CAFFEINE ANHYDROUS (SUSUZ KAFEIN)

CAS No. : 58-08-2

EC No. : 200-362-1

Synonyms:

caffeine; 58-08-2;1,3,7-Trimethylxanthine; Guaranine; Thein; Methyltheobromine; Cafeina; Theine; Koffein; Mateina; Alert-pep; Caffein; Cafipel; Coffeine; Refresh’n; Caffedrine; Stim; Cafamil; Cafecon; Caffine; Dexitac; Nodaca; Anhydrous caffeine; No-Doz;Eldiatric C; 7-Methyltheophylline; Hycomine; Organex; Vivarin; Nix Nap; Methyltheobromide; 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione; Coffein; Phensal; Caffeine, synthetic; Quick-Pep; Coffeinum; Tirend; 1,3,7-Trimethyl-2,6-dioxopurine; 1,3,7-Trimethylpurine-2,6-dione; Theophylline, 7-methyl; DHCplus; Tri-Aqua; Kofein; Miudol; Caffeine, anhydrous;Theobromine, 1-methyl-; Propoxyphene Compound 65; 1H-Purine-2,6-dione, 3,7-dihydro-1,3,7-trimethyl-;1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dione; Kofein [Czech]; Coffein [German]; Koffein [German]; 1-methyltheobromine; Caffeine (natural); Xanthine, 1,3,7-trimethyl; Caffeina [Italian]; Theophylline Me; Methylxanthine theophylline; Theobromine Me; NCI-C02733; caffenium; SK-65 Compound; Anacin; Anacin Maximum Strength; Caffeine [BAN:JAN]; P-A-C Analgesic Tablets; HSDB 36; FEMA No. 2224; BRN 0017705; C8H10N4O2; NSC 5036; A.S.A. and Codeine Compound; UNII-3G6A5W338E; 1,3,7-trimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione; CCRIS 1314; 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione; AI3-20154; EINECS 200-362-1; CHEMBL113;CFF; CHEBI:27732; 3G6A5W338E; NSC-5036; MFCD00005758; SK 65 Compound; Caffeina; DSSTox_CID_232; CAFFEINE-D3; DSSTox_RID_75448; DSSTox_GSID_20232; No Doz; 1,3,7-trimethyl-1,3,7-trihydropurine-2,6-dione; 1,3,7-trimethyl-2,6-dioxo-1,2,3,6-tetrahydropurine; cafeine; peyona; teina; CAS-58-08-2; Caffeine (USP); SMR000326667; SR-01000075187; Anhydrous caffeine (TN); Monomethyl derivative of Theophylline; Caffeine [USP:BAN:JAN]; Anhydrous caffeine (JP15); Caffeine, 98.5%, specified according to the req. of USP/BP; Caffeine hydrous; 1gfz; Caffeine, BioXtra; TNP00310; Monohydrate Caffeine; Respia (TN); 1-methyl-Theobromine; 7-methyl Theophylline; Caffeine_303_ p; PubChem9436; Cafergot (Salt/Mix); 1,7-Trimethylxanthine; Spectrum_001301; 1l5q; 1l7x; 2a3b; 3g6m; 3,7-dihydro-1,3,7-trimethyl-1H-purine; Xanthine,3,7-trimethyl; Theine, methyltheobromine; Spectrum2_001261; Spectrum3_000321; Spectrum4_001782; Spectrum5_000423; Lopac-C-0750; bmse000206; MolMap_000054; Probes1_000150; Probes2_000128; C 0750; EC 200-362-1; SCHEMBL5671; Anhydrous caffeine (JP17); NCIOpen2_008255; BIDD:PXR0172; Lopac0_000228; 1, 3, 7-Trimethylxanthine; BSPBio_001921; GTPL407; KBioGR_002325; KBioSS_001781; 5-26-13-00558 (Beilstein Handbook Reference); MLS001055341; MLS001056714; MLS001066409; ARONIS25359; BIDD:ER0554; BIDD:GT0632; Caffeine, 1mg/ml in methanol; DivK1c_000730; SPECTRUM1500155; CU-01000012617-3; SPBio_001222; Caffeine melting point standard; MEGxp0_001350; ZINC1084; component of Dilone (Salt/Mix); DTXSID0020232; 1,7-Trimethyl-2,6-dioxopurine; ACon1_000085; BDBM10849; CTK1G9501; HMS502E12; KBio1_000730;KBio2_001781; KBio2_004349; KBio2_006917; KBio3_001141; Caffeine 1.0 mg/ml in Methanol; NSC5036; Caffeine, powder, ReagentPlus(R); component of Percodan (Salt/Mix); NINDS_000730;Bio1_000473; Bio1_000962; Bio1_001451; HMS1920I09; HMS2091O11; HMS2232M13; HMS3260N17; HMS3372J18; HMS3435F10; HMS3715D13; Pharmakon1600-01500155; NoDoz Caplets and Chewable Tablets; Caffeine 10 microg/mL in Methanol; CS-M0795; Tox21_201685; Tox21_300010; Tox21_500228;BBL016491; caffeine (1,3,7-trimethylxanthine); CCG-38825; LS-237; NSC755917; PDSP1_001016; PDSP1_001235; PDSP2_001000; PDSP2_001219; SBB006474; STK177283; Propoxyphene Compound 65 (Salt/Mix); AKOS000121334; 5-26-13-00558 (Beilstein); ACN-034787; Bayer Select Headache Pain (Salt/Mix); Caffeine, anhydrous, 99%, FCC, FG; DB00201; LP00228; MCULE-3362813910; NSC-755917; SDCCGMLS-0064595.P001; SDCCGMLS-0064595.P002; SDCCGSBI-0050216.P005; IDI1_000730; KS-0000478B; 3,3,7-trimethyl-1H-purine-2,6-dione; NCGC00015208-01; NCGC00015208-02; NCGC00015208-03; NCGC00015208-04; NCGC00015208-05; NCGC00015208-06; NCGC00015208-07; NCGC00015208-08; NCGC00015208-10; NCGC00015208-11; NCGC00015208-12; NCGC00015208-13; NCGC00015208-14; NCGC00015208-15; NCGC00015208-16; NCGC00015208-17; NCGC00015208-18; NCGC00090699-01; NCGC00090699-02; NCGC00090699-03; NCGC00090699-04; NCGC00090699-05; NCGC00090699-06; NCGC00090699-07; NCGC00090699-08; NCGC00090699-09; NCGC00168808-01; NCGC00168808-02; NCGC00254057-01; NCGC00259234-01; NCGC00260913-01; 95789-13-2; AC-12774; AS-15340; Caffeine, SAJ special grade, >=98.5%; component of P-A-C Compound (Salt/Mix); O926;ST057528; component of A.S.A. Compound (Salt/Mix); SBI-0050216.P004;DB-023002; WLN: T56 BN DN FNVNVJ B1 F1 H1; EU-0100228; FT-0664195; H2815; N1379; N2379; 3378-EP2269610A2; 3378-EP2275420A1; 3378-EP2277848A1; 3378-EP2277867A2; 3378-EP2280003A2; 3378-EP2284160A1; 3378-EP2289510A1; 3378-EP2295409A1; 3378-EP2295434A2; 3378-EP2301937A1; 3378-EP2305219A1; 3378-EP2305662A1; 3378-EP2305671A1; 3378-EP2305677A1; 3378-EP2305682A1; 3378-EP2305695A2; 3378-EP2305696A2; 3378-EP2305697A2; 3378-EP2305698A2; 3378-EP2308562A2; 3378-EP2308840A1; 3378-EP2308867A2; 3378-EP2308870A2; 3378-EP2308879A1; 3378-EP2311801A1; 3378-EP2311802A1; 3378-EP2311803A1; 3378-EP2311806A2; 3378-EP2311808A1; 3378-EP2311829A1; 3378-EP2311842A2; 3378-EP2314588A1; 3378-EP2314590A1; 3378-EP2314593A1; 3378-EP2316457A1; 3378-EP2316458A1; 3378-EP2316825A1; 3378-EP2316826A1; 3378-EP2316827A1; 3378-EP2316828A1; 3378-EP2371814A1; BIM-0050216.0001; C07481; D00528; Q60235; 1,3,7-trimethyl-3,7-dihydropurine-2,6-dione; 1H-Purine-2, 3,7-dihydro-1,3,7-trimethyl-; AB00051930-09; AB00051930_10; Caffeine, purum, anhydrous, >=99.0% (HPLC); 3,7-dihydro-1,3,7-trimethyl-1H-purine (9CI); Caffeine, anhydrous, tested according to Ph.Eur.; L000155; 3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion; Caffeine, Sigma Reference Standard, vial of 250 mg; SR-01000075187-1; SR-01000075187-4; SR-01000075187-7; SR-01000075187-8; BRD-K02404261-001-02-7; BRD-K02404261-001-03-5; BRD-K02404261-001-07-6; Caffeine, certified reference material, TraceCERT(R); Caffeine, meets USP testing specifications, anhydrous; Melting point standard 235-237C, analytical standard;1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dione #; Caffeine, British Pharmacopoeia (BP) Reference Standard; Caffeine, European Pharmacopoeia (EP) Reference Standard; F3371-0262;Z112207564; Caffeine 2000 microg/mL in Water:Methanol (81:19 g/g); 07E4FB58-FD79-4175-8E3D-05BF96954522; 3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion (coffein); Caffeine solution, analytical standard, 1.0 mg/mL in methanol; Caffeine, United States Pharmacopeia (USP) Reference Standard; Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material; Caffeine for system suitability, European Pharmacopoeia (EP) Reference Standard; Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard; Caffeine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material; 114303-55-8; Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material; Caffeine, PharmaGrade, EP, Manufactured under appropriate GMP controls for pharma or biopharmaceutical production;Mettler-Toledo Calibration substance ME 18872, Caffeine, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC); kafein; KAFEN; kafen; KAFEIN; KAHVE; kahve; KAFEYN; kafeyin; kafeyn; KAFEYIN; COFFEE; coffee; cola; drink; caffeine; 58-08-2;1,3,7-Trimethylxanthine; Guaranine; Thein; Methyltheobromine; Cafeina; Theine; Koffein; Mateina; Alert-pep; Caffein; Cafipel; Coffeine; Refresh’n; Caffedrine; Stim; Cafamil; Cafecon; Caffine; Dexitac; Nodaca; Anhydrous caffeine; No-Doz;Eldiatric C; 7-Methyltheophylline; Hycomine; Organex; Vivarin; Nix Nap; Methyltheobromide; 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione; Coffein; Phensal; Caffeine, synthetic; Quick-Pep; Coffeinum; Tirend; 1,3,7-Trimethyl-2,6-dioxopurine; 1,3,7-Trimethylpurine-2,6-dione; Theophylline, 7-methyl; DHCplus; Tri-Aqua; Kofein; Miudol; Caffeine, anhydrous;Theobromine, 1-methyl-; Propoxyphene Compound 65; 1H-Purine-2,6-dione, 3,7-dihydro-1,3,7-trimethyl-;1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dione; Kofein [Czech]; Coffein [German]; Koffein [German]; 1-methyltheobromine; Caffeine (natural); Xanthine, 1,3,7-trimethyl; Caffeina [Italian]; Theophylline Me; Methylxanthine theophylline; Theobromine Me; NCI-C02733; caffenium; SK-65 Compound; Anacin; Anacin Maximum Strength; Caffeine [BAN:JAN]; P-A-C Analgesic Tablets; HSDB 36; FEMA No. 2224; BRN 0017705; C8H10N4O2; NSC 5036; A.S.A. and Codeine Compound; UNII-3G6A5W338E; 1,3,7-trimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione; CCRIS 1314; 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione; AI3-20154; EINECS 200-362-1; CHEMBL113;CFF; CHEBI:27732; 3G6A5W338E; NSC-5036; MFCD00005758; SK 65 Compound; Caffeina; DSSTox_CID_232; CAFFEINE-D3; DSSTox_RID_75448; DSSTox_GSID_20232; No Doz; 1,3,7-trimethyl-1,3,7-trihydropurine-2,6-dione; 1,3,7-trimethyl-2,6-dioxo-1,2,3,6-tetrahydropurine; cafeine; peyona; teina; CAS-58-08-2; Caffeine (USP); SMR000326667; SR-01000075187; Anhydrous caffeine (TN); Monomethyl derivative of Theophylline; Caffeine [USP:BAN:JAN]; Anhydrous caffeine (JP15); Caffeine, 98.5%, specified according to the req. of USP/BP; Caffeine hydrous; 1gfz; Caffeine, BioXtra; TNP00310; Monohydrate Caffeine; Respia (TN); 1-methyl-Theobromine; 7-methyl Theophylline; Caffeine_303_ p; PubChem9436; Cafergot (Salt/Mix); 1,7-Trimethylxanthine; Spectrum_001301; 1l5q; 1l7x; 2a3b; 3g6m; 3,7-dihydro-1,3,7-trimethyl-1H-purine; Xanthine,3,7-trimethyl; Theine, methyltheobromine; Spectrum2_001261; Spectrum3_000321; Spectrum4_001782; Spectrum5_000423; Lopac-C-0750; bmse000206; MolMap_000054; Probes1_000150; Probes2_000128; C 0750; EC 200-362-1; SCHEMBL5671; Anhydrous caffeine (JP17); NCIOpen2_008255; BIDD:PXR0172; Lopac0_000228; 1, 3, 7-Trimethylxanthine; BSPBio_001921; GTPL407; KBioGR_002325; KBioSS_001781; 5-26-13-00558 (Beilstein Handbook Reference); MLS001055341; MLS001056714; MLS001066409; ARONIS25359; BIDD:ER0554; BIDD:GT0632; Caffeine, 1mg/ml in methanol; DivK1c_000730; SPECTRUM1500155; CU-01000012617-3; SPBio_001222; Caffeine melting point standard; MEGxp0_001350; ZINC1084; component of Dilone (Salt/Mix); DTXSID0020232; 1,7-Trimethyl-2,6-dioxopurine; ACon1_000085; BDBM10849; CTK1G9501; HMS502E12; KBio1_000730;KBio2_001781; KBio2_004349; KBio2_006917; KBio3_001141; Caffeine 1.0 mg/ml in Methanol; NSC5036; Caffeine, powder, ReagentPlus(R); component of Percodan (Salt/Mix); NINDS_000730;Bio1_000473; Bio1_000962; Bio1_001451; HMS1920I09; HMS2091O11; HMS2232M13; HMS3260N17; HMS3372J18; HMS3435F10; HMS3715D13; Pharmakon1600-01500155; NoDoz Caplets and Chewable Tablets; Caffeine 10 microg/mL in Methanol; CS-M0795; Tox21_201685; Tox21_300010; Tox21_500228;BBL016491; caffeine (1,3,7-trimethylxanthine); CCG-38825; LS-237; NSC755917; PDSP1_001016; PDSP1_001235; PDSP2_001000; PDSP2_001219; SBB006474; STK177283; Propoxyphene Compound 65 (Salt/Mix); AKOS000121334; 5-26-13-00558 (Beilstein); ACN-034787; Bayer Select Headache Pain (Salt/Mix); Caffeine, anhydrous, 99%, FCC, FG; DB00201; LP00228; MCULE-3362813910; NSC-755917; SDCCGMLS-0064595.P001; SDCCGMLS-0064595.P002; SDCCGSBI-0050216.P005; IDI1_000730; KS-0000478B; 3,3,7-trimethyl-1H-purine-2,6-dione; NCGC00015208-01; NCGC00015208-02; NCGC00015208-03; NCGC00015208-04; NCGC00015208-05; NCGC00015208-06; NCGC00015208-07; NCGC00015208-08; NCGC00015208-10; NCGC00015208-11; NCGC00015208-12; NCGC00015208-13; NCGC00015208-14; NCGC00015208-15; NCGC00015208-16; NCGC00015208-17; NCGC00015208-18; NCGC00090699-01; NCGC00090699-02; NCGC00090699-03; NCGC00090699-04; NCGC00090699-05; NCGC00090699-06; NCGC00090699-07; NCGC00090699-08; NCGC00090699-09; NCGC00168808-01; NCGC00168808-02; NCGC00254057-01; NCGC00259234-01; NCGC00260913-01; 95789-13-2; AC-12774; AS-15340; Caffeine, SAJ special grade, >=98.5%; component of P-A-C Compound (Salt/Mix); O926;ST057528; component of A.S.A. Compound (Salt/Mix); SBI-0050216.P004;DB-023002; WLN: T56 BN DN FNVNVJ B1 F1 H1; EU-0100228; FT-0664195; H2815; N1379; N2379; 3378-EP2269610A2; 3378-EP2275420A1; 3378-EP2277848A1; 3378-EP2277867A2; 3378-EP2280003A2; 3378-EP2284160A1; 3378-EP2289510A1; 3378-EP2295409A1; 3378-EP2295434A2; 3378-EP2301937A1; 3378-EP2305219A1; 3378-EP2305662A1; 3378-EP2305671A1; 3378-EP2305677A1; 3378-EP2305682A1; 3378-EP2305695A2; 3378-EP2305696A2; 3378-EP2305697A2; 3378-EP2305698A2; 3378-EP2308562A2; 3378-EP2308840A1; 3378-EP2308867A2; 3378-EP2308870A2; 3378-EP2308879A1; 3378-EP2311801A1; 3378-EP2311802A1; 3378-EP2311803A1; 3378-EP2311806A2; 3378-EP2311808A1; 3378-EP2311829A1; 3378-EP2311842A2; 3378-EP2314588A1; 3378-EP2314590A1; 3378-EP2314593A1; 3378-EP2316457A1; 3378-EP2316458A1; 3378-EP2316825A1; 3378-EP2316826A1; 3378-EP2316827A1; 3378-EP2316828A1; 3378-EP2371814A1; BIM-0050216.0001; C07481; D00528; Q60235; 1,3,7-trimethyl-3,7-dihydropurine-2,6-dione; 1H-Purine-2, 3,7-dihydro-1,3,7-trimethyl-; AB00051930-09; AB00051930_10; Caffeine, purum, anhydrous, >=99.0% (HPLC); 3,7-dihydro-1,3,7-trimethyl-1H-purine (9CI); Caffeine, anhydrous, tested according to Ph.Eur.; L000155; 3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion; Caffeine, Sigma Reference Standard, vial of 250 mg; SR-01000075187-1; SR-01000075187-4; SR-01000075187-7; SR-01000075187-8; BRD-K02404261-001-02-7; BRD-K02404261-001-03-5; BRD-K02404261-001-07-6; Caffeine, certified reference material, TraceCERT(R); Caffeine, meets USP testing specifications, anhydrous; Melting point standard 235-237C, analytical standard;1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dione #; Caffeine, British Pharmacopoeia (BP) Reference Standard; Caffeine, European Pharmacopoeia (EP) Reference Standard; F3371-0262;Z112207564; Caffeine 2000 microg/mL in Water:Methanol (81:19 g/g); 07E4FB58-FD79-4175-8E3D-05BF96954522; 3,7-Dihydro-1,3,7-trimethyl-1H-purin-2,6-dion (coffein); Caffeine solution, analytical standard, 1.0 mg/mL in methanol; Caffeine, United States Pharmacopeia (USP) Reference Standard; Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material; Caffeine for system suitability, European Pharmacopoeia (EP) Reference Standard; Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard; Caffeine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material; 114303-55-8; Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material; Caffeine, PharmaGrade, EP, Manufactured under appropriate GMP controls for pharma or biopharmaceutical production;Mettler-Toledo Calibration substance ME 18872, Caffeine, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC); kafein; KAFEN; kafen; KAFEIN; KAHVE; kahve; KAFEYN; kafeyin; kafeyn; KAFEYIN; COFFEE; coffee; cola; drink;

CAFFEINE IUPAC Name 1,3,7-trimethylpurine-2,6-dione

CAFFEINE InChI InChI=1S/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3

CAFFEINE InChI Key RYYVLZVUVIJVGH-UHFFFAOYSA-N

CAFFEINE Canonical SMILES CN1C=NC2=C1C(=O)N(C(=O)N2C)C

CAFFEINE Molecular Formula C8H10N4O2

CAFFEINE CAS HelpNew Window58-08-2

CAFFEINE Deprecated CAS 71701-02-5, 95789-13-2

CAFFEINE European Community (EC) Number 200-362-1

CAFFEINE ICSC Number 0405

CAFFEINE NSC Number 755917

CAFFEINE RTECS Number EV6475000

CAFFEINE UN Number 1544

CAFFEINE UNII HelpNew Window3G6A5W338E

CAFFEINE FEMA Number 2224

CAFFEINE DSSTox Substance ID DTXSID0020232

CAFFEINE Wikipedia Caffeine

Computed Properties

CAFFEINE Property Name Property Value Reference

CAFFEINE Molecular Weight 194.19 g/mol

CAFFEINE XLogP3 -0.1

CAFFEINE Hydrogen Bond Donor Count 0

CAFFEINE Hydrogen Bond Acceptor Count 3

CAFFEINE Rotatable Bond Count 0

CAFFEINE Exact Mass 194.080376 g/mol

CAFFEINE Monoisotopic Mass 194.080376 g/mol

CAFFEINE Topological Polar Surface Area 58.4 Å²

CAFFEINE Heavy Atom Count 14

CAFFEINE Formal Charge 0

CAFFEINE Complexity 293

CAFFEINE Isotope Atom Count 0

CAFFEINE Defined Atom Stereocenter Count 0

CAFFEINE Undefined Atom Stereocenter Count 0

CAFFEINE Defined Bond Stereocenter Count 0

CAFFEINE Undefined Bond Stereocenter Count 0

CAFFEINE Covalently-Bonded Unit Count 1

CAFFEINE Compound Is Canonicalized Yes

Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class.[10] It is the world’s most widely consumed psychoactive drug.[11] Unlike many other psychoactive substances, it is legal and unregulated in nearly all parts of the world. There are several known mechanisms of action to explain the effects of caffeine. The most prominent is that it reversibly blocks the action of adenosine on its receptors and consequently prevents the onset of drowsiness induced by adenosine. Caffeine also stimulates certain portions of the autonomic nervous system.

Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid, and 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,[12] and helps to protect them against predator insects and to prevent germination of nearby seeds.[13] The most well-known source of caffeine is the coffee bean, the seed of the Coffea plant. People may drink beverages containing caffeine to relieve or prevent drowsiness and to improve cognitive performance. To make these drinks, caffeine is extracted by steeping the plant product in water, a process called infusion. Caffeine-containing drinks, such as coffee, tea, and cola, are very popular; as of 2014, 85% of American adults consumed some form of caffeine daily, consuming 164 mg on average.[14]

Caffeine can have both positive and negative health effects. It can treat and prevent the premature infant breathing disorders bronchopulmonary dysplasia of prematurity and apnea of prematurity. Caffeine citrate is on the WHO Model List of Essential Medicines.[15] It may confer a modest protective effect against some diseases,[16] including Parkinson’s disease.[17] Some people experience sleep disruption or anxiety if they consume caffeine, but others show little disturbance. Evidence of a risk during pregnancy is equivocal; some authorities recommend that pregnant women limit caffeine to the equivalent of two cups of coffee per day or less.[18][19] Caffeine can produce a mild form of drug dependence – associated with withdrawal symptoms such as sleepiness, headache, and irritability – when an individual stops using caffeine after repeated daily intake.[1][3][5] Tolerance to the autonomic effects of increased blood pressure and heart rate, and increased urine output, develops with chronic use (i.e., these symptoms become less pronounced or do not occur following consistent use).[20]

Caffeine is classified by the US Food and Drug Administration as generally recognized as safe (GRAS). Toxic doses, over 10 grams per day for an adult, are much higher than the typical dose of under 500 milligrams per day.[21] A cup of coffee contains 80-175 mg of caffeine, depending on what “bean” (seed) is used, how it is roasted (darker roasts have less caffeine), and how it is prepared (e.g., drip, percolation, or espresso). Thus it requires roughly 50-100 ordinary cups of coffee to reach the toxic dose. However, pure powdered caffeine, which is available as a dietary supplement, can be lethal in tablespoon-sized amounts.

Contents

1 Use -CAFFEINE

1.1 Medical -CAFFEINE

1.2 Enhancing performance ->CAFFEINE

1.3 Specific populations ->CAFFEINE

2 Adverse effects ->CAFFEINE

2.1 Physical ->CAFFEINE

2.2 Psychological ->CAFFEINE

2.3 Reinforcement disorders ->CAFFEINE

2.4 Risk of other diseases ->CAFFEINE

3 Overdose ->CAFFEINE

4 Interactions ->CAFFEINE

4.1 Alcohol ->CAFFEINE

4.2 Tobacco ->CAFFEINE

4.3 Birth control ->CAFFEINE

4.4 Medications ->CAFFEINE

5 Pharmacology ->CAFFEINE

5.1 Pharmacodynamics ->CAFFEINE

5.2 Pharmacokinetics ->CAFFEINE

6 Chemistry ->CAFFEINE

6.1 Synthesis ->CAFFEINE

6.2 Decaffeination ->CAFFEINE

6.3 Detection in body fluids ->CAFFEINE

6.4 Analogs ->CAFFEINE

6.5 Precipitation of tannins ->CAFFEINE

7 Natural occurrence ->CAFFEINE

8 Products ->CAFFEINE

8.1 Beverages ->CAFFEINE

8.2 Chocolate ->CAFFEINE

8.3 Tablets ->CAFFEINE

8.4 Other oral products ->CAFFEINE

8.5 Inhalants ->CAFFEINE

8.6 Combinations with other drugs ->CAFFEINE

9 History ->CAFFEINE

9.1 Discovery and spread of use ->CAFFEINE

9.2 Chemical identification, isolation, and synthesis ->CAFFEINE

9.3 Historic regulations ->CAFFEINE

10 Society and culture ->CAFFEINE

10.1 Regulations ->CAFFEINE

10.2 Consumption ->CAFFEINE

10.3 Religions ->CAFFEINE

11 Other organisms ->CAFFEINE

12 Research ->CAFFEINE

Medical ->CAFFEINE

Main article: Caffeine citrate

Caffeine is used in:

Some people use caffeine-containing beverages such as coffee or tea to try to treat their asthma.[33] Evidence to support this practice, however, is poor.[33] It appears that caffeine improves airway function in people with asthma, increasing forced expiratory volume (FEV1) by 5% to 18%, with this effect lasting for up to four hours.[34]The addition of caffeine (100-130 mg) to commonly prescribed pain relievers such as paracetamol or ibuprofen modestly improves the proportion of people who achieve pain relief.[35]Enhancing performance

Cognitive

Caffeine is a central nervous system stimulant that reduces fatigue and drowsiness.[10] At normal doses, caffeine has variable effects on learning and memory, but it generally improves reaction time, wakefulness, concentration, and motor coordination.[36][37] The amount of caffeine needed to produce these effects varies from person to person, depending on body size and degree of tolerance.[36] The desired effects arise approximately one hour after consumption, and the desired effects of a moderate dose usually subside after about three or four hours.[6]Caffeine can delay or prevent sleep and improves task performance during sleep deprivation.[38] Shift workers who use caffeine make fewer mistakes due to drowsiness.[39]A systematic review and meta-analysis from 2014 found that concurrent caffeine and l-theanine use has synergistic psychoactive effects that promote alertness, attention, and task switching;[40] these effects are most pronounced during the first hour post-dose.[40]

Physical ->CAFFEINE

Caffeine is a proven ergogenic aid in humans.[41] Caffeine improves athletic performance in aerobic (especially endurance sports) and anaerobic conditions.[41] Moderate doses of caffeine (around 5 mg/kg[41]) can improve sprint performance,[42] cycling and running time trial performance,[41] endurance (i.e., it delays the onset of muscle fatigue and central fatigue),[41][43][44] and cycling power output.[41] Caffeine increases basal metabolic rate in adults.[45][46][47]Caffeine improves muscular strength and power,[48] and may enhance muscular endurance.[49] Caffeine also enhances performance on anaerobic tests.[50] Caffeine consumption before constant load exercise is associated with reduced perceived exertion. While this effect is not present during exercise-to-exhaustion exercise, performance is significantly enhanced. This is congruent with caffeine reducing perceived exertion, because exercise-to-exhaustion should end at the same point of fatigue.[51] Caffeine also improves power output and reduces time to completion in aerobic time trials,[52] an effect positively (but not exclusively) associated with longer duration exercise.[53]

Specific populations ->CAFFEINE

Adults For the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg.[54] This limit was found to be safe by a 2017 systematic review on caffeine toxicology.[55]Children ->CAFFEINEIn healthy children, moderate caffeine intake under 400 mg produces effects that are “modest and typically innocuous”.[56][57] Higher doses of caffeine (>400 mg) can cause physiological, psychological and behavioral harm, particularly for children with psychiatric or cardiac conditions.[56] There is no evidence that coffee stunts a child’s growth.[58] The American Academy of Pediatrics recommends that caffeine consumption is not appropriate for children and adolescents and should be avoided.[59] This recommendation is based on a clinical report released by American Academy of Pediatrics in 2011 with a review of 45 publications from 1994 to 2011 and includes inputs from various stakeholders (Pediatricians, Committee on nutrition, Canadian Pediatric Society, Centers for Disease Control & Prevention, Food and Drug Administration, Sports Medicine & Fitness committee, National Federations of High School Associations).[59] For children age 12 and under, Health Canada recommends a maximum daily caffeine intake of no more than 2.5 milligrams per kilogram of body weight. Based on average body weights of children, this translates to the following age-based intake limits:[54]Age range Maximum recommended daily caffeine intake 4-6 45 mg (slightly more than in 12 oz of a typical caffeinated soft drink) 7-9 62.5 mg 10-12 85 mg (about ½ cup of coffee) AdolescentsHealth Canada has not developed advice for adolescents because of insufficient data. However, they suggest that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight. This is because the maximum adult caffeine dose may not be appropriate for light-weight adolescents or for younger adolescents who are still growing. The daily dose of 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse effects.[54] Pregnancy and breastfeeding The metabolism of caffeine is reduced in pregnancy, especially in the third trimester, and the half life of caffeine during pregnancy can be increased up to 15 hours (as compared to 2.5 to 4.5 hours in non-pregnant adults).[60] Current evidence regarding the effects of caffeine on pregnancy and for breastfeeding are inconclusive.[18] There is limited primary and secondary advice for, or against, caffeine use during pregnancy and its effects on the fetus or newborn.[18]The UK Food Standards Agency has recommended that pregnant women should limit their caffeine intake, out of prudence, to less than 200 mg of caffeine a day – the equivalent of two cups of instant coffee, or one and a half to two cups of fresh coffee.[61] The American Congress of Obstetricians and Gynecologists (ACOG) concluded in 2010 that caffeine consumption is safe up to 200 mg per day in pregnant women.[19] For women who breastfeed, are pregnant, or may become pregnant, Health Canada recommends a maximum daily caffeine intake of no more than 300 mg, or a little over two 8 oz (237 mL) cups of coffee.[54] A 2017 systematic review on caffeine toxicology found evidence supporting that caffeine consumption up to 300 mg/day for pregnant women is generally not associated with adverse reproductive or developmental effect.[55]

There are conflicting reports in the scientific literature about caffeine use during pregnancy.[62] A 2011 review found that caffeine during pregnancy does not appear to increase the risk of congenital malformations, miscarriage or growth retardation even when consumed in moderate to high amounts.[63] Other reviews, however, concluded that there is some evidence that higher caffeine intake by pregnant women may be associated with a higher risk of giving birth to a low birth weight baby,[64] and may be associated with a higher risk of pregnancy loss.[65] A systematic review, analyzing the results of observational studies, suggests that women who consume large amounts of caffeine (greater than 300 mg/day) prior to becoming pregnant may have a higher risk of experiencing pregnancy loss.[66]

Adverse effects ->CAFFEINE

Physical

Coffee and caffeine can affect gastrointestinal motility and gastric acid secretion.[67][68][69] Caffeine in low doses may cause weak bronchodilation for up to four hours in asthmatics.[70] In postmenopausal women, high caffeine consumption can accelerate bone loss.[71][72]

Acute ingestion of caffeine in large doses (at least 250-300 mg, equivalent to the amount found in 2-3 cups of coffee or 5-8 cups of tea) results in a short-term stimulation of urine output in individuals who have been deprived of caffeine for a period of days or weeks.[73] This increase is due to both a diuresis (increase in water excretion) and a natriuresis (increase in saline excretion); it is mediated via proximal tubular adenosine receptor blockade.[74] The acute increase in urinary output may increase the risk of dehydration. However, chronic users of caffeine develop a tolerance to this effect and experience no increase in urinary output.[75][76]

Psychological ->CAFFEINE

Minor undesired symptoms from caffeine ingestion not sufficiently severe to warrant a psychiatric diagnosis are common and include mild anxiety, jitteriness, insomnia, increased sleep latency, and reduced coordination.[36][77] Caffeine can have negative effects on anxiety disorders.[78] According to a 2011 literature review, caffeine use is positively associated with anxiety and panic disorders.[79] At high doses, typically greater than 300 mg, caffeine can both cause and worsen anxiety.[80] For some people, discontinuing caffeine use can significantly reduce anxiety.[81] In moderate doses, caffeine has been associated with reduced symptoms of depression and lower suicide risk.[82]

Reinforcement disorders ->CAFFEINE

Addiction

Whether caffeine can result in an addictive disorder depends on how addiction is defined. Compulsive caffeine consumption under any circumstances has not been observed, and caffeine is therefore not generally considered addictive.[92] However, some diagnostic models, such as the ICDM-9 and ICD-10, include a classification of caffeine addiction under a broader diagnostic model.[93] Some state that certain users can become addicted and therefore unable to decrease use even though they know there are negative health effects.[94][95]

Caffeine does not appear to be a reinforcing stimulus, and some degree of aversion may actually occur, with people preferring placebo over caffeine in a study on drug abuse liability published in an NIDA research monograph.[96] Some state that research does not provide support for an underlying biochemical mechanism for caffeine addiction.[1][97][98][99] Other research states it can affect the reward system.[100]

“Caffeine addiction” was added to the ICDM-9 and ICD-10. However, its addition was contested with claims that this diagnostic model of caffeine addiction is not supported by evidence.[1][2][101] The American Psychiatric Association’s DSM-5 does not include the diagnosis of a caffeine addiction but proposes criteria for the disorder for more study.[91][102]

Dependence and withdrawal

Main article: Caffeine dependence

See also: Caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeinism

Withdrawal can cause mild to clinically significant distress or impairment in daily functioning. The frequency at which this occurs is self-reported at 11%, but in lab tests only half of the people who report withdrawal actually experience it, casting doubt on many claims of dependence.[103] Mild physical dependence and withdrawal symptoms may occur upon abstinence, with greater than 100 mg caffeine per day, although these symptoms last no longer than a day.[1] Some symptoms associated with psychological dependence may also occur during withdrawal.[5] The diagnostic criteria for caffeine withdrawal require a previous prolonged daily use of caffeine.[104] Following 24 hours of a marked reduction in consumption, a minimum of 3 of these signs or symptoms is required to meet withdrawal criteria: difficulty concentrating, depressed mood/irritability, flu-like symptoms, headache, and fatigue.[104] Additionally, the signs and symptoms must disrupt important areas of functioning and are not associated with effects of another condition[104]

The ICD-11 includes caffeine dependence as a distinct diagnostic category, which closely mirrors the DSM-5’s proposed set of criteria for “caffeine-use disorder”.[102][105] Caffeine use disorder refers to dependence on caffeine characterized by failure to control caffeine consumption despite negative physiological consequences.[102][105] The APA, which published the DSM-5, acknowledged that there was sufficient evidence in order to create a diagnostic model of caffeine dependence for the DSM-5, but they noted that the clinical significance of the disorder is unclear.[106] Due to this inconclusive evidence on clinical significance, the DSM-5 classifies caffeine-use disorder as a “condition for further study”.[102]

Tolerance to the effects of caffeine occurs for caffeine induced elevations in blood pressure and the subjective feelings of nervousness. Sensitization, the process whereby effects become more prominent with use, occurs for positive effects such as feelings of alertness and well being.[103] Tolerance varies for daily, regular caffeine users and high caffeine users. High doses of caffeine (750 to 1200 mg/day spread throughout the day) have been shown to produce complete tolerance to some, but not all of the effects of caffeine. Doses as low as 100 mg/day, such as a 6 oz cup of coffee or two to three 12 oz servings of caffeinated soft-drink, may continue to cause sleep disruption, among other intolerances. Non-regular caffeine users have the least caffeine tolerance for sleep disruption.[107] Some coffee drinkers develop tolerance to its undesired sleep-disrupting effects, but others apparently do not.[108]

Risk of other diseases ->CAFFEINE

See also: Coffee § Health and pharmacology

A protective effect of caffeine against Alzheimer’s disease and dementia is possible but the evidence is inconclusive.[109][110][111] It may protect people from liver cirrhosis.[112] Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude.[113] One meta analysis has found that caffeine consumption is associated with a reduced risk of type 2 diabetes.[114] Two meta analyses have reported that caffeine consumption is associated with a linear reduction in risk for Parkinson’s disease.[115][17] Caffeine consumption may be associated with reduced risk of depression,[83] although conflicting results have been reported.[84]

Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals.[116]

The DSM-5 also includes other caffeine-induced disorders consisting of caffeine-induced anxiety disorder, caffeine-induced sleep disorder and unspecified caffeine-related disorders. The first two disorders are classified under “Anxiety Disorder” and “Sleep-Wake Disorder” because they share similar characteristics. Other disorders that present with significant distress and impairment of daily functioning that warrant clinical attention but do not meet the criteria to be diagnosed under any specific disorders are listed under “Unspecified Caffeine-Related Disorders”.[117]

Overdose ->CAFFEINE

Torso of a young man with overlaid text of main side-effects of caffeine overdose.

Primary symptoms of caffeine intoxication[118]

Consumption of 1-1.5 grams (1,000-1,500 mg) per day is associated with a condition known as caffeinism.[119] Caffeinism usually combines caffeine dependency with a wide range of unpleasant symptoms including nervousness, irritability, restlessness, insomnia, headaches, and palpitations after caffeine use.[120]

Caffeine overdose can result in a state of central nervous system over-stimulation known as caffeine intoxication, a clinically significant temporary condition that develops during, or shortly after, the consumption of caffeine.[121] This syndrome typically occurs only after ingestion of large amounts of caffeine, well over the amounts found in typical caffeinated beverages and caffeine tablets (e.g., more than 400-500 mg at a time). According to the DSM-5, caffeine intoxication may be diagnosed if five (or more) of the following symptoms develop after recent consumption of caffeine: restlessness, nervousness, excitement, insomnia, flushed face, diuresis (increased production of urine), gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia (increased heart rate) or cardiac arrythmia, periods of inexhaustibility, and psychomotor agitation.[122]

According to the International Classification of Diseases (ICD-11), cases of very high caffeine intake (e.g. > 5 g) may result in caffeine intoxication with symptoms including mania, depression, lapses in judgement, disorientation, disinhibition, delusions, hallucinations or psychosis, and rhabdomyolysis (breakdown of skeletal muscle tissue).[121]

Death from caffeine ingestion appears to be rare, and most commonly caused by an intentional overdose of medications.[123] In 2016, 3702 caffeine related exposure were reported to Poison Control Centers in the United States, of which 846 required an hospitalization and 16 with a major outcome, and several caffeine-related deaths are reported in case studies.[123] The LD50 of caffeine in humans is dependent on individual sensitivity, but is estimated to be 150-200 milligrams per kilogram (2.2 lb) of body mass (75-100 cups of coffee for a 70 kg (150 lb) adult).[124][failed verification] There are cases where doses as low as 57 milligrams per kilogram have been fatal.[125] A number of fatalities have been caused by overdoses of readily available powdered caffeine supplements, for which the estimated lethal amount is less than a tablespoon.[126] The lethal dose is lower in individuals whose ability to metabolize caffeine is impaired due to genetics or chronic liver disease.[127] A death was reported in a man with liver cirrhosis who overdosed on caffeinated mints.[128][129]

High caffeine consumption in energy drinks (At least 1 liter or 320 mg of caffeine) was associated with short term cardiovascular side effects including hypertension, prolonged QT interval and heart palpitations. These cardiovascular side effects were not seen with smaller amounts of caffeine consumption in energy drinks (less than 200 mg).[60]

Since there is no antidote nor reversal agent for caffeine intoxication, treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require peritoneal dialysis, hemodialysis, or hemofiltration.[118][130]

Interactions ->CAFFEINE

Caffeine is a substrate for CYP1A2, and interacts with many substances through this and other mechanisms.[131]

Alcohol ->CAFFEINE

According to DSST, alcohol provides a reduction in performance and caffeine has a significant improvement in performance.[132] When alcohol and caffeine are consumed jointly, the effects produced by caffeine are affected, but the alcohol effects remain the same.[133] For example, when additional caffeine is added, the drug effect produced by alcohol is not reduced.[133] However, the jitteriness and alertness given by caffeine is decreased when additional alcohol is consumed.[133] Alcohol consumption alone reduces both inhibitory and activational aspects of behavioral control. Caffeine antagonizes the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control.[134] The Dietary Guidelines for Americans recommend avoidance of concomitant consumption of alcohol and caffeine, as this may lead to increased alcohol consumption, with a higher risk of alcohol-associated injury.

Tobacco ->CAFFEINE

Smoking tobacco increases caffeine clearance by 56%.[135]

Birth control ->CAFFEINE

Birth control pills can extend the half-life of caffeine, requiring greater attention to caffeine consumption.[136]

Medications ->CAFFEINE

Caffeine sometimes increases the effectiveness of some medications, such as those for headaches.[137] Caffeine was determined to increase the potency of some over-the-counter analgesic medications by 40%.[138]

The pharmacological effects of adenosine may be blunted in individuals taking large quantities of methylxanthines like caffeine.[139]

Pharmacology ->CAFFEINE

Pharmacodynamics ->CAFFEINE

Structure of a typical chemical synapse

Two skeletal formulas: left – caffeine, right – adenosine.

Caffeine’s primary mechanism of action is as an antagonist of adenosine receptors in the brain

In the absence of caffeine and when a person is awake and alert, little adenosine is present in (CNS) neurons. With a continued wakeful state, over time adenosine accumulates in the neuronal synapse, in turn binding to and activating adenosine receptors found on certain CNS neurons; when activated, these receptors produce a cellular response that ultimately increases drowsiness. When caffeine is consumed, it antagonizes adenosine receptors; in other words, caffeine prevents adenosine from activating the receptor by blocking the location on the receptor where adenosine binds to it. As a result, caffeine temporarily prevents or relieves drowsiness, and thus maintains or restores alertness.[7]

Receptor and ion channel targets ->CAFFEINE

Caffeine is an antagonist of adenosine A2A receptors, and knockout mouse studies have specifically implicated antagonism of the A2A receptor as responsible for the wakefulness-promoting effects of caffeine.[140] Antagonism of A2A receptors in the ventrolateral preoptic area (VLPO) reduces inhibitory GABA neurotransmission to the tuberomammillary nucleus, a histaminergic projection nucleus that activation-dependently promotes arousal.[141] This disinhibition of the tuberomammillary nucleus is the downstream mechanism by which caffeine produces wakefulness-promoting effects.[141] Caffeine is an antagonist of all four adenosine receptor subtypes (A1, A2A, A2B, and A3), although with varying potencies.[7][140] The affinity (KD) values of caffeine for the human adenosine receptors are 12 μM at A1, 2.4 μM at A2A, 13 μM at A2B, and 80 μM at A3.[140]

Antagonism of adenosine receptors by caffeine also stimulates the medullary vagal, vasomotor, and respiratory centers, which increases respiratory rate, reduces heart rate, and constricts blood vessels.[7] Adenosine receptor antagonism also promotes neurotransmitter release (e.g., monoamines and acetylcholine), which endows caffeine with its stimulant effects;[7][142] adenosine acts as an inhibitory neurotransmitter that suppresses activity in the central nervous system. Heart palpitations are caused by blockade of the A1 receptor.[7]

Because caffeine is both water- and lipid-soluble, it readily crosses the blood-brain barrier that separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action is as a nonselective antagonist of adenosine receptors (in other words, an agent that reduces the effects of adenosine). The caffeine molecule is structurally similar to adenosine, and is capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive antagonist.[143]

In addition to its activity at adenosine receptors, caffeine is an inositol trisphosphate receptor 1 antagonist and a voltage-independent activator of the ryanodine receptors (RYR1, RYR2, and RYR3).[144] It is also a competitive antagonist of the ionotropic glycine receptor.[145]

Effects on striatal dopamine

While caffeine does not directly bind to any dopamine receptors, it influences the binding activity of dopamine at its receptors in the striatum by binding to adenosine receptors that have formed GPCR heteromers with dopamine receptors, specifically the A1-D1 receptor heterodimer (this is a receptor complex with 1 adenosine A1 receptor and 1 dopamine D1 receptor) and the A2A-D2 receptor heterotetramer (this is a receptor complex with 2 adenosine A2A receptors and 2 dopamine D2 receptors).[146][147][148][149] The A2A-D2 receptor heterotetramer has been identified as a primary pharmacological target of caffeine, primarily because it mediates some of its psychostimulant effects and its pharmacodynamic interactions with dopaminergic psychostimulants.[147][148][149]

Caffeine also causes the release of dopamine in the dorsal striatum and nucleus accumbens core (a substructure within the ventral striatum), but not the nucleus accumbens shell, by antagonizing A1 receptors in the axon terminal of dopamine neurons and A1-A2A heterodimers (a receptor complex composed of 1 adenosine A1 receptor and 1 adenosine A2A receptor) in the axon terminal of glutamate neurons.[146][141] During chronic caffeine use, caffeine-induced dopamine release within the nucleus accumbens core is markedly reduced due to drug tolerance.[146][141]

Enzyme targets

Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor.[150] As a competitive nonselective phosphodiesterase inhibitor,[151] caffeine raises intracellular cAMP, activates protein kinase A, inhibits TNF-alpha[152][153] and leukotriene[154] synthesis, and reduces inflammation and innate immunity.[154] Caffeine also affects the cholinergic system where it is a moderate inhibitor of the enzyme acetylcholinesterase.[155][156]

Pharmacokinetics -> CAFFEINE

A diagram featuring 4 skeletal chemical formulas. Top (caffeine) relates to similar compounds paraxanthine, theobromine and theophylline.

Caffeine is metabolized in the liver via a single demethylation, resulting in three primary metabolites, paraxanthine (84%), theobromine (12%), and theophylline (4%), depending on which methyl group is removed.

Urinary metabolites of caffeine in humans at 48 hours post-dose.[157]

Caffeine from coffee or other beverages is absorbed by the small intestine within 45 minutes of ingestion and distributed throughout all bodily tissues.[158] Peak blood concentration is reached within 1-2 hours.[159] It is eliminated by first-order kinetics.[160] Caffeine can also be absorbed rectally, evidenced by suppositories of ergotamine tartrate and caffeine (for the relief of migraine)[161] and of chlorobutanol and caffeine (for the treatment of hyperemesis).[162] However, rectal absorption is less efficient than oral: the maximum concentration (Cmax) and total amount absorbed (AUC) are both about 30% (i.e., 1/3.5) of the oral amounts.[163]

Caffeine’s biological half-life – the time required for the body to eliminate one-half of a dose – varies widely among individuals according to factors such as pregnancy, other drugs, liver enzyme function level (needed for caffeine metabolism) and age. In healthy adults, caffeine’s half-life is between 3 and 7 hours.[7] Smoking decreases the half-life by 30-50%,[108] while oral contraceptives can double it[108] and pregnancy can raise it to as much as 15 hours during the third trimester.[108] In newborns the half-life can be 80 hours or more, dropping very rapidly with age, possibly to less than the adult value by age 6 months.[108] The antidepressant fluvoxamine (Luvox) reduces the clearance of caffeine by more than 90%, and increases its elimination half-life more than tenfold; from 4.9 hours to 56 hours.[164]

Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system, in particular, by the CYP1A2 isozyme, into three dimethylxanthines,[165] each of which has its own effects on the body:

Theophylline (4%): Relaxes smooth muscles of the bronchi, and is used to treat asthma. The therapeutic dose of theophylline, however, is many times greater than the levels attained from caffeine metabolism.[70]

1,3,7-Trimethyluric acid is a minor caffeine metabolite.[7] Each of these metabolites is further metabolized and then excreted in the urine. Caffeine can accumulate in individuals with severe liver disease, increasing its half-life.[166]

A 2011 review found that increased caffeine intake was associated with a variation in two genes that increase the rate of caffeine catabolism. Subjects who had this mutation on both chromosomes consumed 40 mg more caffeine per day than others.[167] This is presumably due to the need for a higher intake to achieve a comparable desired effect, not that the gene led to a disposition for greater incentive of habituation.

Chemistry ->CAFFEINE

Pure anhydrous caffeine is a bitter-tasting, white, odorless powder with a melting point of 235-238 °C.[8][9] Caffeine is moderately soluble in water at room temperature (2 g/100 mL), but very soluble in boiling water (66 g/100 mL).[168] It is also moderately soluble in ethanol (1.5 g/100 mL).[168] It is weakly basic (pKa of conjugate acid = ~0.6) requiring strong acid to protonate it.[169] Caffeine does not contain any stereogenic centers[170] and hence is classified as an achiral molecule.[171]

The xanthine core of caffeine contains two fused rings, a pyrimidinedione and imidazole. The pyrimidinedione in turn contains two amide functional groups that exist predominantly in a zwitterionic resonance the location from which the nitrogen atoms are double bonded to their adjacent amide carbons atoms. Hence all six of the atoms within the pyrimidinedione ring system are sp2 hybridized and planar. Therefore, the fused 5,6 ring core of caffeine contains a total of ten pi electrons and hence according to Hückel’s rule is aromatic.[172]

Synthesis ->CAFFEINE

One biosynthetic route of caffeine, as performed by Camellia and Coffea species.[173][174]

One laboratory synthesis of caffeine[175][176]

The biosynthesis of caffeine is an example of convergent evolution among different species.[177][178][179]

Caffeine may be synthesized in the lab starting with dimethylurea and malonic acid.[clarification needed][175][176][180]

Commercial supplies of caffeine are not usually manufactured synthetically because the chemical is readily available as a byproduct of decaffeination.[181]

Decaffeination ->CAFFEINE

Main article: Decaffeination

Fibrous crystals of purified caffeine. Dark-field microscopy image, about 7 mm × 11 mm

Extraction of caffeine from coffee, to produce caffeine and decaffeinated coffee, can be performed using a number of solvents. Following are main methods:

Water extraction: Coffee beans are soaked in water. The water, which contains many other compounds in addition to caffeine and contributes to the flavor of coffee, is then passed through activated charcoal, which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving decaffeinated coffee with its original flavor. Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter caffeine tablets.[182]

Supercritical carbon dioxide extraction: Supercritical carbon dioxide is an excellent nonpolar solvent for caffeine, and is safer than the organic solvents that are otherwise used. The extraction process is simple: CO

2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73 atm. Under these conditions, CO

2 is in a “supercritical” state: It has gaslike properties that allow it to penetrate deep into the beans but also liquid-like properties that dissolve 97-99% of the caffeine. The caffeine-laden CO

2 is then sprayed with high-pressure water to remove the caffeine. The caffeine can then be isolated by charcoal adsorption (as above) or by distillation, recrystallization, or reverse osmosis.[182]

Extraction by organic solvents: Certain organic solvents such as ethyl acetate present much less health and environmental hazard than chlorinated and aromatic organic solvents used formerly. Another method is to use triglyceride oils obtained from spent coffee grounds.[182]

“Decaffeinated” coffees do in fact contain caffeine in many cases – some commercially available decaffeinated coffee products contain considerable levels. One study found that decaffeinated coffee contained 10 mg of caffeine per cup, compared to approximately 85 mg of caffeine per cup for regular coffee.[183]

Detection in body fluids

Caffeine can be quantified in blood, plasma, or serum to monitor therapy in neonates, confirm a diagnosis of poisoning, or facilitate a medicolegal death investigation. Plasma caffeine levels are usually in the range of 2-10 mg/L in coffee drinkers, 12-36 mg/L in neonates receiving treatment for apnea, and 40-400 mg/L in victims of acute overdosage. Urinary caffeine concentration is frequently measured in competitive sports programs, for which a level in excess of 15 mg/L is usually considered to represent abuse.[184]

Analogs ->CAFFEINE

Some analog substances have been created which mimic caffeine’s properties with either function or structure or both. Of the latter group are the xanthines DMPX[185] and 8-chlorotheophylline, which is an ingredient in dramamine. Members of a class of nitrogen substituted xanthines are often proposed as potential alternatives to caffeine.[186][unreliable source?] Many other xanthine analogues constituting the adenosine receptor antagonist class have also been elucidated.[187]

Some other caffeine analogs:

Dipropylcyclopentylxanthine

8-Cyclopentyl-1,3-dimethylxanthine

8-Phenyltheophylline

Precipitation of tannins

Caffeine, as do other alkaloids such as cinchonine, quinine or strychnine, precipitates polyphenols and tannins. This property can be used in a quantitation method.[188]

Natural occurrence ->CAFFEINE

Roasted coffee beans

Around thirty plant species are known to contain caffeine.[189] Common sources are the “beans” (seeds) of the two cultivated coffee plants, Coffea arabica and Coffea canephora (the quantity varies, but 1.3% is a typical value); and of the cocoa plant, Theobroma cacao; the leaves of the tea plant; and kola nuts. Other sources include the leaves of yaupon holly, South American holly yerba mate, and Amazonian holly guayusa; and seeds from Amazonian maple guarana berries. Temperate climates around the world have produced unrelated caffeine-containing plants.

Caffeine in plants acts as a natural pesticide: it can paralyze and kill predator insects feeding on the plant.[190] High caffeine levels are found in coffee seedlings when they are developing foliage and lack mechanical protection.[191] In addition, high caffeine levels are found in the surrounding soil of coffee seedlings, which inhibits seed germination of nearby coffee seedlings, thus giving seedlings with the highest caffeine levels fewer competitors for existing resources for survival.[192] Caffeine is stored in tea leaves in two places. Firstly, in the cell vacuoles where it is complexed with polyphenols. This caffeine probably is released into the mouth parts of insects, to discourage herbivory. Secondly, around the vascular bundles, where it probably inhibits pathogenic fungi from entering and colonizing the vascular bundles.[193] Caffeine in nectar may improve the reproductive success of the pollen producing plants by enhancing the reward memory of pollinators such as honey bees.[194]

The differing perceptions in the effects of ingesting beverages made from various plants containing caffeine could be explained by the fact that these beverages also contain varying mixtures of other methylxanthine alkaloids, including the cardiac stimulants theophylline and theobromine, and polyphenols that can form insoluble complexes with caffeine.[195]

Products ->CAFFEINE

See also: Caffeinated drink

Caffeine content in select food and drugs[196][197][198][199][200]

Product Serving size Caffeine per serving (mg) Caffeine (mg/L)

Caffeine tablet (regular-strength) 1 tablet 100 –

Caffeine tablet (extra-strength) 1 tablet 200 –

Products containing caffeine include coffee, tea, soft drinks (“colas”), energy drinks, other beverages, chocolate,[202] caffeine tablets, other oral products, and inhalation products. According to a 2020 study in the United States, coffee is the major source of caffeine intake in middle-aged adults, while soft drinks and tea are the major sources in adolescents.[60] Energy drinks are more commonly consumed as a source of caffeine in adolescents as compared to adults.[60]

Beverages ->CAFFEINE

Coffee

The world’s primary source of caffeine is the coffee “bean” (the seed of the coffee plant), from which coffee is brewed. Caffeine content in coffee varies widely depending on the type of coffee bean and the method of preparation used;[203] even beans within a given bush can show variations in concentration. In general, one serving of coffee ranges from 80 to 100 milligrams, for a single shot (30 milliliters) of arabica-variety espresso, to approximately 100-125 milligrams for a cup (120 milliliters) of drip coffee.[204][205] Arabica coffee typically contains half the caffeine of the robusta variety.[203] In general, dark-roast coffee has very slightly less caffeine than lighter roasts because the roasting process reduces caffeine content of the bean by a small amount.[204][205]

Tea

Tea contains more caffeine than coffee by dry weight. A typical serving, however, contains much less, since less of the product is used as compared to an equivalent serving of coffee. Also contributing to caffeine content are growing conditions, processing techniques, and other variables. Thus, teas contain varying amounts of caffeine.[206]

Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee. Preparation and many other factors have a significant impact on tea, and color is a very poor indicator of caffeine content. Teas like the pale Japanese green tea, gyokuro, for example, contain far more caffeine than much darker teas like lapsang souchong, which has very little.[206]

Soft drinks and energy drinks

Caffeine is also a common ingredient of soft drinks, such as cola, originally prepared from kola nuts. Soft drinks typically contain 0 to 55 milligrams of caffeine per 12 ounce serving.[207] By contrast, energy drinks, such as Red Bull, can start at 80 milligrams of caffeine per serving. The caffeine in these drinks either originates from the ingredients used or is an additive derived from the product of decaffeination or from chemical synthesis. Guarana, a prime ingredient of energy drinks, contains large amounts of caffeine with small amounts of theobromine and theophylline in a naturally occurring slow-release excipient.[208]

Other beverages ->CAFFENE

Mate is a drink popular in many parts of South America. Its preparation consists of filling a gourd with the leaves of the South American holly yerba mate, pouring hot but not boiling water over the leaves, and drinking with a straw, the bombilla, which acts as a filter so as to draw only the liquid and not the yerba leaves.[209]

Guaraná is a soft drink originating in Brazil made from the seeds of the Guaraná fruit.

The leaves of Ilex guayusa, the Ecuadorian holly tree, are placed in boiling water to make a guayusa tea.[210]

The leaves of Ilex vomitoria, the yaupon holly tree, are placed in boiling water to make a yaupon tea.

Chocolate

Chocolate derived from cocoa beans contains a small amount of caffeine. The weak stimulant effect of chocolate may be due to a combination of theobromine and theophylline, as well as caffeine.[211] A typical 28-gram serving of a milk chocolate bar has about as much caffeine as a cup of decaffeinated coffee. By weight, dark chocolate has one to two times the amount of caffeine as coffee: 80-160 mg per 100 g. Higher percentages of cocoa such as 90% amount to 200 mg per 100 g approximately and thus, a 100-gram 85% cocoa chocolate bar contains about 195 mg caffeine.[197]

Tablets ->CAFFEINE

No-Doz 100 mg caffeine tablets

Tablets offer several advantages over coffee, tea, and other caffeinated beverages, including convenience, known dosage, and avoidance of concomitant intake of sugar, acids, and fluids. Manufacturers of caffeine tablets claim that using caffeine of pharmaceutical quality improves mental alertness.[citation needed] These tablets are commonly used by students studying for their exams and by people who work or drive for long hours.[212]

Other oral products

One U.S. company is marketing oral dissolvable caffeine strips.[213] Another intake route is SpazzStick, a caffeinated lip balm.[214] Alert Energy Caffeine Gum was introduced in the United States in 2013, but was voluntarily withdrawn after an announcement of an investigation by the FDA of the health effects of added caffeine in foods.[215]

Inhalants

There are several products being marketed that offer inhalers that deliver proprietary blends of supplements, with caffeine being a key ingredient.[216] In 2012, the FDA sent a warning letter to one of the companies marketing these inhalers, expressing concerns for the lack of safety information available about inhaled caffeine.[217]

Combinations with other drugs ->CAFFEINE

Some beverages combine alcohol with caffeine to create a caffeinated alcoholic drink. The stimulant effects of caffeine may mask the depressant effects of alcohol, potentially reducing the user’s awareness of their level of intoxication. Such beverages have been the subject of bans due to safety concerns. In particular, the United States Food and Drug Administration has classified caffeine added to malt liquor beverages as an “unsafe food additive”.[218]

Ya ba contains a combination of methamphetamine and caffeine.

Painkillers such as propyphenazone/paracetamol/caffeine combine caffeine with an analgesic.

History

Discovery and spread of use

An old photo of a dozen old and middle-aged men sitting on the ground around a mat. A man in front sits next to a mortar and holds a bat, ready for grinding. A man opposite to him holds a long spoon.

Coffeehouse in Palestine, circa 1900

Main articles: History of chocolate, History of coffee, History of tea, and History of yerba mate

According to Chinese legend, the Chinese emperor Shennong, reputed to have reigned in about 3000 BCE, inadvertently discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted.[219] Shennong is also mentioned in Lu Yu’s Cha Jing, a famous early work on the subject of tea.[220]

The earliest credible evidence of either coffee drinking or knowledge of the coffee plant appears in the middle of the fifteenth century, in the Sufi monasteries of the Yemen in southern Arabia.[221] From Mocha, coffee spread to Egypt and North Africa, and by the 16th century, it had reached the rest of the Middle East, Persia and Turkey. From the Middle East, coffee drinking spread to Italy, then to the rest of Europe, and coffee plants were transported by the Dutch to the East Indies and to the Americas.[222]

Kola nut use appears to have ancient origins. It is chewed in many West African cultures, in both private and social settings, to restore vitality and ease hunger pangs.

The earliest evidence of cocoa bean use comes from residue found in an ancient Mayan pot dated to 600 BCE. Also, chocolate was consumed in a bitter and spicy drink called xocolatl, often seasoned with vanilla, chile pepper, and achiote. Xocolatl was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content. Chocolate was an important luxury good throughout pre-Columbian Mesoamerica, and cocoa beans were often used as currency.[223]

Xocolatl was introduced to Europe by the Spaniards, and became a popular beverage by 1700. The Spaniards also introduced the cacao tree into the West Indies and the Philippines. It was used in alchemical processes, where it was known as “black bean”.[citation needed]

The leaves and stems of the yaupon holly (Ilex vomitoria) were used by Native Americans to brew a tea called asi or the “black drink”.[224] Archaeologists have found evidence of this use far into antiquity,[225] possibly dating to Late Archaic times.[224]

Chemical identification, isolation, and synthesis

Pierre Joseph Pelletier

In 1819, the German chemist Friedlieb Ferdinand Runge isolated relatively pure caffeine for the first time; he called it “Kaffebase” (i.e., a base that exists in coffee).[226] According to Runge, he did this at the behest of Johann Wolfgang von Goethe.[a][228] In 1821, caffeine was isolated both by the French chemist Pierre Jean Robiquet and by another pair of French chemists, Pierre-Joseph Pelletier and Joseph Bienaimé Caventou, according to Swedish chemist Jöns Jacob Berzelius in his yearly journal. Furthermore, Berzelius stated that the French chemists had made their discoveries independently of any knowledge of Runge’s or each other’s work.[229] However, Berzelius later acknowledged Runge’s priority in the extraction of caffeine, stating:[230] “However, at this point, it should not remain unmentioned that Runge (in his Phytochemical Discoveries, 1820, pages 146-147) specified the same method and described caffeine under the name Caffeebase a year earlier than Robiquet, to whom the discovery of this substance is usually attributed, having made the first oral announcement about it at a meeting of the Pharmacy Society in Paris.”

Pelletier’s article on caffeine was the first to use the term in print (in the French form Caféine from the French word for coffee: café).[231] It corroborates Berzelius’s account:

Caffeine, noun (feminine). Crystallizable substance discovered in coffee in 1821 by Mr. Robiquet. During the same period – while they were searching for quinine in coffee because coffee is considered by several doctors to be a medicine that reduces fevers and because coffee belongs to the same family as the cinchona [quinine] tree – on their part, Messrs. Pelletier and Caventou obtained caffeine; but because their research had a different goal and because their research had not been finished, they left priority on this subject to Mr. Robiquet. We do not know why Mr. Robiquet has not published the analysis of coffee which he read to the Pharmacy Society. Its publication would have allowed us to make caffeine better known and give us accurate ideas of coffee’s composition …

Robiquet was one of the first to isolate and describe the properties of pure caffeine,[232] whereas Pelletier was the first to perform an elemental analysis.[233]

In 1827, M. Oudry isolated “théine” from tea,[234] but in 1838 it was proved by Mulder[235] and by Carl Jobst[236] that theine was actually the same as caffeine.

In 1895, German chemist Hermann Emil Fischer (1852-1919) first synthesized caffeine from its chemical components (i.e. a “total synthesis”), and two years later, he also derived the structural formula of the compound.[237] This was part of the work for which Fischer was awarded the Nobel Prize in 1902.[238]

Historic regulations

Because it was recognized that coffee contained some compound that acted as a stimulant, first coffee and later also caffeine has sometimes been subject to regulation. For example, in the 16th century Islamists in Mecca and in the Ottoman Empire made coffee illegal for some classes.[239][240][241] Charles II of England tried to ban it in 1676,[242][243] Frederick II of Prussia banned it in 1777,[244][245] and coffee was banned in Sweden at various times between 1756 and 1823.

In 1911, caffeine became the focus of one of the earliest documented health scares, when the US government seized 40 barrels and 20 kegs of Coca-Cola syrup in Chattanooga, Tennessee, alleging the caffeine in its drink was “injurious to health”.[246] Although the judge ruled in favor of Coca-Cola, two bills were introduced to the U.S. House of Representatives in 1912 to amend the Pure Food and Drug Act, adding caffeine to the list of “habit-forming” and “deleterious” substances, which must be listed on a product’s label.[247]

Society and culture ->CAFFEINE

Regulations

The Food and Drug Administration (FDA) in the United States currently allows only beverages containing less than 0.02% caffeine;[248] but caffeine powder, which is sold as a dietary supplement, is unregulated.[249] It is a regulatory requirement that the label of most prepackaged foods must declare a list of ingredients, including food additives such as caffeine, in descending order of proportion. However, there is no regulatory provision for mandatory quantitative labeling of caffeine, (e.g., milligrams caffeine per stated serving size). There are a number of food ingredients that naturally contain caffeine. These ingredients must appear in food ingredient lists. However, as is the case for “food additive caffeine”, there is no requirement to identify the quantitative amount of caffeine in composite foods containing ingredients that are natural sources of caffeine. While coffee or chocolate are broadly recognized as caffeine sources, some ingredients (e.g., guarana, yerba maté) are likely less recognized as caffeine sources. For these natural sources of caffeine, there is no regulatory provision requiring that a food label identify the presence of caffeine nor state the amount of caffeine present in the food.[250]

Consumption

Global consumption of caffeine has been estimated at 120,000 tonnes per year, making it the world’s most popular psychoactive substance.[11] This amounts to one serving of a caffeinated beverage for every person every day.[11] The consumption of caffeine has remained stable between 1997 and 2015.[251] Coffee, tea and soft drinks are the most important caffeine sources, with energy drinks contributing little to the total caffeine intake across all age groups.[251]

Religions ->CAFFEINE

Some Church of God (Restoration) adherents and Christian Scientists do not consume caffeine.[citation needed] Until recently, the Seventh-day Adventist Church asked for its members to “abstain from caffeinated drinks”, but has removed this from baptismal vows (while still recommending abstention as policy).[252] Some from these religions believe that one is not supposed to consume a non-medical, psychoactive substance, or believe that one is not supposed to consume a substance that is addictive. The Church of Jesus Christ of Latter-day Saints has said the following with regard to caffeinated beverages: ” . . . the Church revelation spelling out health practices (Doctrine and Covenants 89) does not mention the use of caffeine. The Church’s health guidelines prohibit alcoholic drinks, smoking or chewing of tobacco, and ‘hot drinks’ – taught by Church leaders to refer specifically to tea and coffee.”[253]Gaudiya Vaishnavas generally also abstain from caffeine, because they believe it clouds the mind and over-stimulates the senses.[254] To be initiated under a guru, one must have had no caffeine, alcohol, nicotine or other drugs, for at least a year.[255]Caffeinated beverages are widely consumed by Muslims today. In the 16th century, some Muslim authorities made unsuccessful attempts to ban them as forbidden “intoxicating beverages” under Islamic dietary laws.[256][257]

Other organisms

Recently discovered bacteria Pseudomonas putida CBB5 can live on pure caffeine and can cleave caffeine into carbon dioxide and ammonia.[258]

Caffeine is toxic to birds[259] and to dogs and cats,[260] and has a pronounced adverse effect on mollusks, various insects, and spiders.[261] This is at least partly due to a poor ability to metabolize the compound, causing higher levels for a given dose per unit weight.[157] Caffeine has also been found to enhance the reward memory of honey bees.[194]

Research

CAFFEINE Physical Description

Caffeine appears as odorless white powder or white glistening needles, usually melted together. Bitter taste. Solutions in water are neutral to litmus. Odorless. (NTP, 1992)

CAFFEINE Color/Form White, prismatic crystals

CAFFEINE Odor Odorless

CAFFEINE Taste Bitter taste

CAFFEINE Boiling Point352 °F at 760 mm Hg (sublimes) (NTP, 1992)

CAFFEINE Melting Point 460 °F (NTP, 1992)

CAFFEINE Solubility 10 to 50 mg/mL at 73° F (NTP, 1992)

CAFFEINE Density 1.23 at 64 °F (NTP, 1992)

CAFFEINE Vapor Pressure 9.0X10-7 mm Hg at 25 °C /Extrapolated/

CAFFEINE LogP -0.07

CAFFEINE LogS -0.97

CAFFEINE Decomposition When heated to decomposition, it emits toxic fumes of /nitrogen oxides/.

CAFFEINE pH = 6.9 (1% solution)

CAFFEINE Odor Threshold Aroma threshold values: Detection at 29 to 300 ppm

CAFFEINE Caco2 Permeability -4.41

CAFFEINE pKa 14

CAFFEINE Dissociation Constants HelpNew WindowpKa = 14.0 at 25 °C

CAFFEINE Collision Cross Section 140.9 Å² [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

CAFFEINE Other Experimental Properties Solution neutral to litmus

CAFFEINE UV Spectra MAX ABSORPTION (ALCOHOL): 227 NM (LOG E= 4.3); 235 NM (LOG E= 4.3); 274 NM (LOG E= 4.3)

CAFFEINE Other Spectra SADTLER REFERENCE NUMBER: 209 (IR, GRATING)

CAFFEINE Associated Chemicals Caffeine, monohydrate; 5743-12-4

CAFFEINE Drug Classes Herbal and Dietary Supplements

CAFFEINE Pharmacology Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance.[A298,T716,L9857] Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.[T716]

KAFEIN IUPAC Ad 1,3,7-trimetilpurin-2,6-dion

KAFEIN InChI YardmYeni Pencere InChI = 1S / C8H10N4O2 / c1-10-4-9-6-5 (10) 7 (13) 12 (3) 8 (14) 11 (6) 2 / h4H, 1-3H3

KAFEIN InChI Anahtar RYYVLZVUVIJVGH-UHFFFAOYSA-N

KAFEIN Kanonik Gülüler CN1C = NC2 = C1C (= O) N (C (= O) N2C) C

KAFEIN Moleküler Formül C8H10N4O2

KAFEIN CAS YardmYeni Pencere 58-08-2

KAFEIN Kullanmdan Kaldrlm CAS 71701-02-5, 95789-13-2

KAFEIN Avrupa Topluluu (EC) Numaras 200-362-1

KAFEIN ICSC Numaras 0405

KAFEIN NSC Numaras 755917

KAFEIN RTECS Numaras EV6475000

KAFEIN UN Numaras 1544

KAFEIN UNII HelpYeni Pencere 3G6A5W338E

KAFEIN FEMA Numaras 2224

KAFEIN DSSTox Madde Kimlii DTXSID0020232

KAFEIN Wikipedia Kafein

KAFEIN Mülk Ad Mülk Deer Referans

KAFEIN Moleküler Arlk 194.19 g / mol

KAFEIN XLogP3 -0,1

KAFEIN Hidrojen Ba Donör Says 0

KAFEIN Hidrojen Ba Alcs Says 3

KAFEIN Döndürülebilir Tahvil Says 0

KAFEIN Tam Kütle 194.080376 g / mol

KAFEIN Monoizotopik Kütle 194.080376 g / mol

KAFEIN Topolojik Polar Yüzey Alan 58,4 Å²

KAFEIN Ar Atom Says 14

KAFEIN Resmi Ücret 0

KAFEIN Karmaklk 293

KAFEIN zotop Atom Says 0

KAFEIN Tanml Atom Stereo Merkez Says 0

KAFEIN Tanmsz Atom Stereo Merkez Says 0

KAFEIN Tanml Bond Stereocenter Says 0

KAFEIN Tanmsz Ba Stereocenter Says 0

KAFEIN Kovalent Bal Birim Says 1

KAFEIN Bileik Kanonikletirilmitir Evet

çindekiler

1 -KAFEIN kullanm

1.1 Medikal -KAFEIN

1.2 Performans arttrmak -> KAFEIN

1.3 Belirli popülasyonlar -> KAFEIN

2 Ters etkiler -> KAFEIN

2.1 Fiziksel -> KAFEIN

2.2 Psikolojik -> KAFEIN

2.3 Takviye bozukluklar -> KAFEIN

2.4 Dier hastalk riski -> KAFEIN

3 Doz am -> KAFEIN

4 Etkileimler -> KAFEIN

4.1 Alkol -> KAFEIN

4.2 Tütün -> KAFEIN

4.3 Doum kontrolü -> KAFEIN

4.4 laçlar -> KAFEIN

5 Farmakoloji -> KAFEIN

5.1 Farmakodinamik -> KAFEIN

5.2 Farmakokinetik -> KAFEIN

6 Kimya -> KAFEIN

6.1 Sentez -> KAFEIN

6.2 Kafeinsizletirme -> KAFEIN

6.3 Vücut svlarnda tespit -> KAFEIN

6.4 Analoglar -> KAFEIN

6.5 Tanenlerin çökelmesi -> KAFEIN

7 Doal oluum -> KAFEIN

8 Ürünler -> KAFEIN

8.1 çecekler -> KAFEIN

8.2 Çikolata ->KAFEIN

8.3 Tabletler -> KAFEIN

8.4 Dier oral ürünler ->KAFEIN

8.5 nhalanlar -> KAFEIN

8.6 Dier ilaçlarla kombinasyonlar -> KAFEIN

9 Tarih -> KAFEIN

9.1 Keif ve kullanmn yaylmas -> KAFEIN

9.2 Kimyasal tanmlama, izolasyon ve sentez ->KAFEIN

9.3 Tarihi düzenlemeler -> KAFEIN

10 Toplum ve kültür -> KAFEIN

10.1 Yönetmelikler -> KAFEIN

10.2 Tüketim -> KAFEIN

10.3 Dinler -> KAFEIN

11 Dier organizmalar -> KAFEIN

12 Aratrma -> KAFEIN

Tp -> KAFEIN

Ana madde: Kafein sitrat

Kafein u durumlarda kullanlr:

Kafein uykuyu geciktirebilir veya önleyebilir ve uyku yoksunluu srasnda görev performansn iyiletirebilir. [38] Kafein kullanan vardiyal çalanlar uyuukluk nedeniyle daha az hata yapar. [39]2014’ten sistematik bir inceleme ve meta-analiz, ezamanl kafein ve l-teanin kullanmnn uyankl, dikkati ve görev deitirmeyi tevik eden sinerjik psikoaktif etkilere sahip olduunu buldu; [40] Bu etkiler en çok doz sonras ilk saat içinde belirgindir. [40 ]

Fiziksel -> KAFEIN

Kafein, insanlarda kantlanm ergojenik bir yardmcdr. [41] Kafein, aerobik (özellikle dayankllk sporlar) ve anaerobik koullarda atletik performans iyiletirir. [41] Orta doz kafein (yaklak 5 mg / kg [41]) sprint performansn, [42] bisiklet ve kou süresi deneme performansn, [41] dayankll (yani, kas yorgunluunun ve merkezi yorgunluun balangcn geciktirir) artrabilir, [41 ] [43] [44] ve güç çk döngüsü. [41] Kafein yetikinlerde bazal metabolizma hzn artrr. [45] [46] [47]Kafein, kas gücünü ve gücünü [48] gelitirir ve kas dayanklln artrabilir. [49] Kafein ayrca anaerobik testlerde performans artrr. [50] Sabit yük egzersizinden önce kafein tüketimi, alglanan eforun azalmasyla ilikilidir. Egzersizden bitkinlie kadar olan egzersiz srasnda bu etki mevcut olmasa da, performans önemli ölçüde artar. Bu, kafein azaltan alglanan eforla uyumludur, çünkü egzersizden bitkinlie kadar ayn yorgunluk noktasnda bitmelidir. [51] Kafein ayrca aerobik zaman deneylerinde güç çkn iyiletirir ve tamamlanma süresini azaltr, [52] daha uzun süreli egzersizle ilikili pozitif bir etki (ancak sadece deil). [53]

Belirli popülasyonlar -> KAFEIN

Yetikinler Salkl yetikinlerin genel popülasyonu için Health Canada günlük 400 mg’dan fazla alm yaplmamasn tavsiye etmektedir. [54] Bu snrn, kafein toksikolojisi üzerine 2017 sistematik bir inceleme ile güvenli olduu bulundu. [55]Çocuklar Salkl çocuklarda, 400 mg’n altnda orta düzeyde kafein alm “mütevaz ve tipik olarak zararsz” etkiler yaratr. [56] [57] Daha yüksek dozda kafein (> 400 mg), özellikle psikiyatrik veya kalp rahatszl olan çocuklar için fizyolojik, psikolojik ve davransal zararlara neden olabilir. [56] Kahvenin bir çocuun büyümesini engellediine dair hiçbir kant yoktur. [58] Amerikan Pediatri Akademisi, kafein tüketiminin çocuklar ve ergenler için uygun olmadn ve bundan kaçnlmas gerektiini önermektedir. [59] Bu öneri, American Academy of Pediatrics tarafndan 1994’ten 2011’e kadar 45 yaynn gözden geçirilmesi ile 2011 ylnda yaynlanan bir klinik rapora dayanmaktadr ve çeitli paydalardan (Pediatristler, Beslenme Komitesi, Kanada Pediatri Dernei, Hastalk Kontrol ve Önleme Merkezleri, Gda ve laç daresi, Spor Tbb ve Fitness komitesi, Ulusal Lise Dernekleri Federasyonlar). [59] Health Canada, 12 ya ve altndaki çocuklar için, vücut arlnn kilogram bana 2,5 miligramdan fazla olmayan günlük maksimum kafein almn önermektedir. Çocuklarn ortalama vücut arlklarna göre bu, aadaki yaa dayal alm limitlerine karlk gelir: [54]Ya aral Önerilen maksimum günlük kafein alm 4-6 45 mg (tipik bir kafeinli merubatn 12 oz’undan biraz daha fazla) 7-9 62,5 mg 10-12 85 mg (yaklak ½ fincan kahve) Ergenler Health Canada, yetersiz veri nedeniyle ergenler için tavsiye gelitirmemitir. Bununla birlikte, bu ya grubu için günlük kafein almnn 2,5 mg / kg vücut arlndan fazla olmamasn önermektedirler. Bunun nedeni, maksimum yetikin kafein dozunun hafif ergenler veya büyümeye devam eden genç ergenler için uygun olmayabilmesidir. Günlük 2.5 mg / kg vücut arl dozu, ergen kafein tüketicilerinin çounda olumsuz salk etkilerine neden olmayacaktr. Bu, muhafazakar bir öneridir, çünkü daha yal ve daha kilolu ergenler, yan etkilere maruz kalmadan yetikin dozlarnda kafein tüketebilirler. [54]

Hamilelik ve emzirme Gebelikte, özellikle üçüncü trimesterde kafein metabolizmas azalr ve kafeinin gebelikte yarlanma ömrü 15 saate kadar çkarlabilir (hamile olmayan yetikinlerde 2,5 ila 4,5 saate kyasla). [60] Kafeinin hamilelik ve emzirme üzerindeki etkilerine ilikin mevcut kantlar kesin deildir. [18] Hamilelik srasnda kafein kullanm ve bunun fetüs veya yenidoan üzerindeki etkileri konusunda veya aleyhinde snrl birincil ve ikincil tavsiye vardr. [18]Birleik Krallk Gda Standartlar Ajans, hamile kadnlarn kafein almn tedbirli olarak günde 200 mg’dan daha az kafeinle snrlamalarn tavsiye etti – iki fincan hazr kahve veya bir buçuk ila iki fincan taze kahve edeeri. . [61] Amerikan Kadn Hastalklar ve Doum Uzmanlar Kongresi (ACOG) 2010 ylnda hamile kadnlarda kafein tüketiminin günde 200 mg’a kadar güvenli olduu sonucuna varmtr. [19] Health Canada, emziren, hamile olan veya hamile kalabilecek kadnlar için günlük maksimum kafein almnn 300 mg’dan fazla olmamasn veya iki adet 8 ons (237 mL) fincan kahvenin biraz üzerinde olmasn önermektedir. [54] Kafein toksikolojisi üzerine 2017 sistematik bir derleme, hamile kadnlar için günde 300 mg’a kadar kafein tüketiminin genellikle olumsuz üreme veya geliimsel etki ile ilikili olmadn destekleyen kantlar buldu. [55]Bilimsel literatürde hamilelikte kafein kullanmna ilikin çelikili raporlar bulunmaktadr. [62] 2011 ylnda yaplan bir inceleme, hamilelik srasnda kafeinin, orta ila yüksek miktarlarda tüketildiinde bile, konjenital malformasyon, düük veya büyüme gerilii riskini artrmad görülmütür. [63] Bununla birlikte dier incelemeler, hamile kadnlarn daha yüksek kafein almnn düük doum arlkl bir bebek dourma riskiyle ilikili olabileceine [64] ve daha yüksek gebelik kayb riski ile ilikili olabileceine dair baz kantlar olduu sonucuna varmtr. [65] Gözlemsel çalmalarn sonuçlarn analiz eden sistematik bir derleme, hamile kalmadan önce çok miktarda kafein (300 mg / gün’den fazla) tüketen kadnlarn gebelik kayb yaama riskinin daha yüksek olabileceini öne sürüyor. [66]

Olumsuz etkiler -> KAFEIN

Fiziksel

Kahve ve kafein, gastrointestinal motiliteyi ve mide asidi sekresyonunu etkileyebilir. [67] [68] [69] Düük dozlardaki kafein astmllarda dört saate kadar zayf bronkodilatasyona neden olabilir. [70] Postmenopozal kadnlarda yüksek kafein tüketimi kemik kaybn hzlandrabilir. [71] [72]Yüksek dozlarda (en az 250-300 mg, 2-3 fincan kahvede veya 5-8 fincan çayda bulunan miktara edeer) akut kafein alm, alnan kiilerde ksa süreli idrar çknn uyarlmasna neden olur. günler veya haftalarca kafeinden yoksun brakld. [73] Bu art hem diürezden (su atmnda art) hem de natriürezden (salin atlmndaki art) kaynaklanmaktadr; proksimal tübüler adenozin reseptör blokaj araclyla olur. [74] drar çkndaki akut art dehidratasyon riskini artrabilir. Bununla birlikte, kronik kafein kullanclar bu etkiye tolerans gelitirir ve idrar çknda art yaamaz. [75] [76]

Psikolojik -> KAFEIN

Psikiyatrik bir tany garantilemek için yeterince iddetli olmayan kafein almndan kaynaklanan küçük istenmeyen semptomlar yaygndr ve hafif anksiyete, gerginlik, uykusuzluk, artan uyku gecikmesi ve azalm koordinasyonu içerir. [36] [77] Kafein, anksiyete bozukluklar üzerinde olumsuz etkilere sahip olabilir. [78] 2011’de yaplan bir literatür taramasna göre, kafein kullanm anksiyete ve panik bozukluklar ile pozitif olarak ilikilidir. [79] Tipik olarak 300 mg’n üzerindeki yüksek dozlarda kafein hem anksiyeteye neden olabilir hem de daha da kötületirebilir. [80] Baz insanlar için kafein kullanmnn kesilmesi kaygy önemli ölçüde azaltabilir. [81] Orta dozlarda kafein, azalm depresyon semptomlar ve daha düük intihar riski ile ilikilendirilmitir. [82]Artan kahve ve kafein tüketimi, depresyon riskinde azalma ile ilikilidir. [83] [84]Baz ders kitaplar kafeinin hafif bir cokulu olduunu belirtirken, [85] [86] [87] dierleri bunun cokulu olmadn, [88] [89] ve biri bunun cokulu olduunu ve olmadn belirtir. [90]Kafein kaynakl anksiyete bozukluu, madde / ilaç kaynakl anksiyete bozukluunun DSM-5 tansnn bir alt snfdr. [91]

Takviye bozukluklar -> KAFEIN

Bamllk

Kafeinin bir bamllk bozukluuna yol açp açmayaca, bamlln nasl tanmlandna baldr. Hiçbir koulda zorunlu kafein tüketimi gözlemlenmemitir ve bu nedenle kafein genellikle bamllk yapmaz. [92] Bununla birlikte, ICDM-9 ve ICD-10 gibi baz tehis modelleri, daha geni bir tehis modeli altnda kafein bamllnn bir snflandrmasn içerir. [93] Bazlar, baz kullanclarn baml hale gelebileceini ve bu nedenle salk üzerinde olumsuz etkileri olduunu bildikleri halde kullanm azaltamayacaklarn belirtmektedir. [94] [95]Kafein pekitirici bir uyarc gibi görünmüyor ve bir NIDA aratrma monografisinde yaynlanan uyuturucu bamll üzerine yaplan bir çalmada, insanlarn kafein yerine plaseboyu tercih etmesiyle bir dereceye kadar tiksinti olabilir. [96] Bazlar aratrmann kafein bamllnn altnda yatan bir biyokimyasal mekanizmay desteklemediini belirtiyor. [1] [97] [98] [99] Dier aratrmalar ödül sistemini etkileyebileceini belirtiyor. [100]ICDM-9 ve ICD-10’a “Kafein bamll” eklendi. Bununla birlikte, eklenmesi, kafein bamllnn bu tehis modelinin kantlarla desteklenmedii iddialaryla itiraz edildi. [1] [2] [101] Amerikan Psikiyatri Birlii’nin DSM-5’i, kafein bamll tehisini içermez, ancak daha fazla çalma için bozukluk için kriterler önerir. [91] [102]ICD-11, DSM-5’in “kafein kullanm bozukluu” için önerilen kriterler kümesini yakndan yanstan ayr bir tan kategorisi olarak kafein bamlln içerir. [102] [105] Kafein kullanm bozukluu, olumsuz fizyolojik sonuçlara ramen kafein tüketimini kontrol edememe ile karakterize edilen kafeine bamll ifade eder. [102] [105] DSM-5’i yaynlayan APA, DSM-5 için tansal bir kafein bamll modeli oluturmak için yeterli kant olduunu kabul etti, ancak bozukluun klinik öneminin belirsiz olduunu kaydetti. [106] Klinik önemi hakkndaki bu kesin olmayan kant nedeniyle, DSM-5 kafein kullanm bozukluunu “ileri çalmalar için bir koul” olarak snflandrr. [102]Kafeinin etkilerine kar tolerans, kafeinin neden olduu kan basncnda yükselmeler ve öznel sinirlilik duygular için ortaya çkar. Kullanmla birlikte etkilerin daha belirgin hale geldii süreç olan duyarllk, uyanklk ve esenlik duygular gibi olumlu etkiler için ortaya çkar. [103] Tolerans günlük, düzenli kafein kullanclar ve yüksek kafein kullanclar için deiir. Yüksek dozlarda kafeinin (gün boyunca 750 ila 1200 mg / gün), kafeinin tüm etkilerine deil, bazlarna tam tolerans salad gösterilmitir. 100 mg / gün gibi düük dozlar, örnein 6 onsluk bir fincan kahve veya iki ila üç 12 onsluk kafeinli merubat gibi, dier intoleranslarn yan sra uyku bozukluuna neden olmaya devam edebilir. Düzenli olmayan kafein kullanclar uyku bozukluuna kar en az kafein toleransna sahiptir. [107] Baz kahve içenler, istenmeyen uykuyu bozucu etkilere kar tolerans gelitirirken, dierleri görünüe göre böyle deildir. [108]Kafeinin biyolojik yar ömrü – vücudun bir dozun yarsn ortadan kaldrmas için gereken süre – gebelik, dier ilaçlar, karacier enzim fonksiyon seviyesi (kafein metabolizmas için gerekli) ve ya gibi faktörlere göre bireyler arasnda büyük ölçüde deiir. Salkl yetikinlerde kafeinin yarlanma ömrü 3 ile 7 saat arasndadr. [7] Sigara içmek yar ömrü% 30-50 azaltrken [108] oral kontraseptifler yarlanma süresini ikiye katlayabilir [108] ve gebelik üçüncü trimesterde bunu 15 saate kadar çkarabilir. [108] Yenidoanlarda yar ömür 80 saat veya daha fazla olabilir ve yala birlikte çok hzl bir ekilde düebilir, muhtemelen 6 aylk olduunda yetikin deerinin altna düer. [108] Antidepresan fluvoksamin (Luvox), kafeinin klerensini% 90’dan fazla azaltr ve eliminasyon yar ömrünü on kattan fazla artrr; 4,9 saatten 56 saate kadar. [164]Kafein karacierde sitokrom P450 oksidaz enzim sistemi tarafndan, özellikle CYP1A2 izozimi tarafndan üç dimetilksantine [165] metabolize edilir ve bunlarn her birinin vücut üzerinde kendi etkileri vardr:Paraxanthine (% 84): Lipolizi artrr, kan plazmasnda yüksek gliserol ve serbest ya asidi seviyelerine yol açar.Theobromine (% 12): Kan damarlarn geniletir ve idrar hacmini artrr. Teobromin ayrca kakao çekirdeindeki (çikolata) temel alkaloiddir.Teofilin (% 4): Bronlarn düz kaslarn gevetir ve astm tedavi etmek için kullanlr. Bununla birlikte teofilinin terapötik dozu, kafein metabolizmasndan elde edilen düzeylerden birçok kez daha fazladr. [70]1,3,7-Trimetilürik asit, minör bir kafein metabolitidir. [7] Bu metabolitlerin her biri ayrca metabolize edilir ve daha sonra idrarla atlr. Kafein, iddetli karacier hastal olan kiilerde birikerek yar ömrünü uzatabilir. [166]2011 ylnda yaplan bir inceleme, artan kafein almnn, kafein katabolizma orann artran iki gendeki bir varyasyonla ilikili olduunu buldu. Her iki kromozomda da bu mutasyona sahip olan denekler, dierlerine göre günde 40 mg daha fazla kafein tüketmitir. [167] Bu, muhtemelen, benzer bir istenen etkiyi elde etmek için daha yüksek bir alm ihtiyacndan kaynaklanmaktadr, genin daha fazla alkanlk teviki için bir eilim yaratmasndan deil.

Kimya -> KAFEIN

Saf susuz kafein, 235-238 ° C erime noktasna sahip ac tad olan, beyaz, kokusuz bir tozdur. [8] [9] Kafein, oda scaklnda (2 g / 100 mL) suda orta derecede çözünür, ancak kaynar suda (66 g / 100 mL) çok çözünür. [168] Ayrca etanolde (1.5 g / 100 mL) orta derecede çözünür. [168] Zayf baziktir (elenik asidin pKa’s = ~ 0.6), protonlanmas için güçlü asit gerektirir. [169] Kafein herhangi bir stereojenik merkez içermez [170] ve bu nedenle airal bir molekül olarak snflandrlr. [171]

Kafeinin ksantin çekirdei, bir pirimidindiyon ve imidazol olmak üzere iki kaynam halka içerir. Pirimidindiyon ise, arlkl olarak, azot atomlarnn bitiik amid karbon atomlarna çift baland yerde bir zvitteriyonik rezonansta var olan iki amid fonksiyonel grubu içerir. Dolaysyla, pirimidindiyon halka sistemindeki alt atomun tümü sp2 hibridize ve düzlemseldir. Bu nedenle, kafeinin kaynam 5,6 halka çekirdei toplam on pi elektron içerir ve dolaysyla Hückel’in kuralna göre aromatiktir. [172]

Sentez -> KAFEIN

Camellia ve Coffea türleri tarafndan gerçekletirilen bir biyosentetik kafein yolu. [173] [174]Kafeinin bir laboratuar sentezi [175] [176]Kafein biyosentezi, farkl türler arasnda yaknsak evrimin bir örneidir. [177] [178] [179]Kafein, dimetilüre ve malonik asit ile balayarak laboratuvarda sentezlenebilir. [Açklama gerekli] [175] [176] [180]Ticari kafein kaynaklar genellikle sentetik olarak üretilmez, çünkü kimyasal, kafeinsizletirme ileminin bir yan ürünü olarak kolayca elde edilebilir. [181]

Kafeinsizletirme -> KAFEIN

Ana madde: Kafeinsizletirme

Saflatrlm kafeinin lifli kristalleri. Karanlk alan mikroskobu görüntüsü, yaklak 7 mm × 11 mm Kafein ve kafeinsiz kahve üretmek için kahveden kafein ekstraksiyonu birkaç çözücü kullanlarak gerçekletirilebilir. Ana yöntemler unlardr:

Dier baz kafein analoglar:

Dipropilsiklopentilksantin

8-Siklopentil-1,3-dimetilksantin

8-Fenilteofilin

Tanenlerin çökelmesi

Kafein, cinchonin, kinin veya striknin gibi dier alkaloidlerde olduu gibi polifenolleri ve tanenleri çökeltir. Bu özellik bir niceleme yönteminde kullanlabilir. [188]

Doal oluum -> KAFEIN

Kavrulmu kahve çekirdekleri

Otuz civarnda bitki türünün kafein içerdii bilinmektedir. [189] Ortak kaynaklar, yetitirilen iki kahve bitkisinin, Coffea arabica ve Coffea canephora’nn “çekirdekleri” dir (miktar deiir, ancak% 1,3 tipik bir deerdir); ve kakao bitkisinden Theobroma cacao; çay bitkisinin yapraklar; ve kola fst. Dier kaynaklar arasnda yaupon holly’nin yapraklar, Güney Amerika kutsal yerba mate ve Amazon kutsal guayusa; ve Amazon akçaaaç guarana meyvelerinden elde edilen tohumlar. Dünyann dört bir yanndaki lman iklimler, ilgisiz kafein içeren bitkiler üretti.

Bitkilerdeki kafein doal bir böcek ilac görevi görür: bitki üzerinde beslenen yrtc böcekleri felç edebilir ve öldürebilir. [190] Yeillik gelitirdiklerinde ve mekanik korumadan yoksun olduklarnda kahve fidelerinde yüksek kafein seviyeleri bulunur. [191] Buna ek olarak, kahve fidelerinin çevresindeki topraklarda yüksek kafein seviyeleri bulunur, bu da yakndaki kahve fidelerinin tohum çimlenmesini engeller ve böylece en yüksek kafein seviyelerine sahip fidelere hayatta kalmak için mevcut kaynaklar için daha az rakip verir. [192] Kafein, çay yapraklarnda iki yerde depolanr. lk olarak, polifenollerle kompleks oluturduu hücre boluklarnda. Bu kafein, otçulluu caydrmak için muhtemelen böceklerin az ksmlarna salnr. kinci olarak, muhtemelen patojenik mantarlarn vasküler demetlere girip kolonize etmesini engelledii vasküler demetler etrafnda. [193] Nektardaki kafein, bal arlar gibi tozlayclarn ödül hafzasn güçlendirerek polen üreten bitkilerin üreme baarsn artrabilir. [194]Kafein içeren çeitli bitkilerden yaplan içeceklerin yutulmasnn etkilerindeki farkl alglar, bu içeceklerin ayn zamanda kardiyak uyarclar teofilin ve teobromin ve kafein ile çözünmez kompleksler oluturabilen polifenoller dahil olmak üzere dier metilksantin alkaloidlerinin çeitli karmlarn içermesiyle açklanabilir. . [195]

Ürünler -> KAFEIN

Ayrca baknz: Kafeinli içecek

Seçilmi gda ve ilaçlarda kafein içerii [196] [197] [198] [199] [200]

Ürün Hizmet boyutu Hizmet bana Kafein (mg) Kafein (mg / L)

Kafein tableti (normal younlukta) 1 tablet 100 –

Kafein tableti (ekstra güçlü) 1 tablet 200 –

Kafein içeren ürünler arasnda kahve, çay, alkolsüz içecekler (“kola”), enerji içecekleri, dier içecekler, çikolata, [202] kafein tabletleri, dier oral ürünler ve inhalasyon ürünleri bulunur. Amerika Birleik Devletleri’nde 2020 ylnda yaplan bir aratrmaya göre kahve, orta yal yetikinlerde kafein almnn balca kayna iken, ergenlerde alkolsüz içecekler ve çay ana kaynaklardr. [60] Enerji içecekleri yetikinlere kyasla ergenlerde daha çok kafein kayna olarak tüketilir. [60]

çecekler -> KAFEIN

Kahve

Dünyann balca kafein kayna, kahvenin demlendii kahve çekirdeidir (kahve bitkisinin tohumu). Kahvede bulunan kafein içerii, kahve çekirdeinin türüne ve kullanlan hazrlama yöntemine bal olarak büyük ölçüde deiir; [203] belirli bir çaldaki çekirdekler bile konsantrasyonda farkllklar gösterebilir. Genel olarak, bir porsiyon kahve, tek atlk (30 mililitre) arabica çeidi espresso için 80 ila 100 miligram arasnda, bir fincan (120 mililitre) damla kahve için yaklak 100-125 miligram arasnda deiir. [204] [205 ] Arabica kahvesi tipik olarak robusta çeidinin yars kadar kafein içerir. [203] Genel olarak, koyu kavrulmu kahvede hafif kavurmalara göre çok az kafein vardr çünkü kavurma ilemi çekirdekteki kafein içeriini küçük bir miktar azaltr. [204] [205]

Çay

Çay, kuru arla göre kahveden daha fazla kafein içerir. Bununla birlikte, tipik bir porsiyon, edeer bir porsiyon kahveye kyasla üründen daha az kullanldndan çok daha azn içerir. Ayrca kafein içeriine katkda bulunanlar, büyüme koullar, ileme teknikleri ve dier deikenlerdir. Bu nedenle çaylar çeitli miktarlarda kafein içerir. [206]Çay, küçük miktarlarda teobromin ve kahveden biraz daha yüksek seviyelerde teofilin içerir. Hazrlk ve dier birçok faktörün çay üzerinde önemli bir etkisi vardr ve renk, kafein içeriinin çok zayf bir göstergesidir. Örnein, soluk Japon yeil çay gyokuro gibi çaylar, çok az kahve içeren lapsang souchong gibi çok daha koyu çaylardan çok daha fazla kafein içerir. [206]

Alkolsüz içecekler ve enerji içecekleri

Kafein ayn zamanda kola fstndan hazrlanan kola gibi alkolsüz içeceklerin de yaygn bir bileenidir. Alkolsüz içecekler tipik olarak 12 onsluk porsiyon bana 0 ila 55 miligram kafein içerir. [207] Red Bull gibi enerji içecekleri ise porsiyon bana 80 miligram kafeinden balayabilir. Bu içeceklerdeki kafein, ya kullanlan bileenlerden kaynaklanr ya da kafeinsizletirme ürününden ya da kimyasal sentezden türetilen bir katk maddesidir. Enerji içeceklerinin ana bileeni olan guarana, doal olarak oluan yava salimli bir yardmc maddede az miktarda teobromin ve teofilin içeren büyük miktarlarda kafein içerir. [208]

Dier içecekler -> KAFEIN

Mate, Güney Amerika’nn birçok yerinde popüler bir içecektir. Hazrlan, Güney Amerika kutsal yerba dostunun yapraklaryla bir kaba doldurmak, yapraklarn üzerine scak ama kaynamadan su dökmek ve bir pipetle içmek, sadece svy çekmek için filtre görevi gören bombilla ve yerba gitmez. [209]

Guaraná, Brezilya meneli, Guaraná meyvesinin tohumlarndan yaplan merubattr.

Ekvador kutsal aac Ilex guayusa’nn yapraklar, guayusa çay yapmak için kaynar suya konur. [210]

Yaupon kutsal aac olan Ilex vomitoria’nn yapraklar, yaupon çay yapmak için kaynar suya yerletirilir.

Çikolata

Kakao çekirdeklerinden elde edilen çikolata, az miktarda kafein içerir. Çikolatann zayf uyarc etkisi, teobromin ve teofilin kombinasyonunun yan sra kafeinden kaynaklanyor olabilir. [211] Bir sütlü çikolatann tipik 28 gramlk bir porsiyonu, bir fincan kafeinsiz kahve kadar kafein içerir. Arlk olarak bitter çikolata, kahveye göre bir ila iki kat daha fazla kafein içerir: 100 g’da 80-160 mg. Yaklak% 90 gibi daha yüksek kakao yüzdeleri, yaklak olarak 100 g bana 200 mg’dr ve bu nedenle, 100 gramlk% 85’lik bir kakao çikolatasnda yaklak 195 mg kafein bulunur. [197]

Tabletler -> KAFEIN

Dozsuz 100 mg kafein tabletleri

Tabletler kahve, çay ve dier kafeinli içeceklere göre uygunluk, bilinen dozaj ve birlikte eker, asit ve sv almndan kaçnma gibi çeitli avantajlar sunar. Kafein tableti üreticileri, farmasötik kalitede kafein kullanmann zihinsel uyankl artrdn iddia ediyor. [Kaynak belirtilmeli] Bu tabletler, snavlar için okuyan örenciler ve uzun saatler boyunca çalan veya araba kullanan kiiler tarafndan yaygn olarak kullanlmaktadr. [212]

Dier oral ürünler

Bir ABD irketi, oral çözülebilir kafein eritleri pazarlyor. [213] Baka bir alm yolu da kafeinli bir dudak kremi olan SpazzStick’tir. [214] Alert Energy Kafein Sakz, 2013 ylnda Amerika Birleik Devletleri’nde piyasaya sürüldü, ancak FDA tarafndan gdalardaki eklenen kafeinin salk üzerindeki etkilerine ilikin bir aratrmann duyurulmasnn ardndan gönüllü olarak geri çekildi. [215]

Solunanlar

Kafein anahtar içerikli olmak üzere, tescilli takviye karmlar sunan inhalerler sunan pazarlanan birkaç ürün var. [216] 2012 ylnda FDA, bu inhalerleri pazarlayan irketlerden birine, inhale kafein hakknda mevcut güvenlik bilgilerinin eksikliinden endielerini dile getiren bir uyar mektubu gönderdi. [217]

Dier ilaçlarla kombinasyonlar -> KAFEIN

Baz içecekler kafeinli alkollü içecek oluturmak için alkolü kafeinle birletirir. Kafeinin uyarc etkileri, alkolün depresan etkilerini maskeleyebilir ve potansiyel olarak kullancnn sarholuk seviyesi konusundaki farkndaln azaltabilir. Bu tür içecekler, güvenlik endieleri nedeniyle yasaklara konu olmutur. Özellikle, Amerika Birleik Devletleri Gda ve laç Dairesi malt likörlü içeceklere eklenen kafeini “güvenli olmayan gda katk maddesi” olarak snflandrmtr. [218]

Ya ba, metamfetamin ve kafein kombinasyonunu içerir.

Propifenazon / parasetamol / kafein gibi ar kesiciler, kafeini bir analjezik ile birletirir.

Tarih

Keif ve kullanmn yaylmas

Yerde bir paspasn etrafnda oturan bir düzine yal ve orta yal adamn eski bir fotoraf. Öndeki bir adam bir havann yanna oturur ve bir sopay öütmeye hazr hale getirir. Karsndaki bir adam uzun bir kak tutar.

1900 dolaylarnda Filistin’de kahvehane

Ana maddeler: Çikolatann Tarihi, Kahvenin Tarihi, Çayn Tarihi ve Yerba Mate Tarihi

Çin efsanesine göre, MÖ 3000 yllarnda hüküm sürdüü söylenen Çin imparatoru Shennong, baz yapraklarn kaynar suya dütüünde, bunun kokulu ve canlandrc bir içecein ortaya çktn fark ettiinde yanllkla çay kefetti. [219] Shennong’dan ayrca Lu Yu’nun çay konusunda erken dönem ünlü bir eseri olan Cha Jing’de bahsedilir. [220]Kahve içmenin ya da kahve bitkisinin bilgisinin en eski güvenilir kant, on beinci yüzyln ortalarnda, Güney Arabistan’daki Yemen’deki Sufi manastrlarnda ortaya çkt. [221] Kahve, Mocha’dan Msr ve Kuzey Afrika’ya yayld ve 16. yüzylda Orta Dou’nun geri kalanna, ran’a ve Türkiye’ye ulat. Kahve içmek Ortadou’dan talya’ya, oradan da Avrupa’nn geri kalanna yayld ve kahve bitkileri Hollandallar tarafndan Dou Hint Adalar’na ve Amerika’ya tand. [222]Kola cevizi kullanmnn kökeni eski gibi görünüyor. Birçok Bat Afrika kültüründe, hem özel hem de sosyal ortamlarda, canll yeniden salamak ve açlk sanclarn hafifletmek için çinenir.Kakao çekirdei kullanmnn en eski kant, MÖ 600’e tarihlenen eski bir Maya kabnda bulunan kalntlardan geliyor. Ayrca çikolata, xocolatl ad verilen ac ve baharatl bir içecekte, genellikle vanilya, ac biber ve achiote ile tatlandrlrd. Xocolatl’n, muhtemelen teobromin ve kafein içeriine atfedilebilecek bir inanç olan yorgunlukla mücadele ettiine inanlyordu. Çikolata, Kolomb öncesi Mezoamerika’da önemli bir lüks mald ve kakao çekirdekleri genellikle para birimi olarak kullanlyordu. [223]Xocolatl, spanyollar tarafndan Avrupa’ya tantld ve 1700 ylnda popüler bir içecek haline geldi. spanyollar ayrca kakao aacn Bat Hint Adalar ve Filipinler’e de tantt. “Kara fasulye” olarak bilinen simya ilemlerinde kullanld. [Kaynak belirtilmeli]Yaupon holly’nin (Ilex vomitoria) yapraklar ve gövdeleri, Yerli Amerikallar tarafndan asi veya “siyah içecek” ad verilen bir çay demlemek için kullanld. [224] Arkeologlar, bu kullanmn antik çalara kadar uzanan kantlarn buldular, [225] muhtemelen Geç Arkaik zamanlara [224] aittir.

Kimyasal tanmlama, izolasyon ve sentez

Pierre Joseph Pelletier

1819’da Alman kimyager Friedlieb Ferdinand Runge ilk kez nispeten saf kafeini izole etti; buna “Kaffebase” (yani kahvede var olan bir baz) adn verdi. [226] Runge’ye göre, bunu Johann Wolfgang von Goethe’nin emriyle yapt. [A] [228] 1821’de kafein hem Fransz kimyager Pierre Jean Robiquet hem de baka bir çift Fransz kimyager Pierre-Joseph Pelletier ve Joseph tarafndan izole edildi. Bienaimé Caventou, sveçli kimyager Jöns Jacob Berzelius’un yllk dergisine göre. Dahas Berzelius, Fransz kimyagerlerinin keiflerini Runge’nin veya birbirlerinin çalmalaryla ilgili herhangi bir bilgiden bamsz olarak yaptklarn belirtti. [229] Ancak Berzelius daha sonra Runge’nin kafein ekstraksiyonundaki önceliini kabul etti: [230] “Ancak bu noktada, Runge’nin (Phytochemical Discoveries, 1820, sayfa 146-147) ayn yöntemi belirlediinden ve Kafeini, bu maddenin kefinin genellikle atfedildii Robiquet’ten bir yl önce Caffeebase ad altnda, Paris’teki Eczaclar Birlii toplantsnda yapt ilk sözlü duyuruyu yapm olarak tanmlad. “Pelletier’in kafein hakkndaki makalesi, terimi basl olarak kullanan ilk makale oldu (Franszca’da Caféine, kahve için Franszca kelime: café’den). [231] Berzelius’un hesabn doruluyor:Kafein, isim (diil). 1821’de Bay Robiquet tarafndan kahvede bulunan kristalize edilebilir madde. Ayn dönemde – kahvede kinin ararlarken, birçok doktor tarafndan kahvenin atei düüren bir ilaç olduu ve kahvenin knakna [kinin] aacyla ayn aileye ait olduu düünüldüü için – kendi adna, Messrs. ve Caventou kafein elde etti; ancak aratrmalarnn farkl bir amac olduu ve aratrmalar bitmedii için bu konudaki öncelii Bay Robiquet’e braktlar. Sayn Robiquet’in okuduu kahvenin analizini Eczaclar Birlii’ne neden yaynlamadn bilmiyoruz. Yaynlanmas, kafeini daha iyi tanmamza ve bize kahvenin bileimi hakknda doru fikirler vermemize izin verirdi …Robiquet, saf kafeinin özelliklerini izole eden ve açklayan ilk kiilerden biriydi [232], buna karn Pelletier bir element analizi yapan ilk kiiydi. [233]1827’de, M. Oudry çaydan “théine” i izole etti [234], ancak 1838’de Mulder [235] ve Carl Jobst [236] tarafndan teinin aslnda kafeinle ayn olduu kantland.1895’te Alman kimyager Hermann Emil Fischer (1852-1919), ilk olarak kimyasal bileenlerinden (yani “toplam sentez”) kafeini sentezledi ve iki yl sonra, bileiin yapsal formülünü de türetti. [237] Bu, Fischer’e 1902’de Nobel Ödülü verilen çalmann bir parçasyd. [238]

Tarihi düzenlemeler

Kahvenin uyarc olarak ilev gören baz bileikler içerdii kabul edildiinden, önce kahve ve daha sonra kafein de bazen düzenlemeye tabi tutuldu. Örnein, 16. yüzylda Mekke ve Osmanl mparatorluu’ndaki slamclar kahveyi baz dersler için yasad yaptlar. [239] [240] [241] ngiltere Kral II. Charles 1676’da [242] [243] Prusyal II. Frederick 1777’de yasaklad [244] [245] ve 1756 ile 1823 yllar arasnda sveç’te çeitli zamanlarda kahve yasakland.1911’de, Amerikan hükümeti Tennessee, Chattanooga’da 40 varil ve 20 fç Coca-Cola urubu ele geçirdiinde, kafein, içeceindeki kafeinin “sala zararl” olduunu iddia ettiinde, belgelenmi en eski salk korkularndan birinin odak noktas haline geldi. [ 246] Yargç Coca-Cola lehine karar verse de, 1912’de ABD Temsilciler Meclisi’ne Saf Gda ve laç Yasasn deitirmek için iki yasa tasars sunuldu ve “alkanlk oluturan” ve “zararl” maddeler listesine kafein eklendi. bir ürünün etiketinde listelenmelidir. [247]

Toplum ve kültür -> KAFEIN

Yönetmelikler

Amerika Birleik Devletleri’ndeki Gda ve laç Dairesi (FDA) u anda yalnzca% 0,02’den daha az kafein içeren içeceklere izin vermektedir; [248] ancak diyet takviyesi olarak satlan kafein tozu düzenlenmemitir. [249] Çou hazr ambalajl gdann etiketinde, kafein gibi gda katk maddeleri de dahil olmak üzere, azalan oran srasna göre bileenlerin bir listesini beyan etmesi yasal bir gerekliliktir. Bununla birlikte, kafeinin zorunlu kantitatif etiketlemesi için düzenleyici bir hüküm yoktur (örnein, belirtilen porsiyon büyüklüü bana miligram kafein). Doal olarak kafein içeren bir dizi gda maddesi vardr. Bu içerikler gda içerii listelerinde görünmelidir. Bununla birlikte, “gda katk maddesi kafein” durumunda olduu gibi, doal kafein kaynaklar olan bileenler içeren kompozit gdalardaki kantitatif kafein miktarn belirlemeye gerek yoktur. Kahve veya çikolata genel olarak kafein kaynaklar olarak kabul edilirken, baz içerikler (örnein guarana, yerba maté) muhtemelen kafein kayna olarak daha az tannmaktadr. Bu doal kafein kaynaklar için, bir gda etiketinin kafein varln tanmlamasn veya gdada bulunan kafein miktarn belirtmesini gerektiren herhangi bir düzenleyici hüküm yoktur. [250]

Tüketim

Küresel kafein tüketiminin ylda 120.000 ton olduu tahmin ediliyor ve bu da onu dünyann en popüler psikoaktif maddesi yapyor. [11] Bu, her gün her insan için bir porsiyon kafeinli içecek anlamna gelir. [11] Kafein tüketimi 1997 ile 2015 yllar arasnda sabit kalmtr. [251] Kahve, çay ve alkolsüz içecekler en önemli kafein kaynaklardr ve enerji içecekleri tüm ya gruplarnda toplam kafein almna çok az katkda bulunur. [251]

Dinler -> KAFEIN

Baz Tanr Kilisesi (Restorasyon) taraftarlar ve Hristiyan Bilim nsanlar kafein tüketmiyor. [Kaynak belirtilmeli] Yakn zamana kadar Yedinci Gün Adventistleri Kilisesi üyelerinden “kafeinli içeceklerden kaçnmalarn” istedi, ancak bunu vaftiz yeminlerinden çkard ( hala politika olarak çekimser kalmay tavsiye ediyor). [252] Bu dinlerden bazlar, kiinin tbbi olmayan, psikoaktif bir maddeyi tüketmemesi gerektiine veya bamllk yapan bir maddeyi tüketmemesi gerektiine inanyor. sa Mesih’in Son Zaman Azizler Kilisesi, kafeinli içeceklerle ilgili olarak unlar söylemitir: “… Salk uygulamalarn açklayan Kilise vahiyinde (Doktrin ve Antlamalar 89) kafein kullanmndan söz edilmiyor. Kilise’nin salk ilkeleri yasaklar. alkollü içecekler, sigara içilmesi veya tütün çinenmesi ve ‘scak içecekler’ – Kilise liderleri tarafndan özellikle çay ve kahveden bahsetmek için öretilir. “[253]

Gaudiya Vaishnavas da genellikle kafeinden kaçnr, çünkü zihni bulutlandrdna ve duyular ar uyardna inanrlar. [254] Bir guru altnda balayabilmek için en az bir yldr hiç kafein, alkol, nikotin veya dier ilaçlarn olmam olmas gerekir. [255]

Kafeinli içecekler günümüzde Müslümanlar tarafndan yaygn olarak tüketilmektedir. 16. yüzylda baz Müslüman yetkililer, bunlar slami beslenme yasalarna göre yasak “sarho edici içecekler” olarak yasaklamak için baarsz giriimlerde bulundu. [256] [257]

Dier organizmalar

Örümcek alarnda kafein etkisi

Ayrca baknz: Psikoaktif ilaçlarn hayvanlar üzerindeki etkisi

Yakn zamanda kefedilen bakteri Pseudomonas putida CBB5 saf kafein üzerinde yaayabilir ve kafeini karbondioksit ve amonyaa ayrabilir. [258]

Kafein, kular [259] ve köpekler ve kediler için [260] toksiktir ve yumuakçalar, çeitli böcekler ve örümcekler üzerinde belirgin bir olumsuz etkiye sahiptir. [261] Bu, en azndan ksmen, bileii metabolize etme yeteneinin zayf olmasndan ve birim arlk bana belirli bir doz için daha yüksek seviyelere neden olmasndan kaynaklanmaktadr. [157] Kafeinin ayrca bal arlarnn ödül hafzasn güçlendirdii bulunmutur. [194]

KAFEIN NEDR, NE E YARAR, FAYDALARI VE ZARARLARI

Kafein, doru ölçüde tüketilmesi halinde oldukça faydal ve sihirli etkileri olan bir maddedir. Ancak yer yer zararl yönleri de görülmektedir. Dünyann en yüksek kafein oranna sahip kahvesinin üreticisi olarak pozisyonumuzdan bamsz, tamamen objektif bir ekilde kafeini inceledik. Kafein nedir, kafein etkileri, kafein faydalar, kafein zararlar gibi akla taklan sorular bu yazmzda sizin için detaylca cevapladk.

Aratrma

KAFEIN Fiziksel tanm

Kafein, genellikle birlikte eriyen kokusuz beyaz toz veya beyaz parlak ineler olarak görünür. Ac tat. Sudaki çözümler turnusol için nötrdür. Kokusuz. (NTP, 1992)

KAFEIN Renk / Form Yardm Beyaz, prizmatik kristaller

KAFEIN Koku Yardm Kokusuz

KAFEIN Tat Yardm Ac tat

KAFEIN Kaynama Noktas 760 mm Hg’de 352 ° F (süblimler) (NTP, 1992)

KAFEIN Erime Noktas 460 ° F (NTP, 1992)

KAFEIN Çözünürlük 73 ° F’de 10 ila 50 mg / mL (NTP, 1992)

KAFEIN Younluk 64 ° F’de 1.23 (NTP, 1992)

KAFEIN Buhar Basnc 9.0X10-7 mm Hg, 25 ° C’de / Ekstrapole edilmi /

KAFEIN LogP -0.07

KAFEIN LogS -0,97

KAFEIN Ayrtrma Ayrmaya kadar stldnda, / nitrojen oksitler / zehirli dumanlar çkarr.

KAFEIN pH = 6,9 (% 1 çözelti)

KAFEIN Koku Eii Aroma eik deerleri: 29 ila 300 ppm’de alglama

KAFEIN Caco2 Geçirgenlik -4.41

KAFEIN pKa 14

KAFEIN Ayrlma Sabitleri 25 ° C’de pKa = 14,0

KAFEIN Çarpma Kesiti 140,9 Å² [M + H] + [CCS Tipi: DT, Yöntem: Agilent tune karm (Agilent) ile kalibre edilmi tek alan]

KAFEIN Dier Deneysel Özellikler Turnusol için nötr çözüm

KAFEIN UV Spectra MAKS EMME (ALKOL): 227 NM (LOG E = 4,3); 235 NM (LOG E = 4,3); 274 NM (LOG E = 4,3)

KAFEIN Dier Spectra SADTLER REFERANS NUMARASI: 209 (IR, GRATING)

KAFEIN likili Kimyasallar Kafein, monohidrat; 5743-12-4

KAFEIN laç Snflar Bitkisel ve Diyet Takviyeleri

KAFEIN Farmakoloji Kafein, merkezi sinir sistemini (CNS) uyarr, uyankl artrr ve bazen huzursuzlua ve ajitasyona neden olur. Düz kas gevetir, kalp kas kaslmasn uyarr ve atletik performans artrr. [A298, T716, L9857] Kafein, mide asidi salglanmasn tevik eder ve gastrointestinal hareketlilii arttrr. Genellikle analjezikler ve ergot alkaloidleri içeren ürünlerde birletirilerek migren ve dier ba ars türlerinin semptomlarn hafifletir. Son olarak, kafein hafif bir diüretik görevi görür. [T716]

CAFFEINE ANHYDROUS (SUSUZ KAFEIN)

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