Project: Systematic review of the adverse cardiovascular effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children
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Title

Systematic review of the adverse cardiovascular effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children

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Description

To date, one of the most heavily cited assessments of caffeine safety in the peer-reviewed literature is that issued by Health Canada (Nawrot et al., 2003). Since then, >10,000 papers have been published related to caffeine, including hundreds of reviews on specific human health effects; however, to date, none have compared the wide range of topics evaluated by Nawrot et al. (2003). Thus, as an update to this foundational publication, we conducted a systematic review of data on potential adverse effects of caffeine published from 2001 to June 2015. Subject matter experts and research team participants developed five PECO (population, exposure, comparator, and outcome) questions to address five types of outcomes (acute toxicity, cardiovascular toxicity, bone and calcium effects, behavior, and development and reproduction) in four healthy populations (adults, pregnant women, adolescents, and children) relative to caffeine intake doses determined not to be associated with adverse effects by Health Canada (comparators: 400 mg/day for adults [10 g for lethality], 300 mg/day for pregnant women, and 2.5 mg/kg/day for children and adolescents). The a priori search strategy identified >5000 articles that were screened, with 381 meeting inclusion/exclusion criteria for the five outcomes (pharmacokinetics was addressed contextually, adding 46 more studies). Data were extracted by the research team and rated for risk of bias and indirectness (internal and external validity). Selected no- and low-effect intakes were assessed relative to the population-specific comparator. Conclusions were drawn for the body of evidence for each outcome, as well as endpoints within an outcome, using a weight of evidence approach. When the total body of evidence was evaluated and when study quality, consistency, level of adversity, and magnitude of response were considered, the evidence generally supports that consumption of up to 400 mg caffeine/day in healthy adults is not associated with overt, adverse cardiovascular effects, behavioral effects, reproductive and developmental effects, acute effects, or bone status. Evidence also supports consumption of up to 300 mg caffeine/day in healthy pregnant women as an intake that is generally not associated with adverse reproductive and developmental effects. Limited data were identified for child and adolescent populations; the available evidence suggests that 2.5 mg caffeine/kg body weight/day remains an appropriate recommendation. The results of this systematic review support a shift in caffeine research to focus on characterizing effects in sensitive populations and establishing better quantitative characterization of interindividual variability (e.g., epigenetic trends), subpopulations (e.g., unhealthy populations, individuals with preexisting conditions), conditions (e.g., coexposures), and outcomes (e.g., exacerbation of risk-taking behavior) that could render individuals to be at greater risk relative to healthy adults and healthy pregnant women. This review, being one of the first to apply systematic review methodologies to toxicological assessments, also highlights the need for refined guidance and frameworks unique to the conduct of systematic review in this field.

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Methodology

Problem formulation was based on providing an update of Nawrot et al. (2003), “Effects of caffeine on human health,” [PMID 12519715]. No comprehensive studies of similar scope have been published in the peer-reviewed literature, and thus the overall objective is to conduct an update to Nawrot et al. that applies the rigor of a systematic review. This review is one of five systematic reviews being conducted simultaneously (other endpoints include acute toxicity and adverse effects on reproduction/development, cardiovascular, and bone and calcium balance outcomes. Exposure and comparators were thus based on levels determined by Nawrot et al., (2003). Searches: The searches were conducted using: PubMed, EMBASE, and the Cochrane Database of Systematic Review. The restrictions will be articles published in English between 2001 and June 8, 2015. EMBASE searches were exclusive of MEDLINE and restricted to selected journals (430 journals were selected based on relevance). The Cochrane library was searched between Jan 2001 and June 2015 for review articles. Search strategies were informed and reviewed by a librarian. Types of studies included: All study types (excluding case studies) characterizing a quantitative exposure to caffeine and an adverse bone and calcium balance endpoint will be included. Both exposure and response must be evaluated at the individual level. Reviews will not be included in the systematic assessment (unless original data, such as a meta analysis, were conducted), but selected reviews will be consulted for context. Include: studies reporting parameters or effects associated with adverse effects within a benefit/therapy study. Exclude: Studies assessing only beneficial or therapeutic endpoints or outcomes following exposure to caffeine. Participants/ population: Populations: healthy adults, healthy pregnant women, healthy adolescents (aged 12-19), healthy children (aged 3-12). Exposure: = 400 mg/day, 300 mg/day, 2.5 mg/kg-bw day*, respectively (by population). Comparator: < 400 mg/day, 300 mg/day, 2.5 mg/kg-bw day*, respectively (by population). *Applies to both adolescents and children. Include: Studies evaluating a healthy population; this will include athletes, military, and pregnant women, unless otherwise noted as unhealthy. Healthy in this context was defined as subjects who were not specifically described as hospitalized, diagnosed with disease, and/or receiving medical treatment for a disease at the time of the study. Include: Studies that evaluate the effects of caffeine exposure in humans. This included studies in which healthy individuals were included as a control group (or similar) as part of a study on unhealthy populations (only information from the healthy individuals would be carried forward). Include: crossover balance studies could with a control period rather than a control group. Exclude: Studies evaluating unhealthy populations with no healthy control arm; this includes asthmatics and smoking populations. Exclude: Studies that describe effects of caffeine exposure in animal species or in vitro studies. Exclude: Case studies with no comparison group.

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DOI

https://dx.doi.org/10.26300/g3a1-d434

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Funding Source

This Systematic Review of the adverse cardiovascular effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children was sponsored by the North American Branch of the International Life Sciences Institute (ILSI) Caffeine Working Group. Unrestricted grants from the American Beverage Association (ABA) and the National Coffee Association (NCA) were also received.

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Notes

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Key Questions

For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on cardiovascular outcomes?

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Associated Extraction Forms

Title	Created by	Key Questions Addressed	Form Notes
Cardiovascular Design	Ray DeVirgiliis	1

Associated Studies (each link opens a new tab)

Title	Author	Year
The effects of dietary caffeine use and abstention on blood oxygen level-dependent activation and cerebral blood flow	M. A. Addicott, A. M. Peiffer and P. J. Laurienti	2012
Ergogenic effects of caffeine on simulated time-trial performance are independent of fitness level	T. A. Astorino, T. Cottrell, A. T. Lozano, K. Aburto-Pratt and J. Duhon	2011
Catechol-o-methyltransferase genotype is associated with self-reported increased heart rate following caffeine consumption	J. M. Brathwaite, L. A. Da Costa and A. El-Sohemy	2011
The effect of caffeine on performance in collegiate tennis players	C. S. Klein, A. Clawson, M. Martin, M. J. Saunders, J. A. Flohr, M. K. Bechtel, W. Dunham, M. Hancock and C. J. Womack	2012
Subjective state, blood pressure, and behavioral control changes produced by an "energy shot"	C. A. Marczinski, A. L. Stamates, J. Ossege, S. F. Maloney, M. E. Bardgett and C. J. Brown	2014
Lifestyle practices and cardiovascular disease mortality in the elderly: The leisure world cohort study	A. Paganini-Hill	2011
A Cup of Black Tea Does Not Modify Heart Rate Variability	D. V. Syce	2015
Gender differences in subjective and physiological responses to caffeine and the role of steroid hormones	J. L. Temple and A. M. Ziegler	2011
Effects of alcohol, coffee, and tobacco, alone or in combination, on physiological parameters and anxiety in a young population	C. Vinader-Caerols, S. Monleon, C. Carrasco and A. Parra	2012
Caffeine and intraocular pressure in a Nigerian population.	OB Ajayi,MT Ukwade,	2001
Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.	PF Jacques,AG Bostom,PW Wilson,S Rich,IH Rosenberg,J Selhub,	2001
Evaluation of electrocardiographic and hemodynamic effects of caffeine with acute dosing in healthy volunteers.	R Ammar,JC Song,J Kluger,CM White,	2001
The influence of a taurine containing drink on cardiac parameters before and after exercise measured by echocardiography.	M Baum,M Weiss,	2001
An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers.	MF Caron,J Song,R Ammar,J Kluger,CM White,	2001
Acute effect of caffeine on arterial stiffness and aortic pressure waveform.	A Mahmud,J Feely,	2001
Abstention from filtered coffee reduces the concentrations of plasma homocysteine and serum cholesterol--a randomized controlled trial.	B Christensen,A Mosdol,L Retterstol,S Landaas,DS Thelle,	2001
Effects of caffeine and high ambient temperature on haemodynamic and body temperature responses to dynamic exercise.	CL Stebbins,JW Daniels,W Lewis,	2001
Influence of caffeine, cold and exercise on multiple choice reaction time.	B Kruk,J Chmura,K Krzeminski,AW Ziemba,K Nazar,H Pekkarinen,H Kaciuba-Uscilko,	2001
Effects of caffeine, caffeine-associated stimuli, and caffeine-related information on physiological and psychological arousal.	A Mikalsen,B Bertelsen,MA Flaten,	2001
Maximum cognitive performance and physiological time trend measurements after caffeine intake.	C Kourtidou-Papadeli,C Papadelis,AL Louizos,O Guiba-Tziampiri,	2002
The influence of placebo awareness on stimulant drug response in a double-blind trial.	JM Nash,KA Holroyd,LA Rokicki,S Kvaal,DB Penzien,	2002
Effects of caffeine on microcirculation of the human ocular fundus.	T Okuno,T Sugiyama,M Tominaga,S Kojima,T Ikeda,
Caffeine affects cardiovascular and neuroendocrine activation at work and home.	JD Lane,CF Pieper,BG Phillips-Bute,JE Bryant,CM Kuhn,
Hypoalgesic effect of caffeine in normotensive men and women.	E Keogh,G Witt,	2001
Influence of caffeine ingestion on autonomic nervous activity during endurance exercise in humans.	Y Nishijima,T Ikeda,M Takamatsu,Y Kiso,H Shibata,T Fushiki,T Moritani,	2002
Acute effects of caffeine on heart rate variability.	HP Sondermeijer,AG van Marle,P Kamen,H Krum,	2002
Duration of coffee- and exercise-induced changes in the fatty acid profile of human serum.	V Mougios,S Ring,A Petridou,MG Nikolaidis,	2003
Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.	P Verhoef,WJ Pasman,T Van Vliet,R Urgert,MB Katan,	2002
The moderating effect of anxiety sensitivity on caffeine-induced hypoalgesia in healthy women.	E Keogh,N Chaloner,	2002
Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking.	R Corti,C Binggeli,I Sudano,L Spieker,E Hänseler,F Ruschitzka,WF Chaplin,TF Lüscher,G Noll,	2002
Caffeine ingestion does not alter performance during a 100-km cycling time-trial performance.	AM Hunter,A St Clair Gibson,M Collins,M Lambert,TD Noakes,	2002
Dietary caffeine consumption and withdrawal: confounding variables in quantitative cerebral perfusion studies?	AS Field,PJ Laurienti,YF Yen,JH Burdette,DM Moody,	2003
Effects of mental workload and caffeine on catecholamines and blood pressure compared to performance variations.	C Papadelis,C Kourtidou-Papadeli,E Vlachogiannis,P Skepastianos,P Bamidis,N Maglaveras,K Pappas,	2003
Effect of caffeine on aortic elastic properties and wave reflection.	C Vlachopoulos,K Hirata,MF O'Rourke,	2003
Expectations and placebo responses to caffeine-associated stimuli.	MA Flaten,O Aasli,TD Blumenthal,	2003
The effect of caffeine on the cardiovascular responses to head-up tilt.	NM Berry,CA Rickards,DG Newman,	2003
Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults.	MJ Davies,JT Judd,DJ Baer,BA Clevidence,DR Paul,AJ Edwards,SA Wiseman,RA Muesing,SC Chen,	2003
Acute caffeine intake influences central more than peripheral blood pressure in young adults.	WS Waring,J Goudsmit,J Marwick,DJ Webb,SR Maxwell,	2003
Sensitivity of the Finometer device in detecting acute and medium-term changes in cardiovascular function.	AE Schutte,HW Huisman,JM Van Rooyen,W Oosthuizen,JC Jerling,	2003
Blood pressure response to caffeine shows incomplete tolerance after short-term regular consumption.	WR Lovallo,MF Wilson,AS Vincent,BH Sung,BS McKey,TL Whitsett,	2004
Effects of coffee consumption on oxidative susceptibility of low-density lipoproteins and serum lipid levels in humans.	GS Yukawa,M Mune,H Otani,Y Tone,XM Liang,H Iwahashi,W Sakamoto,	2004
Enhanced stimulant and metabolic effects of combined ephedrine and caffeine.	CA Haller,P Jacob,NL Benowitz,	2004
Cardiovascular effects of caffeine in men and women.	TR Hartley,WR Lovallo,TL Whitsett,	2004
Influence of caffeine on heart rate variability in patients with long-standing type 1 diabetes.	T Richardson,A Rozkovec,P Thomas,J Ryder,C Meckes,D Kerr,	2004
The association of caffeinated beverages with blood pressure in adolescents.	MR Savoca,CD Evans,ME Wilson,GA Harshfield,DA Ludwig,	2004
Dose-dependent effect of caffeine on reducing leg muscle pain during cycling exercise is unrelated to systolic blood pressure.	PJ O'Connor,RW Motl,SP Broglio,MR Ely,	2004
Black tea increases coronary flow velocity reserve in healthy male subjects.	K Hirata,K Shimada,H Watanabe,R Otsuka,K Tokai,M Yoshiyama,S Homma,J Yoshikawa,	2004
Coffee drinking is dose-dependently related to the risk of acute coronary events in middle-aged men.	P Happonen,S Voutilainen,JT Salonen,	2004
Does an energy drink modify the effects of alcohol in a maximal effort test?	SE Ferreira,MT de Mello,MV Rossi,ML Souza-Formigoni,	2004
Cognitive and physiological effects of an "energy drink": an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions.	AB Scholey,DO Kennedy,	2004
Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo.	MA Flaten,T Simonsen,K Zahlsen,T Aamo,G Sager,H Olsen,	2004
Hemodynamic effects of dietary caffeine, sleep restriction, and laboratory stress.	JE James,ME Gregg,	2004
Cognitive and psychomotor performance, mood, and pressor effects of caffeine after 4, 6 and 8 h caffeine abstinence.	SV Heatherley,RC Hayward,HE Seers,PJ Rogers,	2005
Acute effects of caffeine on blood pressure and wave reflections in healthy subjects: should we consider monitoring central blood pressure?	E Karatzis,TG Papaioannou,K Aznaouridis,K Karatzi,K Stamatelopoulos,A Zampelas,C Papamichael,J Lekakis,M Mavrikakis,	2005
Caffeine and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study.	L Frost,P Vestergaard,	2005
The association between coffee consumption and plasma total homocysteine levels: the "ATTICA" study.	DB Panagiotakos,C Pitsavos,A Zampelas,A Zeimbekis,C Chrysohoou,L Papademetriou,C Stefanadis,	2004
Effect of coffee on endothelial function in healthy subjects: the role of caffeine.	CM Papamichael,KA Aznaouridis,EN Karatzis,KN Karatzi,KS Stamatelopoulos,G Vamvakou,JP Lekakis,ME Mavrikakis,	2005
Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials.	M Noordzij,CS Uiterwaal,LR Arends,FJ Kok,DE Grobbee,JM Geleijnse,	2005
Influences of caffeine, acetazolamide and cognitive stimulation on cerebral blood flow velocities.	CG Haase,M Becka,J Kuhlmann,G Wensing,	2005
Caffeine tolerance is incomplete: persistent blood pressure responses in the ambulatory setting.	NH Farag,AS Vincent,BH Sung,TL Whitsett,MF Wilson,WR Lovallo,	2005
Hemodynamic mechanisms underlying the incomplete tolerance to caffeine's pressor effects.	NH Farag,AS Vincent,BS McKey,TL Whitsett,WR Lovallo,	2005
Chronic coffee consumption has a detrimental effect on aortic stiffness and wave reflections.	C Vlachopoulos,D Panagiotakos,N Ioakeimidis,I Dima,C Stefanadis,	2005
Effects of caffeine on linear and nonlinear measures of heart rate variability before and after exercise.	VK Yeragani,S Krishnan,HJ Engels,R Gretebeck,	2005
Coffee blunts mental stress-induced blood pressure increase in habitual but not in nonhabitual coffee drinkers.	I Sudano,L Spieker,C Binggeli,F Ruschitzka,TF Lüscher,G Noll,R Corti,	2005
Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men.	S Bérubé-Parent,C Pelletier,J Doré,A Tremblay,	2005
Effects of caffeine on heart rate and QT variability during sleep.	M Bonnet,M Tancer,T Uhde,VK Yeragani,	2005
Caffeine effects on resting-state arousal.	RJ Barry,JA Rushby,MJ Wallace,AR Clarke,SJ Johnstone,I Zlojutro,	2005
Caffeine decreases exercise-induced myocardial flow reserve.	M Namdar,P Koepfli,R Grathwohl,PT Siegrist,M Klainguti,T Schepis,R Delaloye,CA Wyss,SP Fleischmann,O Gaemperli,PA Kaufmann,	2006
Thermoregulatory responses to exercise in the heat: chronic caffeine intake has no effect.	MW Roti,DJ Casa,AC Pumerantz,G Watson,DA Judelson,JC Dias,K Ruffin,LE Armstrong,	2006
The effect of caffeine ingestion on 8 km run performance in a field setting.	CA Bridge,MA Jones,	2006
Coffee, CYP1A2 genotype, and risk of myocardial infarction.	MC Cornelis,A El-Sohemy,EK Kabagambe,H Campos,	2006
Effects of caffeine on physiological responses to exercise in young boys and girls.	KR Turley,JW Gerst,	2006
Effect of caffeine on leg muscle pain during cycling exercise among females.	RW Motl,PJ O'connor,L Tubandt,T Puetz,MR Ely,	2006
Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users.	E Childs,H de Wit,	2006
Acute effects of caffeine on heart rate variability in habitual caffeine consumers.	R Rauh,M Burkert,M Siepmann,M Mueck-Weymann,	2006
A combination of caffeine and taurine has no effect on short term memory but induces changes in heart rate and mean arterial blood pressure.	A Bichler,A Swenson,MA Harris,	2006
Effect of caffeine on lower esophageal sphincter pressure in Thai healthy volunteers.	S Lohsiriwat,N Puengna,S Leelakusolvong,	2006
Acute effect of black and green tea on aortic stiffness and wave reflections.	C Vlachopoulos,N Alexopoulos,I Dima,K Aznaouridis,I Andreadou,C Stefanadis,	2006
Nonlinear dynamics of blood pressure variability after caffeine consumption.	TG Papaioannou,C Vlachopoulos,N Ioakeimidis,N Alexopoulos,C Stefanadis,	2006
Influence of caffeine on perception of effort, metabolism and exercise performance following a high-fat meal.	M Hadjicharalambous,E Georgiades,LP Kilduff,AP Turner,F Tsofliou,YP Pitsiladis,	2006
Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction.	A Baylin,S Hernandez-Diaz,EK Kabagambe,X Siles,H Campos,	2006
Sex differences in the hemodynamic responses to mental stress: Effect of caffeine consumption.	NH Farag,AS Vincent,BS McKey,M Al'Absi,TL Whitsett,WR Lovallo,	2006
Acute effects of caffeine and tobacco on arterial function and wave travel.	J Swampillai,F Rakebrandt,K Morris,CJ Jones,AG Fraser,	2006
Effects of acute administration of caffeine on vascular function.	T Umemura,K Ueda,K Nishioka,T Hidaka,H Takemoto,S Nakamura,D Jitsuiki,J Soga,C Goto,K Chayama,M Yoshizumi,Y Higashi,	2006
Coffee consumption and risk of coronary heart disease: a meta-analysis.	F Sofi,AA Conti,AM Gori,ML Eliana Luisi,A Casini,R Abbate,GF Gensini,	2007
Catechol-o-methyltransferase gene polymorphism modifies the effect of coffee intake on incidence of acute coronary events.	P Happonen,S Voutilainen,TP Tuomainen,JT Salonen,	2006
Effects of expectation and caffeine on arousal, well-being, and reaction time.	R Schneider,M Grüner,A Heiland,M Keller,Z Kujanová,M Peper,M Riegl,S Schmidt,P Volz,H Walach,	2006
Physiological and cognitive responses to caffeine during repeated, high-intensity exercise.	MJ Crowe,AS Leicht,WL Spinks,	2006
Effect of a thermogenic beverage on 24-hour energy metabolism in humans.	S Rudelle,MG Ferruzzi,I Cristiani,J Moulin,K Macé,KJ Acheson,L Tappy,	2007
The physiological effects of caffeine in women during treadmill walking.	JN Ahrens,SH Crixell,LK Lloyd,JL Walker,	2007
Nonfatal acute myocardial infarction in Costa Rica: modifiable risk factors, population-attributable risks, and adherence to dietary guidelines.	EK Kabagambe,A Baylin,H Campos,	2007
The effect of caffeine on dilated cerebral circulation and on diagnostic CO2 reactivity testing.	M Blaha,V Benes,CM Douville,DW Newell,	2007
The effects of caffeine in women during aerobic-dance bench stepping.	JN Ahrens,LK Lloyd,SH Crixell,JL Walker,	2007
Hydration during exercise in warm, humid conditions: effect of a caffeinated sports drink.	ML Millard-Stafford,KJ Cureton,JE Wingo,J Trilk,GL Warren,M Buyckx,	2007
Effect of caffeine ingestion on one-repetition maximum muscular strength.	TA Astorino,RL Rohmann,K Firth,	2008
The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake.	A Belza,S Toubro,A Astrup,	2009
Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together.	PJ Rogers,JE Smith,SV Heatherley,CW Pleydell-Pearce,	2008
Caffeine-induced changes in cardiovascular function during resistance training.	TA Astorino,RL Rohmann,K Firth,S Kelly,	2007
Coffee consumption and mortality in a 14-year follow-up of an elderly northern Finnish population.	P Happonen,E Läärä,L Hiltunen,H Luukinen,	2008
Effects of caffeine on physiological responses to exercise: boys versus men.	KR Turley,T Desisso,JW Gerst,	2007
Pharmacological and psychological effects of caffeine ingestion in 40-km cycling performance.	AJ Foad,CJ Beedie,DA Coleman,	2008
Timing of caffeine's impact on autonomic and central nervous system measures: clarification of arousal effects.	RJ Barry,AR Clarke,SJ Johnstone,JA Rushby,	2008
Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study.	JE Perthen,AE Lansing,J Liau,TT Liu,RB Buxton,	2008
Investigations on the effect of caffeine on cerebral venous vessel contrast by using susceptibility-weighted imaging (SWI) at 1.5, 3 and 7 T.	J Sedlacik,K Helm,A Rauscher,J Stadler,HJ Mentzel,JR Reichenbach,	2008
Enhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individuals.	E Childs,H de Wit,	2008
Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects.	E Giacomin,E Palmerini,P Ballo,V Zacà,G Bova,S Mondillo,	2008
Effect of coffee ingestion on physiological responses and ratings of perceived exertion during submaximal endurance exercise.	S Demura,T Yamada,N Terasawa,	2007
Effects of different doses of caffeine on exercise responses in young children.	KR Turley,JR Bland,WJ Evans,	2008
Caffeine reduces the activation extent and contrast-to-noise ratio of the functional cerebral blood flow response but not the BOLD response.	J Liau,JE Perthen,TT Liu,	2008
The acute effect of green tea consumption on endothelial function in healthy individuals.	N Alexopoulos,C Vlachopoulos,K Aznaouridis,K Baou,C Vasiliadou,P Pietri,P Xaplanteris,E Stefanadi,C Stefanadis,	2008
The relationship of coffee consumption with mortality.	E Lopez-Garcia,RM van Dam,TY Li,F Rodriguez-Artalejo,FB Hu,	2008
The effect of caffeine as an ergogenic aid in anaerobic exercise.	K Woolf,WK Bidwell,AG Carlson,	2008
The relationship between caffeine and blood pressure in preadolescent African American girls.	JG Reddy,JO Ebbert,LM Klesges,FT Enders,RC Klesges,JQ Lanctot,BS McClanahan,	2008
The effect of caffeine on retrobulbar hemodynamics.	B Ozkan,N Yüksel,Y Anik,O Altintas,A Demirci,Y Cağlar,	2008
Caffeine supplementation and multiple sprint running performance.	M Glaister,G Howatson,CS Abraham,RA Lockey,JE Goodwin,P Foley,G McInnes,	2008
Caffeine improves physical and cognitive performance during exhaustive exercise.	E Hogervorst,S Bandelow,J Schmitt,R Jentjens,M Oliveira,J Allgrove,T Carter,M Gleeson,	2008
Effects of caffeine and aspirin on light resistance training performance, perceived exertion, and pain perception.	GM Hudson,JM Green,PA Bishop,MT Richardson,	2008
No effect of nutritional adenosine receptor antagonists on exercise performance in the heat.	SN Cheuvront,BR Ely,RW Kenefick,BB Michniak-Kohn,JC Rood,MN Sawka,	2009
Caffeinated coffee consumption, cardiovascular disease, and heart valve disease in the elderly (from the Framingham Study).	JA Greenberg,G Chow,RC Ziegelstein,	2008
The cumulative effect of coffee and a mental stress task on heart rate, blood pressure, and mental alertness is similar in caffeine-naïve and caffeine-habituated females.	MD Kennedy,AV Galloway,LJ Dickau,MK Hudson,	2008
Effects of caffeine on repetitions to failure and ratings of perceived exertion during resistance training.	JM Green,PJ Wickwire,JR McLester,S Gendle,G Hudson,RC Pritchett,CM Laurent,	2007
Caffeinated coffee enhances co-operative behavior in the Mixed Motive Game in healthy volunteers.	WS Tse,CC Chan,SY Shiu,PY Chung,SH Cheng,	2009
The effects of caffeine ingestion on time trial cycling performance.	LR McNaughton,RJ Lovell,J Siegler,AW Midgley,L Moore,DJ Bentley,	2008
The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate?	MA Addicott,LL Yang,AM Peiffer,LR Burnett,JH Burdette,MY Chen,S Hayasaka,RA Kraft,JA Maldjian,PJ Laurienti,	2009
Caffeine withdrawal, acute effects, tolerance, and absence of net beneficial effects of chronic administration: cerebral blood flow velocity, quantitative EEG, and subjective effects.	SC Sigmon,RI Herning,W Better,JL Cadet,RR Griffiths,	2009
Effect of "energy drink" consumption on hemodynamic and electrocardiographic parameters in healthy young adults.	L Steinke,DE Lanfear,V Dhanapal,JS Kalus,	2009
Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.	AL Rack-Gomer,J Liau,TT Liu,	2009
Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controls.	M Namdar,T Schepis,P Koepfli,O Gaemperli,PT Siegrist,R Grathwohl,I Valenta,R Delaloye,M Klainguti,CA Wyss,TF Lüscher,PA Kaufmann,	2009
Effect of caffeine as an ergogenic aid during anaerobic exercise performance in caffeine naïve collegiate football players.	K Woolf,WK Bidwell,AG Carlson,	2009
Effect of Red Bull energy drink on cardiovascular and renal function.	FR Ragsdale,TD Gronli,N Batool,N Haight,A Mehaffey,EC McMahon,TW Nalli,CM Mannello,CJ Sell,PJ McCann,GM Kastello,T Hooks,T Wilson,	2010
Evaluation of experience-based fatigue countermeasures.	P Gershon,D Shinar,A Ronen,	2009
Does the presence of a pharmacological substance alter the placebo effect?--results of two experimental studies using the placebo-caffeine paradigm.	H Walach,R Schneider,	2009
Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women.	Y Mineharu,A Koizumi,Y Wada,H Iso,Y Watanabe,C Date,A Yamamoto,S Kikuchi,Y Inaba,H Toyoshima,T Kondo,A Tamakoshi, ,	2011
Detrimental effects of energy drink consumption on platelet and endothelial function.	MI Worthley,A Prabhu,P De Sciscio,C Schultz,P Sanders,SR Willoughby,	2010
Acute effects of coffee on endothelial function in healthy subjects.	S Buscemi,S Verga,JA Batsis,M Donatelli,MR Tranchina,S Belmonte,A Mattina,A Re,G Cerasola,	2010
The effects of EGCG on fat oxidation and endurance performance in male cyclists.	S Dean,A Braakhuis,C Paton,	2009
Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial.	K Kempf,C Herder,I Erlund,H Kolb,S Martin,M Carstensen,W Koenig,J Sundvall,S Bidel,S Kuha,J Tuomilehto,	2010
Prevalence and incidence of hypertension in adolescent girls.	E Obarzanek,CO Wu,JA Cutler,RE Kavey,GD Pearson,SR Daniels,	2010
Caffeine and blood pressure response: sex, age, and hormonal status.	NH Farag,TL Whitsett,BS McKey,MF Wilson,AS Vincent,SA Everson-Rose,WR Lovallo,	2010
Caffeine consumption and incident atrial fibrillation in women.	D Conen,SE Chiuve,BM Everett,SM Zhang,JE Buring,CM Albert,	2010
Caffeine and stress alter salivary alpha-amylase activity in young men.	LC Klein,JM Bennett,CA Whetzel,DA Granger,FE Ritter,	2010
The influence of caffeine and carbohydrate coingestion on simulated soccer performance.	N Gant,A Ali,A Foskett,	2010
Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study.	JP Reis,CM Loria,LM Steffen,X Zhou,L van Horn,DS Siscovick,DR Jacobs,JJ Carr,	2010
Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot & humid climate.	WC Ping,CC Keong,A Bandyopadhyay,	2010
Coffee and acute ischemic stroke onset: the Stroke Onset Study.	E Mostofsky,G Schlaug,KJ Mukamal,WD Rosamond,MA Mittleman,	2010
Coffee, nutritional status, and renal artery resistive index.	GM Trovato,C Pirri,GF Martines,F Trovato,D Catalano,	2010
The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness.	T Giesbrecht,JA Rycroft,MJ Rowson,EA De Bruin,	2010
The effect of four coffee types on normotensive rats and normal/hypertensive human volunteers.	AS Awaad,GA Soliman,MR Al-Outhman,IF Al-Shdoukhi,RS Al-Nafisah,J Al-Shamery,R Al-Samkhan,M Baqer,NA Al-Jaber,	2011
Interaction between drug and placebo effects: a cross-over balanced placebo design trial.	MM Hammami,EA Al-Gaai,S Alvi,MB Hammami,	2010
The effect of caffeine ingestion on mood state and bench press performance to failure.	MJ Duncan,SW Oxford,	2011
Effect of caffeine ingestion after creatine supplementation on intermittent high-intensity sprint performance.	CL Lee,JC Lin,CF Cheng,	2011
Cerebral blood flow and behavioural effects of caffeine in habitual and non-habitual consumers of caffeine: a near infrared spectroscopy study.	DO Kennedy,CF Haskell,	2011
Acute effects of coffee on QT interval in healthy subjects.	S Buscemi,A Mattina,MR Tranchina,S Verga,	2011
Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease.	M Shechter,G Shalmon,M Scheinowitz,N Koren-Morag,MS Feinberg,D Harats,BA Sela,Y Sharabi,P Chouraqui,	2011
Differential effects of intranasal insulin and caffeine on cerebral blood flow.	Y Grichisch,M Çavuşoğlu,H Preissl,K Uludağ,M Hallschmid,N Birbaumer,HU Häring,A Fritsche,R Veit,	2012
Coffee consumption and risk of stroke in women.	SC Larsson,J Virtamo,A Wolk,	2011
Habitual coffee and tea drinkers experienced increases in blood pressure after consuming low to moderate doses of caffeine; these increases were larger upright than in the supine posture.	MK McMullen,JM Whitehouse,G Shine,A Towell,	2011
Differential contributions of theobromine and caffeine on mood, psychomotor performance and blood pressure.	ES Mitchell,M Slettenaar,N vd Meer,C Transler,L Jans,F Quadt,M Berry,	2011
The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity.	MK McMullen,JM Whitehouse,G Shine,PA Whitton,A Towell,	2011
Storm in a coffee cup: caffeine modifies brain activation to social signals of threat.	JE Smith,AD Lawrence,A Diukova,RG Wise,PJ Rogers,	2012
The effects of different doses of caffeine on endurance cycling time trial performance.	B Desbrow,C Biddulph,B Devlin,GD Grant,S Anoopkumar-Dukie,MD Leveritt,	2012
Genetic determinants of blood pressure responses to caffeine drinking.	G Renda,M Zimarino,I Antonucci,A Tatasciore,B Ruggieri,T Bucciarelli,T Prontera,L Stuppia,R De Caterina,	2012
Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion.	EJ Ryan,CH Kim,MD Muller,DM Bellar,JE Barkley,MV Bliss,A Jankowski-Wilkinson,M Russell,R Otterstetter,D Macander,EL Glickman,GH Kamimori,	2012
Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.	A Floegel,T Pischon,MM Bergmann,B Teucher,R Kaaks,H Boeing,	2012
Increases in cycling performance in response to caffeine ingestion are repeatable.	TA Astorino,T Cottrell,AT Lozano,K Aburto-Pratt,J Duhon,	2012
Independent and combined effects of carbohydrate and caffeine ingestion on aerobic cycling performance in the fed state.	TL Acker-Hewitt,BM Shafer,MJ Saunders,Q Goh,ND Luden,	2012
Effect of caffeine on LT, VT and HRVT.	GK Karapetian,HJ Engels,KA Gretebeck,RJ Gretebeck,	2012
Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.	MK McMullen,JM Whitehouse,G Shine,PA Whitton,A Towell,	2012
Acute caffeine ingestion enhances performance and dampens muscle pain following resistance exercise to failure.	MJ Duncan,SW Oxford,	2012
Habitual coffee consumption and risk of heart failure: a dose-response meta-analysis.	E Mostofsky,MS Rice,EB Levitan,MA Mittleman,	2012
Caffeine increases psychomotor performance on the effort expenditure for rewards task.	MC Wardle,MT Treadway,H de Wit,	2012
Caffeine does not alter RPE or pain perception during intense exercise in active women.	TA Astorino,LR Roupoli,BR Valdivieso,	2012
Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose.	GE Giles,CR Mahoney,TT Brunyé,AL Gardony,HA Taylor,RB Kanarek,	2012
The effect of caffeine on retinal vessel diameter in young healthy subjects.	N Terai,E Spoerl,LE Pillunat,R Stodtmeister,	2012
Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses.	A Yoto,M Motoki,S Murao,H Yokogoshi,	2012
Caffeine ingestion and intense resistance training minimize postexercise hypotension in normotensive and prehypertensive men.	TA Astorino,BJ Martin,L Schachtsiek,K Wong,	2013
A moderate dose of caffeine ingestion does not change energy expenditure but decreases sleep time in physically active males: a double-blind randomized controlled trial.	PB Júdice,JP Magalhães,DA Santos,CN Matias,AI Carita,PA Armada-Da-Silva,LB Sardinha,AM Silva,	2013
Psychopharmacology of theobromine in healthy volunteers.	MJ Baggott,E Childs,AB Hart,E de Bruin,AA Palmer,JE Wilkinson,H de Wit,	2013
Safety profile of caffeine and 1,3-dimethylamylamine supplementation in healthy men.	RJ Bloomer,TM Farney,IC Harvey,RJ Alleman,	2013
The effect of black tea and caffeine on regional cerebral blood flow measured with arterial spin labeling.	R Vidyasagar,A Greyling,R Draijer,DR Corfield,LM Parkes,	2013
Effects of caffeine and stress on biomarkers of cardiovascular disease in healthy men and women with a family history of hypertension.	JM Bennett,IM Rodrigues,LC Klein,	2013
The effect of a caffeinated energy drink on various psychological measures during submaximal cycling.	MJ Duncan,J Hankey,	2013
Long-term alcohol and caffeine intake and risk of sudden cardiac death in women.	ML Bertoia,EW Triche,DS Michaud,A Baylin,JW Hogan,ML Neuhouser,MS Freiberg,MA Allison,MM Safford,W Li,Y Mossavar-Rahmani,MC Rosal,CB Eaton,	2013
Effects of caffeinated versus decaffeinated energy shots on blood pressure and heart rate in healthy young volunteers.	AM Kurtz,J Leong,M Anand,AE Dargush,SA Shah,	2013
Effect of caffeine on upper-body anaerobic performance in wrestlers in simulated competition-day conditions.	M Aedma,S Timpmann,V Ööpik,	2013
Coffee and tea consumption are inversely associated with mortality in a multiethnic urban population.	H Gardener,T Rundek,CB Wright,MS Elkind,RL Sacco,	2013
Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise.	MJ Duncan,M Stanley,N Parkhouse,K Cook,M Smith,	2013
Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: a BOLD and perfusion MRI study.	S Haller,C Rodriguez,D Moser,S Toma,J Hofmeister,I Sinanaj,D Van De Ville,P Giannakopoulos,KO Lovblad,	2013
Effect of caffeine on cycling time-trial performance in the heat.	NW Pitchford,JW Fell,MD Leveritt,B Desbrow,CM Shing,	2014
Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies.	D Caldeira,C Martins,LB Alves,H Pereira,JJ Ferreira,J Costa,	2013
Caffeine alters anaerobic distribution and pacing during a 4000-m cycling time trial.	Rde A Santos,MA Kiss,MD Silva-Cavalcante,CR Correia-Oliveira,R Bertuzzi,DJ Bishop,AE Lima-Silva,	2013
Double-blind placebo and active (caffeine) controlled study to examine the effects of the herbal nutritional supplement beverage "Wake up" on vigilance and function after lunch.	O Kassis,N Katz,S Ravid,G Pillar,	2013
Caffeine supplementation and reactive agility in elite youth soccer players.	JB Jordan,A Korgaokar,RS Farley,JM Coons,JL Caputo,	2014
Caffeine administration does not alter salivary α-amylase activity in young male daily caffeine consumers.	LC Klein,CA Whetzel,JM Bennett,FE Ritter,UM Nater,M Schoelles,	2014
Cardiovascular health and caffeine consumption. A population-based study in rural Ecuador.	OH Del Brutto,RM Mera,M Zambrano,	2014
Self-reported physiological and psychological side-effects of an acute alcohol and energy drink dose.	A Peacock,R Bruno,FH Martin,A Carr,	2014
Caffeine alters resting-state functional connectivity measured by blood oxygenation level-dependent MRI.	WC Wu,SH Lien,JH Chang,SC Yang,	2014
Effect of caffeinated versus noncaffeinated energy drinks on central blood pressures.	JK Phan,SA Shah,	2014
Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies.	M Cheng,Z Hu,X Lu,J Huang,D Gu,	2014
The combination of short rest and energy drink consumption as fatigue countermeasures during a prolonged drive of professional truck drivers.	A Ronen,T Oron-Gilad,P Gershon,	2014
Ingesting a preworkout supplement containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active men.	KL Kendall,JR Moon,CM Fairman,BD Spradley,CY Tai,PH Falcone,LR Carson,MM Mosman,JM Joy,MP Kim,ER Serrano,EN Esposito,	2014
Cardiovascular responses to caffeine by gender and pubertal stage.	JL Temple,AM Ziegler,A Graczyk,A Bendlin,T Sion,K Vattana,	2014
Acute effect of caffeine intake on hemodynamics after resistance exercise in young non-hypertensive subjects.	D Souza,J Casonatto,R Poton,J Willardson,M Polito,	2014

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The data contained in this project are distributed under the terms of the Creative Commons Attribution-NonCommerical license, which permits the use, dissemination, and reproduction in any medium, provided the original work is properly cited, and that the use is non-commercial and otherwise in compliance with the license. See: https://creativecommons.org/licenses/by-nc/3.0/

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Project: Systematic review of the adverse cardiovascular effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children Public Report Complete

Project: Systematic review of the adverse cardiovascular effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children

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Project: Systematic review of the adverse cardiovascular effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children
Public Report Complete