of Red Bull® Energy Drink on driving performance during prolonged driving. Psychopharmacology 214:737–45 [Google Scholar]
  90. Mitchell DC, Knight CA, Hockenberry J, Teplansky R, Hartman TJ. 2014. Beverage caffeine intakes in the U.S. Food Chem. Toxicol. 63:136–42 [Google Scholar]
  91. Morrison AS. 1984. Control of cigarette smoking in evaluating the association of coffee drinking and bladder cancer. Banbury Report 17: Coffee and Health BT Macmahon, T Sugimura 127–34 Cold Spring Harbor, NY: Cold Spring Harb. Lab. [Google Scholar]
  92. Myers MG, Basinski A. 1992. Coffee and coronary heart disease. Arch. Intern. Med. 152:1767–72 [Google Scholar]
  93. Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. 2003. Effects of caffeine on human health. Food Addit. Contam. 20:1–30 [Google Scholar]
  94. Nehlig A. 1999. Are we dependent upon coffee and caffeine? A review on human and animal data. Neurosci. Biobehav. Rev. 23:563–76 [Google Scholar]
  95. Nilsson LM, Wennberg M, Lindahl B, Eliasson M, Jansson JH, Van Guelpen B. 2010. Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction; a nested case/referent study. Nutr. Metab. Cardiovasc. Dis. 20:527–35 [Google Scholar]
  96. Palatini P, Ceolotto G, Ragazzo F, Dorigatti F, Saladini F. et al. 2009. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J. Hypertens. 27:1594–601 [Google Scholar]
  97. Panagiotakos DB, Pitsavos C, Chrysohoou C, Kokkinos P, Toutouzas P, Stefanadis C. 2003. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J. Nutr. 133:3228–32 [Google Scholar]
  98. Peck JD, Leviton A, Cowan LD. 2010. A review of the epidemiologic evidence concerning the reproductive health effects of caffeine consumption: a 2000–2009 update. Food Chem. Toxicol. 48:2549–76 [Google Scholar]
  99. Ranheim T, Halvorsen B. 2005. Coffee consumption and human health: beneficial or detrimental?: mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus. Mol. Nutr. Food Res. 49:274–84 [Google Scholar]
  100. Reissig CJ, Strain EC, Griffiths RR. 2009. Caffeinated energy drinks: a growing problem. Drug Alcohol Depend. 99:1–10 [Google Scholar]
  101. Riksen NP, Rongen GA, Smits P. 2009. Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol. Ther. 121:185–91 [Google Scholar]
  102. Rogers PJ, Hohoff C, Heatherley SV, Mullings EL, Maxfield PJ. et al. 2010. Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology 35:1973–83 [Google Scholar]
  103. Rosenfeld LS, Mihalov JJ, Carlson SJ, Mattia A. 2014. Regulatory status of caffeine in the United States. Nutr. Rev. 72:Suppl. 123–33 [Google Scholar]
  104. Rosner SA, Akesson A, Stampfer MJ, Wolk A. 2007. Coffee consumption and risk of myocardial infarction among older Swedish women. Am. J. Epidemiol. 165:288–93 [Google Scholar]
  105. Sachse C, Brockmoller J, Bauer S, Roots I. 1999. Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br. J. Clin. Pharmacol. 47:445–49 [Google Scholar]
  106. Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N. 2010. Caffeine intake and dementia: systematic review and meta-analysis. J. Alzheimer's Dis. 20:Suppl. 1S187–204 [Google Scholar]
  107. Savitz DA, Chan RL, Herring AH, Howards PP, Hartmann KE. 2008. Caffeine and miscarriage risk. Epidemiology 19:55–62 [Google Scholar]
  108. Scholey AB, Kennedy DO. 2004. Cognitive and physiological effects of an “energy drink”: an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions. Psychopharmacology 176:320–30 [Google Scholar]
  109. Schreiber GB, Robins M, Maffeo CE, Masters MN, Bond AP, Morganstein D. 1988. Confounders contributing to the reported associations of coffee or caffeine with disease. Prev. Med. 17:295–309 [Google Scholar]
  110. Schwartz DL, Gilstad-Hayden K, Carroll-Scott A, Grilo SA, McCaslin C. et al. 2015. Energy drinks and youth self-reported hyperactivity/inattention symptoms. Acad. Pediatr. 15:297–304 [Google Scholar]
  111. Seifert SM, Schaechter JL, Hershorin ER, Lipshultz SE. 2011. Health effects of energy drinks on children, adolescents, and young adults. Pediatrics 127:511–28 [Google Scholar]
  112. Sengpiel V, Elind E, Bacelis J, Nilsson S, Grove J. et al. 2013. Maternal caffeine intake during pregnancy is associated with birth weight but not with gestational length: results from a large prospective observational cohort study. BMC Med. 11:42 [Google Scholar]
  113. Shi D, Nikodijevic O, Jacobson KA, Daly JW. 1993. Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Cell. Mol. Neurobiol. 13:247–61 [Google Scholar]
  114. Signorello LB, McLaughlin JK. 2004. Maternal caffeine consumption and spontaneous abortion: a review of the epidemiologic evidence. Epidemiology 15:229–39 [Google Scholar]
  115. Smith A. 2002. Effects of caffeine on human behavior. Food Chem. Toxicol. 40:1243–55 [Google Scholar]
  116. Smith A, Sutherland D, Christopher G. 2005. Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers. J. Psychopharmacol. 19:620–26 [Google Scholar]
  117. Smith AP. 2005a. Caffeine. Nutritional Neuroscience H Lieberman, R Kanarek, C Prasad 335–39 London: Taylor & Francis [Google Scholar]
  118. Smith AP. 2005b. Caffeine at work. Hum. Psychopharmacol. 20:441–45 [Google Scholar]
  119. Smith AP. 2009. Caffeine, cognitive failures and health in a non-working community sample. Hum. Psychopharmacol. 24:29–34 [Google Scholar]
  120. Smith AP. 2011. Caffeine: practical implications. Diet, Brain, Behavior: Practical Implications RB Kanarek, HR Lieberman 271–92 London: Taylor & Francis [Google Scholar]
  121. Smith AP. 2013. Caffeinated energy drinks. Principles of Addiction: Comprehensive Addictive Behaviors and Disorders PM Miller, AW Blume, DJ Kavanagh, KM Kampman, ME Bates 777–85 San Diego, CA: Academic [Google Scholar]
  122. Smith AP. 2014. Caffeine, performance and well-being: caffeine effects on the central nervous system and behavioral effects associated with caffeine consumption. Caffeine in Food and Dietary Supplements: Examining Safety: Workshop Summary114–18 Washington, DC: Natl. Acad. Sci. [Google Scholar]
  123. Smith AP, Christopher G, Sutherland D. 2013. Acute effects of caffeine on attention: a comparison of non-consumers and withdrawn consumers. J. Psychopharmacol. 27:77–83 [Google Scholar]
  124. Smith AP, Maben A, Brockman P. 1993. The effects of caffeine and evening meals on sleep and performance, mood and cardiovascular functioning the following day. J. Psychopharmacol. 7:203–6 [Google Scholar]
  125. Smith GD, Ebrahim S. 2003. “Mendelian randomization”: Can genetic epidemiology contribute to understanding environmental determinants of disease?. Int. J. Epidemiol. 32:1–22 [Google Scholar]
  126. Snyder SH. 1981. Adenosine receptors and the actions of methylxanthines. Trends Neurosci. 4:242–44 [Google Scholar]
  127. Sofi F, Conti AA, Gori AM, Eliana Luisi ML, Casini A. et al. 2007. Coffee consumption and risk of coronary heart disease: a meta-analysis. Nutr. Metab. Cardiovasc. Dis. 17:209–23 [Google Scholar]
  128. Spiller GA. 1998. Caffeine Boca Raton, FL: CRC Press
  129. Srinath Reddy K, Katan MB. 2004. Diet, nutrition and the prevention of hypertension and cardiovascular diseases. Public Health Nutr. 7:167–86 [Google Scholar]
  130. Stein Z, Susser M. 1991. Miscarriage, caffeine, and the epiphenomena of pregnancy: the causal model. Epidemiology 2:163–67 [Google Scholar]
  131. Szklo M, Nieto FJ. 2014. Epidemiology: Beyond the Basics Burlington, MA: Jones & Bartlett Publ.
  132. Tantcheva-Poor I, Zaigler M, Rietbrock S, Fuhr U. 1999. Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics 9:131–44 [Google Scholar]
  133. Taylor KC, Small CM, Dominguez CE, Murray LE, Tang W. et al. 2011. Alcohol, smoking, and caffeine in relation to fecundability, with effect modification by NAT2. Ann. Epidemiol. 21:864–72 [Google Scholar]
  134. Temple JL. 2009. Caffeine use in children: what we know, what we have left to learn, and why we should worry. Neurosci. Biobehav. Rev. 33:793–806 [Google Scholar]
  135. Terry-McElrath YM, O'Malley PM, Johnston LD. 2014. Energy drinks, soft drinks, and substance use among United States secondary school students. J. Addict. Med. 8:6–13 [Google Scholar]
  136. U.S. Food Drug Admin 2012a. First letter to Senator Richard J. Durbin from Jeanne Ireland, Assistant Commissioner for Legislation (August 10, 2012 Rockville, MD: FDA [Google Scholar]
  137. U.S. Food Drug Admin 2012b. Second letter to Senator Richard J. Durbin from Michele Mital, Acting Associate Commissioner for Legislation (November 21, 2012) Rockville, MD: FDA [Google Scholar]
  138. Victor BS, Lubetsky M, Greden JF. 1981. Somatic manifestations of caffeinism. J. Clin. Psychiatry 42:185–88 [Google Scholar]
  139. Vidry S, Hoekstra J, Hart A, Watzl B, Verhagen H. et al. 2013. Benefit-Risk Analysis for Foods (BRAFO): executive project summary. Eur. J. Nutr. Food Saf. 3:146–53 [Google Scholar]
  140. Weathersbee PS, Lodge JR. 1977. Caffeine: its direct and indirect influence on reproduction. J. Reprod. Med. 19:55–63 [Google Scholar]
  141. Wen W, Shu XO, Jacobs DR Jr, Brown JE. 2001. The associations of maternal caffeine consumption and nausea with spontaneous abortion. Epidemiology 12:38–42 [Google Scholar]
  142. Weng X, Odouli R, Li DK. 2008. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am. J. Obstet. Gynecol. 198:279e1–8 [Google Scholar]
  143. Woodward M, Tunstall-Pedoe H. 1999. 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 53:481–87 [Google Scholar]
  144. Wright GA, Baker DD, Palmer MJ, Stabler D, Mustard JA. et al. 2013. Caffeine in floral nectar enhances a pollinator's memory of reward. Science 339:1202–4 [Google Scholar]
  145. Wu JN, Ho SC, Zhou C, Ling WH, Chen WQ. et al. 2009. Coffee consumption and risk of coronary heart diseases: a meta-analysis of 21 prospective cohort studies. Int. J. Cardiol. 137:216–25 [Google Scholar]
  146. Yang A, Palmer AA, de Wit H. 2010. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology 211:245–57 [Google Scholar]
  147. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A. et al. 2004. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937–52 [Google Scholar]
  148. Zavela KJ, Barnett JE, Smedi KJ, Istvan JA, Matarazzo JD. 1990. Concurrent use of cigarettes, alcohol, and coffee. J. Appl. Soc. Psychol. 20:835–45 [Google Scholar]
  • Article Type: Review Article
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