Np mrd loader

You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on NP-MRD.
Record Information
Version1.0
Created at2006-02-16 08:53:46 UTC
Updated at2021-12-19 14:04:27 UTC
NP-MRD IDNP0000009
Secondary Accession NumbersNone
Natural Product Identification
Common NameCaffeine
DescriptionCaffeine is a methyl xanthine alkaloid that is also classified as a purine. Formally, caffeine belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety. Caffeine is chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It is found in the seeds, nuts, or leaves of a number of plants native to Africa, East Asia and South America and helps to protect them against predator insects and to prevent germination of nearby seeds. The most well-known source of caffeine is the coffee bean. Caffeine is the most widely consumed psychostimulant drug in the world. 85% Of American adults consumed some form of caffeine daily, consuming 164 mg on average. Caffeine is mostly is consumed in the form of coffee. Caffeine is a central nervous system stimulant that reduces fatigue and drowsiness. At normal doses, caffeine has variable effects on learning and memory, but it generally improves reaction time, wakefulness, concentration, and motor coordination. Caffeine is a proven ergogenic aid in humans. Caffeine improves athletic performance in aerobic (especially endurance sports) and anaerobic conditions. Moderate doses of caffeine (around 5 mg/kg) can improve sprint performance, cycling and running time trial performance, endurance and cycling power output (PMID: 32551869 ). At intake levels associated with coffee consumption, caffeine appears to exert most of its biological effects through the antagonism of the A1 and A2A subtypes of the adenosine receptor. Adenosine is an endogenous neuromodulator with mostly inhibitory effects, and adenosine antagonism by caffeine results in effects that are generally stimulatory. Some physiological effects associated with caffeine administration include central nervous system stimulation, acute elevation of blood pressure, increased metabolic rate, and diuresis. A number of in vitro and in vivo studies have demonstrated that caffeine modulates both innate and adaptive immune responses. For instance, studies indicate that caffeine and its major metabolite paraxanthine suppress neutrophil and monocyte chemotaxis, and also suppress production of the pro-inflammatory cytokine tumor necrosis factor (TNF) alpha from human blood. Caffeine has also been reported to suppress human lymphocyte function as indicated by reduced T-cell proliferation and impaired production of Th1 (interleukin [IL]-2 and interferon [IFN]-gamma), Th2 (IL-4, IL-5) and Th3 (IL-10) cytokines. Studies also indicate that caffeine suppresses antibody production. The evidence suggests that at least some of the immunomodulatory actions of caffeine are mediated via inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE), and consequential increase in intracellular cAMP concentrations. Overall, these studies indicate that caffeine, like other members of the methylxanthine family, is largely anti-inflammatory in nature, and based on the pharmacokinetics of caffeine, many of its immunomodulatory effects occur at concentrations that are relevant to normal human consumption. (PMID: 16540173 ). Caffeine is rapidly and almost completely absorbed in the stomach and small intestine and distributed to all tissues, including the brain. Caffeine metabolism occurs primarily in the liver, where the activity of the cytochrome P450 isoform CYP1A2 accounts for almost 95% of the primary metabolism of caffeine. CYP1A2-catalyzed 3-demethylation of caffeine results in the formation of 1,7-dimethylxanthine (paraxanthine). Paraxanthine may be demethylated by CYP1A2 to form 1-methylxanthine, which may be oxidized to 1-methyluric acid by xanthine oxidase. Paraxanthine may also be hydroxylated by CYP2A6 to form 1,7-dimethyluric acid, or acetylated by N-acetyltransferase 2 (NAT2) to form 5-acetylamino-6-formylamino-3-methyluracil, an unstable compound that may be deformylated nonenzymatically to form 5-acetylamino-6-amino-3-methyluracil. Caffeine concentrations in coffee beverages can be quite variable. A standard cup of coffee is often assumed to provide 100 mg of caffeine, but a recent analysis of 14 different specialty coffees purchased at coffee shops in the US found that the amount of caffeine in 8 oz (=240 ml) of brewed coffee ranged from 72 to 130 mg. Caffeine in espresso coffees ranged from 58 to 76 mg in a single shot. (PMID: 16507475 ).
Structure
Thumb
Synonyms
ValueSource
1,3,7-Trimethyl-2,6-dioxopurineChEBI
1,3,7-Trimethylpurine-2,6-dioneChEBI
1,3,7-TrimethylxanthineChEBI
1-MethyltheobromineChEBI
3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dionChEBI
7-MethyltheophyllineChEBI
Anhydrous caffeineChEBI
CafeinaChEBI
CafeineChEBI
CoffeinChEBI
GuaranineChEBI
KoffeinChEBI
MateinaChEBI
MethyltheobromineChEBI
TeinaChEBI
TheinChEBI
TheineChEBI
RespiaKegg
1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dioneHMDB
1-Methyl-theobromineHMDB
3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dioneHMDB
7-Methyl theophyllineHMDB
Anhydrous caffeine (JP15)HMDB
HycomineHMDB
LanorinalHMDB
MethyltheobromideHMDB
Methylxanthine theophyllineHMDB
Monohydrate caffeineHMDB
PropoxypheneHMDB
Merck dura brand OF caffeineHMDB
Thompson brand 1 OF caffeineHMDB
Bristol-myers squibb brand OF caffeineHMDB
CaffedrineHMDB
DexitacHMDB
Percoffedrinol NHMDB
Pierre fabre brand OF caffeineHMDB
Republic drug brand OF caffeineHMDB
Thompson brand 2 OF caffeineHMDB
VivarinHMDB
Coffeinum NHMDB
Coffeinum purrumHMDB
DurvitanHMDB
GlaxoSmithKline brand OF caffeineHMDB
No dozHMDB
PercutaféineHMDB
Quick-pepHMDB
Seid brand OF caffeineHMDB
Berlin-chemie brand OF caffeineHMDB
Passauer brand OF caffeineHMDB
Quick pepHMDB
QuickPepHMDB
Chemical FormulaC8H10N4O2
Average Mass194.1906 Da
Monoisotopic Mass194.08038 Da
IUPAC Name1,3,7-trimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
Traditional Namecaffeine
CAS Registry Number58-08-2
SMILES
CN1C=NC2=C1C(=O)N(C)C(=O)N2C
InChI Identifier
InChI=1S/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
InChI KeyRYYVLZVUVIJVGH-UHFFFAOYSA-N
Spectra
Spectrum TypeDescriptionDepositor IDDeposition DateView
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Wishart Lab2021-06-20View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, CDCl3, experimental)Wishart Lab2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, simulated)Varshavi.d262021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, simulated)Varshavi.d262021-10-27View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Varshavi.d262021-10-27View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, simulated)Varshavi.d262021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Varshavi.d262021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, simulated)Varshavi.d262021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Varshavi.d262021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, simulated)Varshavi.d262021-10-08View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Varshavi.d262021-10-08View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, simulated)Varshavi.d262021-10-08View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Varshavi.d262021-10-08View Spectrum
Species
Species of Origin
Species NameSourceReference
Abelmoschus esculentusFooDB
Abramis bramaFooDB
Acacia polyacanthaLOTUS Database
AcipenserFooDB
AcipenseridaeFooDB
AgaveFooDB
Allium ampeloprasumFooDB
Allium ascalonicumFooDB
Allium cepaFooDB
Allium fistulosumFooDB
Allium sativumFooDB
Allium schoenoprasumFooDB
Allium tuberosumFooDB
Alosa sapidissimaFooDB
Anacardium occidentaleFooDB
Ananas comosusFooDB
Anas platyrhynchosFooDB
AnatidaeFooDB
AnguillaFooDB
AnguilliformesFooDB
Annona cherimolaFooDB
Annona muricataFooDB
Anser anserFooDB
Anthriscus cerefoliumFooDB
Apium graveolensFooDB
Apium graveolens var. dulceFooDB
Apium graveolens var. rapaceumFooDB
Arachis hypogaeaFooDB
Arctium lappaFooDB
Armoracia rusticanaFooDB
Artocarpus altilisFooDB
Aspalathus linearisLOTUS Database
Asparagus officinalisFooDB
AstacideaFooDB
Avena sativa L.FooDB
Averrhoa carambolaFooDB
Bertholletia excelsaFooDB
Beta vulgarisFooDB
Beta vulgaris ssp. ciclaFooDB
Bidens pilosaLOTUS Database
Bison bisonFooDB
Bos taurusFooDB
Bos taurus X Bison bisonFooDB
Brassica alboglabraFooDB
Brassica junceaFooDB
Brassica napusFooDB
Brassica oleraceaFooDB
Brassica oleracea var. botrytisFooDB
Brassica oleracea var. capitataFooDB
Brassica oleracea var. gemmiferaFooDB
Brassica oleracea var. gongylodesFooDB
Brassica oleracea var. sabaudaFooDB
Brassica rapaFooDB
Brassica rapa ssp. chinensisFooDB
Brassica rapa var. rapaFooDB
Bubalus bubalisFooDB
BuccinidaeFooDB
Camellia assamicaKNApSAcK Database
Camellia irawadiensisKNApSAcK Database
Camellia kissiKNApSAcK Database
Camellia ptilophyllaLOTUS Database
Camellia sinensisKNApSAcK Database
Camellia sinensis var. assamicaPlant
Camellia sinensis var. sinensisKNApSAcK Database
Camellia taliensisKNApSAcK Database
Camellia theaKNApSAcK Database
Camellia toliensisKNApSAcK Database
Cammellia assamica var.kucha-
Capparis spinosaFooDB
Capra aegagrus hircusFooDB
Capsicum annuumFooDB
Carica papayaKNApSAcK Database
Carica papaya L.FooDB
CarideaFooDB
Carum carviFooDB
Carya illinoinensisFooDB
Ceratonia siliquaFooDB
CervidaeFooDB
Cervus canadensisFooDB
Chamaemelum nobileFooDB
Chondrus crispusFooDB
Cicer arietinumFooDB
CichlidaeFooDB
Cichorium endiviaFooDB
Cichorium intybusFooDB
CinnamomumFooDB
Citrullus lanatusFooDB
Citrus ×limon (L.) Burm. f. (pro sp.)FooDB
Citrus aurantiifoliaFooDB
Citrus aurantiumLOTUS Database
Citrus latifoliaFooDB
Citrus limonKNApSAcK Database
Citrus maximaKNApSAcK Database
Citrus paradisiKNApSAcK Database
Citrus reticulataFooDB
Citrus X sinensis (L.) Osbeck (pro. sp.)FooDB
Clupea harengus harengusFooDB
Cocos nuciferaFooDB
Coffea arabicaKNApSAcK Database
Coffea arabica L.FooDB
    • Shmuel Yannai Dictionary of Food Compounds with CD-ROM: Additives, Flavors, and Ingredients. Chap...
Coffea canephoraKNApSAcK Database
Coffea dewevreiKNApSAcK Database
Coffea eugeniodesKNApSAcK Database
Coffea eugenioidesKNApSAcK Database
Coffea excelsaKNApSAcK Database
Coffea kianjavatensisKNApSAcK Database
Coffea libericaKNApSAcK Database
Coffea racemosaKNApSAcK Database
Coffea salvatrixKNApSAcK Database
Coffea sppKNApSAcK Database
Coffea spp.KNApSAcK Database
Coffea, Thea-
Coffee arabica-
Cola acuminataKNApSAcK Database
Cola nitidaLOTUS Database
Cola sp.KNApSAcK Database
Cola spp.KNApSAcK Database
Colocasia esculentaFooDB
ColumbaFooDB
ColumbidaeFooDB
CoregonusFooDB
Coriandrum sativum L.FooDB
CorylusFooDB
Corylus avellanaFooDB
Crassostrea gigasFooDB
Crassostrea virginicaFooDB
Crocus sativusFooDB
Cucumis meloFooDB
Cucumis sativus L.FooDB
Cucurbita maximaFooDB
Cucurbita moschataFooDB
Cuminum cyminumFooDB
Curcuma longaFooDB
Cyprinus carpioFooDB
DioscoreaFooDB
Dioscorea pentaphyllaFooDB
Diospyros kakiFooDB
Dromaius novaehollandiaeFooDB
ElaeisFooDB
EngraulidaeFooDB
Engraulis encrasicolusFooDB
Equus caballusFooDB
Eruca vesicaria subsp. SativaFooDB
Esox luciusFooDB
EucheumaFooDB
Eutrema japonicumFooDB
Fagopyrum esculentumFooDB
Festuca rubraLOTUS Database
Firmiana simplexKNApSAcK Database
Foeniculum vulgareFooDB
GadiformesFooDB
GadusFooDB
Gadus macrocephalusFooDB
Gadus morhuaFooDB
Gallus gallusFooDB
GastropodaFooDB
Glycine maxFooDB
Grifola frondosaFooDB
Helianthus tuberosusFooDB
Herreania sp.-
Hibiscus sabbariffaFooDB
HippoglossusFooDB
Hippoglossus hippoglossusFooDB
Hippoglossus stenolepisFooDB
Homarus americanusFooDB
Hoplostethus atlanticusFooDB
Hordeum vulgareFooDB
Ictalurus punctatusFooDB
Ilex cornutaKNApSAcK Database
Ilex dumosaLOTUS Database
Ilex paraguariensisKNApSAcK Database
Ilex paraguayensisKNApSAcK Database
Illicium verumFooDB
Ipomoea batatasFooDB
JuglansFooDB
Juglans nigra L.FooDB
Juglans regiaFooDB
Lablab purpureusFooDB
Lagenaria sicerariaFooDB
Lagopus mutaFooDB
LaminariaFooDB
Lens culinarisFooDB
Lepidium sativumFooDB
LeporidaeFooDB
Lepus timidusFooDB
Linum usitatissimumFooDB
Litchi chinensisFooDB
LupinusFooDB
LutjanidaeFooDB
MacadamiaFooDB
Macadamia tetraphyllaFooDB
Malus pumilaFooDB
Mangifera indicaFooDB
Manihot esculentaFooDB
Matricaria recutitaFooDB
Medicago sativaFooDB
Melanitta fuscaFooDB
Meleagris gallopavoFooDB
Merlangius merlangusFooDB
Micropogonias undulatusFooDB
Microstomus kittFooDB
Mugil cephalusFooDB
Murraya exoticaLOTUS Database
Mus musculusLOTUS Database
Musa acuminataFooDB
Myristica fragransFooDB
MytilidaeFooDB
Mytilus edulisFooDB
NelumboFooDB
NephropidaeFooDB
Numida meleagrisFooDB
Nuphar luteaFooDB
Ocimum basilicumFooDB
Octopus vulgarisFooDB
OdocoileusFooDB
Oncorhynchus gorbuschaFooDB
Oncorhynchus ketaFooDB
Oncorhynchus kisutchFooDB
Oncorhynchus mykissFooDB
Oncorhynchus nerkaFooDB
Oncorhynchus tshawytschaFooDB
Opuntia cochenilliferaFooDB
Origanum majoranaFooDB
Origanum vulgareFooDB
Origanum X majoricumFooDB
OryctolagusFooDB
Oryza rufipogonFooDB
Oryza sativaFooDB
OsmeridaeFooDB
Osmerus mordaxFooDB
Ovis ariesFooDB
Pachyrhizus erosusFooDB
Panicum miliaceumFooDB
Paramuricea clavataLOTUS Database
Passiflora edulisFooDB
Pastinaca sativaFooDB
Paullinia cupanaKNApSAcK Database
Paullinia trifoliataKNApSAcK Database
PectinidaeFooDB
PerciformesFooDB
Persea americanaFooDB
Petroselinum crispumFooDB
Phaseolus lunatusFooDB
Phaseolus vulgarisFooDB
PhasianidaeFooDB
Phasianus colchicusFooDB
Phyllostachys edulisFooDB
Pimenta dioicaFooDB
Pimpinella anisumFooDB
PinusFooDB
Piper nigrum L.FooDB
Pistacia veraFooDB
Pisum sativumFooDB
PleuronectiformesFooDB
Pleurotus ostreatusFooDB
Pollachius pollachiusFooDB
Portulaca oleraceaFooDB
Prunus armeniacaFooDB
Prunus domesticaFooDB
Prunus dulcisFooDB
Prunus virginianaFooDB
Pseudo-nitzschia multistriataLOTUS Database
Psidium guajavaFooDB
Psophocarpus tetragonolobusFooDB
Punica granatumFooDB
Pyrus pyrifoliaFooDB
RanidaeFooDB
Raphanus sativusFooDB
Raphanus sativus var. longipinnatusFooDB
Reinhardtius hippoglossoidesFooDB
Rheum rhabarbarumFooDB
Ribes nigrumFooDB
Ribes rubrumFooDB
Ribes uva-crispaFooDB
Scomberomorus maculatusFooDB
Scurrula atropurpureaKNApSAcK Database
Scurrura atropurpurea-
SebastesFooDB
Sebastes alutusFooDB
Secale cerealeFooDB
Sechium eduleFooDB
Sesamum indicumFooDB
Sinomenium acutumLOTUS Database
Solanum melongenaFooDB
Solanum tuberosumFooDB
SoleidaeFooDB
Spinacia oleraceaFooDB
SpirulinaFooDB
SqualiformesFooDB
Stenodus leucichthysFooDB
Stenotomus chrysopsFooDB
StrombidaeFooDB
Struthio camelusFooDB
Sus scrofaFooDB
Sus scrofa domesticaFooDB
Syzygium aromaticumFooDB
Tamarindus indicaFooDB
Taraxacum officinaleFooDB
Tetragonia tetragonioidesFooDB
TeuthidaFooDB
Thea siensisKNApSAcK Database
Theobroma angustifoliumLOTUS Database
Theobroma cacaoKNApSAcK Database
Theobroma grandiflorumKNApSAcK Database
Thunnus albacaresFooDB
Thunnus thynnusFooDB
Thymus vulgarisFooDB
Trachinotus carolinusFooDB
Trachurus symmetricusFooDB
Trewia nudifloraLOTUS Database
TriticumFooDB
Triticum aestivumFooDB
Triticum durumFooDB
Undaria pinnatifidaFooDB
Vaccinium macrocarponFooDB
Vaccinium ovalifoliumFooDB
VanillaFooDB
Vicia fabaFooDB
Vigna mungoFooDB
Vigna radiataFooDB
Vigna unguiculata ssp. unguiculataFooDB
Virola surinamensisFooDB
VitisFooDB
Xiphias gladiusFooDB
Zea mays L.FooDB
Zingiber officinaleFooDB
ZizaniaFooDB
Species Where Detected
Species NameSourceReference
Homo sapiens (Urine)KNApSAcK Database
Chemical Taxonomy
Description Belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentXanthines
Alternative Parents
Substituents
  • Xanthine
  • Purinone
  • 6-oxopurine
  • Alkaloid or derivatives
  • Pyrimidone
  • Pyrimidine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Urea
  • Lactam
  • Azacycle
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point238 °Chttps://pubchem.ncbi.nlm.nih.gov/compound/caffeine#section=Melting-Point
Boiling Point178 °Chttps://pubchem.ncbi.nlm.nih.gov/compound/caffeine#section=Boiling-Point
Water Solubility21.6 mg/mL at 25 °CNot Available
LogP-0.07Hansch CH, Leo A and Hoekman DH. "Exploring QSAR: Hydrophobic, Electronic, and Steric Constraints. Volume 1" ACS Publications (1995).
Predicted Properties
PropertyValueSource
Water Solubility11 g/LALOGPS
logP-0.24ALOGPS
logP-0.55ChemAxon
logS-1.2ALOGPS
pKa (Strongest Basic)-0.92ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area58.44 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity49.83 m³·mol⁻¹ChemAxon
Polarizability18.95 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
HMDB IDHMDB0001847
DrugBank IDDB00201
Phenol Explorer Compound IDNot Available
FoodDB IDFDB017732
KNApSAcK IDC00001492
Chemspider ID2424
KEGG Compound IDC07481
BioCyc ID1-3-7-TRIMETHYLXANTHINE
BiGG IDNot Available
Wikipedia LinkCaffeine
METLIN ID1455
PubChem Compound2519
PDB IDNot Available
ChEBI ID27732
Good Scents IDrw1014161
References
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
  2. Miyake Y, Sakaguchi K, Iwasaki Y, Ikeda H, Makino Y, Kobashi H, Araki Y, Ando M, Kita K, Shiratori Y: New prognostic scoring model for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure. Transplantation. 2005 Oct 15;80(7):930-6. [PubMed:16249741 ]
  3. Wilkinson SC, Maas WJ, Nielsen JB, Greaves LC, van de Sandt JJ, Williams FM: Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies. Int Arch Occup Environ Health. 2006 May;79(5):405-13. Epub 2006 Jan 25. [PubMed:16435152 ]
  4. Spiller HA, Winter ML, Klein-Schwartz W, Bangh SA: Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. J Emerg Med. 2006 Jan;30(1):1-5. [PubMed:16434328 ]
  5. Ayotte P, Dewailly E, Lambert GH, Perkins SL, Poon R, Feeley M, Larochelle C, Pereg D: Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines. Environ Health Perspect. 2005 Oct;113(10):1318-24. [PubMed:16203240 ]
  6. Shah S, Budev M, Blazey H, Fairbanks K, Mehta A: Hepatic veno-occlusive disease due to tacrolimus in a single-lung transplant patient. Eur Respir J. 2006 May;27(5):1066-8. [PubMed:16707401 ]
  7. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiodt FV, Ostapowicz G, Shakil AO, Lee WM: Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005 Dec;42(6):1364-72. [PubMed:16317692 ]
  8. Septer S, Thompson ES, Willemsen-Dunlap A: Anesthesia concerns for children with tuberous sclerosis. AANA J. 2006 Jun;74(3):219-25. [PubMed:16786916 ]
  9. Horrigan LA, Kelly JP, Connor TJ: Immunomodulatory effects of caffeine: friend or foe? Pharmacol Ther. 2006 Sep;111(3):877-92. Epub 2006 Mar 15. [PubMed:16540173 ]
  10. Rodrigues IM, Klein LC: Boiled or filtered coffee? Effects of coffee and caffeine on cholesterol, fibrinogen and C-reactive protein. Toxicol Rev. 2006;25(1):55-69. [PubMed:16856769 ]
  11. Lamarine RJ: Selected health and behavioral effects related to the use of caffeine. J Community Health. 1994 Dec;19(6):449-66. [PubMed:7844249 ]
  12. James JE: Critical review of dietary caffeine and blood pressure: a relationship that should be taken more seriously. Psychosom Med. 2004 Jan-Feb;66(1):63-71. [PubMed:14747639 ]
  13. Higdon JV, Frei B: Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr. 2006;46(2):101-23. [PubMed:16507475 ]
  14. Nehlig A, Daval JL, Debry G: Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev. 1992 May-Aug;17(2):139-70. [PubMed:1356551 ]
  15. Benjamin LT Jr, Rogers AM, Rosenbaum A: Coca-Cola, caffeine, and mental deficiency: Harry Hollingworth and the Chattanooga trial of 1911. J Hist Behav Sci. 1991 Jan;27(1):42-55. [PubMed:2010614 ]
  16. Nathanson JA: Caffeine and related methylxanthines: possible naturally occurring pesticides. Science. 1984 Oct 12;226(4671):184-7. [PubMed:6207592 ]
  17. Smit HJ, Gaffan EA, Rogers PJ: Methylxanthines are the psycho-pharmacologically active constituents of chocolate. Psychopharmacology (Berl). 2004 Nov;176(3-4):412-9. Epub 2004 May 5. [PubMed:15549276 ]
  18. Haskell CF, Kennedy DO, Wesnes KA, Milne AL, Scholey AB: A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans. J Psychopharmacol. 2007 Jan;21(1):65-70. Epub 2006 Mar 13. [PubMed:16533867 ]
  19. Ferreira TT, da Silva JVF, Bueno NB: Effects of caffeine supplementation on muscle endurance, maximum strength, and perceived exertion in adults submitted to strength training: a systematic review and meta-analyses. Crit Rev Food Sci Nutr. 2020 Jun 18:1-14. doi: 10.1080/10408398.2020.1781051. [PubMed:32551869 ]