Naturally occurring in plants and synthetic caffeine doses.
1. Caffeine consumption around the World
Global caffeine consumption is estimated to be around 120,000 tonnes per year, which corresponded to one cup of coffee per day for every human on the planet. Based on the statistics, the top tea-producing countries in the world are: China, India, Kenya, Sri Lanka, Turkey, Indonesia, Vietnam, Japan, Iran and Argentina. Main producers and exporters of coffee are: Brazil, Vietnam, Colombia, Indonesia, Ethiopia, India, Honduras, Uganda, Mexico and Guatemala, Figure 1.
Caffeine consumption is the highest in tonnes in the United States (971), followed by Brazil (969), Germany (425), Italy (211) and France (202). About 79% of total consumed caffeine comes from coffee, 15% from tea, only 3% from mate and 4% from cocoa [1]. In general, people in the west drink more coffee, while the eastern world drinks more tea, Figure 1. Tea consumption per capita predominates in Turkey, Russia, Iran, Mauritania, Syria and China. In Paraguay, Argentina and Brazil, the consumption of mate is dominant. The rest of the world prefers coffee. Europeans are the world’s biggest coffee drinkers. Coffee consumption in Europe varies from around 10 kg per capita per year in the Nordic countries (Finland, Norway) to around 3 kg per capita per year in the United Kingdom and most Eastern Europe countries. Annual consumption over 5 kg per capita per year in Brazil is exceptionally high among over 60 coffee exporters. The largest cocoa consumption is noted in Switzerland, Germany, Ireland, the United Kingdom and Norway. The world’s biggest Coca-Cola drinkers are in Mexico, Chile, the United States, Panama and Argentina. Energy drinks containing caffeine like Red Bull, Monster, Suntory, Rockstar have experienced a considerable growth in popularity in the last 25 years, but still represents only 1% of the overall non-alcoholic beverages market. Austria led the global per capita consumption and is followed by Ireland, the United Kingdom, Switzerland, the United States and Australia. Caffeine, in any form, is consumed daily by about 90% of adults, which makes this psychoactive, but legal substance the world’s most widely used drug.
Despite caffeine huge popularity and its countless studies, there is still much confusion, inconsistencies and contradictions in the results, poorly known side effects and unknown applications.
2. Historical aspects
Caffeine-containing species from
According to Cha Jing by Lu Yu, a mythical ruler of prehistoric China Shen Nong (also known as Wugushen or Wuguxiandi), reigning 3000 BC, discovered tea, when a few leaves of the nearby tree
The history of coffee has its beginnings in the sixth-century Ethopia [11], however, Ethiopian Galla tribe ground up coffee beans (actually the pit of the berry), mixed them with animal fat and consumed as an energy food, much earlier. The famous legend attributes it to the shepherd of Caldas from Abyssinia, who in 525 AD noticed that the goats that had grazed among the bushes became excited and sleep-deprived. After sampling the fruit from the bushes growing there, he experienced a similar surge of strength. Arab traders brought coffee to Yemen [12]. The oldest written references to coffee (‘
Another source of caffeine is cocoa (
Kola (
Another old, but much less popular source of caffeine are the leaves and stalks of three species of holly tree genus
Also guaraná (
3. Health considerations
For a long time, it has been a dilemma if coffee and tea are non-toxic and which is better for health—tea or coffee. From among all natural sources of caffeine, only tea started a career as a medicine and became a beverage in the course of time. In the eighteenth century, the Swedish king Gustav III, proposed the twin brothers who were sentenced to death for murder, a death row pardon in exchange for their participation in the scientific experiment [38]. One of the twins had to drink four cups of coffee a day, the other four cups of tea a day. A group of professors from Swedish Kings Academy of Sciences examined them to check the influence of these beverages on their organisms. The twins drank and drank, in the meantime, the king was murdered, the professors died. The first died the tea-drinking brother, while the compulsory coffee fun lived several years longer. But the tea drinker died at the age of 84, which at the time when the average life span was about 40, was considered as unbelievable achievement. What about the final verdict? No doubt by this simple long-lasting experiment, both dietary habits were considered as an important factor positively influencing human health. But the question remained which turned out better for health, tea or coffee, and first of all what factors were responsible for it.
Although all these natural sources of caffeine have been used for a long time as a beverage or drug, the fact that caffeine is the main factor responsible for their effect remained a mystery. Only in 1819, at the personal request of Johann Wolfgang von Goethe, the relatively pure chemical form of caffeine was isolated by Friedrich Ferdinand Runge [11], who called it ‘
Caffeine source | Origin | Plant | Plant part | Caffeine concentration per milligram (%) | No. of all chemical compounds |
---|---|---|---|---|---|
Tea | natural | Leaf or shoot | 4.8–9.3* | 771 | |
Coffee | natural | Bean or fruit | 0.06–3.2* | 154 | |
Cacao | natural | Seed | 0.062–1.29* | 261 | |
Mate | natural | Leaf | 0.2–2.0* | 39 | |
Guarana | natural | Seed or fruit | 0.9–7.6* | 23 | |
Kola | natural | Seed | 1.5–2.5* | 9 | |
Citrus | natural | Leaf or flower | 0–0.008* | 495 | |
Caffeine anhydrous | synthetic | - | >98.5 | 1 | |
Dicaffeine malate | synthetic | - | 65–70 | 2 | |
Caffeine citrate | synthetic | - | 45–55 | 3 |
When it seemed that everything was known about the structure of caffeine, it turned out that the matter was much more complicated—an untypical polymorphism of caffeine was discovered [43]. An anhydrous caffeine exists in two enatiotropically related polymorphic forms: stable (phase II or β-form) which melts at 508K and metastable (phase I or α-form) melting at 512K [44] and each form displays different physicochemical properties [45].
Some authors consider the existence of phase III [46], while the others a mixture of two phases I and II [47]. The phenomenon of polymorphism further complicates the co-existence of structural and dynamical disorder. A number of experimental techniques (e.g. X-ray [47–49], synchrotron X-ray diffraction [50] mid-infrared (MIR), near-infrared (NIR) Raman spectroscopies [51, 52], dielectric measurements [46], NMR-NQR spectroscopy [53, 54]) have been applied to clarify the matter but still new doubts arise. Screening of polymorphs is of importance due to the differences in solubility, long-term stability, dissolution rate and bioavailability. Many novel beverages like soda or energy drinks [55] as well as drugs contain pure caffeine, thus there is considerable public health interest in its effects on humans.
Because caffeine is the most widely used stimulant, its metabolism and effect on the human body have been intensively studied. Caffeine is known to stimulate the central nervous system (affects sleep, arousal, cognition, learning and memory), as well as muscular, respiratory and circular systems [56–59]. But it is supposed that a broad spectrum of caffeine effects is a result of action of its metabolites. Caffeine demethylation yields to about 4–5.4% of theophylline, 10.8–12% of theobromine and 81.5–84% of paraxanthine [60]. While caffeine, theophylline and theobromine naturally occur in about 80 green plants species, paraxanthine does not, because it is not accumulated in plants due to the very slow N1-methylation of 7-methylxanthine [61, 62]. But, paraxanthine discovered in human urine by Solmon [61] results from demethylation of caffeine at the 3-position through the catalytic action of polymorphic cytochrome P450 subtypes 1A2 (90%) and 1A1, 2E1, 3A4 and 2D6 (10%) [63, 64]. It was discovered that caffeine and its metabolites belong to the pharmacological group of adenosine A-receptor (A1, A2A, A2B and A3) antagonists [65]. The A1 and A2 receptors bind caffeine at low doses and the A2B receptor at high doses. The A3 is caffeine insensitive. Caffeine and its metabolites theophylline and theobromine act primarily as non-selective antagonists at A1 and A2A receptors in both human central nervous system and heart. Surprisingly, only paraxanthine acts similarly to caffeine [66], theobromine acts as vasodilator, diuretic and heart stimulant [67], theophylline relaxes smooth muscles of the bronchi and is effective in chronic obstructive pulmonary disease and asthma [68]. Theobromine is a weaker antagonist of adenosine receptors and therefore has a lesser impact on central nervous system, but stronger on heart. Most caffeine activity has been attributed to this antagonism and raised attention to it as potential parent compound in designing dual-target-directed drugs that simultaneously inhibit monoamine oxidase B (MAO-B) and antagonize adenosine A2A receptors (AA2AR) in the brain [69]. But caffeine also acts by the inhibition of non-adenosine receptor GABAA, an ionotropic receptor, responsible for most of the physiological activities of GABA in the central nervous system [70], while paraxanthine by the inhibition of cyclic guanosine monophosphate (cGMP), which is a key-factor for anti-inflammatory and psychostimulant effects [71].
It is known that caffeine has the ability to reduce the physical, cellular and molecular damage caused by spinal cord injury (SCI), stroke or neurodegenerative chronic diseases of Parkinson [72–74] and Alzheimer's [75–78]. But it has been reported that paraxanthine, rather than caffeine itself, reduces the risk of developing Parkinson's disease [79, 80] and contrary to caffeine it is strongly protective against neurodegeneration and loss of synaptic function [71]. Besides, caffeine exhibits inhibitory activity against diabetes II, gallstones and cirrhosis of the liver [81]. It acts as diuretic [82, 83] and stimulate tear secretion [84] which makes it helpful in the dry eye syndrome treatment [85]. Antioxidant properties of caffeine and scavenging abilities of reactive oxygen species (ROS) are associated with its ability to reduce the risk of liver, kidney, basal, colorectal and endometrial cancers [86–90]. Only recently caffeine-based gold compound has been discovered as a potential anti-cancer drug selective for ovarian cancer [91]. Caffeine mitigates the adverse mutagenic effect of ultraviolet radiation [92–95] or anti-cancer drugs [96–98]. It is difficult to study pure caffeine effect on health because it is consumed with many different additional chemical compounds (tea up to 771, coffee up 154, cacao up to 261, mate up to 39, guarana up to 23, kola up to 9 and citrus up to 495), Table 1. The problem is further complicated by the presence of metabolites of caffeine in their composition.
Such a broad spectrum of its action has stimulated a significant interest in studies of caffeine at much more sophisticated level, which should explain the differences in the individual reactions to caffeine. How we react to caffeine varies between individuals because it is largely dependent on individual genome. The earliest studies on the possible link between genes and coffee consumption date back to the 1960s [99]. Although a number of further twin experiments provided some evidence for the heritability factor in response to caffeine [100], the genetic contribution to caffeine consumption strongly depends on sex and decreases with age. Thus, true importance of individual genetic variability has been testified in larger diverse populations and focused on caffeine rich diet-disease studies at molecular level [101, 102]. According to them, five genes
Although coffee intake has been supposed to be a risk factor for heart disease, it was not related to genes. The enzyme catechol-O-methyl transferase (COMT) is known to break down catecholamines, which in high concentrations can induce a heart attack. Due to variability of the ‘
One more aspect related to the individual caffeine sensitivity should be mentioned—the difficulties in estimation of caffeine lethal dose (LD50), which is about 150–200 mg/kg [111, 112] i.e. 80–100 cups of coffee. When we compare a case of death after ingestion of 6.5 g/person and a case of survival after ingestion of 24 g/person [113, 114], the range of tolerance/intolerance makes an impression and is a warning. Too much caffeine in a few cans of energy drink had killed a 19-year-old Austrian football player, 33-year-old Brooklyn construction’s worker or three Swedish teenagers. The statistical data of victims of caffeine overdosing collected by National Poison Data System in the United States indicate that 67% of all 6309 cases of poisoning affect children and adolescents under 20. How much caffeine was in the caps of coffee which Honoré de Balzac, true coffee lover, drank in 60 coffee cups per/day? Caffeine content in popular drinks is collected in Table 2. The US Food and Drug Administration, FDA, recently issued warnings due to risk to consumers for overdosing caffeinated products containing pure powdered caffeine. A single teaspoon of pure anhydrous caffeine (5 g) is roughly equivalent to the amount in 28 cups of brewed coffee or in 6 energy shots, Table 2.
Caffeine drink | Size in oz (ml) | Caffeine (mg) | |
---|---|---|---|
Brewed | 8 (237) | 95–165 | |
Brewed, decaffeinated | 8 (237) | 2–5 | |
Espresso | 1 (30) | 47–64 | |
Espresso, decaffeinated | 1 (30) | 0 | |
Instant | 8 (237) | 63 | |
Instant, decaffeinated | 8 (237) | 2 | |
Latte or mocha | 8 (237) | 63–126 | |
Brewed black | 8 (237) | 25–48 | |
Brewed black, decaffeinated | 8 (237) | 2–5 | |
Brewed green | 8 (237) | 25–29 | |
Instant | 8 (237) | 40 | |
Ready-to-drink, bottled | 8 (237) | 5–40 | |
Green tea | 8 (237) | 25 | |
White tea | 8 (237) | 28 | |
Yerba mate | 8 (237) | 85 | |
Guayusa | 8 (237) | 66 | |
Coca Cola | 8 (237) | 24–46 | |
Pepsi Cola | 8 (237) | 25 | |
Energy drink | 8 (237) | 27–164 | |
Energy shot | 1 (30) | 40–100 | |
Liquid caffeine | 1 (30) | 500 | |
NoDoz | 1.89 (56) | 115 | |
Pure anhydrous caffeine | 1 teaspoon (5 g) | 4706 |
Similarly to humans, the individual sensitivity and additionally breed/division diversity have also been observed in animals. A poor ability to metabolize caffeine which makes it toxic to dogs, cats [115–118] and birds [119, 120] is quite well documented in domestic animals. The toxic doses are so small that single chocolate bar can kill our beloved pet. But ‘Creme Puff’ cat, the ‘oldest cat ever’, listed in the
4. Final remarks
Caffeine is a chemical component of the oldest known food plants (about 5000 years), the most widely consumed (not counting water) and the most extensively studied (1,468 books, 39,551 journal articles, 2,211 dissertations) component of diet. The seeds or seedlings of plants containing caffeine were stolen, smuggled, hated and desired, accused of demonic or radical influence—banned and baptized. The wars for plantations/colonies were fought and fortunes gained and lost. Caffeine drinks were used in religious asceticism and creative amok, behind closed doors of the cafes were written operas, manifestos and revolutions started. After all coffee seeds were used as a currency and reward, tea and chocolate were sipped by emperors, kings and tsars, coffee was loved by artists, writers, musicians, philosophers, students, popes, revolutionists and belt down by soldiers, mate is preferred by actual pope, a few presidents, writers and celebrities, and energy-drinks containing pure caffeine are nowadays trendy and desired by teens and adolescents. Caffeine under the pretence of tea or coffee changed social manners and war results—coffee has been considered the ‘
Day by day we are coming into contact with caffeine—in drinks (coffee, tea, soft-drinks as Coca-Cola, soda, chocolate, energy drinks), drugs (above 50 different drugs contain
Researchers have shown that caffeine increases memory [126], improves reaction time and logical reasoning, helps in periods of sleep restriction related to job and reduces drivers or pilots errors [127] and reduces risk of suicide [128] and depression [129]. It may protect against Parkinson’s and Alzheimer’s diseases [130]. Caffeine increases stamina during exercise [131], relieves post-workout muscle pain (cut the pain) [132] and may prevent weight gain [133]. Caffeine is beneficial in age-related chronic inflammation [134], which leads to high blood pressure, hardening of the arteries and heart diseases. It may protect against eyelid spasm [135], cataracts [136] and retinal degeneration [137], leading to blindness, against different kinds of cancer including skin cancer [138] and may prevent tinnitus (ringing in the ears) [139]. Caffeine is shown to be useful in asthma [140], lowering blood pressure [141], detoxication of the liver and the colon [142], reduction of fatty liver in non-alcoholic-related diseases [143], reduction of the liver fibrosis risk in hepatitis C [144], reduction of kidney stones risk and gout prevention [145]. It increases quality of semen in men [146] and acts as hair stimulant used in balding of men and women [147].
But due to the differences in individual sensitivity, caffeine can be easily overdosed, which may results in death—more than four cups of coffee are linked to premature death. Caffeine consumption may raise blood pressure [148], increase a risk of heart attacks among young adults [149] and gout attacks in the case of scarce caffeine overdosing [150]. It can reduce fertility [151], increase the risk of miscarriage [152], worsen the menopausal symptoms [153] and it may be a cause of breast tissue cysts in women [154]. Increased anxiety [155], depression [156], insomnia [157] and prolonged sleep deprivation problems, migraine headaches [158] are common side effects of its use. Adverse effects like incontinence [159], indigestion [160] forceful heart contractions, allergies, risk of bone fractures [161], impairment of hearing loss recovery [162], inhibition of the collagen production in the skin [163], even obesity and diabetes [164] are also on the list of potential negative effects. Recently, a large population study in the United States showed that an increase in caffeine consummation results in decrease in telomere length, which signifies accelerated ageing [165].
Many above observations, results, conclusions are mutually contradictory, which proves that despite of many years of scientific research, there are still unrevealed mysteries concerning caffeine chemical structure, physicochemical properties, its impact on living organisms, etc. Caffeine’s role in producing beneficial and harmful effects is still poorly understood and definitely requires more extensive investigation.
References
- 1.
Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacological Reviews. 1999; 51 (1):83-133 - 2.
Plants, Health and Healing. On the Interface of Ethnobotany and Medical Anthropology. Hsu E, Harris S, Editors. New York, Oxford: Berghahn Books; 2010. ISBN 978-0-85745-633-5 - 3.
Harbowy ME, Balentine DA, Davies AP, Cai Y. Tea chemistry. Critical Reviews in Plant Sciences. 1997; 16 (5):415-480. DOI: 10.1080/07352689709701956 - 4.
Heiss ML, Heiss RJ. The Story of Tea: A Cultural History and Drinking Guide. Berkeley, Calif.: Ten Speed Press; 2007. ISBN 9781580087452 - 5.
Lu H, Zhang J, Yang Y, Yang X, Xu B, Yang W, et al. Earliest tea as evidence for one branch of the Silk Road across the Tibetan Plateau. Scientific Reports. 2016; 6 :18955. doi: 10.1038/srep18955 - 6.
Forrest DM. Tea for the British: The Social and Economic History of a Famous Trade. London: Chatto & Windus; 1973. ISBN 0701119217 - 7.
Donaldson B. The Everything Healthy Tea Book: Discover the Healing Benefits of Tea. Avon, Massachusetts: Adams Media; 2014. ISBN 978-1440574597 - 8.
Epstein FT. Great Soviet Encyclopedia: A Translation of the Third Edition. Vol. 35: Association for Slavic, East European, and Eurasian Studies; 1976.ISBN 00376779 - 9.
Russian Tea: A Tradition Three Centuries Old. Soviet Life. 1971; 177 (6):22-23 - 10.
Ketchum RM. Divided Loyalties: How the American Revolution Came to New York. New York: Holt, Henry & Company, Inc; 2002. ISBN 978-0-8050-6119-2 - 11.
Weinberg BA, Bealer BK. The World of Caffeine: The Science and Culture of the World’s Most Popular Drug. New York: Routledge; 2002. ISBN 9780203011799 - 12.
Caton SC. Yemen. Santa Barbara, Calif.: ABC-CLIO; 2013. ISBN 9781598849271 - 13.
Tibi S. Al-Razi and Islamic medicine in the 9th century. Journal of the Royal Society of Medicine. . 2006; 99 (4):206-207. DOI: 10.1258/jrsm.99.4.206 - 14.
Ukers WH. All about Coffee. Avon, Massachusetts: F+W Media; 2012. ISBN 9781440556326 - 15.
Dannenfeldt KH. Leonhard Rauwolf: Sixteenth-century Physician, Botanist, and Traveler. Bridgewater, NJ: Replica Books; 2000. ISBN 9780735102453 - 16.
Schwaner B, Westermann K-M. Das Wiener Kaffeehaus Legende, Kultur, Atmosphäre. Wien: Pichler; 2007. ISBN 9783854314356 - 17.
Doyle W. Old Regime France, 1648-1788. Oxford: Oxford Univ. Press; 2007. ISBN 978019 8731306 - 18.
Massie RK. Peter the Great: His Life and World. New York: Random House Inc; 2013. ISBN 9781781851289 - 19.
Dixon S. Catherine the Great. New York: Ecco; 2009. ISBN 9780060786274 - 20.
Vallee BL. Alcohol in the western world. Scientific American. 1998; 278 (6):80-85 - 21.
Fausto B, Fausto Sr, Brakel A. A concise history of Brazil. New York: Cambridge University Press; 2014. ISBN 9781107635241 - 22.
Li S., Hartland S. A new industrial process for extracting cocoa butter and xanthines with supercritical carbon dioxide. Journal of the American Oil Chemists’ Society; 73 (4):423-429. doi: 10.1007/bf02523913 - 23.
Dillinger TL, Barriga P, Escarcega S, Jimenez M, Salazar Lowe D, Grivetti LE. Food of the gods: Cure for humanity? A cultural history of the medicinal and ritual use of chocolate. Journal of Nutrition. 2000: 130 (8S Suppl):2057s-2072s - 24.
Swinnen J, Squicciarini MP. Economics of Chocolate: E-Content Generic Vendor; 2015. ISBN 9780191793264 - 25.
Hawkins SA. Sir Hans Sloane (1660-1735): His Life and Legacy. The Ulster Medical Journal. 2010; 79 (1):25-29 - 26.
Grivetti LE, Shapiro H-Y. Chocolate: History, Culture and Heritage. Hoboken, N.J.: A John Wiley & Sons; 2009. ISBN 9780470121658 0470121653 - 27.
The Oxford Companion to Sugar and Sweets. Oxford: Oxford University Press; 2015. ISBN 9780199313396 - 28.
Burdock GA, Carabin IG, Crincoli CM. Safety assessment of kola nut extract as a food ingredient. Food and Chemical Toxicology. 2009; 47 (8):1725-1732. DOI: 10.1016/j.fct.2009.04.019 - 29.
Bibra E, Ott J. Plant Intoxicants: A Classic Text on the Use of Mind-Altering Plants. Rochester, Vt.: Healing Arts Press; 1995. ISBN 9780892814985 - 30.
Pendergrast M. For God, Country, and Coca-Cola. New York: Basic Books; 2013. ISBN 9780465046997 - 31.
Kiple KF, Ornelas KC. The Cambridge World History of Food. Cambridge, U.K.: Cambridge University Press; 2001. ISBN 9780521402149 - 32.
Liu Y, Heying E, Tanumihardjo SA. History, global distribution, and nutritional importance of citrus fruits. Comprehensive Reviews in Food Science and Food Safety. 2012; 11 (6):530-545. DOI: 10.1111/j.1541-4337.2012.00201.x - 33.
Stewart I. Identification of caffeine in citrus flowers and leaves. Journal of Agricultural and Food Chemistry. 1985; 33 (6):1163-1165. DOI: 10.1021/jf00066a035 - 34.
Yoon E, Kim J, Lee J. The U.S. consumers’ acceptability and emotion measures when consuming novel Korean traditional non-alcoholic beverages. Journal of Sensory Studies. 2016; 31 (3):256-271. DOI: 10.1111/joss.12209 - 35.
Pybus DH, Sell CS. The chemistry of fragrances. Cambridge, UK: Royal Society of Chemistry; 1999. ISBN 9780854045280 - 36.
Waller GR, Macvean CD, Suzuki T. High production of caffeine and related enzyme activities in callus cultures of Coffea arabica L . Plant Cell Reports;2 (3):109-112. doi: 10.1007/bf00269330 - 37.
Wright GA, Baker DD, Palmer MJ, Stabler D, Mustard JA, Power EF, et al. Caffeine in floral nectar enhances a pollinator’s memory of reward. Science. 2013; 339 (6124):1202-1204. doi: 10.1126/science.1228806 - 38.
Crozier A, Ashihara H, Tomas-Barberan FA. Teas, cocoa and coffee: Plant secondary metabolites and health. Chichester, West Sussex; Hoboken, NJ: Wiley-Blackwell; 2012. ISBN 9781444347067 - 39.
Oudry M. Note sur la théine. Nouvelle Bibliothèque Médicale; 1827: 1 :477-479 - 40.
Mulder GJ. Ueber Theïn und Caffeïn. Journal für Praktische Chemie. 1838; 15 (1):280-284. DOI: 10.1002/prac.18380150124 - 41.
Jobst C. Thein identisch mit Caffein. Annalen der Pharmacie. 1838; 25 (1):63-66. DOI: 10.1002/jlac.18380250106 - 42.
Théel H. Presentation Speech by Professor Hj. Théel, President of the Swedish Royal Academy of Sciences on December 10, 1902; 1902 - 43.
Carlucci L, Gavezzotti A. Molecular recognition and crystal energy landscapes: An X-ray and computational study of caffeine and other methylxanthines. Chemistry. 2004; 11 (1):271-279. DOI: 10.1002/chem.200400499 - 44.
Bothe H, Cammenga HK. Phase transitions and thermodynamic properties of anhydrous caffeine. Journal of Thermal Analysis. 1979; 16 (2):267-275. DOI: 10.1007/BF01910688 - 45.
Latosińska JN, Latosińska M. Towards understanding drugs on the molecular level to design drugs with desirable profiles. In I. M. Kapetanovic (Ed.), Drug Discovery and Development - Present and Future. Rieka, Croatia: Intech; 2011. pp. 231-274. ISBN 9789533076157 - 46.
Descamps M, Decroix AA. Polymorphism and disorder in caffeine: Dielectric investigation of molecular mobilities. Journal of Molecular Structure. 2014; 1078 :165-173. DOI: 10.1016/j.molstruc.2014.04.042 - 47.
Enright GD, Terskikh VV, Brouwer DH, Ripmeester JA. The structure of two anhydrous polymorphs of caffeine from single-crystal diffraction and ultrahigh-field solid-state 13C NMR spectroscopy. Crystal Growth & Design. 2007; 7 (8):1406-1410. doi: 10.1021/cg070291o - 48.
Lehmann CW, Stowasser F. The crystal structure of anhydrous beta-caffeine as determined from X-ray powder-diffraction data. Chemistry. 2007; 13 (10):2908-2911. doi: 10.1002/chem.200600973 - 49.
Derollez P, Correia NT, Danède F, Capet F, Affouard F, Lefebvre J, Descamps M. Ab initio structure determination of the high-temperature phase of anhydrous caffeine by X-ray powder diffraction. Acta Crystallographica B. 2005; 61 (3):329-334. doi: 10.1107/s010876810500546x - 50.
Leiterer J, Emmerling F, Panne U, Christen W, Rademann K. Tracing coffee tabletop traces. Langmuir. 2008;24(15):7970-7978. DOI: 10.1021/la800768v - 51.
Hedoux A, Decroix AA, Guinet Y, Paccou L, Derollez P, Descamps M. Low- and high-frequency Raman investigations on caffeine: Polymorphism, disorder and phase transformation. The Journal of Physical Chemistry B. 2011; 115 (19):5746-5753. DOI: 10.1021/jp112074w - 52.
Larkin PJ, Dabros M, Sarsfield B, Chan E, Carriere JT, Smith BC. Polymorph characterization of active pharmaceutical ingredients (APIs) using low-frequency Raman spectroscopy. Applied Spectroscopy. 2014; 68 (7):758-776. DOI: 10.1366/13-07329 - 53.
Seliger J, Žagar V, Apih T, Gregorovic A, Latosińska M, Olejniczak GA, Latosińska JN. Polymorphism and disorder in natural active ingredients. Low and high-temperature phases of anhydrous caffeine: Spectroscopic ((1)H-(14)N NMR-NQR/(14)N NQR) and solid-state computational modelling (DFT/QTAIM/RDS) study. European Journal of Pharmaceutical Sciences. 2016; 85 :18-30. DOI: 10.1016/j.ejps.2016.01.025 - 54.
Latosińska JN, Latosińska M, Olejniczak GA, Seliger J, Žagar V. Topology of the interactions pattern in pharmaceutically relevant polymorphs of methylxanthines (caffeine, theobromine, and theophiline): Combined experimental ((1)H-(1)(4)N nuclear quadrupole double resonance) and computational (DFT and Hirshfeld-based) study. Journal of Chemical Information and Modeling. 2014; 54 (9):2570-2584. DOI: 10.1021/ci5004224 - 55.
Fulgoni VL 3rd, Keast DR, Lieberman HR. Trends in intake and sources of caffeine in the diets of US adults: 2001-2010. The American Journal of Clinical Nutrition. 2015; 101 (5):1081-1087. DOI: 10.3945/ajcn.113.080077 - 56.
Grobbee DE, Rimm EB, Giovannucci E, Colditz G, Stampfer M, Willett W. Coffee, caffeine, and cardiovascular disease in men. The New England Journal of Medicine. 1990; 323 (15):1026-1032. doi: 10.1056/nejm199010113231504 - 57.
Jee SH, He, J, Whelton PK, Suh I, Klag MJ. The effect of chronic coffee drinking on blood pressure: A meta-analysis of controlled clinical trials. Hypertension. 1999; 33 (2):647-652. doi: 10.1161/01.hyp.33.2.647 - 58.
Robertson D, Hollister AS, Kincaid D, Workman R, Goldberg MR, Tung CS, Smith B. Caffeine and hypertension. The American Journal of Medicine. 1984; 77 (1):54-60. doi: 10.1016/0002-9343(84)90435-2 - 59.
Nurminen M-L, Niittynen L, Korpela R, Vapaatalo H. Coffee, caffeine and blood pressure: a critical review. European Journal of Clinical Nutrition. 1999; 53 (11):831-839. doi: 10.1038/sj.ejcn.1600899 - 60.
Arnaud MJ. The pharmacology of caffeine. Progress in Drug Research. 1987; 31 :273-313 - 61.
Berthou F, Guillois B, Riche C, Dreano Y, Jacqz-Aigrain E, Beaune PH. Interspecies variations in caffeine metabolism related to cytochrome P4501A enzymes. Xenobiotica. 1992; 22 (6):671-680. DOI: 10.3109/00498259209053129 - 62.
Ashihara H, Sano H, Crozier A. Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry. 2008; 69 (4):841-856. DOI: 10.1016/j.phytochem.2007.10.029 - 63.
Caffeine. (1991/01/01 ed. Vol. 51). Lyon: IARC; 1991. ISBN 1017-1606. - 64.
Tassaneeyakul W, Birkett DJ, McManus ME, Tassaneeyakul W, Veronese ME, Andersson T, Miners JO. Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochemical Pharmacology. 1994; 47 (10):1767-1776. DOI: 10.1016/0006-2952(94)90304-2 - 65.
Smith BD, Gupta U, Gupta BS. Caffeine and activation theory: Effects on health and behavior. Boca Raton: CRC Press; 2007.ISBN 0-8493-7102-3 - 66.
Orru M, Guitart X, Karcz-Kubicha M, Solinas M, Justinova Z, Barodia SK, et al. Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans. Neuropharmacology. 2013; 67 :476-484. DOI: 10.1016/j.neuropharm.2012.11.029 - 67.
Smit HJ. Theobromine and the pharmacology of cocoa. The Handbook of Experimental Pharmacology(200); 2011:201-234. DOI: 10.1007/978-3-642-13443-2_7 - 68.
Dubuis E, Wortley MA, Grace MS, Maher SA, Adcock JJ, Birrell MA, Belvisi MG. Theophylline inhibits the cough reflex through a novel mechanism of action. Journal of Allergy and Clinical Immunology. 2014; 133 (6):1588-1598. DOI: 10.1016/j.jaci.2013.11.017 - 69.
Petzer JP, Castagnoli N, Schwarzschild MA, Chen J-F, Van der Schyf CJ. Dual-target-directed drugs that block monoamine oxidase B and adenosine A(2A) receptors for Parkinson’s disease. Neurotherapeutics. 2009; 6 (1):141-151. doi: 10.1016/j.nurt.2008.10.035 - 70.
Lopez F, Miller LG, Greenblatt DJ, Kaplan GB, Shader RI. Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding. The European Journal of Pharmacology. 1989; 172 (6):453-459. DOI: 10.1016/0922-4106(89)90028-X - 71.
Ferre S, Orru M, Guitart X. Paraxanthine: Connecting caffeine to nitric oxide neurotransmission. Journal of Caffeine Research. 2013; 3 (2):72-78. DOI: 10.1089/jcr.2013.0006 - 72.
Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. Journal of the American Medical Association. 2000; 283 (20):2674-2679. DOI: 10.1001/jama.283.20.2674 - 73.
Postuma RB, Lang AE, Munhoz RP, Charland K, Pelletier A, Moscovich M, et al. Caffeine for treatment of Parkinson disease: A randomized controlled trial. Neurology. 2012; 79 (7):651-658. doi: 10.1212/WNL.0b013e318263570d - 74.
Popat RA, Van Den Eeden SK, Tanner CM, Kamel F, Umbach DM, Marder K, et al. Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease. European Journal of Neurology. 2011; 18 (5):756-765. doi: 10.1111/j.1468-1331.2011.03353.x - 75.
Eskelinen MH, Kivipelto M. Caffeine as a protective factor in dementia and Alzheimer’s disease. Journal of Alzheimer’s Disease. 2010; 20 :167-174. DOI: 10.3233/jad-2010-1404 - 76.
Maia L, Mendonca A. Does caffeine intake protect from Alzheimer’s disease? European Journal of Neurology. 2002; 9 (4):377-382. doi: 10.1046/j.1468-1331.2002.00421.x - 77.
Biessels GJ. Caffeine, diabetes, cognition, and dementia. Journal of Alzheimer’s Disease. 2010; 20 :143-150. DOI: 10.3233/jad-2010-091228 - 78.
Chen J-F, Chern Y. Impacts of methylxanthines and adenosine receptors on neurodegeneration: Human and experimental studies. The Handbook of Experimental Pharmacology(200). 2011:267-310. doi: 10.1007/978-3-642-13443-2_10 - 79.
Guerreiro S, Toulorge D, Hirsch E, Marien M, Sokoloff P, Michel PP. Paraxanthine, the primary metabolite of caffeine, provides protection against dopaminergic cell death via stimulation of ryanodine receptor channels. Molecular Pharmacology. 2008; 74 (4):980-989. DOI: 10.1124/mol.108.048207 - 80.
Costentin J. Main neurotropic and psychotropic effects of methylxanthines (caffeine, theophylline, theobromine, paraxanthine). Psychiatrie Sciences Humaines Neurosciences. 2010; 8 (4):182-186. DOI: 10.1007/s11836-010-0141-z - 81.
Dórea JG, da Costa THM. Is coffee a functional food? British Journal of Nutrition. 2005; 93 (06):773-782. DOI: 10.1079/bjn20051370 - 82.
Nechay BR. Potentiation of diuretic effects of methyl xanthines and pyrimidines by carbonic anhydrase inhibitors. Journal of Pharmacology and Experimental Therapeutics. 1964; 144 :276-283 - 83.
Dorfman LJ, Jarvik ME. Comparative stimulant and diuretic actions of caffeine and theobromine in man. Clinical Pharmacology & Therapeutics. 1970; 11 :869-872. DOI: 10.1002/cpt1970116869 - 84.
Osei KA, Ovenseri-Ogbomo G, Kyei S, Ntodie M. The effect of caffeine on tear secretion. Optometry and Vision Science. 2014; 91 :171-177. DOI: 10.1097/OPX.0000000000000129 - 85.
Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Archives of Ophthalmology. 2000; 118 :1264-1268. DOI: 10.1001/archopht.118.9.1264 - 86.
Nkondjock A. Coffee consumption and the risk of cancer: An overview. Cancer Letters. 2009; 277 (2):121-125. doi: 10.1016/j.canlet.2008.08.022 - 87.
Bøhn SK, Blomhoff R, Paur I. Coffee and cancer risk, epidemiological evidence, and molecular mechanisms. Molecular Nutrition & Food Research. 2014; 58 (5):915-930. doi: 10.1002/mnfr.201300526 - 88.
Song F, Qureshi AA, Han J. Increased caffeine intake is associated with reduced risk of basal cell carcinoma of the skin. Cancer Research. 2012; 72 (13):3282-3289. doi: 10.1158/0008-5472.can-11-3511 - 89.
Li G, Ma D, Zhang Y, Zheng W, Wang P. Coffee consumption and risk of colorectal cancer: a meta-analysis of observational studies. Public Health Nutrition. 2013; 16 (2):346-357. doi: 10.1017/s1368980012002601 - 90.
Hashibe M, Galeone C, Buys SS, Gren L, Boffetta P, Zhang ZF, La Vecchia C. Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort. British Journal of Cancer. 2015. doi: 10.1038/bjc.2015.276 - 91.
Bertrand B, Stefan L, Pirrotta M, Monchaud D, Bodio E, Richard P, et al. Caffeine-based Gold(I) N-heterocyclic carbenes as possible anticancer agents: Synthesis and biological properties. Inorganic Chemistry. 2014; 53 (4):2296-2303. DOI: 10.1021/ic403011h - 92.
Kronschläger M, Löfgren S, Yu Z, Talebizadeh N, Varma SD, Söderberg P. Caffeine eye drops protect against UV-B cataract. Experimental Eye Research. 2013; 113 (0):26-31. DOI: 10.1016/j.exer.2013.04.015 - 93.
Heffernan TP, Kawasumi M, Blasina A, Anderes K, Conney AH, Nghiem P. ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: Potential basis for the UV protective effects of caffeine. The Journal of Investigative Dermatology. 2009; 129 (7):1805-1815. doi: 10.1038/jid.2008.435 - 94.
Kerzendorfer C, O’Driscoll M. UVB and caffeine: inhibiting the DNA damage response to protect against the adverse effects of UVB. The Journal of Investigative Dermatology. 2009; 129 (7):1611-1613. DOI: 10.1038/jid.2009.99 - 95.
Lu Y-P, Lou Y-R, Xie J-G, Peng Q-Y, Liao J, Yang CS, et al. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proceedings of the National Academy of Sciences of the United States of America. 2002; 99 (19):12455-12460. doi: 10.1073/pnas.182429899 - 96.
Sabisz M, Skladanowski A. Modulation of cellular response to anticancer treatment by caffeine: Inhibition of cell cycle checkpoints, DNA repair and more. Current Pharmaceutical Biotechnology; 9 (4):325-336. doi: 10.2174/138920108785161497 - 97.
Ohta A, Sitkovsky M. The adenosinergic immuno-modulatory drugs. Current Opinion in Pharmacology. 2009; 9 (4):501-506. DOI: 10.1016/j.coph.2009.05.005 - 98.
Zigman S, Schultz J, Yulo T. Possible roles of near UV light in the cataractous process. Experimental Eye Research. 1973;15(2):201-208. DOI: 10.1016/0014-4835(73)90120-6 - 99.
Conterio F, Chiarelli B. Study of the inheritance of some daily life habits. Heredity (Edinburgh). 1962; 17 :347-359. DOI: 10.1038/hdy.1962.36 - 100.
Kendler KS, Prescott CA. Caffeine intake, tolerance, and withdrawal in women: A population-based twin study. The American Journal of Psychiatry. 1999; 156 (2):223-228. DOI: 10.1176/ajp.156.2.223 - 101.
Goodman MT, Tung KH, McDuffie K, Wilkens LR, Donlon TA. Association of caffeine intake and CYP1A2 genotype with ovarian cancer. Nutrition and Cancer. 2003; 46 (1):23-29. DOI: 10.1207/s15327914nc4601_03 - 102.
Kotsopoulos J, Ghadirian P, El-Sohemy A, Lynch HT, Snyder C, Daly M, et al. The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers. Cancer Epidemiology, Biomarkers & Prevention. 2007; 16 (5):912-916. DOI: 10.1158/1055-9965.epi-06-1074 - 103.
Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C-->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. British Journal of Clinical Pharmacology. 1999; 47 (4):445-449. DOI: 10.1046/j.1365-2125.1999.00898.x - 104.
Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berlin). 2010; 211 (3):245-257. DOI: 10.1007/s00213-010-1900-1 - 105.
Cornelis MC, Monda KL, Yu K, Paynter N, Azzato EM, Bennett SN, et al. Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. PLOS Genetics. 2011; 7 (4):e1002033. doi: 10.1371/journal.pgen.1002033 - 106.
Josse AR, Da Costa LA, Campos H, El-Sohemy A. Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumption. The American Journal of Clinical Nutrition. 2012; 96 (3):665-671. DOI: 10.3945/ajcn.112.038794 - 107.
Retey JV, Adam M, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP. A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clinical Pharmacology & Therapeutics. 2007; 81 (5):692-698. DOI: 10.1038/sj.clpt.6100102 - 108.
Happonen P, Voutilainen S, Tuomainen T-P, Salonen JT. Catechol-O-methyltransferase gene polymorphism modifies the effect of coffee intake on incidence of acute coronary events. PLOS ONE. 2006; 1 (1):e117. doi: 10.1371/journal.pone.0000117 - 109.
Kohlmeier M. Nutrigenetics: Applying the Science of Personal Nutrition: Academic Press; 2012. ISBN 9780123859013 - 110.
Cornelis MC, El-Sohemy A, Campos H. Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. The American Journal of Clinical Nutrition. 2007; 86 (1):240-244 - 111.
Peters JM. Factors affecting caffeine toxicity: A review of the literature. The Journal of Clinical Pharmacology and The Journal of New Drugs. 1967; 7 (3):131-141. DOI: 10.1002/j.1552-4604.1967.tb00034.x - 112.
Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Additives & Contaminants. 2003; 20 (1):1-30. DOI: 10.1080/0265203021000007840 - 113.
Stavric B. Methylxanthines: Toxicity to humans. 2. Caffeine. Food and Chemical Toxicology. 1988; 26 (7):645-662. DOI: 10.1016/0278-6915(88)90236-0 - 114.
James JE. Caffeine and health. London: Academic Press; 1991. ISBN 9780123801050 - 115.
Stidworthy MF, Bleakley JS, Cheeseman MT, Kelly DF. Chocolate poisoning in dogs. Veterinary Record. 1997; 141 (1):28 - 116.
Sutton RH. Cocoa poisoning in a dog. Veterinary Record. 1981; 109 (25-26):563-564 - 117.
Kovalkovičová N, Šutiaková I, Pistl J, Šutiak V. Some food toxic for pets. Interdisciplinary Toxicology. 2009; 2 (3):169-176. DOI: 10.2478/v10102-009-0012-4 - 118.
Watson RR, Preedy VR, Zibadi S. Chocolate in health and nutrition: Springer; 2013. ISBN 9781617798030 - 119.
Gartrell BD, Reid C. Death by chocolate: A fatal problem for an inquisitive wild parrot. The New Zealand Veterinary Journal. 2007; 55 (3):149-151. DOI: 10.1080/00480169.2007.36759 - 120.
Lightfoot TL, Yeager JM. Pet bird toxicity and related environmental concerns. Veterinary Clinics of North America: Exotic Animal Practice. 2008; 11 (2):229-259. DOI: 10.1016/j.cvex.2008.01.006 - 121.
Brandon DM, Bicket TL. Hugs for cat lovers. New York: Howard Books; 2014.ISBN 9781416560340 - 122.
Hollingsworth RG, Armstrong JW, Campbell E. Caffeine as a repellent for slugs and snails. Nature. 2002; 417 (6892):915-916. DOI: 10.1038/417915a - 123.
Nathanson JA. Caffeine and related methylxanthines: possible naturally occurring pesticides. Science. 1984; 226 (4671):184-187. DOI: 10.1126/science.6207592 - 124.
Noever DA, Cronise RJ, Relwani RA. Using spider-web patterns to determine toxicity. NASA Technical Briefs. 1995; 19 (4):82 - 125.
Jaramillo J, Borgemeister C, Baker P. Coffee berry borer Hypothenemus hampei (Coleoptera: Curculionidae): searching for sustainable control strategies. Bulletin of Entomological Research. 2006; 96 (3):223-233. DOI: 10.1079/BER2006434 - 126.
Borota D, Murray E, Keceli G, Chang A, Watabe JM, Ly M, et al. Post-study caffeine administration enhances memory consolidation in humans. Nature Neuroscience. 2014; 17 (2):201-203. DOI: 10.1038/nn.3623 - 127.
Horne JA, Reyner LA. Counteracting driver sleepiness: effects of napping, caffeine, and placebo. Psychophysiology. 1996; 33 (3):306-309. DOI: 10.1111/j.1469-8986.1996.tb00428.x - 128.
Lucas M, O’Reilly EJ, Pan A, Mirzaei F, Willett WC, Okereke OI, Ascherio A. Coffee, caffeine, and risk of completed suicide: Results from three prospective cohorts of American adults. The World Journal of Biological Psychiatry. 2014; 15 (5):377-386. DOI: 10.3109/15622975.2013.795243 - 129.
Lucas M, Mirzaei F, Pan A, et al. Coffee, caffeine, and risk of depression among women. Archives of Internal Medicine. 2011; 171 (17):1571-1578. DOI: 10.1001/archinternmed.2011.393 - 130.
Cao C, Cirrito JR, Lin X, Wang L, Verges DK, Dickson A, et al. Caffeine suppresses β-amyloid levels in plasma and brain of Alzheimer’s transgenic mice. Journal of Alzheimer’s Disease. 2009; 17 (3):681-697. DOI: 10.3233/JAD-2009-1071 - 131.
Tauler P, Martínez S, Moreno C, Monjo M, Martínez P, Aguiló A. Effects of caffeine on the inflammatory response induced by a 15-km run competition. Medicine and Science in Sports and Exercise. 2013; 45 (7):1269-1276. DOI: 10.1249/mss.0b013e3182857c8a - 132.
Maridakis V, O’Connor PJ, Dudley GA, McCully KK. Caffeine attenuates delayed-onset muscle pain and force loss following eccentric exercise. The Journal of Pain; 8 (3):237-243. DOI: 10.1016/j.jpain.2006.08.006 - 133.
Icken D, Feller S, Engeli S, Mayr A, Muller A, Hilbert A, de Zwaan M. Caffeine intake is related to successful weight loss maintenance. European Journal of Clinical Nutrition. 2016; 70 (4):532-534. DOI: 10.1038/ejcn.2015.183 - 134.
Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Faustin B. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nature Medicine. 2017; 23 (2):174-184. DOI: 10.1038/nm.4267 - 135.
Defazio G, Martino D, Abbruzzese G, Girlanda P, Tinazzi M, Fabbrini G, Berardelli A. Influence of coffee drinking and cigarette smoking on the risk of primary late onset blepharospasm: Evidence from a multicentre case control study. Journal of Neurology, Neurosurgery, and Psychiatry. 2007; 78 (8):877-879. DOI: 10.1136/jnnp.2007.119891 - 136.
Varma SD, Kovtun S, Hegde K. Effectiveness of topical caffeine in cataract prevention: Studies with galactose cataract. Molecular Vision. 2010; 16 :2626-2633 - 137.
Jang H, Ahn HR, Jo H, Kim K-A, Lee EH, Lee KW, et al. Chlorogenic acid and coffee prevent hypoxia-induced retinal degeneration. Journal of Agricultural and Food Chemistry. 2014; 62 (1):182-191. DOI: 10.1021/jf404285v - 138.
Loftfield E, Mayne S, Shebl F, Freedman N, Graubard B, Sinha R. Abstract LB-280: Prospective study of coffee drinking and risk of melanoma in the United States. Cancer Research. 2014; 74 (19):LB-280-LB-280. doi: 10.1158/1538-7445.am2014-lb-280 - 139.
Glicksman JT, Curhan SG, Curhan GC. A prospective study of caffeine intake and risk of incident tinnitus. The American Journal of Medicine; 127 (8):739-743. DOI: 10.1016/j.amjmed.2014.02.033 - 140.
Welsh EJ, Bara A, Barley E, Cates, CJ. Caffeine for asthma. Cochrane Database of Systematic Reviews. 2010;(1). doi: 10.1002/14651858.CD001112.pub2 - 141.
Hodgson JM, Puddey IB, Burke V, Beilin LJ, Jordan N. Effects on blood pressure of drinking green and black tea. Journal of Hypertension. 1999; 17 (4):457-463. DOI: 10.1097/00004872-199917040-00002 - 142.
Teekachunhatean S, Tosri N, Rojanasthien N, Srichairatanakool S, Sangdee C. Pharmacokinetics of caffeine following a single administration of coffee enema versus oral coffee consumption in healthy male subjects. ISRN Pharmacology. 2013; 2013 :147238. doi: 10.1155/2013/147238 - 143.
Sinha RA, Farah BL, Singh BK, Siddique MM, Li Y, Wu Y, et al. Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. Hepatology. 2014; 59 (4):1366-1380. DOI: 10.1002/hep.26667 - 144.
Khalaf N, White D, Kanwal F, Ramsey D, Mittal S, Tavakoli-Tabasi S,et al. Coffee and caffeine are associated with decreased risk of advanced hepatic fibrosis among patients with hepatitis C. Clinical Gastroenterology and Hepatology. 2015; 13 (8):1521-1531.e1523. doi: 10.1016/j.cgh.2015.01.030 - 145.
Choi HK, Willett W, Curhan G. Coffee consumption and risk of incident gout in men: A prospective study. Arthritis & Rheumatism. 2007; 56 (6):2049-2055. DOI: 10.1002/art.22712 - 146.
Karmon AE, Toth TL, Chiu YH, Gaskins AJ, Tanrikut C, Wright DL. Male caffeine and alcohol intake in relation to semen parameters and in vitro fertilization outcomes among fertility patients. Andrology. 2017; 5 (2):354-361. DOI: 10.1111/andr.12310 - 147.
Fischer TW, Hipler UC, Elsner P. Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. International Journal of Dermatology. 2007; 46 (1):27-35. DOI: 10.1111/j.1365-4632.2007.03119.x - 148.
Vlachopoulos C, Hirata K, Stefanadis C, Toutouzas P, O’Rourke MF. Caffeine increases aortic stiffness in hypertensive patients. American Journal of Hypertension. 2003; 16 (1):63-66. DOI: 10.1016/S0895-7061(02)03155-2 - 149.
Mos L, Fania C, Benetti E, Bratti P, Maraglino G, Mazzer A, et al. Coffee consumption is a predictor of cardiovascular events in young and middle aged hypertensive subjects. Journal of Hypertension. 2015; 33 :10. doi: 10.1097/01.hjh.0000467378.82732.55 - 150.
Choi HK, Curhan G. Coffee consumption and risk of incident gout in women: The Nurses’ Health Study. The American Journal of Clinical Nutrition. 2010; 92 (4):922-927. DOI: 10.3945/ajcn.2010.29565 - 151.
Cao H, Ren J, Feng X, Yang G, Liu J. Is caffeine intake a risk factor leading to infertility? A protocol of an epidemiological systematic review of controlled clinical studies. Systematic Reviews. 2016; 5 :45. doi: 10.1186/s13643-016-0221-9 - 152.
Hahn KA, Wise LA, Rothman KJ, Mikkelsen EM, Brogly SB, Sørensen HT, Hatch EE. Caffeine and caffeinated beverage consumption and risk of spontaneous abortion. Human Reproduction. 2015; 30 (5):1246-1255. DOI: 10.1093/humrep/dev063 - 153.
Faubion SS, Sood R, Thielen JM, Shuster LT. Caffeine and menopausal symptoms: what is the association? Menopause. 2015; 22 (2):155-158. DOI: 10.1097/gme.0000000000000301 - 154.
Boyle CA, Berkowitz GS, LiVolsi VA, Ort S, Merino MJ, White C, Kelsey JL. Caffeine consumption and fibrocystic breast disease: A case-control epidemiologic study. Journal of the National Cancer Institute. 1984; 72 (5):1015-1019. DOI: 10.1093/jnci/72.5.1015 - 155.
Veleber DM, Templer DI. Effects of caffeine on anxiety and depression. The Journal of Abnormal Psychology. 1984; 93 (1):120-122. DOI: 10.1037/0021-843X.93.1.120 - 156.
Richards G, Smith AP. A review of energy drinks and mental health, with a focus on stress, anxiety, and depression. Journal of Caffeine Research. 2016; 6 (2):49-63. DOI: 10.1089/jcr.2015.0033 - 157.
Karacan I, Thornby JI, Anch M, Booth GH, Williams RL, Salis PJ. Dose-related sleep disturbances induced by coffee and caffeine. Clinical Pharmacology and Therapeutics. 1976; 20 (6):682-689. DOI: 10.1002/cpt1976206682 - 158.
Scher AI, Stewart WF, Lipton RB. Caffeine as a risk factor for chronic daily headache: A population-based study. Neurology. 2004; 63 (11):2022-2027. DOI: 10.1046/j.1365-2125.1999.00898.x - 159.
Gleason JL, Richter HE, Redden DT, Goode PS, Burgio KL, Markland AD. Caffeine and urinary incontinence in US women. International Urogynecology Journal. 2013; 24 (2):295-302. DOI: 10.1007/s00192-012-1829-5 - 160.
Shirlow MJ, Mathers CD. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. International Journal of Epidemiology. 1985; 14 (2):239-248. DOI: 10.1093/ije/14.2.239 - 161.
Tomaszewski M, Olchowik G, Tomaszewska M, Dworzanski W, Burdan F. The influence of caffeine administered at 10 degrees C on bone tissue development. The Annals of Agricultural and Environmental Medicine. 2016; 23 (2):319-323. DOI: 10.5604/12321966.1203898 - 162.
Zawawi F, Bezdjian A, Mujica-Mota M, Rappaport J, Daniel SJ. Association of caffeine and hearing recovery after acoustic overstimulation events in a guinea pig model. Otolaryngology–Head & Neck Surgery. 2016; 142 (4):383-388. DOI: 10.1001/jamaoto.2015.3938 - 163.
Donejko M, Przylipiak A, Rysiak E, Głuszuk K, Surażyński A. Influence of caffeine and hyaluronic acid on collagen biosynthesis in human skin fibroblasts. Drug Design, Development and Therapy. 2014; 8 :1923-1928. DOI: 10.2147/DDDT.S69791 - 164.
Malik VS, Popkin BM, Bray GA, Després J-P, Willett WC, Hu FB. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: A meta-analysis. Diabetes Care. 2010; 33 (11):2477-2483. DOI: 10.2337/dc10-1079 - 165.
Tucker LA. Caffeine consumption and telomere length in men and women of the National Health and Nutrition Examination Survey (NHANES). Nutrition & Metabolism. 2017; 14 (1):10. doi: 10.1186/s12986-017-0162-x