My watch list
my.bionity.com  
Login  

Caffeine



Caffeine
IUPAC name 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione
Other names 1,3,7-trimethylxanthine, trimethylxanthine,
theine, methyltheobromine
Identifiers
CAS number 58-08-2
RTECS number EV6475000
SMILES C[n]1cnc2N(C)C(=O)N(C)C(=O)c12
Properties
Molecular formula C8H10N4O2
Molar mass 194.19 g·mol−1
Appearance Odorless, white needles or powder
Density 1.2 g·cm−3, solid
Melting point

237 °C (non-equilibrium, superheated)

Boiling point

178 °C (sublimes)

Solubility in water 22 mg·mL−1 (25 °C)
180 mg·mL−1 (80 °C)
670 mg·mL−1 (100 °C)
Hazards
MSDS External MSDS
Main hazards May be fatal if inhaled, swallowed
or absorbed through the skin.
NFPA 704
1
2
0
 
Flash point N/A
LD50 192 mg/kg (rat)[1]
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Caffeine is a stimulant drug. It is a xanthine alkaloid compound that acts as a psychoactive stimulant and diuretic in humans. The word comes from the French term for coffee, café.[2] Caffeine is also called guaranine when found in guarana, mateine when found in mate, and theine when found in tea; all of these names are synonyms for the same chemical compound.

Caffeine is found in varying quantities in the beans, leaves, and fruit of over 60 plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants. It is most commonly consumed by humans in infusions extracted from the beans of the coffee plant and the leaves of the tea bush, as well as from various foods and drinks containing products derived from the kola nut or from cacao. Other sources include yerba mate, guarana berries, and the Yaupon Holly.

In humans, caffeine is a central nervous system (CNS) stimulant, having the effect of temporarily warding off drowsiness and restoring alertness. Beverages containing caffeine, such as coffee, tea, soft drinks and energy drinks enjoy great popularity; caffeine is the world's most widely consumed psychoactive substance, but unlike most other psychoactive substances, it is legal and unregulated in nearly all jurisdictions. In North America, 90% of adults consume caffeine daily.[3] The U.S. Food and Drug Administration lists caffeine as a "Multiple Purpose Generally Recognized as Safe Food Substance".[4]

Additional recommended knowledge

Contents

Sources

 

Caffeine is a plant alkaloid, found in many plant species, where it acts as a natural pesticide with high caffeine levels being reported in seedlings that are still developing foliages, but are lacking mechanical protection;[5] caffeine paralyzes and kills certain insects feeding upon the plant.[6] High caffeine levels have also been found in the surrounding soil of coffee bean seedlings. It is therefore understood that caffeine has a natural function in both a natural pesticide and as an inhibitor of seed germination of other nearby coffee seedlings[7] thus giving it a better chance of survival.

The most commonly used caffeine-containing plants are coffee, tea, and to a lesser extent cocoa. Other, less commonly used, sources of caffeine include the yerba mate[8] and guarana plants, which are sometimes used in the preparation of teas and energy drinks. Two of caffeine's alternative names, mateine[9] and guaranine,[10] are derived from the names of these plants. Some yerba mate enthusiasts assert that mateine is a stereoisomer of caffeine, which would make it a different substance altogether.[8] However, caffeine is an achiral molecule, and therefore has no stereoisomers. Many natural sources of caffeine also contain widely varying mixtures of other xanthine alkaloids, including the cardiac stimulants theophylline and theobromine and other substances such as polyphenols which can form insoluble complexes with caffeine.[11]

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;[12] even beans within a given bush can show variations in concentration. In general, one serving of coffee ranges from 40 milligrams, for a single shot (30 milliliters) of arabica-variety espresso, to about 100 milligrams for a cup (120 milliliters) of drip coffee. Generally, dark-roast coffee has less caffeine than lighter roasts because the roasting process reduces the bean's caffeine content.[13][14] Arabica coffee normally contains less caffeine than the robusta variety.[12] Coffee also contains trace amounts of theophylline, but no theobromine.

Tea is another common source of caffeine. Tea usually contains about half as much caffeine per serving as coffee, depending on the strength of the brew. Certain types of tea, such as black and oolong, contain somewhat more caffeine than most other teas. Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee. Preparation has a significant impact on tea, and color is a very poor indicator of caffeine content.[15] 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.

Caffeine is also a common ingredient of soft drinks such as cola, originally prepared from kola nuts. Soft drinks typically contain about 10 to 50 milligrams of caffeine per serving. By contrast, energy drinks such as Red Bull contain as much as 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.[16]

Chocolate derived from cocoa 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.[17] Chocolate contains too little of these compounds for a reasonable serving to create effects in humans that are on par with coffee. A typical 28-gram serving of a milk chocolate bar has about as much caffeine as a cup of decaffeinated coffee.

Caffeine can be absorbed through the skin, and so in recent years various manufacturers have begun putting caffeine into shower products such as shampoo and soap.[18]

History

 

Main articles: History of cocoa, History of coffee, Origin and early history of tea

Humans have consumed caffeine since the Stone Age.[19] Early peoples found that chewing the seeds, bark, or leaves of certain plants had the effects of easing fatigue, stimulating awareness, and elevating mood. Only much later was it found that the effect of caffeine was increased by steeping such plants in hot water. Many cultures have legends that attribute the discovery of such plants to people living many thousands of years ago.

According to one popular Chinese legend, the Emperor of China Shennong, reputed to have reigned in about 3,000 BC, accidentally discovered that when some leaves fell into boiling water, a fragrant and restorative drink resulted.[20] Shennong is also mentioned in Lu Yu's Cha Jing, a famous early work on the subject of tea.[21] The history of coffee has been recorded as far back as the ninth century. During that time, coffee beans were available only in their native habitat, Ethiopia. A popular legend traces its discovery to a goatherder named Kaldi, who apparently observed goats that became elated and sleepless at night after browsing on coffee shrubs and, upon trying the berries that the goats had been eating, experienced the same vitality. The earliest literary mention of coffee may be a reference to Bunchum in the works of the 9th century Persian physician al-Razi. In 1587, Malaye Jaziri compiled a work tracing the history and legal controversies of coffee, entitled "Umdat al safwa fi hill al-qahwa". In this work, Jaziri recorded that one Sheikh, Jamal-al-Din al-Dhabhani, mufti of Aden, was the first to adopt the use of coffee in 1454, and that in the 15th century the Sufis of Yemen routinely used coffee to stay awake during prayers.

Towards the close of the 16th century, the use of coffee was recorded by a European resident in Egypt, and about this time it came into general use in the Near East. The appreciation of coffee as a beverage in Europe, where it was first known as "Arabian wine," dates from the 17th century. During this time "coffee houses" were established, the first being opened in Constantinople and Venice. In Britain, the first coffee houses were opened in London in 1652, at St Michael's Alley, Cornhill. They soon became popular throughout Western Europe, and played a significant role in social relations in the 17th and 18th centuries.[22]

The kola nut, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in many West African cultures, individually or in a social setting, to restore vitality and ease hunger pangs. In 1911, kola 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 that the caffeine in its drink was "injurious to health".[23] On March 13, 1911, the government initiated The United States v. Forty Barrels and Twenty Kegs of Coca-Cola, hoping to force Coca-Cola to remove caffeine from its formula by making claims, such as that the excessive use of Coca-Cola at one girls' school led to "wild nocturnal freaks, violations of college rules and female proprieties, and even immoralities."[24] 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.

The earliest evidence of cocoa use comes from residue found in an ancient Mayan pot dated to 600 BC. In the New World, chocolate was consumed in a bitter and spicy drink called xocoatl, often seasoned with vanilla, chile pepper, and achiote. Xocoatl was believed to fight fatigue, a belief that is 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.

Chocolate was introduced to Europe by the Spaniards and became a popular beverage by 1700. They 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.

In 1819, the German chemist Friedrich Ferdinand Runge isolated relatively pure caffeine for the first time. According to Runge, he did this at the behest of Johann Wolfgang von Goethe.[25] In 1927, Oudry isolated "theine" from tea, but it was later proved by Mulder and Jobat that theine was the same as caffeine.[25] The structure of caffeine was elucidated near the end of the 19th century by Hermann Emil Fischer, who was also the first to achieve its total synthesis.[26] This was part of the work for which Fischer was awarded the Nobel Prize in 1902.

Today, global consumption of caffeine has been estimated at 120,000 tons per annum,[27] making it the world's most popular psychoactive substance. This number equates to one serving of a caffeine beverage for every person, per day. In North America, 90% of adults consume some amount of caffeine daily.[3]

Stereochemistry

The nitrogen atoms are all essentially planar. Even though some are often drawn with three single bonds, the lone pairs on these atoms are involved in resonance with adjacent double-bonded carbon atoms, and thus adopt an sp2 orbital hybridisation.

Pharmacology

Caffeine is a central nervous system and metabolic stimulant,[28] and is used both recreationally and medically to reduce physical fatigue and restore mental alertness when unusual weakness or drowsiness occurs. Caffeine stimulates the central nervous system first at the higher levels, resulting in increased alertness and wakefulness, faster and clearer flow of thought, increased focus, and better general body coordination, and later at the spinal cord level at higher doses.[29] Once inside the body, it has a complex chemistry, and acts through several mechanisms as described below.

Metabolism

  Caffeine is completely absorbed by the stomach and small intestine within 45 minutes of ingestion. After ingestion it is distributed throughout all tissues of the body and is eliminated by first-order kinetics.[30]

The half-life of caffeine—the time required for the body to eliminate one-half of the total amount of caffeine consumed at a given time—varies widely among individuals according to such factors as age, liver function, pregnancy, some concurrent medications, and the level of enzymes in the liver needed for caffeine metabolism. In healthy adults, caffeine's half-life is approximately 3–4 hours. In women taking oral contraceptives this is increased to 5–10 hours,[31] and in pregnant women the half-life is roughly 9–11 hours.[32] Caffeine can accumulate in individuals with severe liver disease when its half-life can increase to 96 hours.[33] In infants and young children, the half-life may be longer than in adults; half-life in a newborn baby may be as long as 30 hours. Other factors such as smoking can shorten caffeine's half-life.[34]

Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system (specifically, the 1A2 isozyme) into three metabolic dimethylxanthines,[35] which each have their own effects on the body:

Each of these metabolites is further metabolized and then excreted in the urine.

Mechanism of action

 

Caffeine acts through multiple mechanisms involving both action on receptors and channels on the cell membrane, as well as intracellular action on calcium and cAMP pathways. By virtue of its purine structure it can act on some of the same targets as adenosine related nucleosides and nucleotides, like the cell surface P1 GPCRs for adenosine, as well as the intracellular Ryanodine receptor (RyR) which is the physiological target of cADPR (cyclic ADP-ribose), and cAMP-phosphodiesterase (cAMP-PDE). Although the action is agonistic in some cases, it is antagonistic in others. Physiologically, however, caffeine action is unlikely due to increased RyR opening, as it requires plasma concentration above lethal dosage. The action is most likely through adenosine receptors.

Like alcohol, nicotine, and antidepressants, caffeine readily crosses the blood brain barrier. Once in the brain, the principal mode of action of caffeine is as an antagonist of adenosine receptors found in the brain.[36] The caffeine molecule is structurally similar to adenosine, and binds to adenosine receptors on the surface of cells without activating them (an "antagonist" mechanism of action). Therefore, caffeine acts as a competitive inhibitor. The reduction in adenosine activity results in increased activity of the neurotransmitter dopamine, largely accounting for the stimulatory effects of caffeine. Caffeine can also increase levels of epinephrine/adrenaline,[37] possibly via a different mechanism. Acute usage of caffeine also increases levels of serotonin, causing positive changes in mood.[38]

Caffeine is also a known competitive inhibitor of the enzyme cAMP-phosphodiesterase (cAMP-PDE), which converts cyclic AMP (cAMP) in cells to its noncyclic form, allowing cAMP to build up in cells. Cyclic AMP participates in activation of Protein Kinase A (PKA) to begin the phosphorylation of specific enzymes used in glucose synthesis. By blocking its removal caffeine intensifies and prolongs the effects of epinephrine and epinephrine-like drugs such as amphetamine, methamphetamine, or methylphenidate. Increased concentrations of cAMP in parietal cells causes an increased activation of protein kinase A (PKA) which in turn increases activation of H+/K+ ATPase, resulting finally in increased gastric acid secretion by the cell.

Caffeine (and theophylline) can freely diffuse into cells and causes intracellular calcium release (independent of extracellular calcium) from the calcium stores in the endoplasmic reticulum(ER). This release is only partially blocked by Ryanodine receptor blockade with ryanodine, dantrolene, ruthenium red, and procaine (thus may involve ryanodine receptor and probably some additional calcium channels), but completely abolished after calcium depletion of ER by SERCA inhibitors like Thapsigargin (TG) or cyclopiazonic acid (CPA).[39] The action of caffeine on the ryanodine receptor may depend on both cytosolic and the luminal ER concentrations of Ca2+. At low millimolar concentration of caffeine, the RyR channel open probability (Po) is significantly increased mostly due to a shortening of the lifetime of the closed state. At concentrations >5 mM, caffeine opens RyRs even at picomolar cytosolic Ca2+ and dramatically increases the open time of the channel so that the calcium release is stronger than even an action potential can generate. This mode of action of caffeine is probably due to mimicking the action of the physiologic metabolite of NAD called cADPR (cyclic ADP ribose) which has a similar potentiating action on Ryanodine receptors.

Caffeine may also directly inhibit delayed rectifier and A-type K+ currents and activate plasmalemmal Ca2+ influx in certain vertebrate and invertebrate neurons.

The metabolites of caffeine contribute to caffeine's effects. Theobromine is a vasodilator that increases the amount of oxygen and nutrient flow to the brain and muscles. Theophylline, the second of the three primary metabolites, acts as a smooth muscle relaxant that chiefly affects bronchioles and acts as a chronotrope and inotrope that increases heart rate and efficiency. The third metabolic derivative, paraxanthine, is responsible for an increase in the lipolysis process, which releases glycerol and fatty acids into the blood to be used as a source of fuel by the muscles.[40]

 

Effects when taken in moderation

The precise amount of caffeine necessary to produce effects varies from person to person depending on body size and degree of tolerance to caffeine. It takes less than an hour for caffeine to begin affecting the body and a mild dose wears off in three to four hours.[29] Consumption of caffeine does not eliminate the need for sleep: it only temporarily reduces the sensation of being tired.

With these effects, caffeine is an ergogenic: increasing the capacity for mental or physical labor. A study conducted in 1979 showed a 7% increase in distance cycled over a period of two hours in subjects who consumed caffeine compared to control tests.[41] Other studies attained much more dramatic results; one particular study of trained runners showed a 44% increase in "race-pace" endurance, as well as a 51% increase in cycling endurance, after a dosage of 9 milligrams of caffeine per kilogram of body weight.[42] The extensive boost shown in the runners is not an isolated case; additional studies have reported similar effects. Another study found 5.5 milligrams of caffeine per kilogram of body mass resulted in subjects cycling 29% longer during high intensity circuits.[43]

Breathing problems in premature infants, apnea of prematurity, are sometimes treated with citrated caffeine, which is available only by prescription in many countries.[44] A reduction in bronchopulmonary dysplasia has been exhibited in premature infants treated with caffeine citrate therapy regimens. The only short term risk associated with this treatment is a temporary reduction in weight gain during the therapy.[45] Longer term studies (18 to 21 months) have shown lasting benefits of treatment of premature infants with caffeine. [46] [47]

While relatively safe for humans, caffeine is considerably more toxic to some other animals such as dogs, horses and parrots due to a much poorer ability to metabolize this compound. Caffeine has a much more significant effect on spiders, for example, than most other drugs do.[48]

Tolerance and withdrawal

Caffeine content of select common food and drugs.[49] [50]
*This table assumes that coffee is drunk fairly strong, and tea very weak; as is normally the case in North America, and ignores other caffeine-like substances, for instance theobromine, present in some sources.
Product Serving size Caffeine per serving (mg) Caffeine per litre (mg)
Caffeine tablet (regular strength) 1 tablet 100
Caffeine tablet (extra strength) 1 tablet 200
Excedrin tablet 1 tablet 65
Chocolate, Dark (Hershey's Special Dark) 1 bar (43 g; 1.5 oz) 31
Chocolate, Milk (Hershey Bar) 1 bar (43 g; 1.5 oz) 10
Coffee, brewed 240 mL (8 U.S. fl oz) 135* 563*
Coffee, decaffeinated 240 mL (8 U.S. fl oz) 5* 21*
Coffee, espresso 57 mL (2 U.S. fl oz) 100* 1750*
Tea, leaf or bag 240 mL (8 U.S. fl oz) 50* 208*
Tea, green 240 mL (8 U.S. fl oz) 30* 63*
Soft drink, Coca-Cola Classic 355 mL (12 U.S. fl oz) 34 96
Soft drink, Mountain Dew 355 mL (12 U.S. fl oz) 54.5 154
Mountain Dew AMP 473ml (16 U.S. fl oz) 142 300
Soft drink, Jolt Cola 694 mL (23.5 U.S. fl oz) 150 216
Red Bull 250 mL (8.2 U.S. fl oz) 80 320
Powershot 30 mL (1 U.S. fl oz) 100 3333
Cocaine Energy Drink 250 mL (8.4 U.S. fl oz) 280 1120
Wired X 344 344 mL (16 U.S. fl oz) 344 727
Rockstar Energy Drink 473 mL (16 U.S. fl oz) 160 338
Full Throttle 473 mL (16 U.S. fl oz) 141 298
Bawls Guarana 296 mL (10 U.S. fl oz) 67 226
Alcoholic drink, Buckfast Tonic Wine 750ml (24.6 U.S. fl oz) 281.25 375
Caramel Macchiato (Typical Starbucks Coffee) Grande/Venti - 16/20 fl. oz. 150
Foosh Energy Mints one mint 102
Mountain Dew Game Fuel 355ml (12 U.S. fl oz) 72 203

Because caffeine is primarily an antagonist of the central nervous system's receptors for the neurotransmitter adenosine, the bodies of individuals who regularly consume caffeine adapt to the continual presence of the drug by substantially increasing the number of adenosine receptors in the central nervous system. This increase in the number of the adenosine receptors makes the body much more sensitive to adenosine, with two primary consequences.[51] First, the stimulatory effects of caffeine are substantially reduced, a phenomenon known as a tolerance adaptation. Second, because these adaptive responses to caffeine make individuals much more sensitive to adenosine, a reduction in caffeine intake will effectively increase the normal physiological effects of adenosine, resulting in unwelcome withdrawal symptoms in tolerant users.[51]

Other research questions the idea that up-regulation of adenosine receptors is responsible for tolerance to the locomotor stimulant effects of caffeine, noting, among other things, that this tolerance is insurmountable by higher doses of caffeine (it should be surmountable if tolerance was due to an increase in receptors), and that the increase in adenosine receptor number is modest and doesn't explain the large tolerance which develops to caffeine.[52]

Caffeine tolerance develops very quickly, especially among heavy coffee and energy drink consumers. Complete tolerance to sleep disruption effects of caffeine develops after consuming 400 mg of caffeine 3 times a day for 7 days. Complete tolerance to subjective effects of caffeine was observed to develop after consuming 300 mg 3 times per day for 18 days, and possibly even earlier.[53] Partial tolerance to caffeine has been observed in all other areas, studies with mice indicate that after a long period of caffeine exposure the learning benefits of caffeine observed earlier cannot be found to any significant level. Considering that 80% to 90% of American adults consume caffeine daily, and their mean daily caffeine intake exceeds 200 mg/day,[54] it can be surmised that a large fraction of the U.S. adult population is completely tolerant to most of the effects of caffeine.

Because adenosine, in part, serves to regulate blood pressure by causing vasodilation, the increased effects of adenosine due to caffeine withdrawal cause the blood vessels of the head to dilate, leading to an excess of blood in the head and causing a headache and nausea. Reduced catecholamine activity may cause feelings of fatigue and drowsiness. A reduction in serotonin levels when caffeine use is stopped can cause anxiety, irritability, inability to concentrate and diminished motivation to initiate or to complete daily tasks; in extreme cases it may cause mild depression. Together, these effects have come to be known as a "crash".[55]

Withdrawal symptoms—possibly including headache, irritability, an inability to concentrate, and stomach aches[56]—may appear within 12 to 24 hours after discontinuation of caffeine intake, peak at roughly 48 hours, and usually last from one to five days, representing the time required for the number of adenosine receptors in the brain to revert to "normal" levels, uninfluenced by caffeine consumption. Analgesics, such as aspirin, can relieve the pain symptoms, as can a small dose of caffeine.[57] Most effective is a combination of both an analgesic and a small amount of caffeine.

This is not the only case where caffeine increases the effectiveness of a drug. Caffeine makes pain relievers 40% more effective in relieving headaches and helps the body absorb headache medications more quickly, bringing faster relief.[58] For this reason, many over-the-counter headache drugs include caffeine in their formula. It is also used with ergotamine in the treatment of migraine and cluster headaches as well as to overcome the drowsiness caused by antihistamines.

Overuse

In large amounts, and especially over extended periods of time, caffeine can lead to a condition known as caffeinism.[59][60] Caffeinism usually combines caffeine dependency with a wide range of unpleasant physical and mental conditions including nervousness, irritability, anxiety, tremulousness, muscle twitching (hyperreflexia), insomnia, headaches, respiratory alkalosis[61] and heart palpitations.[62] Furthermore, because caffeine increases the production of stomach acid, high usage over time can lead to peptic ulcers, erosive esophagitis, and gastroesophageal reflux disease.[63] However, since both "regular" and decaffeinated coffees have been shown to stimulate the gastric mucosa and increase stomach acid secretion, caffeine is probably not the sole component of coffee responsible.[64]

There are four caffeine-induced psychiatric disorders recognized by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified (NOS).

Caffeine intoxication

An acute overdose of caffeine, usually in excess of 400 milligrams (more than 3–4 cups of brewed coffee), can result in a state of central nervous system overstimulation called caffeine intoxication. Some people seeking caffeine intoxication resort to insufflation (snorting) of caffeine powder, usually finely crushed caffeine tablets. This induces a faster and more intense reaction. The symptoms of caffeine intoxication are not unlike overdoses of other stimulants. It may include restlessness, nervousness, excitement, insomnia, flushing of the face, increased urination, gastrointestinal disturbance, muscle twitching, a rambling flow of thought and speech, irritability, irregular or rapid heart beat, and psychomotor agitation.[62] In cases of much larger overdoses mania, depression, lapses in judgment, disorientation, loss of social inhibition, delusions, hallucinations, psychosis, rhabdomyolysis, and death may occur.[65][66]

In cases of extreme overdose, death can result. The median lethal dose (LD50) of caffeine is 192 milligrams per kilogram in rats.[1] The LD50 of caffeine in humans is dependent on weight and individual sensitivity and estimated to be about 150 to 200 milligrams per kilogram of body mass, roughly 80 to 100 cups of coffee for an average adult taken within a limited timeframe that is dependent on half-life. Though achieving lethal dose with caffeine would be exceptionally difficult with regular coffee, there have been reported deaths from overdosing on caffeine pills, with serious symptoms of overdose requiring hospitalization occurring from as little as 2 grams of caffeine.[67][68][69][70] Death typically occurs due to ventricular fibrillation brought about by effects of caffeine on the cardiovascular system.

Treatment of severe caffeine intoxication is generally supportive, providing treatment of the immediate symptoms, but if the patient has very high serum levels of caffeine then peritoneal dialysis, hemodialysis, or hemofiltration may be required.

Anxiety and sleep disorders

Long-term overuse of caffeine can elicit a number of psychiatric disturbances. Two such disorders recognized by the American Psychiatric Association (APA) are caffeine-induced sleep disorder and caffeine-induced anxiety disorder.

In the case of caffeine-induced sleep disorder, an individual regularly ingests high doses of caffeine sufficient to induce a significant disturbance in his or her sleep, sufficiently severe to warrant clinical attention.[71]

In some individuals, the large amounts of caffeine can induce anxiety severe enough to necessitate clinical attention. This caffeine-induced anxiety disorder can take many forms, from generalized anxiety to panic attacks, obsessive-compulsive symptoms, or even phobic symptoms.[71] Because this condition can mimic organic mental disorders, such as panic disorder, generalized anxiety disorder, bipolar disorder, or even schizophrenia, a number of medical professionals believe caffeine-intoxicated people are routinely misdiagnosed and unnecessarily medicated when the treatment for caffeine-induced psychosis would simply be to withhold further caffeine.[72] A study in the British Journal of Addiction concluded that caffeinism, although infrequently diagnosed, may afflict as many as one person in ten of the population.[60]

Parkinson's disease

Several large studies have shown that caffeine intake is associated with a reduced risk of developing Parkinson's disease (PD) in men, but studies in women have been inconclusive.[73] The mechanism by which caffeine affects PD remains a mystery. In animal models, researchers have shown that caffeine can prevent the loss of dopamine-producing nerve cells seen in Parkinson's Disease, but researchers still do not know how this occurs.[74]

Effects on memory and learning

An array of studies found that caffeine could induce certain changes in memory and learning. However, it is still not definitely clear whether the effect is negative or positive.

In one study, caffeine was added to rat neurons in vitro. The dendritic spines (a part of the brain cell used in forming connections between neurons) taken from the hippocampus (a part of the brain associated with memory), grew by 33% and new spines formed. After an hour or two, however, these cells returned to their original shape.[75]

Another study showed that subjects—after receiving 100 milligrams of caffeine—had increased activity in brain regions located in the frontal lobe, where a part of the working memory network is located, and the anterior cingulum, a part of the brain that controls attention. The caffeinated subjects also performed better on the memory tasks.[76]

However, a different study showed that caffeine could impair short term memory and increase the likelihood of the tip of the tongue phenomenon. The study allowed the researchers to suggest that caffeine could aid short-term memory when the information to be recalled is related to the current train of thought, but also to hypothesize that caffeine hinders short-term memory when the train of thought is unrelated.[77] In essence, focused thought coupled with caffeine consumption increases mental performance.

Effects on the heart

Caffeine increases the levels of cAMP in the heart cells, mimicking the effects of epinephrine. cAMP diffuses through the cell and acts as a "secondary messenger," activating protein kinase A (PKA; cAMP-dependent protein kinase). According to one study, caffeine, in the form of coffee, significantly reduces the risk of heart disease in epidemiological studies. However, the protective effect was found only in participants who were not severely hypertensive (i.e. patients that are not suffering from a very high blood pressure). Furthermore, no significant protective effect was found in participants aged less than 65 years or in cerebrovascular disease mortality for those aged equal or more than 65 years.[78]

Effects on children

It is commonly believed that caffeine consumption causes stunted growth in children, but this is not supported by scientific research.[79] However, just as with adults, there is legitimate reason to limit the amount consumed by children.[80]

Caffeine intake during pregnancy

The Food Standards Agency has recommended that pregnant women should limit their caffeine intake to less than 300 mg of caffeine a day – the equivalent of four cups of coffee a day. A higher intake may be associated with miscarriage.[81]

Extraction of pure caffeine

Main article: Decaffeination

 

Pure caffeine is a white powder, and can be extracted from a variety of natural sources. Caffeine extraction is an important industrial process and can be performed using a number of different solvents. Benzene, chloroform, trichloroethylene and dichloromethane have all been used over the years but for reasons of safety, environmental impact, cost and flavor, they have been superseded by the following main methods:

Water extraction

Coffee beans are soaked in water. The water, which contains not only caffeine but also many other compounds which contribute 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 a good flavor.[82] Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter caffeine tablets.

Supercritical carbon dioxide extraction

Supercritical carbon dioxide is an excellent nonpolar solvent for caffeine (as well as many other organic compounds), and is safer than the organic solvents that are used for caffeine extraction. The extraction process is simple: CO2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73 atm. Under these conditions, CO2 is in a "supercritical" state: it has gaslike properties which allow it to penetrate deep into the beans but also liquid-like properties which dissolve 97–99% of the caffeine. The caffeine-laden CO2 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.[82]

Extraction by nonhazardous organic solvents

Organic solvents such as ethyl acetate present much less health and environmental hazard than previously used chlorinated and aromatic solvents. The hydrolysis products of ethyl acetate are ethanol and acetic acid, both nonhazardous in small quantities. Another method is to use triglyceride oils obtained from spent coffee grounds.

References

  1. ^ a b Erowid Caffeine Vault: Caffeine Dosage. The Vaults of Erowid (July 8, 2006). Retrieved on 2006-08-14.
  2. ^ "Caffeine" in The American Heritage Dictionary of the English Language, Fourth Edition, 2000, [1]
  3. ^ a b Lovett, Richard (24 September 2005). "Coffee: The demon drink?" (fee required). New Scientist (2518). Retrieved on 2007-11-19.
  4. ^ 21 CFR 182.1180. U.S. Code of Federal Regulations 462. U.S. Office of the Federal Register (April 1, 2003). Retrieved on 2007-02-16.
  5. ^ Frischknecht, P. M.; Urmer-Dufek J and Baumann T.W. (1986). "Purine alkaloid formation in buds and developing leaflets of Coffea arabica: expression of an optimal defence strategy?" (PDF). Phytochemistry 25 (3): 613 - 616. Journal of the Phytochemical Society of Europe and the Phytochemical Society of North America.. ISSN: 0031-9422.
  6. ^ Nathanson, J A (12 October 1984). "Caffeine and related methylxanthines: possible naturally occurring pesticides". Science 226 (4671): 184-187. PMID 6207592.
  7. ^ Baumann, T. W.; Gabriel H. (1984). "Metabolism and excretion of caffeine during germination of Coffea arabica L." (PDF). Plant and Cell Physiology 25 (8): 1431 - 1436. Oxford Journals. ISSN: 0032-0781.
  8. ^ a b Does Yerba Maté Contain Caffeine or Mateine?. The Vaults of Erowid (December 2003). Retrieved on 2006-08-16.
  9. ^ PubChem: mateina. National Library of Medicine. Retrieved on 2006-08-16.. Generally translated as mateine in articles written in English
  10. ^ PubChem: guaranine. National Library of Medicine. Retrieved on 2006-08-16.
  11. ^ Balentine DA, Harbowy ME and Graham HN, Tea: the Plant and its Manufacture; Chemistry and Consumption of the Beverage in Caffeine (1998), ed. G Spiller
  12. ^ a b Caffeine. International Coffee Organization. Retrieved on 2006-08-21.
  13. ^ Coffee and Caffeine FAQ: Does dark roast coffee have less caffeine than light roast?. Retrieved on 2007-01-02.
  14. ^ All About Coffee: Caffeine Level. Jeremiah’s Pick Coffee Co. Retrieved on 2007-06-14.
  15. ^ Caffeine in tea vs. steeping time (September 1996). Retrieved on 2006-08-12.
  16. ^ Haskell, CF; Kennedy D, Wesnes KA, Milne AL, Scholey AB (January 2007). "A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans". J Psychopharmacol 21 (1): 65–70. PMID 16533867.
  17. ^ Smit, HJ; Gaffan EA, Rogers PJ. (2004 Nov). "Methylxanthines are the psycho-pharmacologically active constituents of chocolate". Psychopharmacology 176 (3–4): 412-9. PMID 15549276.
  18. ^ Caffeine Accessories. ThinkGeek, Inc. Retrieved on 2007-12-31.
  19. ^ Escohotado, Antonio; Ken Symington (May 1999). A Brief History of Drugs: From the Stone Age to the Stoned Age. Park Street Press. ISBN 0-89281-826-3. 
  20. ^ Chow p. 19–20 (Czech edition); also Arcimovicova p. 9, Evans p. 2 and others
  21. ^ Yu, Lu (October 1995). The Classic of Tea: Origins & Rituals. Ecco Pr; Reissue edition. ISBN 0-88001-416-4. 
  22. ^ "Coffee". Encyclopædia Britannica. (1911). 
  23. ^ Benjamin, LT Jr; Rogers AM, Rosenbaum A (1991 January). "Coca-Cola, caffeine, and mental deficiency: Harry Hollingworth and the Chattanooga trial of 1911". J Hist Behav Sci 27 (1): 42–55. PMID 2010614.
  24. ^ Jarvis, Gail (May 21 2002). The Rise and Fall of Cocaine Cola. Retrieved on 2006-08-19.
  25. ^ a b Weinberg, BA; BK Bealer (January 2001). The World of Caffeine. Routledge. ISBN 0-415-92722-6. 
  26. ^ Nobel Prize Presentation Speech by Professor Hj. Théel, President of the Swedish Royal Academy of Sciences on December 10, 1902.
  27. ^ What's your poison: caffeine. Australian Broadcasting Corporation (1997). Retrieved on 2006-08-20.
  28. ^ Nehlig, A; Daval JL, Debry G (1992 May-Aug). "Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic, and psychostimulant effects". Brain Res Rev 17 (2): 139-70. PMID 1356551.
  29. ^ a b Bolton, Ph.D., Sanford; Gary Null, M.S. (1981). "Caffeine: Psychological Effects, Use and Abuse". Orthomolecular Psychiatry 10 (3): 202–211. Retrieved on 2006-08-12.
  30. ^ Newton, R; Broughton LJ, Lind MJ, Morrison PJ, Rogers HJ, Bradbrook ID (1981). "Plasma and salivary pharmacokinetics of caffeine in man". European Journal of Clinical Pharmacology 21 (1): 45–52. PMID 7333346.
  31. ^ Meyer, FP; Canzler E, Giers H, Walther H. (1991). "Time course of inhibition of caffeine elimination in response to the oral depot contraceptive agent Deposiston. Hormonal contraceptives and caffeine elimination". Zentralbl Gynakol 113 (6): 297–302. PMID 2058339.
  32. ^ Ortweiler, W; Simon HU, Splinter FK, Peiker G, Siegert C, Traeger A. (1985). "Determination of caffeine and metamizole elimination in pregnancy and after delivery as an in vivo method for characterization of various cytochrome p-450 dependent biotransformation reactions". Biomed Biochim Acta. 44 (7–8): 1189–99. PMID 4084271.
  33. ^ Bolton, Ph.D., Sanford; Gary Null, M.S. (1981). "Caffeine: Psychological Effects, Use and Abuse". Orthomolecular Psychiatry 10 (3): 202–211. Retrieved on 2006-08-14.
  34. ^ Springhouse (January 1 2005). Physician's Drug Handbook; 11th edition. Lippincott Williams & Wilkins. ISBN 1-58255-396-3. 
  35. ^ Caffeine. The Pharmacogenetics and Pharmacogenomics Knowledge Base. Retrieved on 2006-08-14.
  36. ^ Fisone G, G; Borgkvist A, Usiello A (2004 April). "Caffeine as a psychomotor stimulant: mechanism of action". Cell Mol Life Sci 61 (7–8): 857-72. PMID 15095008.
  37. ^ Graham T, Rush J, van Soeren M (1994). "Caffeine and exercise: metabolism and performance.". Can J Appl Physiol 19 (2): 111-38. PMID 8081318.
  38. ^ Fredholm B, Bättig K, Holmén J, Nehlig A, Zvartau E (1999). "Actions of caffeine in the brain with special reference to factors that contribute to its widespread use.". Pharmacol Rev 51 (1): 83–133. PMID 10049999.Full text
  39. ^ Verkhratsky A. (2005). "Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons". Physiol. Rev. 85 (1): 201–279. doi:10.1152/physrev.00004.2004.
  40. ^ Dews, P.B. (1984). Caffeine: Perspectives from Recent Research. Berlin: Springer-Valerag. ISBN 978-0387135328. 
  41. ^ Ivy, JL; Costill DL, Fink WJ, Lower RW (1979 Spring). "Influence of caffeine and carbohydrate feedings on endurance performance". Med Sci Sports 11 (1): 6–11. PMID 481158.
  42. ^ Graham, TE; Spriet, LL (1991 December). "Performance and metabolic responses to a high caffeine dose during prolonged exercise". J Appl Physiol 71 (6): 2292–8. PMID 1778925.
  43. ^ Trice, I; Haymes, EM (March 1995). "Effects of caffeine ingestion on exercise-induced changes during high-intensity, intermittent exercise". Int J Sport Nutr 5 (1): 37–44. PMID 7749424.
  44. ^ Caffeine (Systemic). MedlinePlus (05/25/2000). Archived from the original on 2007-02-23. Retrieved on 2006-08-12.
  45. ^ Schmidt, B; Roberts, RS, Davis, P, Doyle, LW, et al (May 18 2006). "Caffeine therapy for apnea of prematurity". N Engl J Med 354 (20): 2112–21.
  46. ^ Schmidt, B; Robin S. Roberts, M.Sc., Peter Davis, M.D., Lex W. Doyle, M.D., Keith J. Barrington, M.D., Arne Ohlsson, M.D., Alfonso Solimano, M.D., Win Tin, M.D. (November 8 2007). "Long-Term Effects of Caffeine Therapy for Apnea of Prematurity". N Engl J Med 357 (19): 1893-1902.
  47. ^ Schmidt, B (2005). "Methylxanthine Therapy for Apnea of Prematurity: Evaluation of Treatment Benefits and Risks at Age 5 Years in the International Caffeine for Apnea of Prematurity (CAP) Trial". Neonatology 88 (3): 208-213.
  48. ^ Noever, R., J. Cronise, and R. A. Relwani. 1995. Using spider-web patterns to determine toxicity. NASA Tech Briefs 19(4):82. Published in New Scientist magazine, 27 April 1995.
  49. ^ a b Caffeine Content of Food and Drugs. Nutrition Action Health Newsletter. Center for Science in the Public Interest (December 1996). Archived from the original on 2007-06-14. Retrieved on 2006-08-22.
  50. ^ a b Caffeine Content of Beverages, Foods, & Medications. The Vaults of Erowid (July 7 2006). Retrieved on 2006-08-22.
  51. ^ a b Green, RM; Stiles GL (January 1986). "Chronic caffeine ingestion sensitizes the A1 adenosine receptor-adenylate cyclase system in rat cerebral cortex". J Clin Invest 77 (1): 222–227. PMID 3003150.
  52. ^ Holtzman SG, Mante S, Minneman KP (1991). "Role of adenosine receptors in caffeine tolerance". J. Pharmacol. Exp. Ther. 256 (1): 62-8. PMID 1846425.
  53. ^ Caffeine - A Drug of Abuse?
  54. ^ Intakes of Selenium, Caffeine, and Theobromine by Adults, 1994–1996
  55. ^ Health risks of Stimulants, healthandgoodness.com
  56. ^ Juliano, L M (21 September 2004). "A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features.". Psychopharmacology 176 (1): 1–29. doi:10.1007/s00213-004-2000-x.
  57. ^ Sawynok, J (January 1995). "Pharmacological rationale for the clinical use of caffeine.". Drugs 49 (1): 37–50. PMID 7705215. Retrieved on 2006-08-14.
  58. ^ Headache Triggers: Caffeine. WebMD (June 2004). Retrieved on 2006-08-14.
  59. ^ Mackay, DC; Rollins JW. (1989 Summer). "Caffeine and caffeinism". Journal of the Royal Naval Medical Service 75 (2): 65-7. PMID 2607498.
  60. ^ a b James, JE; KP Stirling (September 1983). "Caffeine: A summary of some of the known and suspected deleterious effects of habitual use". British Journal of Addiction 78 (3): 251-8. PMID 6354232.
  61. ^ Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol. Retrieved on 2006-08-14.
  62. ^ a b Caffeine-related disorders. Encyclopedia of Mental Disorders. Retrieved on 2006-08-14.
  63. ^ Gastroesophageal Reflux Disease (GERD). Cedars-Sinai. Retrieved on 2006-08-14.
  64. ^ Erowid Caffeine Vault: Effects. The Vaults of Erowid (July 8, 2006). Retrieved on 2006-08-14.
  65. ^ Caffeine overdose. MedlinePlus (4/4/2006). Retrieved on 2006-08-14.
  66. ^ Kamijo, Y; Soma K, Asari Y, Ohwada T (1999 December). "Severe rhabdomyolysis following massive ingestion of oolong tea: caffeine intoxication with coexisting hyponatremia". Veterinary and Human Toxicology 41 (6): 381-3. PMID 10592946.
  67. ^ Kerrigan, S; Lindsey T (October 4, 2005). "Fatal caffeine overdose: two case reports" (reprint). Forensic Sci Int 153 (1): 67–69. PMID 15935584.
  68. ^ Holmgren, P; Nordén-Pettersson L, Ahlner J (January 6, 2004). "Caffeine fatalities — four case reports" (reprint). Forensic Sci Int 139 (1): 71–73. PMID 14687776.
  69. ^ Walsh, I; Wasserman GS, Mestad P, Lanman RC (December 1987). "Near-fatal caffeine intoxication treated with peritoneal dialysis". Pediatr Emerg Care 3 (4): 244-9. PMID 3324064.
  70. ^ Mrvos, RM; Reilly PE, Dean BS, Krenzelok EP (December 1989). "Massive caffeine ingestion resulting in death". Vet Hum Toxicol 31 (6): 571-2. PMID 2617841.
  71. ^ a b (1994) Diagnostic and Statistical Manual of Mental Disorders, fourth Edition.. American Psychiatric Association. ISBN 0-89042-062-9. 
  72. ^ Shannon, MW; Haddad LM, Winchester JF (1998). Clinical Management of Poisoning and Drug Overdose, 3rd ed.. ISBN 0-7216-6409-1. 
  73. ^ Effects of caffeine on Parkinson's disease, Harvard research
  74. ^ "New Findings About Parkinson's Disease: Coffee and Hormones Don't Mix", National Institute of Neurological Disorders and Stroke. 
  75. ^ "Caffeine clue to better memory", BBC News, October 12, 1999. 
  76. ^ Caffeine Boosts Short-Time Memory.
  77. ^ "A coffee can make you forgetful", BBC News, 20 July, 2004. 
  78. ^ Greenberg, J.A.; Dunbar, C.C.; Schnoll, R.; Kokolis, R.; Kokolis, S.; Kassotis, J. (Feb 2007). "Caffeinated beverage intake and the risk of heart disease mortality in the elderly: a prospective analysis". Am J Clin Nutr 85 (2): 392–398. PMID 17284734. Retrieved on 2007-02-26.
  79. ^ Fact or fiction: Common diet myths dispelled. MSNBC (December 2006). Retrieved on 2007-05-10.
  80. ^ Caffeine and Your Child. KidsHealth (January 2005). Retrieved on 2007-05-10.
  81. ^ Agency issues caffeine advice to pregnant women
  82. ^ a b Senese, Fred (2005-09-20). How is coffee decaffeinated?. General Chemistry Online. Retrieved on 2006-08-21.

Appendix

Relative content: comparison of different sources

Caffeine equivalents[49][50]
In general, each of the following contains approximately 200 milligrams of caffeine:
  • One 200 milligram caffeine pill
  • One 12 fluid ounce cup of regular Starbucks coffee (355 millilitres)
  • One and one quarter 16 fluid ounce cans of Monster Energy (590 millilitres)
  • One and a half pounds of milk chocolate[a] (680 grams)
  • Two 8 fluid ounce containers of regular coffee (470  millilitres)
  • 1/2 tube of Spazzstick Caffeinated Lip Balm
  • Two Foosh Energy Mints
  • Two and a half 10 fluid ounce bottles of Bawls caffeinated drink (740 millilitres)
  • Three standard Excedrin pills
  • Three 8 fluid ounce cups of Red Bull energy drink (710 millilitres)
  • Four 8 fluid ounce cups of Vault energy drink (1.0 litre)
  • Five 1 fluid ounce shots of espresso from robusta beans (150 millilitres)
  • Five 8 fluid ounce cups of black tea[b] (1.2 litres)
  • Five 8 fluid ounce cups of Mountain Dew (1.2 litres)
  • Five 12 fluid ounce cans of typical soda pop (1.8 litres) (variable)
  • Eight and a half 8 fluid ounce cups of Coca-Cola Classic (68 fl oz is approximately 2.0 litres)
  • Ten 8 fluid ounce cups of green tea[b] (2.4 litres)
  • Fifty 8 fluid ounce cups of decaffeinated coffee (12 litres)

Notes:

a. Chocolate and other products of cacao contain substantial quantities of other caffeine-like chemicals (especially theobromine) as well as actual caffeine. The properties of these substances are in at least some respects very similar to caffeine.

b. The figures are probably reasonably accurate for the very weak tea typically consumed in North America, but may be considerably understated for the much stronger tea drunk in some other places.

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Caffeine". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE