Last Updated: February 1 2023

Caffeine is a stimulatory anti-sleep compound extracted from coffee beans. Habitual caffeine use leads to tolerance, which dulls several of caffeine’s effects.

Caffeine is most often used for


What does caffeine do?

Caffeine comes from coffee beans, but it can also be synthesized in a laboratory. It has the same structure whether it’s in coffee, energy drinks, tea, or pills.

Caffeine is a powerful stimulant, and it can be used to improve physical strength and endurance. It is classified as a nootropic because it sensitizes neurons and provides mental stimulation.

Habitual caffeine use is also associated with a reduced risk of Alzheimer's disease, cirrhosis, and liver cancer.

Caffeine’s main mechanism concerns antagonizing adenosine receptors. Adenosine causes sedation and relaxation when it acts upon its receptors, located in the brain. Caffeine prevents this action and causes alertness and wakefulness. This inhibition of adenosine can influence the dopamine, serotonin, acetylcholine, and adrenaline systems.

For practical tips on the optimal use of caffeine, check out our Supplement Guides.

What else is Caffeine known as?
Note that Caffeine is also known as:
  • Coffee extract
  • Tea extract
  • 1 3 7-Trimethylxanthine
Caffeine should not be confused with:
  • Caffeic acid
Dosage information

Caffeine dosages should be tailored to individuals. If you are new to caffeine supplements, start with a 100mg dose. Typically, 200mg of caffeine is used for fat-burning supplementation, while higher doses of 3–6 mg/kg of body weight are typically used to increase strength.

Caffeine can be supplemented through popular beverages, like coffee, tea, and energy drinks, but it can also be taken in a pill form.

Many of caffeine’s effects, including fat burning, strength benefits, and euphoria, are subject to tolerance, and may not occur in people used to caffeine, no matter how large the dose is.

Join our supplement information course

Examine Database: Caffeine
What works and what doesn't?

Unlock the full potential of Examine

Get started

Don't miss out on the latest research

Frequently asked questions

Other FAQs

Research Breakdown

2.^Vieira MA, Maraschin M, Pagliosa CM, Podestá R, de Simas KN, Rockenbach II, Amboni RD, Amante ERPhenolic acids and methylxanthines composition and antioxidant properties of mate (Ilex paraguariensis) residueJ Food Sci.(2010 Apr)
3.^Burdock GA, Carabin IG, Crincoli CMSafety assessment of kola nut extract as a food ingredientFood Chem Toxicol.(2009 Aug)
4.^Heishman SJ, Henningfield JEStimulus functions of caffeine in humans: relation to dependence potentialNeurosci Biobehav Rev.(1992 Fall)
5.^Barone JJ, Roberts HRCaffeine consumptionFood Chem Toxicol.(1996 Jan)
6.^Frary CD, Johnson RK, Wang MQFood sources and intakes of caffeine in the diets of persons in the United StatesJ Am Diet Assoc.(2005 Jan)
7.^Knight CA, Knight I, Mitchell DCBeverage caffeine intakes in young children in Canada and the USCan J Diet Pract Res.(2006 Summer)
11.^Gummadi SN, Bhavya B, Ashok NPhysiology, biochemistry and possible applications of microbial caffeine degradationAppl Microbiol Biotechnol.(2012 Jan)
13.^Zhang L, Kujawinski DM, Federherr E, Schmidt TC, Jochmann MACaffeine in your drink: natural or syntheticAnal Chem.(2012 Mar 20)
18.^Jeukendrup AE, Randell RFat burners: nutrition supplements that increase fat metabolismObes Rev.(2011 Oct)
19.^Diepvens K, Westerterp KR, Westerterp-Plantenga MSObesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green teaAm J Physiol Regul Integr Comp Physiol.(2007 Jan)
21.^Carrillo JA, Christensen M, Ramos SI, Alm C, Dahl ML, Benitez J, Bertilsson LEvaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urineTher Drug Monit.(2000 Aug)
22.^Liguori A, Hughes JR, Grass JAAbsorption and subjective effects of caffeine from coffee, cola and capsulesPharmacol Biochem Behav.(1997 Nov)
24.^Thakur RA, Michniak BB, Meidan VMTransdermal and buccal delivery of methylxanthines through human tissue in vitroDrug Dev Ind Pharm.(2007 May)
25.^Kamimori GH, Karyekar CS, Otterstetter R, Cox DS, Balkin TJ, Belenky GL, Eddington NDThe rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteersInt J Pharm.(2002 Mar 2)
29.^Blanchard J, Sawers SJComparative pharmacokinetics of caffeine in young and elderly menJ Pharmacokinet Biopharm.(1983 Apr)
30.^Blanchard J, Sawers SJThe absolute bioavailability of caffeine in manEur J Clin Pharmacol.(1983)
31.^Bonati M, Latini R, Galletti F, Young JF, Tognoni G, Garattini SCaffeine disposition after oral dosesClin Pharmacol Ther.(1982 Jul)
34.^Cox GR, Desbrow B, Montgomery PG, Anderson ME, Bruce CR, Macrides TA, Martin DT, Moquin A, Roberts A, Hawley JA, Burke LMEffect of different protocols of caffeine intake on metabolism and endurance performanceJ Appl Physiol.(2002 Sep)
35.^Marks V, Kelly JFAbsorption of caffeine from tea, coffee, and coca colaLancet.(1973 Apr 14)
36.^Mumford GK, Benowitz NL, Evans SM, Kaminski BJ, Preston KL, Sannerud CA, Silverman K, Griffiths RRAbsorption rate of methylxanthines following capsules, cola and chocolateEur J Clin Pharmacol.(1996)
37.^Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EEActions of caffeine in the brain with special reference to factors that contribute to its widespread usePharmacol Rev.(1999 Mar)
38.^Eteng MU, Eyong EU, Akpanyung EO, Agiang MA, Aremu CYRecent advances in caffeine and theobromine toxicities: a reviewPlant Foods Hum Nutr.(1997)
39.^Tansy MF, Kendall FMExperimental and clinical aspects of gastrocolic reflexesAm J Dig Dis.(1973 Jun)
40.^Lohsiriwat S, Kongmuang P, Leelakusolvong SEffects of caffeine on anorectal manometric findingsDis Colon Rectum.(2008 Jun)
41.^Stacewicz-Sapuntzakis M, Bowen PE, Hussain EA, Damayanti-Wood BI, Farnsworth NRChemical composition and potential health effects of prunes: a functional foodCrit Rev Food Sci Nutr.(2001 May)
42.^Crozier TW, Stalmach A, Lean ME, Crozier AEspresso coffees, caffeine and chlorogenic acid intake: potential health implicationsFood Funct.(2012 Jan)
47.^Chen Y, Xiao CQ, He YJ, Chen BL, Wang G, Zhou G, Zhang W, Tan ZR, Cao S, Wang LP, Zhou HHGenistein alters caffeine exposure in healthy female volunteersEur J Clin Pharmacol.(2011 Apr)
51.^Kennedy JS, Leduc BW, Scavone JM, Harmatz JS, Shader RI, Greenblatt DJPharmacokinetics of intravenous caffeine: comparison of high-performance liquid chromatographic and gas chromatographic methodsJ Chromatogr.(1987 Nov 27)
52.^Newton R, Broughton LJ, Lind MJ, Morrison PJ, Rogers HJ, Bradbrook IDPlasma and salivary pharmacokinetics of caffeine in manEur J Clin Pharmacol.(1981)
53.^Collomp K, Anselme F, Audran M, Gay JP, Chanal JL, Prefaut CEffects of moderate exercise on the pharmacokinetics of caffeineEur J Clin Pharmacol.(1991)
54.^Burg AW, Werner ETissue distribution of caffeine and its metabolites in the mouseBiochem Pharmacol.(1972 Apr 1)
57.^Yang A, Palmer AA, de Wit HGenetics of caffeine consumption and responses to caffeinePsychopharmacology (Berl).(2010 Aug)
62.^Womack CJ, Saunders MJ, Bechtel MK, Bolton DJ, Martin M, Luden ND, Dunham W, Hancock MThe influence of a CYP1A2 polymorphism on the ergogenic effects of caffeineJ Int Soc Sports Nutr.(2012 Mar 15)
64.^Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson LComparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and KoreansEur J Clin Pharmacol.(2007 Jun)
65.^Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu EInduction of CYP1A2 by heavy coffee consumption in Serbs and SwedesEur J Clin Pharmacol.(2008 Apr)
66.^Djordjevic N, Ghotbi R, Jankovic S, Aklillu EInduction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 -163C>A polymorphismEur J Clin Pharmacol.(2010 Jul)
67.^Djordjevic N, Carrillo JA, Roh HK, Karlsson S, Ueda N, Bertilsson L, Aklillu EComparison of N-Acetyltransferase-2 Enzyme Genotype-Phenotype and Xanthine Oxidase Enzyme Activity Between Swedes and KoreansJ Clin Pharmacol.(2011 Nov 21)
68.^Djordjevic N, Carrillo JA, Gervasini G, Jankovic S, Aklillu EIn vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian populationEur J Clin Pharmacol.(2010 Jun)
70.^Aklillu E, Carrillo JA, Makonnen E, Bertilsson L, Ingelman-Sundberg MXanthine oxidase activity is influenced by environmental factors in EthiopiansEur J Clin Pharmacol.(2003 Oct)
71.^Saruwatari J, Nakagawa K, Shindo J, Tajiri T, Fujieda M, Yamazaki H, Kamataki T, Ishizaki TA population phenotyping study of three drug-metabolizing enzymes in Kyushu, Japan, with use of the caffeine testClin Pharmacol Ther.(2002 Aug)
72.^Guerciolini R, Szumlanski C, Weinshilboum RMHuman liver xanthine oxidase: nature and extent of individual variationClin Pharmacol Ther.(1991 Dec)
75.^Tantcheva-Poór I, Zaigler M, Rietbrock S, Fuhr UEstimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine testPharmacogenetics.(1999 Apr)
78.^Schrenk D, Brockmeier D, Mörike K, Bock KW, Eichelbaum MA distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteersEur J Clin Pharmacol.(1998 Jan)
79.^Butler MA, Lang NP, Young JF, Caporaso NE, Vineis P, Hayes RB, Teitel CH, Massengill JP, Lawsen MF, Kadlubar FFDetermination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolitesPharmacogenetics.(1992 Jun)
80.^Parsons WD, Neims AHEffect of smoking on caffeine clearanceClin Pharmacol Ther.(1978 Jul)
81.^Simon T, Becquemont L, Hamon B, Nouyrigat E, Chodjania Y, Poirier JM, Funck-Brentano C, Jaillon PVariability of cytochrome P450 1A2 activity over time in young and elderly healthy volunteersBr J Clin Pharmacol.(2001 Nov)
85.^Arnaud MJThe pharmacology of caffeineProg Drug Res.(1987)
87.^Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X, Patel H, Mobbs CVRole of CBP and SATB-1 in aging, dietary restriction, and insulin-like signalingPLoS Biol.(2009 Nov)
88.^Lublin A, Isoda F, Patel H, Yen K, Nguyen L, Hajje D, Schwartz M, Mobbs CFDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicityPLoS One.(2011)
89.^Wanke V, Cameroni E, Uotila A, Piccolis M, Urban J, Loewith R, De Virgilio CCaffeine extends yeast lifespan by targeting TORC1Mol Microbiol.(2008 Jul)
90.^Powers RW 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, Fields SExtension of chronological life span in yeast by decreased TOR pathway signalingGenes Dev.(2006 Jan 15)
91.^Wanke V, Pedruzzi I, Cameroni E, Dubouloz F, De Virgilio CRegulation of G0 entry by the Pho80-Pho85 cyclin-CDK complexEMBO J.(2005 Dec 21)
92.^Cameroni E, Hulo N, Roosen J, Winderickx J, De Virgilio CThe novel yeast PAS kinase Rim 15 orchestrates G0-associated antioxidant defense mechanismsCell Cycle.(2004 Apr)
93.^Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VDRegulation of longevity and stress resistance by Sch9 in yeastScience.(2001 Apr 13)
94.^Reinders A, Bürckert N, Boller T, Wiemken A, De Virgilio CSaccharomyces cerevisiae cAMP-dependent protein kinase controls entry into stationary phase through the Rim15p protein kinaseGenes Dev.(1998 Sep 15)
95.^Liu Y, Burger SK, Ayers PW, Vöhringer-Martinez EComputational study of the binding modes of caffeine to the adenosine A2A receptorJ Phys Chem B.(2011 Dec 1)
96.^Paluska SACaffeine and exerciseCurr Sports Med Rep.(2003 Aug)
97.^Porkka-Heiskanen TMethylxanthines and sleepHandb Exp Pharmacol.(2011)
98.^Huang ZL, Urade Y, Hayaishi OThe role of adenosine in the regulation of sleepCurr Top Med Chem.(2011)
99.^Ferre S, Ciruela F, Borycz J, Solinas M, Quarta D, Antoniou K, Quiroz C, Justinova Z, Lluis C, Franco R, Goldberg SRAdenosine A1-A2A receptor heteromers: new targets for caffeine in the brainFront Biosci.(2008 Jan 1)
100.^Elmenhorst D, Meyer PT, Matusch A, Winz OH, Bauer ACaffeine Occupancy of Human Cerebral A1 Adenosine Receptors: In Vivo Quantification with 18F-CPFPX and PETJ Nucl Med.(2012 Nov)
103.^Fredholm BB, Abbracchio MP, Burnstock G, Daly JW, Harden TK, Jacobson KA, Leff P, Williams MNomenclature and classification of purinoceptorsPharmacol Rev.(1994 Jun)
106.^Björklund O, Halldner-Henriksson L, Yang J, Eriksson TM, Jacobson MA, Daré E, Fredholm BBDecreased behavioral activation following caffeine, amphetamine and darkness in A3 adenosine receptor knock-out micePhysiol Behav.(2008 Dec 15)
108.^Holtzman SG, Mante S, Minneman KPRole of adenosine receptors in caffeine toleranceJ Pharmacol Exp Ther.(1991 Jan)
109.^Varani K, Portaluppi F, Merighi S, Ongini E, Belardinelli L, Borea PACaffeine alters A2A adenosine receptors and their function in human plateletsCirculation.(1999 May 18)
110.^Conlay LA, Conant JA, deBros F, Wurtman RCaffeine alters plasma adenosine levelsNature.(1997 Sep 11)
112.^Khaliq S, Haider S, Naqvi F, Perveen T, Saleem S, Haleem DJAltered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in ratsPak J Pharm Sci.(2012 Jan)
113.^Chen MD, Lin WH, Song YM, Lin PY, Ho LTEffect of caffeine on the levels of brain serotonin and catecholamine in the genetically obese miceZhonghua Yi Xue Za Zhi (Taipei).(1994 May)
114.^Okada M, Kawata Y, Kiryu K, Mizuno K, Wada K, Tasaki H, Kaneko SEffects of adenosine receptor subtypes on hippocampal extracellular serotonin level and serotonin reuptake activityJ Neurochem.(1997 Dec)
115.^Chin A, Svejda B, Gustafsson BI, Granlund AB, Sandvik AK, Timberlake A, Sumpio B, Pfragner R, Modlin IM, Kidd MThe role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretionAm J Physiol Gastrointest Liver Physiol.(2012 Feb)
119.^Shi D, Daly JWChronic effects of xanthines on levels of central receptors in miceCell Mol Neurobiol.(1999 Dec)
120.^Conde SV, Nunes da Silva T, Gonzalez C, Mota Carmo M, Monteiro EC, Guarino MPChronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in ratsBr J Nutr.(2012 Jan)
121.^Bangsbo J, Jacobsen K, Nordberg N, Christensen NJ, Graham TAcute and habitual caffeine ingestion and metabolic responses to steady-state exerciseJ Appl Physiol.(1992 Apr)
122.^Solinas M, Ferré S, You ZB, Karcz-Kubicha M, Popoli P, Goldberg SRCaffeine induces dopamine and glutamate release in the shell of the nucleus accumbensJ Neurosci.(2002 Aug 1)
123.^Quarta D, Borycz J, Solinas M, Patkar K, Hockemeyer J, Ciruela F, Lluis C, Franco R, Woods AS, Goldberg SR, Ferré SAdenosine receptor-mediated modulation of dopamine release in the nucleus accumbens depends on glutamate neurotransmission and N-methyl-D-aspartate receptor stimulationJ Neurochem.(2004 Nov)
126.^Carter AJ, O'Connor WT, Carter MJ, Ungerstedt UCaffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptorsJ Pharmacol Exp Ther.(1995 May)
127.^Corradetti R, Pedata F, Pepeu G, Vannucchi MGChronic caffeine treatment reduces caffeine but not adenosine effects on cortical acetylcholine releaseBr J Pharmacol.(1986 Jul)
132.^Garrett BE, Holtzman SGDoes adenosine receptor blockade mediate caffeine-induced rotational behaviorJ Pharmacol Exp Ther.(1995 Jul)
135.^Powell KR, Iuvone PM, Holtzman SGThe role of dopamine in the locomotor stimulant effects and tolerance to these effects of caffeinePharmacol Biochem Behav.(2001 May-Jun)
140.^Shi D, Nikodijević O, Jacobson KA, Daly JWEffects of chronic caffeine on adenosine, dopamine and acetylcholine systems in miceArch Int Pharmacodyn Ther.(1994 Nov-Dec)
141.^Smillie LD, Gökçen ECaffeine enhances working memory for extravertsBiol Psychol.(2010 Dec)
146.^Lindskog M, Svenningsson P, Pozzi L, Kim Y, Fienberg AA, Bibb JA, Fredholm BB, Nairn AC, Greengard P, Fisone GInvolvement of DARPP-32 phosphorylation in the stimulant action of caffeineNature.(2002 Aug 15)
147.^Svenningsson P, Nairn AC, Greengard PDARPP-32 mediates the actions of multiple drugs of abuseAAPS J.(2005 Oct 5)
148.^Walaas SI, Hemmings HC Jr, Greengard P, Nairn ACBeyond the dopamine receptor: regulation and roles of serine/threonine protein phosphatasesFront Neuroanat.(2011)
149.^Dawkins L, Shahzad FZ, Ahmed SS, Edmonds CJExpectation of having consumed caffeine can improve performance and moodAppetite.(2011 Dec)
150.^Backhouse SH, Biddle SJ, Bishop NC, Williams CCaffeine ingestion, affect and perceived exertion during prolonged cyclingAppetite.(2011 Aug)
154.^Field AS, Laurienti PJ, Yen YF, Burdette JH, Moody DMDietary caffeine consumption and withdrawal: confounding variables in quantitative cerebral perfusion studiesRadiology.(2003 Apr)
156.^Mathew RJ, Wilson WHCaffeine consumption, withdrawal and cerebral blood flowHeadache.(1985 Sep)
158.^Perthen JE, Lansing AE, Liau J, Liu TT, Buxton RBCaffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI studyNeuroimage.(2008 Mar 1)
161.^Watson J, Deary I, Kerr DCentral and peripheral effects of sustained caffeine use: tolerance is incompleteBr J Clin Pharmacol.(2002 Oct)
162.^Chiu GS, Chatterjee D, Darmody PT, Walsh JP, Meling DD, Johnson RW, Freund GGHypoxia/Reoxygenation Impairs Memory Formation via Adenosine-Dependent Activation of Caspase 1J Neurosci.(2012 Oct 3)
163.^Dager SR, Layton ME, Strauss W, Richards TL, Heide A, Friedman SD, Artru AA, Hayes CE, Posse SHuman brain metabolic response to caffeine and the effects of toleranceAm J Psychiatry.(1999 Feb)
164.^Rogers PJ, Hohoff C, Heatherley SV, Mullings EL, Maxfield PJ, Evershed RP, Deckert J, Nutt DJAssociation of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumptionNeuropsychopharmacology.(2010 Aug)
165.^Childs E, Hohoff C, Deckert J, Xu K, Badner J, de Wit HAssociation between ADORA2A and DRD2 polymorphisms and caffeine-induced anxietyNeuropsychopharmacology.(2008 Nov)
166.^Alsene K, Deckert J, Sand P, de Wit HAssociation between A2a receptor gene polymorphisms and caffeine-induced anxietyNeuropsychopharmacology.(2003 Sep)
168.^Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KACaffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate dietBehav Brain Res.(2012 Sep 20)
170.^Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner PAdenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeysAnn Neurol.(1998 Apr)
171.^Grondin R, Bédard PJ, Hadj Tahar A, Grégoire L, Mori A, Kase HAntiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeysNeurology.(1999 May 12)
172.^Postuma RB, Lang AE, Munhoz RP, Charland K, Pelletier A, Moscovich M, Filla L, Zanatta D, Rios Romenets S, Altman R, Chuang R, Shah BCaffeine for treatment of Parkinson disease: A randomized controlled trialNeurology.(2012 Aug 14)
173.^Fernandez HH, Greeley DR, Zweig RM, Wojcieszek J, Mori A, Sussman NM; 6002-US-051 Study GroupIstradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trialParkinsonism Relat Disord.(2010 Jan)
174.^Hauser RA, Shulman LM, Trugman JM, Roberts JW, Mori A, Ballerini R, Sussman NM; Istradefylline 6002-US-013 Study GroupStudy of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuationsMov Disord.(2008 Nov 15)
175.^Stacy M, Silver D, Mendis T, Sutton J, Mori A, Chaikin P, Sussman NMA 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson diseaseNeurology.(2008 Jun 3)
176.^LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM; 6002-US-005 Study GroupAdenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005)Ann Neurol.(2008 Mar)
177.^Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LRAssociation of coffee and caffeine intake with the risk of Parkinson diseaseJAMA.(2000 May 24-31)
178.^Ascherio A, Zhang SM, Hernán MA, Kawachi I, Colditz GA, Speizer FE, Willett WCProspective study of caffeine consumption and risk of Parkinson's disease in men and womenAnn Neurol.(2001 Jul)
179.^Sääksjärvi K, Knekt P, Rissanen H, Laaksonen MA, Reunanen A, Männistö SProspective study of coffee consumption and risk of Parkinson's diseaseEur J Clin Nutr.(2008 Jul)
180.^Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, Marler JRNeuroprotective agents for clinical trials in Parkinson's disease: a systematic assessmentNeurology.(2003 Apr 22)
181.^Schwarzschild MA, Xu K, Oztas E, Petzer JP, Castagnoli K, Castagnoli N Jr, Chen JFNeuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson's diseaseNeurology.(2003 Dec 9)
182.^Xu K, Xu Y, Brown-Jermyn D, Chen JF, Ascherio A, Dluzen DE, Schwarzschild MAEstrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's diseaseJ Neurosci.(2006 Jan 11)
184.^Griffiths RR, Woodson PPReinforcing effects of caffeine in humansJ Pharmacol Exp Ther.(1988 Jul)
185.^Wise RA, Bozarth MAA psychomotor stimulant theory of addictionPsychol Rev.(1987 Oct)
186.^De Luca MA, Bassareo V, Bauer A, Di Chiara GCaffeine and accumbens shell dopamineJ Neurochem.(2007 Oct)
189.^Burke TM, Markwald RR, McHill AW, Chinoy ED, Snider JA, Bessman SC, Jung CM, O'Neill JS, Wright KP JrEffects of caffeine on the human circadian clock in vivo and in vitroSci Transl Med.(2015 Sep)
190.^Mora-Rodríguez R, Pallarés JG, López-Samanes A, Ortega JF, Fernández-Elías VECaffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained menPLoS One.(2012)
191.^Souissi N, Driss T, Chamari K, Vandewalle H, Davenne D, Gam A, Fillard JR, Jousselin EDiurnal variation in Wingate test performances: influence of active warm-upChronobiol Int.(2010 May)
193.^Cook C, Beaven CM, Kilduff LP, Drawer SAcute caffeine ingestion increases voluntarily chosen resistance training load following limited sleepInt J Sport Nutr Exerc Metab.(2012 Feb 15)
196.^Renda G, Zimarino M, Antonucci I, Tatasciore A, Ruggieri B, Bucciarelli T, Prontera T, Stuppia L, De Caterina RGenetic determinants of blood pressure responses to caffeine drinkingAm J Clin Nutr.(2012 Jan)
197.^Robertson D, Wade D, Workman R, Woosley RL, Oates JATolerance to the humoral and hemodynamic effects of caffeine in manJ Clin Invest.(1981 Apr)
198.^Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier MAggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptorNature.(1997 Aug 14)
200.^Varani K, Portaluppi F, Gessi S, Merighi S, Vincenzi F, Cattabriga E, Dalpiaz A, Bortolotti F, Belardinelli L, Borea PACaffeine intake induces an alteration in human neutrophil A2A adenosine receptorsCell Mol Life Sci.(2005 Oct)
201.^Bassini-Cameron A, Sweet E, Bottino A, Bittar C, Veiga C, Cameron LCEffect of caffeine supplementation on haematological and biochemical variables in elite soccer players under physical stress conditionsBr J Sports Med.(2007 Aug)
202.^Bak AA, van Vliet HH, Grobbee DECoffee, caffeine and hemostasis: results from two randomized studiesAtherosclerosis.(1990 Aug)
203.^Steptoe A, Gibson EL, Vuononvirta R, Williams ED, Hamer M, Rycroft JA, Erusalimsky JD, Wardle JThe effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trialPsychopharmacology (Berl).(2007 Jan)
206.^Keijzers GB, De Galan BE, Tack CJ, Smits PCaffeine can decrease insulin sensitivity in humansDiabetes Care.(2002 Feb)
207.^Pizziol A, Tikhonoff V, Paleari CD, Russo E, Mazza A, Ginocchio G, Onesto C, Pavan L, Casiglia E, Pessina ACEffects of caffeine on glucose tolerance: a placebo-controlled studyEur J Clin Nutr.(1998 Nov)
208.^Thong FS, Derave W, Kiens B, Graham TE, Ursø B, Wojtaszewski JF, Hansen BF, Richter EACaffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exerciseDiabetes.(2002 Mar)
209.^Shearer J, Farah A, de Paulis T, Bracy DP, Pencek RR, Graham TE, Wasserman DHQuinides of roasted coffee enhance insulin action in conscious ratsJ Nutr.(2003 Nov)
210.^van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RMAcute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose toleranceDiabetes Care.(2009 Jun)
211.^Bassoli BK, Cassolla P, Borba-Murad GR, Constantin J, Salgueiro-Pagadigorria CL, Bazotte RB, da Silva RS, de Souza HMChlorogenic acid reduces the plasma glucose peak in the oral glucose tolerance test: effects on hepatic glucose release and glycaemiaCell Biochem Funct.(2008 Apr)
213.^Pedersen DJ, Lessard SJ, Coffey VG, Churchley EG, Wootton AM, Ng T, Watt MJ, Hawley JAHigh rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeineJ Appl Physiol.(2008 Jul)
215.^Natella F, Scaccini CRole of coffee in modulation of diabetes riskNutr Rev.(2012 Apr)
216.^van Dam RM, Feskens EJCoffee consumption and risk of type 2 diabetes mellitusLancet.(2002 Nov 9)
217.^Carlsson S, Hammar N, Grill V, Kaprio JCoffee consumption and risk of type 2 diabetes in Finnish twinsInt J Epidemiol.(2004 Jun)
218.^Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FBCoffee consumption and risk for type 2 diabetes mellitusAnn Intern Med.(2004 Jan 6)
219.^Sartorelli DS, Fagherazzi G, Balkau B, Touillaud MS, Boutron-Ruault MC, de Lauzon-Guillain B, Clavel-Chapelon FDifferential effects of coffee on the risk of type 2 diabetes according to meal consumption in a French cohort of women: the E3N/EPIC cohort studyAm J Clin Nutr.(2010 Apr)
221.^Tuomilehto J, Hu G, Bidel S, Lindström J, Jousilahti PCoffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and womenJAMA.(2004 Mar 10)
223.^Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, Grobbee DE, Batty D, Woodward MCoffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysisArch Intern Med.(2009 Dec 14)
225.^Acheson KJ, Zahorska-Markiewicz B, Pittet P, Anantharaman K, Jéquier ECaffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individualsAm J Clin Nutr.(1980 May)
228.^LeBlanc J, Jobin M, Côté J, Samson P, Labrie AEnhanced metabolic response to caffeine in exercise-trained human subjectsJ Appl Physiol.(1985 Sep)
229.^Poehlman ET, Després JP, Bessette H, Fontaine E, Tremblay A, Bouchard CInfluence of caffeine on the resting metabolic rate of exercise-trained and inactive subjectsMed Sci Sports Exerc.(1985 Dec)
231.^Pasman WJ, Westerterp-Plantenga MS, Saris WHThe effectiveness of long-term supplementation of carbohydrate, chromium, fibre and caffeine on weight maintenanceInt J Obes Relat Metab Disord.(1997 Dec)
234.^Gavrieli A1, Yannakoulia M, Fragopoulou E, Margaritopoulos D, Chamberland JP, Kaisari P, Kavouras SA, Mantzoros CSCaffeinated coffee does not acutely affect energy intake, appetite, or inflammation but prevents serum cortisol concentrations from falling in healthy menJ Nutr.(2011 Apr 1)
237.^Hadjicharalambous M, Georgiades E, Kilduff LP, Turner AP, Tsofliou F, Pitsiladis YPInfluence of caffeine on perception of effort, metabolism and exercise performance following a high-fat mealJ Sports Sci.(2006 Aug)
244.^Astorino TA, Rohmann RL, Firth KEffect of caffeine ingestion on one-repetition maximum muscular strengthEur J Appl Physiol.(2008 Jan)
245.^Williams AD, Cribb PJ, Cooke MB, Hayes AThe effect of ephedra and caffeine on maximal strength and power in resistance-trained athletesJ Strength Cond Res.(2008 Mar)
246.^Izquierdo M, Häkkinen K, Gonzalez-Badillo JJ, Ibáñez J, Gorostiaga EMEffects of long-term training specificity on maximal strength and power of the upper and lower extremities in athletes from different sportsEur J Appl Physiol.(2002 Jul)
247.^González-Badillo JJ, Sánchez-Medina LMovement velocity as a measure of loading intensity in resistance trainingInt J Sports Med.(2010 May)
249.^Astorino TA, Martin BJ, Schachtsiek L, Wong K, Ng KMinimal effect of acute caffeine ingestion on intense resistance training performanceJ Strength Cond Res.(2011 Jun)
250.^Mohr T, Van Soeren M, Graham TE, Kjaer MCaffeine ingestion and metabolic responses of tetraplegic humans during electrical cyclingJ Appl Physiol.(1998 Sep)
251.^Glaister M, Howatson G, Abraham CS, Lockey RA, Goodwin JE, Foley P, McInnes GCaffeine supplementation and multiple sprint running performanceMed Sci Sports Exerc.(2008 Oct)
252.^Schneiker KT, Bishop D, Dawson B, Hackett LPEffects of caffeine on prolonged intermittent-sprint ability in team-sport athletesMed Sci Sports Exerc.(2006 Mar)
254.^Bishop DDietary supplements and team-sport performanceSports Med.(2010 Dec 1)
255.^Desbrow B, Biddulph C, Devlin B, Grant GD, Anoopkumar-Dukie S, Leveritt MDThe effects of different doses of caffeine on endurance cycling time trial performanceJ Sports Sci.(2012)
257.^Bell DG, McLellan TMEffect of repeated caffeine ingestion on repeated exhaustive exercise enduranceMed Sci Sports Exerc.(2003 Aug)
261.^Beaven CM, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TEDose effect of caffeine on testosterone and cortisol responses to resistance exerciseInt J Sport Nutr Exerc Metab.(2008 Apr)
262.^Gillingham R, Keefe AA, Keillor J, Tikuisis PEffect of caffeine on target detection and rifle marksmanshipErgonomics.(2003 Dec 15)
263.^Celec P, Behuliak MBehavioural and endocrine effects of chronic cola intakeJ Psychopharmacol.(2010 Oct)
264.^Wedick NM, Mantzoros CS, Ding EL, Brennan AM, Rosner B, Rimm EB, Hu FB, van Dam RMThe effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trialNutr J.(2012 Oct 19)
265.^Södergård R, Bäckström T, Shanbhag V, Carstensen HCalculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperatureJ Steroid Biochem.(1982 Jun)
268.^Kotsopoulos J, Eliassen AH, Missmer SA, Hankinson SE, Tworoger SSRelationship between caffeine intake and plasma sex hormone concentrations in premenopausal and postmenopausal womenCancer.(2009 Jun 15)
270.^London S, Willett W, Longcope C, McKinlay SAlcohol and other dietary factors in relation to serum hormone concentrations in women at climactericAm J Clin Nutr.(1991 Jan)
271.^Lucero J, Harlow BL, Barbieri RL, Sluss P, Cramer DWEarly follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee useFertil Steril.(2001 Oct)
272.^Lovallo WR, Al'Absi M, Blick K, Whitsett TL, Wilson MFStress-like adrenocorticotropin responses to caffeine in young healthy menPharmacol Biochem Behav.(1996 Nov)
273.^Lin AS, Uhde TW, Slate SO, McCann UDEffects of intravenous caffeine administered to healthy males during sleepDepress Anxiety.(1997)
274.^Lovallo WR, Whitsett TL, al'Absi M, Sung BH, Vincent AS, Wilson MFCaffeine stimulation of cortisol secretion across the waking hours in relation to caffeine intake levelsPsychosom Med.(2005 Sep-Oct)
275.^Sung BH, Lovallo WR, Pincomb GA, Wilson MFEffects of caffeine on blood pressure response during exercise in normotensive healthy young menAm J Cardiol.(1990 Apr 1)
276.^Laurent D, Schneider KE, Prusaczyk WK, Franklin C, Vogel SM, Krssak M, Petersen KF, Goforth HW, Shulman GIEffects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exerciseJ Clin Endocrinol Metab.(2000 Jun)
278.^Woolf K, Bidwell WK, Carlson AGThe effect of caffeine as an ergogenic aid in anaerobic exerciseInt J Sport Nutr Exerc Metab.(2008 Aug)
279.^Lovallo WR, Farag NH, Vincent AS, Thomas TL, Wilson MFCortisol responses to mental stress, exercise, and meals following caffeine intake in men and womenPharmacol Biochem Behav.(2006 Mar)
280.^Pincomb GA, Lovallo WR, Passey RB, Brackett DJ, Wilson MFCaffeine enhances the physiological response to occupational stress in medical studentsHealth Psychol.(1987)
281.^Lovallo WR, Pincomb GA, Sung BH, Passey RB, Sausen KP, Wilson MFCaffeine may potentiate adrenocortical stress responses in hypertension-prone menHypertension.(1989 Aug)
282.^Pincomb GA, Lovallo WR, Passey RB, Wilson MFEffect of behavior state on caffeine's ability to alter blood pressureAm J Cardiol.(1988 Apr 1)
284.^Giles GE, Mahoney CR, Brunyé TT, Gardony AL, Taylor HA, Kanarek RBDifferential cognitive effects of energy drink ingredients: caffeine, taurine, and glucosePharmacol Biochem Behav.(2012 Oct)
288.^Sinha R, Cross AJ, Daniel CR, Graubard BI, Wu JW, Hollenbeck AR, Gunter MJ, Park Y, Freedman NDCaffeinated and decaffeinated coffee and tea intakes and risk of colorectal cancer in a large prospective studyAm J Clin Nutr.(2012 Aug)
290.^Evans SM, Griffiths RRCaffeine tolerance and choice in humansPsychopharmacology (Berl).(1992)
291.^Zwyghuizen-Doorenbos A, Roehrs TA, Lipschutz L, Timms V, Roth TEffects of caffeine on alertnessPsychopharmacology (Berl).(1990)
293.^Sharp DS, Benowitz NLPharmacoepidemiology of the effect of caffeine on blood pressureClin Pharmacol Ther.(1990 Jan)
295.^Myers MG, Reeves RAThe effect of caffeine on dayt