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Caffeine and cardiovascular diseases: critical review of current research

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Abstract

Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains “Which dose is safe?”, as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.

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References

  1. Ferruzzi MG (2010) The influence of beverage composition on delivery of phenolic compounds from coffee and tea. Physiol Behav 100:33–41

    Article  CAS  Google Scholar 

  2. Magalhães ST, Fernandes FL, Demuner AJ, Picanço MC, Guedes RN (2010) Leaf alkaloids, phenolics, and coffee resistance to the leaf miner Leucoptera coffeella (Lepidoptera: Lyonetiidae). J Econ Entomol 103:1438–1443

    Article  CAS  Google Scholar 

  3. Kravchenko LV, Trusov NV, Aksenov IV, Avren’eva LI, Guseva GV, Lashneva NV, Tutel’ian VA (2011) Effects of green tea extract and its components on antioxidant status and activities of xenobiotic metabolizing enzymes of rats. Vopr Pitan 80:9–15

    CAS  Google Scholar 

  4. Zollner H, Giebelmann R (2004) Cultural-historical remarks on caffeine, coffee and tea. Dtsch Lebensm-Rundsch 100(7):255–262

    Google Scholar 

  5. Singer P, McGarrity S, Shen HY, Boison D, Yee BK (2012) Working memory and the homeostatic control of brain adenosine by adenosine kinase. Neuroscience 213:81–92

    Article  CAS  Google Scholar 

  6. Paluch AS, Parameswaran S, Liu S, Kolavennu A, Mobley DL (2015) Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation. J Chem Phys 142:044508

    Article  CAS  Google Scholar 

  7. Saldaña MD, Zetzl C, Mohamed RS, Brunner G (2002) Extraction of methylxanthines from guaraná seeds, maté leaves, and cocoa beans using supercritical carbon dioxide and ethanol. J Agric Food Chem 50:4820–4826

    Article  CAS  Google Scholar 

  8. Tang WQ, Li DC, Lv YX, Jiang JG (2010) Extraction and removal of caffeine from green tea by ultrasonic-enhanced supercritical fluid. J Food Sci 75:363–368

    Article  CAS  Google Scholar 

  9. Ashihara H, Sano H, Crozier A (2008) Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry 69:841–856

    Article  CAS  Google Scholar 

  10. Utoh M, Murayama N, Uno Y, Onose Y, Hosaka S, Fujino H, Shimizu M, Iwasaki K, Yamazaki H (2013) Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline. Xenobiotica 43:1037–1042

    Article  CAS  Google Scholar 

  11. Ohyama K, Murayama N, Shimizu M, Yamazaki H (2014) Drug interactions of diclofenac and its oxidative metabolite with human liver microsomal cytochrome P450 1A2-dependent drug oxidation. Xenobiotica 44:10–16

    Article  CAS  Google Scholar 

  12. Mort JR, Kruse HR (2008) Timing of blood pressure measurement related to caffeine consumption. Ann Pharmacother 42:105–110

    Article  CAS  Google Scholar 

  13. Magkos F, Kavouras SA (2005) Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Crit Rev Food Sci Nutr 45:535–562

    Article  CAS  Google Scholar 

  14. Ribeiro JA, Sebastião AM (2010) Caffeine and adenosine. J Alzheimers Dis 20:S3–S15

    CAS  Google Scholar 

  15. Chen JF, Eltzschig HK, Fredholm BB (2013) Adenosine receptors as drug targets—What are the challenges? Nat Rev Drug Discov 12:265–286

    Article  CAS  Google Scholar 

  16. Gyoneva S, Shapiro L, Lazo C, Garnier-Amblard E, Smith Y, Miller GW, Traynelis SF (2014) Adenosine A(2A) receptor antagonism reverses inflammation-induced impairment of microglial process extension in a model of Parkinson’s disease. Neurobiol Dis 67:191–202

    Article  CAS  Google Scholar 

  17. Hofer M, Pospisil M, Dusek L, Hoferova Z, Komurkova D (2014) Combined pharmacological therapy of the acute radiation disease using a cyclooxygenase-2 inhibitor and an adenosine A(3) receptor agonist. Centr Eur J Biol 9:642–646

    CAS  Google Scholar 

  18. Vincenzi F, Targa M, Romagnoli R, Merighi S, Gessi S, Baraldi PG, Borea PA, Varani K (2014) TRR469, a potent A(1) adenosine receptor allosteric modulator, exhibits anti-nociceptive properties in acute and neuropathic pain models in mice. Neuropharmacology 81:6–14

    Article  CAS  Google Scholar 

  19. Sullivan GW, Luong LS, Carper HT, Barnes RC, Mandell GL (1995) Methylxanthines with adenosine alter TNF-alpha-primed PMN activation. Immunopharmacology 31:19–29

    Article  CAS  Google Scholar 

  20. Fukunaga AF, Alexander GE, Stark CW (2003) Characterization of the analgesic actions of adenosine: comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures. Pain 101:129–138

    Article  CAS  Google Scholar 

  21. Chan ESL, Fernandez P, Cronstein BN (2007) Adenosine in inflammatory joint diseases. Purinergic Signal 3:145–152

    Article  CAS  Google Scholar 

  22. Joulia F, Coulange M, Lemaitre F, Costalat G, Franceschi F, Gariboldi V, Nee L, Fromonot J, Bruzzese L, Gravier G, Kipson N, Jammes Y, Boussuges A, Brignole M, Deharo JC, Guieu R (2013) Plasma adenosine release is associated with bradycardia and transient loss of consciousness during experimental breath-hold diving. Int J Cardiol 168:E138–E141

    Article  Google Scholar 

  23. Walaschewski R, Begrow F, Verspohl EJ (2013) Impact and benefit of A2B-adenosine receptor agonists for the respiratory tract: mucociliary clearance, ciliary beat frequency, trachea muscle tonus and cytokine release. J Pharm Pharmacol 65:123–132

    Article  CAS  Google Scholar 

  24. Petzer A, Pienaar A, Petzer JP (2013) The interactions of caffeine with monoamine oxidase. Life Sci 93:283–287

    Article  CAS  Google Scholar 

  25. Petzer A, Grobler P, Bergh JJ, Petzer JP (2014) Inhibition of monoamine oxidase by selected phenylalkylcaffeine analogues. J Pharm Pharmacol 66:677–687

    Article  CAS  Google Scholar 

  26. Pohanka M (2014) The effects of caffeine on the cholinergic system. Mini Rev Med Chem 16:543–549

    Article  CAS  Google Scholar 

  27. Pohanka M, Dobes P (2013) Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase. Int J Mol Sci 14:9873–9882

    Article  CAS  Google Scholar 

  28. Bhaskara S, Chandrasekharan MB, Ganguly R (2008) Caffeine induction of Cyp6a2 and Cyp6a8 genes of Drosophila melanogaster is modulated by cAMP and D-JUN protein levels. Gene 415:49–59

    Article  CAS  Google Scholar 

  29. Herman A, Herman AP (2013) Caffeine’s mechanisms of action and its cosmetic use. Skin Pharmacol Physiol 26:8–14

    Article  CAS  Google Scholar 

  30. Geraets L, Moonen HJ, Wouters EF, Bast A, Hageman GJ (2006) Caffeine metabolites are inhibitors of the nuclear enzyme poly(ADP-ribose)polymerase-1 at physiological concentrations. Biochem Pharmacol 72:902–910

    Article  CAS  Google Scholar 

  31. Kumala S, Fujarewicz K, Jayaraju D, Rzeszowska-Wolny J, Hancock R (2013) Repair of DNA strand breaks in a minichromosome in vivo: kinetics, modeling, and effects of inhibitors. PLoS One 8(1):e52966

    Article  CAS  Google Scholar 

  32. Li XY, Xu L, Lin GS, Li XY, Jiang XJ, Wang T, Lü JJ, Zeng B (2011) Protective effect of caffeine administration on myocardial ischemia/reperfusion injury in rats. Shock 36:289–294

    Article  CAS  Google Scholar 

  33. Ku BM, Lee YK, Jeong JY, Ryu J, Choi J, Kim JS, Cho YW, Roh GS, Kim HJ, Cho GJ, Choi WS, Kang SS (2011) Caffeine inhibits cell proliferation and regulates PKA/GSK3 beta pathways in U87MG human glioma cells. Mol Cells 31:275–279

    Article  CAS  Google Scholar 

  34. Arnáiz-Cot JJ, Damon BJ, Zhang XH, Cleemann L, Yamaguchi N, Meissner G, Morad M (2013) Cardiac calcium signalling pathologies associated with defective calmodulin regulation of type 2 ryanodine receptor. J Physiol 591:4287–4299

    Article  CAS  Google Scholar 

  35. Shou Q, Pan S, Tu J, Jiang J, Ling Y, Cai Y, Chen M, Wang D (2013) Modulation effect of Smilax glabra flavonoids on ryanodine receptor mediated intracellular Ca2+ release in cardiomyoblast cells. J Ethnopharmacol 150:389–392

    Article  CAS  Google Scholar 

  36. Friedrich O, Yi B, Edwards JN, Reischl B, Wirth-Hücking A, Buttgereit A, Lang R, Weber C, Polyak F, Liu I, von Wegner F, Cully TR, Lee A, Most P, Völkers M (2014) IL-1 alpha reversibly inhibits skeletal muscle ryanodine receptor a novel mechanism for critical illness myopathy? Am J Respir Cell Mol Biol 50:1096–1106

    Article  CAS  Google Scholar 

  37. Pettersen SA, Krustrup P, Bendiksen M, Randers MB, Brito J, Bangsbo J, Jin Y, Mohr M (2014) Caffeine supplementation does not affect match activities and fatigue resistance during match play in young football players. J Sports Sci 32:1958–1965. doi:10.1080/02640414.2014.965189

    Article  Google Scholar 

  38. Okudaira N, Kuwahara M, Hirata Y, Oku Y, Nishio H (2014) A knock-in mouse model of N-terminal R420W mutation of cardiac ryanodine receptor exhibits arrhythmogenesis with abnormal calcium dynamics in cardiomyocytes. Biochem Biophys Res Commun 452:665–668. doi:10.1016/j.bbrc.2014.08.132

    Article  CAS  Google Scholar 

  39. Yamakawa H, Murata M, Suzuki T, Yada H, Ishida H, Aizawa Y, Adachi T, Kamiya K, Fukuda K (2014) Suppression of Rad leads to arrhythmogenesis via PKA-mediated phosphorylation of ryanodine receptor activity in the heart. Biochem Biophys Res Commun 452:701–707. doi:10.1016/j.bbrc.2014.08.126

    Article  CAS  Google Scholar 

  40. Miles-Chan JL, Charrière N, Grasser EK, Montani JP, Dulloo AG (2015) The blood pressure-elevating effect of Red Bull energy drink is mimicked by caffeine but through different hemodynamic pathways. Physiol Rep. doi:10.14814/phy2.12290

    Google Scholar 

  41. Bardou M, Goirand F, Bernard A, Guerard P, Gatinet M, Devillier P, Dumas JP, Morcillo EJ, Rochette L, Dumas M (2002) Relaxant effects of selective phosphodiesterase inhibitors on U46619 precontracted human intralobar pulmonary arteries and role of potassium channels. J Cardiovasc Pharmacol 40:153–161

    Article  CAS  Google Scholar 

  42. Brodmann M, Lischnig U, Lueger A, Pilger E, Stark G (2003) The effect of caffeine on peripheral vascular resistance in isolated perfused guinea pig hind limbs. J Cardiovasc Pharmacol 42:506–510

    Article  CAS  Google Scholar 

  43. Sekiguchi F, Miyake Y, Kashimoto T, Sunano S (2002) Unaltered caffeine-induced relaxation in the aorta of stroke-prone spontaneously hypertensive rats (SHRSP). J Smooth Muscle Res 38:11–22

    Article  CAS  Google Scholar 

  44. Corsetti G, Pasini E, Assanelli D, Bianchi R (2008) Effects of acute caffeine administration on NOS and Bax/Bcl2 expression in the myocardium of rat. Pharmacol Res 57:19–25. doi:10.1016/j.phrs.2007.07.007

    Article  CAS  Google Scholar 

  45. El Agaty SM, Seif AA (2015) Cardiovascular effects of long-term caffeine administration in aged rats. Ir J Med Sci 184:265–272. doi:10.1007/s11845-014-1098-z

    Article  CAS  Google Scholar 

  46. Panchal SK, Wong WY, Kauter K, Ward LC, Brown L (2012) Caffeine attenuates metabolic syndrome in diet-induced obese rats. Nutrition 28:1055–1062. doi:10.1016/j.nut.2012.02.013

    Article  CAS  Google Scholar 

  47. Nordestgaard AT, Thomsen M, Nordestgaard BG (2015) Coffee intake and risk of obesity, metabolic syndrome and type 2 diabetes: a Mendelian randomization study. Int J Epidemiol 44:551–565. doi:10.1093/ije/dyv083

    Article  Google Scholar 

  48. O’Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ (2013) Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. J Am Coll Cardiol 62:1043–1051. doi:10.1016/j.jacc.2013.06.035

    Article  Google Scholar 

  49. Basaranoglu M, Basaranoglu G, Bugianesi E (2015) Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction. Hepatobiliary Surg Nutr 4:109–116

    Google Scholar 

  50. Loopstra-Masters RC, Liese AD, Haffner SM, Wagenknecht LE, Hanley AJ (2011) Associations between the intake of caffeinated and decaffeinated coffee and measures of insulin sensitivity and beta cell function. Diabetologia 54:320–328

    Article  CAS  Google Scholar 

  51. Yeh TC, Liu CP, Cheng WH, Chen BR, Lu PJ, Cheng PW, Ho WY, Sun GC, Liou JC, Tseng CJ (2014) Caffeine intake improves fructose-induced hypertension and insulin resistance by enhancing central insulin signaling. Hypertension 63:535–541

    Article  CAS  Google Scholar 

  52. Sinha RA, Farah BL, Singh BK, Siddique MM, Li Y, Wu Y, Ilkayeva OR, Gooding J, Ching J, Zhou J, Martinez L, Xie S, Bay BH, Summers SA, Newgard CB, Yen PM (2014) Caffeine stimulates hepatic lipid metabolism by the autophagy–lysosomal pathway in mice. Hepatology 59:1366–1380

    Article  CAS  Google Scholar 

  53. Panchal SK, Poudyal H, Waanders J, Brown L (2012) Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J Nutr 142:690–697

    Article  CAS  Google Scholar 

  54. Sacramento JF, Ribeiro MJ, Yubero S, Melo BF, Obeso A, Guarino MP, Gonzalez C, Conde SV (2015) Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle. Eur J Pharm Sci 70:107–116

    Article  CAS  Google Scholar 

  55. Fronz U, Deten A, Baumann F, Kranz A, Weidlich S, Härtig W, Nieber K, Boltze J, Wagner DC (2014) Continuous adenosine A2A receptor antagonism after focal cerebral ischemia in spontaneously hypertensive rats. Naunyn Schmiedebergs Arch Pharmacol 387:165–173

    Article  CAS  Google Scholar 

  56. Sun L, Tian X, Gou L, Ling X, Wang L, Feng Y, Yin X, Liu Y (2013) Beneficial synergistic effects of concurrent treatment with theanine and caffeine against cerebral ischemia–reperfusion injury in rats. Can J Physiol Pharmacol 91:562–569

    Article  CAS  Google Scholar 

  57. Momoi N, Tinney JP, Keller BB, Tobita K (2012) Maternal hypoxia and caffeine exposure depress fetal cardiovascular function during primary organogenesis. J Obstet Gynaecol Res 38:1343–1351

    Article  CAS  Google Scholar 

  58. Pagnussat N, Almeida AS, Marques DM, Nunes F, Chenet GC, Botton PH, Mioranzza S, Loss CM, Cunha RA, Porciúncula LO (2015) Adenosine A receptors are necessary and sufficient to trigger memory impairment in adult mice. Br J Pharmacol 172:3831–3845

    Article  CAS  Google Scholar 

  59. Nishida K, Qi XY, Wakili R, Comtois P, Chartier D, Harada M, Iwasaki YK, Romeo P, Maguy A, Dobrev D, Michael G, Talajic M, Nattel S (2011) Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model. Circulation 123:137–146

    Article  CAS  Google Scholar 

  60. Zhao X, Strong R, Piriyawat P, Palusinski R, Grotta JC, Aronowski J (2010) Caffeinol at the receptor level: anti-ischemic effect of N-methyl-d-aspartate receptor blockade is potentiated by caffeine. Stroke 41:363–367

    Article  CAS  Google Scholar 

  61. Serapiao-Moraes DF, Souza-Mello V, Aguila MB, Mandarim-de-Lacerda CA, Faria TS (2013) Maternal caffeine administration leads to adverse effects on adult mice offspring. Eur J Nutr 52:1891–1900. doi:10.1007/s00394-012-0490-6

    Article  CAS  Google Scholar 

  62. Buscariollo DL, Fang X, Greenwood V, Xue H, Rivkees SA, Wendler CC (2014) Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice. PLoS One 9(1):e87547. doi:10.1371/journal.pone.0087547

    Article  CAS  Google Scholar 

  63. Momoi N, Tinney JP, Liu LJ, Elshershari H, Hoffmann PJ, Ralphe JC, Keller BB, Tobita K (2008) Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth. Am J Physiol Heart Circ Physiol 294:H2248–H2256. doi:10.1152/ajpheart.91469.2007

    Article  CAS  Google Scholar 

  64. Yang JN, Chen JF, Fredholm BB (2009) Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. Am J Physiol Heart Circ Physiol 296:H1141–H1149. doi:10.1152/ajpheart.00754.2008

    Article  CAS  Google Scholar 

  65. Iglesias I, Albasanz JL, Martín M (2014) Effect of caffeine chronically consumed during pregnancy on adenosine A1 and A2A receptors signaling in both maternal and fetal heart from wistar rats. J Caffeine Res 4:115–126. doi:10.1089/jcr.2014.0010

    Article  CAS  Google Scholar 

  66. Buscariollo DL, Breuer GA, Wendler CC, Rivkees SA (2011) Caffeine acts via A1 adenosine receptors to disrupt embryonic cardiac function. PLoS One 6(12):e28296. doi:10.1371/journal.pone.0028296

    Article  CAS  Google Scholar 

  67. Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G (2011) Effect of Caffeine, norfloxacin and nimesulide on heartbeat and VEGF expression of zebrafish larvae. J Environ Biol 32:179–183

    CAS  Google Scholar 

  68. Yeh CH, Liao YF, Chang CY, Tsai JN, Wang YH, Cheng CC, Wen CC, Chen YH (2012) Caffeine treatment disturbs the angiogenesis of zebrafish embryos. Drug Chem Toxicol 35:361–365. doi:10.3109/01480545.2011.627864

    Article  CAS  Google Scholar 

  69. Abdelkader TS, Chang SN, Kim TH, Song J, Kim DS, Park JH (2013) Exposure time to caffeine affects heartbeat and cell damage-related gene expression of zebrafish Danio rerio embryos at early developmental stages. J Appl Toxicol 33:1277–1283. doi:10.1002/jat.2787

    CAS  Google Scholar 

  70. Mercer JR, Gray K, Figg N, Kumar S, Bennett MR (2012) The methyl xanthine caffeine inhibits DNA damage signaling and reactive species and reduces atherosclerosis in ApoE(−/−) Mice. Arterioscler Thromb Vasc Biol 32:2461–2467. doi:10.1161/ATVBAHA.112.251322

    Article  CAS  Google Scholar 

  71. Verma R, Huang Z, Deutschman CS, Levy RJ (2009) Caffeine restores myocardial cytochrome oxidase activity and improves cardiac function during sepsis. Crit Care Med 37:1397–1402. doi:10.1097/CCM.0b013e31819cecd6

    Article  CAS  Google Scholar 

  72. Fang X, Mei W, Barbazuk WB, Rivkees SA, Wendler CC (2014) Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes. Am J Physiol Regul Integr Comp Physiol 307:R1471–R1487. doi:10.1152/ajpregu.00307.2014

    Article  CAS  Google Scholar 

  73. Riksen NP, Smits P, Rongen GA (2011) The cardiovascular effects of methylxanthines. Handb Exp Pharmacol 200:413–437. doi:10.1007/978-3-642-13443-2_16

    Article  CAS  Google Scholar 

  74. Noguchi K, Matsuzaki T, Sakanashi M, Hamadate N, Uchida T, Kina-Tanada M, Kubota H, Nakasone J, Sakanashi M, Ueda S, Masuzaki H, Ishiuchi S, Ohya Y, Tsutsui M (2015) Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects. J Pharmacol Sci 127:217–222. doi:10.1016/j.jphs.2015.01.003

    Article  CAS  Google Scholar 

  75. Lemery R, Pecarskie A, Bernick J, Williams K, Wells GA (2015) A prospective placebo controlled randomized study of caffeine in patients with supraventricular tachycardia undergoing electrophysiologic testing. J Cardiovasc Electrophysiol 26:1–6. doi:10.1111/jce.12504

    Article  Google Scholar 

  76. Phan JK, Shah SA (2014) Effect of caffeinated versus noncaffeinated energy drinks on central blood pressures. Pharmacotherapy 34:555–560. doi:10.1002/phar.1419

    Article  CAS  Google Scholar 

  77. Astorino TA, Martin BJ, Schachtsiek L, Wong K (2013) Caffeine ingestion and intense resistance training minimize postexercise hypotension in normotensive and prehypertensive men. Res Sports Med 21:52–65. doi:10.1080/15438627.2012.738443

    Google Scholar 

  78. Del Coso J, Salinero JJ, González-Millán C, Abián-Vicén J, Pérez-González B (2012) Dose response effects of a caffeine-containing energy drink on muscle performance: a repeated measures design. J Int Soc Sports Nutr 9:21. doi:10.1186/1550-2783-9-21

    Article  CAS  Google Scholar 

  79. Farag NH, Vincent AS, McKey BS, Whitsett TL, Lovallo WR (2005) Hemodynamic mechanisms underlying the incomplete tolerance to caffeine’s pressor effects. Am J Cardiol 95:1389–1392. doi:10.1016/j.amjcard.2005.01.093

    Article  CAS  Google Scholar 

  80. Terai N, Spoerl E, Pillunat LE, Stodtmeister R (2012) The effect of caffeine on retinal vessel diameter in young healthy subjects. Acta Ophthalmol 90:e524–e528. doi:10.1111/j.1755-3768.2012.02486.x

    Article  CAS  Google Scholar 

  81. Ozkan B, Yüksel N, Anik Y, Altintas O, Demirci A, Cağlar Y (2008) The effect of caffeine on retrobulbar hemodynamics. Curr Eye Res 33:804–809. doi:10.1080/02713680802344708

    Article  CAS  Google Scholar 

  82. Kennedy DO, Haskell CF (2011) cerebral blood flow and behavioural effects of caffeine in habitual and non-habitual consumers of caffeine: a near infrared spectroscopy study. Biol Psychol 86:298–306. doi:10.1016/j.biopsycho.2010.12.010

    Article  Google Scholar 

  83. Shechter M, Shalmon G, Scheinowitz M, Koren-Morag N, Feinberg MS, Harats D, Sela BA, Sharabi Y, Chouraqui P (2011) Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease. Am J Cardiol 107:1255–1261. doi:10.1016/j.amjcard.2010.12.035

    Article  CAS  Google Scholar 

  84. Buscemi S, Mattina A, Tranchina MR, Verga S (2011) Acute effects of coffee on QT interval in healthy subjects. Nutr J 10:15. doi:10.1186/1475-2891-10-15

    Article  Google Scholar 

  85. Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis ME (2005) Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci 109:55–60. doi:10.1042/CS20040358

    Article  CAS  Google Scholar 

  86. Mahmud A, Feely J (2001) Acute effect of caffeine on arterial stiffness and aortic pressure waveform. Hypertension 38:227–231

    Article  CAS  Google Scholar 

  87. Vlachopoulos C, Hirata K, Stefanadis C, Toutouzas P, O’Rourke MF (2003) Caffeine increases aortic stiffness in hypertensive patients. Am J Hypertens 16:63–66

    Article  CAS  Google Scholar 

  88. Karatzis E, Papaioannou TG, Aznaouridis K, Karatzi K, Stamatelopoulos K, Zampelas A, Papamichael C, Lekakis J, Mavrikakis M (2005) Acute effects of caffeine on blood pressure and wave reflections in healthy subjects: should we consider monitoring central blood pressure? Int J Cardiol 98:425–430. doi:10.1016/j.ijcard.2003.11.013

    Article  Google Scholar 

  89. Vlachopoulos C, Hirata K, O’Rourke MF (2003) Effect of caffeine on aortic elastic properties and wave reflection. J Hypertens 21:563–570. doi:10.1097/01.hjh.0000052463.40108.b2

    Article  CAS  Google Scholar 

  90. Trovato GM, Pirri C, Martines GF, Trovato F, Catalano D (2010) Coffee, nutritional status, and renal artery resistive index. Renal Fail 32:1137–1147. doi:10.3109/0886022X.2010.516853

    Article  Google Scholar 

  91. Katheria AC, Sauberan JB, Akotia D, Rich W, Durham J, Finer NN (2015) A pilot randomized controlled trial of early versus routine caffeine in extremely premature infants. Am J Perinatol 32:879–886. doi:10.1055/s-0034-1543981

    Article  Google Scholar 

  92. Hassanein SM, Gad GI, Ismail RI, Diab M (2014) Effect of caffeine on preterm infants’ cerebral cortical activity: an observational study. J Matern Fetal Neonatal Med 14:1–6. doi:10.3109/14767058.2014.978757

    Google Scholar 

  93. Ulanovsky I, Haleluya NS, Blazer S, Weissman A (2014) The effects of caffeine on heart rate variability in newborns with apnea of prematurity. J Perinatol 34:620–623. doi:10.1038/jp.2014.60

    Article  CAS  Google Scholar 

  94. Nováková Z, Honzíková N, Závodná E, Hrstková H, Václavková P (2001) Baroreflex sensitivity and body growth parameters in children and adolescents. Exp Clin Cardiol 6:35–37

    Google Scholar 

  95. Monda M, Viggiano A, Vicidomini C, Viggiano A, Iannaccone T, Tafuri D, De Luca B (2009) Espresso coffee increases parasympathetic activity in young, healthy people. Nutr Neurosci 12:43–48. doi:10.1179/147683009X388841

    Article  CAS  Google Scholar 

  96. Mosqueda-Garcia R, Tseng CJ, Biaggioni I, Robertson RM, Robertson D (1990) Effects of caffeine on baroreflex activity in humans. Clin Pharmacol Ther 48:568–574

    Article  CAS  Google Scholar 

  97. Zimmermann-Viehoff F, Thayer J, Koenig J, Herrmann C, Weber CS, Deter HC (2015) Short-term effects of espresso coffee on heart rate variability and blood pressure in habitual and non-habitual coffee consumers—a randomized crossover study. Nutr Neurosci. doi:10.1179/1476830515Y.0000000018

    Google Scholar 

  98. Notarius CF, Floras JS (2012) Caffeine enhances heart rate variability in middle-aged healthy, but not heart failure subjects. J Caffeine Res 2:77–82. doi:10.1089/jcr.2012.0010

    Article  CAS  Google Scholar 

  99. Kammerer M, Jaramillo JA, García A, Calderón JC, Valbuena LH (2014) Effects of energy drink major bioactive compounds on the performance of young adults in fitness and cognitive tests: a randomized controlled trial. J Int Soc Sports Nutr 11:44. doi:10.1186/s12970-014-0044-9

    Article  CAS  Google Scholar 

  100. Andrade-Souza VA, Bertuzzi R, de Araujo GG, Bishop D, Lima-Silva AE (2015) Effects of isolated or combined carbohydrate and caffeine supplementation between 2 daily training sessions on soccer performance. Appl Physiol Nutr Metab 40:457–463. doi:10.1139/apnm-2014-0268

    Article  CAS  Google Scholar 

  101. Lopes-Silva JP, Felippe LJ, Silva-Cavalcante MD, Bertuzzi R, Lima-Silva AE (2014) Caffeine ingestion after rapid weight loss in judo athletes reduces perceived effort and increases plasma lactate concentration without improving performance. Nutrients 6:2931–2945. doi:10.3390/nu6072931

    Article  CAS  Google Scholar 

  102. Duncan MJ, Stanley M, Parkhouse N, Cook K, Smith M (2013) Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise. Eur J Sports Sci 13:392–399. doi:10.1080/17461391.2011.635811

    Article  Google Scholar 

  103. Fernández-Elías VE, Del Coso J, Hamouti N, Ortega JF, Muñoz G, Muñoz-Guerra J, Mora-Rodríguez R (2015) Ingestion of a moderately high caffeine dose before exercise increases postexercise energy expenditure. Int J Sport Nutr Exerc Metab 25:46–53. doi:10.1123/ijsnem.2014-0037

    Article  Google Scholar 

  104. Bunsawat K, White DW, Kappus RM, Baynard T (2014) Caffeine delays autonomic recovery following acute exercise. Eur J Prev Cardiol. doi:10.1177/2047487314554867

    Google Scholar 

  105. Paton C, Costa V, Guglielmo L (2015) Effects of caffeine chewing gum on race performance and physiology in male and female cyclists. J Sports Sci 33:1076–1083. doi:10.1080/02640414.2014.984752

    Article  Google Scholar 

  106. Bortolotti H, Altimari LR, Vitor-Costa M, Cyrino ES (2014) Performance during a 20-km cycling time-trial after caffeine ingestion. J Int Soc Sports Nutr 11:45. doi:10.1186/s12970-014-0045-8

    Article  CAS  Google Scholar 

  107. Scott AT, O’Leary T, Walker S, Owen R (2015) Improvement of 2000-m rowing performance with caffeinated carbohydrate-gel ingestion. Int J Sports Physiol Perform 10:464–468. doi:10.1123/ijspp.2014-0210

    Article  Google Scholar 

  108. Stadheim HK, Kvamme B, Olsen R, Drevon CA, Ivy JL, Jensen J (2013) Caffeine increases performance in cross-country double-poling time trial exercise. Med Sci Sports Exerc 45:2175–2183. doi:10.1249/MSS.0b013e3182967948

    Article  CAS  Google Scholar 

  109. Chrysant SG (2015) Coffee consumption and cardiovascular health. Am J Cardiol 116:818–821. doi:10.1016/j.amjcard.2015.05.057

    Article  Google Scholar 

  110. Ding M, Satija A, Bhupathiraju SN, Hu Y, Sun Q, Han J, Lopez-Garcia E, Willett W, van Dam RM, Hu FB (2015) Association of coffee consumption with total and cause-specific mortality in 3 large prospective cohorts. Circulation 132:2305–2315. doi:10.1161/CIRCULATIONAHA.115.017341

    Article  CAS  Google Scholar 

  111. Notara V, Panagiotakos DB, Kouvari M, Tzanoglou D, Kouli G, Mantas Y, Kogias Y, Stravopodis P, Papanagnou G, Zombolos S, Babatsikou F, Koutis C, Pitsavos C, GREECS Study Investigators (2015) The role of coffee consumption on the 10-year (2004–2014) Acute Coronary Syndrome (ACS) incidence among cardiac patients: the GREECS observational study. Int J Food Sci Nutr 66:722–728. doi:10.3109/09637486.2015.1077795

    Article  CAS  Google Scholar 

  112. Choi Y, Chang Y, Ryu S, Cho J, Rampal S, Zhang Y, Ahn J, Lima JA, Shin H, Guallar E (2015) Coffee consumption and coronary artery calcium in young and middle-aged asymptomatic adults. Heart 101(9):686–691. doi:10.1136/heartjnl-2014-306663

    Article  CAS  Google Scholar 

  113. Reis JP, Loria CM, Steffen LM, Zhou X, van Horn L, Siscovick DS, Jacobs DR Jr, Carr JJ (2010) Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study. Arterioscler Thromb Vasc Biol 30:2059–2066. doi:10.1161/ATVBAHA.110.208280

    Article  CAS  Google Scholar 

  114. Wu JN, Ho SC, Zhou C, Ling WH, Chen WQ, Wang CL, Chen YM (2009) Coffee consumption and risk of coronary heart diseases: a meta-analysis of 21 prospective cohort studies. Int J Cardiol 137:216–225. doi:10.1016/j.ijcard.2008.06.051

    Article  Google Scholar 

  115. Lopez-Garcia E, Rodriguez-Artalejo F, Rexrode KM, Logroscino G, Hu FB, van Dam RM (2009) Coffee consumption and risk of stroke in women. Circulation 119:1116–1123. doi:10.1161/CIRCULATIONAHA.108.826164

    Article  CAS  Google Scholar 

  116. Zhang WL, Lopez-Garcia E, Li TY, Hu FB, van Dam RM (2009) Coffee consumption and risk of cardiovascular events and all-cause mortality among women with type 2 diabetes. Diabetologia 52:810–817. doi:10.1007/s00125-009-1311-1

    Article  CAS  Google Scholar 

  117. Mineharu Y, Koizumi A, Wada Y, Iso H, Watanabe Y, Date C, Yamamoto A, Kikuchi S, Inaba Y, Toyoshima H, Kondo T, Tamakoshi A, JACC study Group (2011) Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women. J Epidemiol Community Health 65:230–240. doi:10.1136/jech.2009.097311

    Article  Google Scholar 

  118. Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J (2013) Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart 99:1383–1389. doi:10.1136/heartjnl-2013-303950

    Article  Google Scholar 

  119. Shen J, Johnson VM, Sullivan LM, Jacques PF, Magnani JW, Lubitz SA, Pandey S, Levy D, Vasan RS, Quatromoni PA, Junyent M, Ordovas JM, Benjamin EJ (2011) Dietary factors and incident atrial fibrillation: the Framingham Heart Study. Am J Clin Nutr 93:261–266. doi:10.3945/ajcn.110.001305

    Article  CAS  Google Scholar 

  120. Cheng M, Hu Z, Lu X, Huang J, Gu D (2014) Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies. Can J Cardiol 30:448–454. doi:10.1016/j.cjca.2013.12.026

    Article  CAS  Google Scholar 

  121. Larsson SC, Drca N, Jensen-Urstad M, Wolk A (2015) Coffee consumption is not associated with increased risk of atrial fibrillation: results from two prospective cohorts and a meta-analysis. BMC Med 13:207. doi:10.1186/s12916-015-0447-8

    Article  CAS  Google Scholar 

  122. Mostofsky E, Johansen MB, Lundbye-Christensen S, Tjønneland A, Mittleman MA, Overvad K (2015) Risk of atrial fibrillation associated with coffee intake: findings from the danish diet, cancer, and health study. Eur J Prev Cardiol. doi:10.1177/2047487315624524

  123. Glatter KA, Myers R, Chiamvimonvat N (2012) Recommendations regarding dietary intake and caffeine and alcohol consumption in patients with cardiac arrhythmias: What do you tell your patients to do or not to do? Curr Treat Options Cardiovasc Med 14:529–535. doi:10.1007/s11936-012-0193-6

    Article  Google Scholar 

  124. Zuchinali P, Ribeiro PA, Pimentel M, da Rosa PR, Zimerman LI, Rohde LE (2015) Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies. Europace. doi:10.1093/europace/euv261

  125. Saito E, Inoue M, Sawada N, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Noda M, Iso H, Tsugane S (2015) 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 101:1029–1037. doi:10.3945/ajcn.114.104273

    Article  CAS  Google Scholar 

  126. Malerba S, Turati F, Galeone C, Pelucchi C, Verga F, La Vecchia C, Tavani A (2013) A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases. Eur J Epidemiol 28:527–539. doi:10.1007/s10654-013-9834-7

    Article  Google Scholar 

  127. Mostofsky E, Rice MS, Levitan EB, Mittleman MA (2012) Habitual coffee consumption and risk of heart failure: a dose–response meta-analysis. Circ Heart Fail 5:401–405. doi:10.1161/CIRCHEARTFAILURE.112.967299

    Article  CAS  Google Scholar 

  128. Santos PR, Ferrari GSL, Ferrari CKB (2015) Diet, sleep and metabolic syndrome among a legal Amazon population, Brazil. Clin Nutr Res 4:41–45. doi:10.7762/cnr.2015.4.1.41

    Article  Google Scholar 

  129. Agardh EE, Carlsson S, Ahlbom A, Efendic S, Grill V, Hammar N, Hilding A, Ostenson CG (2004) Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women. J Intern Med 255:645–652

    Article  CAS  Google Scholar 

  130. Bhaktha G, Nayak BS, Mayya S, Shantaram M (2015) Relationship of caffeine with adiponectin and blood sugar levels in subjects with and without diabetes. J Clin Diagn Res 9:BC01–BC03. doi:10.7860/JCDR/2015/10587.5371

    Google Scholar 

  131. da Silva LA, de Freitas L, Medeiros TE, Osiecki R, Garcia Michel R, Snak AL, Malfatti CR (2014) Caffeine modifies blood glucose availability during prolonged low-intensity exercise in individuals with type-2 diabetes. Colomb Med (Cali) 45:72–76

    Google Scholar 

  132. Li MF, Cheung BM (2011) Rise and fall of anti-obesity drugs. World J Diabetes 2:19–23. doi:10.4239/wjd.v2.i2.19

    Article  Google Scholar 

  133. Cheung BMY, Cheung TT, Samaranayake NR (2013) Safety of antiobesity drugs. Ther Adv Drug Saf 4:171–181. doi:10.1177/2042098613489721

    Article  CAS  Google Scholar 

  134. Ciszowski K, Biedroń W, Gomólka E (2014) Acute caffeine poisoning resulting in atrial fibrillation after guarana extract overdose. Prz Lek 71:495–498

    Google Scholar 

  135. Rashid A, Hines M, Scherlag BJ, Yamanashi WS, Lovallo W (2006) The effects of caffeine on the inducibility of atrial fibrillation. J Electrocardiol 39:421–425. doi:10.1016/j.jelectrocard.2005.12.007

    Article  Google Scholar 

  136. Kinugawa T, Kurita T, Nohara R, Smith ML (2011) A case of atrial tachycardia sensitive to increased caffeine intake. Int Heart J 52:398–400

    Article  Google Scholar 

  137. Bioh G, Gallagher MM, Prasad U (2013) Survival of a highly toxic dose of caffeine. BMJ Case Rep. doi:10.1136/bcr-2012-007454

    Google Scholar 

  138. Vukcević NP, Babić G, Segrt Z, Ercegović GV, Janković S, Aćimović L (2012) Severe acute caffeine poisoning due to intradermal injections: mesotherapy hazard. Vojnosanit Pregl 69:707–713

    Article  Google Scholar 

  139. Clausen T (2010) Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam Clin Pharmacol 24:595–605. doi:10.1111/j.1472-8206.2010.00859.x

    Article  CAS  Google Scholar 

  140. Dufendach KA, Horner JM, Cannon BC, Ackerman MJ (2012) Congenital type 1 long QT syndrome unmasked by a highly caffeinated energy drink. Heart Rhythm 9:285–288. doi:10.1016/j.hrthm.2011.10.011

    Article  Google Scholar 

  141. Cai Y, Kurita-Ochiai T, Hashizume T, Yamamoto M (2013) Green tea epigallocatechin-3-gallate attenuates Porphyromonas gingivalis-induced atherosclerosis. Pathog Dis 67:76–83

    Article  CAS  Google Scholar 

  142. Martína MJ, Pablosa F, Gonzáleza AG, Valdenebrob MS, León-Camachob M (2001) Fatty acid profiles as discriminant parameters for coffee varieties differentiation. Talanta 54:291–297

    Article  Google Scholar 

  143. Whayne TF Jr (2015) Coffee: a selected overview of beneficial or harmful effects on the cardiovascular system? Curr Vasc Pharmacol 13(5):637–648

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Authors and Affiliations

  1. Centre for Chronic Disease (CCD), College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia

    Anthony Zulli, Renee M. Smith, Hayley Loftus, Tawar Qaradakhi & Alan Hayes

  2. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia

    Peter Kubatka

  3. 2nd Department of Internal Medicine, St. Anne’s University Hospital and Masaryk University, Brno, Czech Republic

    Jan Novak & Miroslav Soucek

  4. Department of Physiology, Masaryk University, Brno, Czech Republic

    Jan Novak

  5. Division of Clinical Nutrition, Faculty of Home Economics, Kyoritsu Women’s University, Tokyo, Japan

    Yoshio Uehara

  6. Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic

    Miroslav Pohanka

  7. Bogomolets National Medical University, Kiev, Ukraine

    Nazarii Kobyliak

  8. Cardiology Center Medika, St. Petersburg, Russia

    Angela Zagatina

  9. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odborarov 10, 832 32, Bratislava, Slovak Republic

    Jan Klimas

  10. Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy

    Giampiero La Rocca

  11. Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy

    Giampiero La Rocca

  12. Laboratory of Structural Biology and Proteomics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho tr 1/1946, Brno, 612 42, Czech Republic

    Peter Kruzliak

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  1. Anthony Zulli
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Zulli, A., Smith, R.M., Kubatka, P. et al. Caffeine and cardiovascular diseases: critical review of current research. Eur J Nutr 55, 1331–1343 (2016). https://doi.org/10.1007/s00394-016-1179-z

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