Caffeine
Overview
 
Caffeine is a bitter, white crystalline xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....

 alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

 that acts as a stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

 drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some 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 bean of the coffee plant
Coffea arabica
Coffea arabica is a species of Coffea originally indigenous to the mountains of Yemen in the Arabian Peninsula, hence its name, and also from the southwestern highlands of Ethiopia and southeastern Sudan. It is also known as the "coffee shrub of Arabia", "mountain coffee" or "arabica coffee"...

 and the leaves of the tea bush
Camellia sinensis
Camellia sinensis is the species of plant whose leaves and leaf buds are used to produce Chinese tea. It is of the genus Camellia , a genus of flowering plants in the family Theaceae. White tea, green tea, oolong, pu-erh tea and black tea are all harvested from this species, but are processed...

, as well as from various foods and drinks containing products derived from the kola nut
Kola nut
Kola Nut is the nut of the kola tree, a genus of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae . It is related to the South American genus Theobroma, or cocoa...

.
Encyclopedia
Caffeine is a bitter, white crystalline xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....

 alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

 that acts as a stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

 drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some 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 bean of the coffee plant
Coffea arabica
Coffea arabica is a species of Coffea originally indigenous to the mountains of Yemen in the Arabian Peninsula, hence its name, and also from the southwestern highlands of Ethiopia and southeastern Sudan. It is also known as the "coffee shrub of Arabia", "mountain coffee" or "arabica coffee"...

 and the leaves of the tea bush
Camellia sinensis
Camellia sinensis is the species of plant whose leaves and leaf buds are used to produce Chinese tea. It is of the genus Camellia , a genus of flowering plants in the family Theaceae. White tea, green tea, oolong, pu-erh tea and black tea are all harvested from this species, but are processed...

, as well as from various foods and drinks containing products derived from the kola nut
Kola nut
Kola Nut is the nut of the kola tree, a genus of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae . It is related to the South American genus Theobroma, or cocoa...

. Other sources include yerba maté
Yerba mate
Maté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...

, guarana
Guarana
Guarana , Paullinia cupana, syn. P. crysan, P. sorbilis) is a climbing plant in the maple family, Sapindaceae, native to the Amazon basin and especially common in Brazil. Guarana features large leaves and clusters of flowers, and is best known for its fruit, which is about the size of a coffee bean...

 berries, guayusa
Ilex guayusa
Ilex guayusa is an Amazonian tree of the holly genus, native to the Ecuadorian Amazon Rainforest. One of three known caffeinated holly trees, the leaves of the guayusa tree are dried and brewed like a tea for their stimulative effects....

, and the yaupon holly.

In humans, caffeine acts as a central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 stimulant, temporarily warding off drowsiness and restoring alertness. It is the world's most widely consumed psychoactive drug
Psychoactive drug
A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...

, but, unlike many other psychoactive substances, it is both legal and unregulated in nearly all parts of the world. Beverages containing caffeine, such as coffee
Coffee
Coffee is a brewed beverage with a dark,init brooo acidic flavor prepared from the roasted seeds of the coffee plant, colloquially called coffee beans. The beans are found in coffee cherries, which grow on trees cultivated in over 70 countries, primarily in equatorial Latin America, Southeast Asia,...

, tea
Tea
Tea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...

, soft drink
Soft drink
A soft drink is a non-alcoholic beverage that typically contains water , a sweetener, and a flavoring agent...

s, and energy drink
Energy drink
Energy drinks are beverages whose producers advertise that they "boost energy." These advertisements usually do not emphasize energy derived from the sugar and caffeine they contain but rather increased energy release due to a variety of stimulants and vitamins....

s, enjoy great popularity; in North America, 90% of adults consume caffeine daily.

Caffeine is toxic at sufficiently high doses, but ordinary consumption poses few known risks to health, even when carried on for years — there may actually be a modest protective effect against some diseases, including certain types of cancer. Some people experience sleep disruption if they consume caffeine, especially during the evening hours, but other people show little disturbance: the effect of caffeine on sleep is highly variable across individuals. Evidence for a risk to pregnancy is equivocal, but some authorities have concluded that prudent advice is for pregnant women to limit consumption to the equivalent of two cups of coffee per day or less. Caffeine has diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...

 properties when administered to people who are not used to it, but regular users develop a strong tolerance to this effect, and studies have generally failed to support the common notion that ordinary consumption of caffeinated beverages contributes significantly to dehydration. With heavy use, strong tolerance develops rapidly and caffeine can produce clinically significant physical and mental dependence.

Health effects

Stimulant effects

Caffeine is a central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 and metabolic stimulant, and is used both recreationally and medically to reduce physical fatigue and to restore alertness when drowsiness occurs. It produces increased wakefulness, faster and clearer flow of thought, increased focus, and better general body coordination. The amount of caffeine necessary to produce effects varies from person to person, depending on body size and degree of tolerance. Effects begin less than an hour after consumption, and a moderate dose usually wears off in about five hours.

Caffeine has a number of effects on sleep, but does not affect all people in the same way. It improves performance during sleep deprivation
Sleep deprivation
Sleep deprivation is the condition of not having enough sleep; it can be either chronic or acute. A chronic sleep-restricted state can cause fatigue, daytime sleepiness, clumsiness and weight loss or weight gain. It adversely affects the brain and cognitive function. Few studies have compared the...

 but may lead to subsequent insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

. In shift workers it leads to fewer mistakes caused by tiredness. In athletics, moderate doses of caffeine can improve sprint, endurance and team sports performance, but the improvements are not usually very large. High doses of caffeine, however, can impair athletic performance by interfering with coordination. Evidence shows that, contrary to common advice, caffeine may be helpful at high altitude.

Physical effects

Consumption of large amounts of caffeine — usually more than 500 mg per day — especially over extended periods of time, can lead to a condition known as caffeinism. Caffeinism usually combines caffeine dependency
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...

 with a wide range of unpleasant physical and mental conditions including nervousness, irritability, restlessness, insomnia, headaches, and heart palpitations after caffeine use.

Coffee consumption is associated with a lower overall risk of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. This is primarily due to a decrease in the risks of hepatocellular
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...

 and endometrial cancer
Endometrial cancer
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...

, but it may also have a modest effect on colorectal cancer. There does not appear to be a significant protective effect against other types of cancers, and heavy coffee consumption may increase the risk of bladder cancer
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...

.

There is little or no evidence that caffeine consumption increases the risk of cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

, and it may somewhat reduce the risk of type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...

. Drinking four or more cups of coffee per day does not affect the risk of hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 compared to drinking little or no coffee, however those who drink 1-3 cups per day may be at a slightly increased risk.

Caffeine increases intraocular pressure
Intraocular pressure
Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk from glaucoma...

 in those with glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

 but does not appear to affect normal individuals. It may protect people from liver cirrhosis. There is no evidence that coffee stunts a child's growth. Caffeine may increase the effectiveness of some medications including ones used to treat headaches.

Caffeine consumption during pregnancy does not appear to increase the risk of congenital malformations, miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...

 or growth retardation even when consumed in moderate to high amounts. However as the data supporting this conclusion is of poor quality some suggest limiting caffeine consumption during pregnancy. For example the UK Food Standards Agency
Food Standards Agency
The Food Standards Agency is a non-ministerial government department of the Government of the United Kingdom. It is responsible for protecting public health in relation to food throughout the United Kingdom and is led by a board appointed to act in the public interest...

 has recommended that pregnant women should limit their caffeine intake, out of prudence, to less than 200 mg of caffeine a day—the equivalent of two cups of instant coffee, or one and a half to two cups of fresh coffee. Although the evidence that caffeine may be harmful during pregnancy is equivocal, there is clear evidence that the hormonal changes associated with pregnancy slow the metabolic clearance of caffeine from the system, causing a given dose to have longer-lasting effects (as long as 15 hours in the third trimester).

On the positive side, caffeine is the primary treatment of the breathing disorders apnea of prematurity
Apnea of prematurity
Apnea of prematurity is defined as cessation of breathing by a premature infant that lasts for more than 15 seconds and/or is accompanied by hypoxia or bradycardia. Apnea is traditionally classified as either obstructive, central, or mixed. Obstructive apnea may occur when the infant's neck is...

 and may also be effective in preventing bronchopulmonary dysplasia
Bronchopulmonary dysplasia
Bronchopulmonary dysplasia is a chronic lung disorder that is most common among children who were born prematurely, with low birthweights and who received prolonged mechanical ventilation to treat respiratory distress syndrome...

 in premature
Premature birth
In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...

 infants. The only short-term risk associated with caffeine citrate
Caffeine citrate
Caffeine citrate is a citrate salt of caffeine, sometimes used in medical treatment, including short-term treatment of apnea of prematurity . Caffeine citrate functions in much the same capacity as does caffeine, but takes effect more quickly; its speed of dissociation is faster than that of...

 treatment is a temporary reduction in weight gain during the therapy, and longer term studies (18 to 21 months) have shown lasting benefits of treatment of premature infants with caffeine. The possibility of subtle long-term developmental problems cannot, however, entirely be ruled out.

When doses of caffeine equivalent to 2-3 cups of coffee are administered to people who have not consumed caffeine over the previous days, they produce a stimulation in urinary output. Because of this diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...

 effect, some authorities have recommended that athletes or airline passengers avoid caffeine in order to reduce the risk of dehydration. Most people who consume caffeine, however, ingest it daily. Regular users of caffeine have been shown to develop a strong tolerance to the diuretic effect, and studies have generally failed to support the notion that ordinary consumption of caffeinated beverages contributes significantly to dehydration, even in athletes.

Psychological

Four caffeine-induced disorders are recognized by the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

 (APA) including: caffeine intoxication, caffeine-induced sleep disorder
Caffeine-induced sleep disorder
Caffeine-induced sleep disorder is a psychiatric disorder that results from overconsumption of the stimulant caffeine. "When caffeine is consumed immediately before bedtime or continuously throughout the day, sleep onset may be delayed, total sleep time reduced, normal stages of sleep altered, and...

, caffeine-induced anxiety disorder and caffeine-related disorder not otherwise specified (NOS). In moderate doses it may reduce symptoms of depression and lower suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

 risk. High doses may trigger anxiety and rarely mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

 and psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

. As of 2010 the effect of caffeine on people with ADHD is not known. The DSM-IV defines caffeine-induced sleep disorder
Caffeine-induced sleep disorder
Caffeine-induced sleep disorder is a psychiatric disorder that results from overconsumption of the stimulant caffeine. "When caffeine is consumed immediately before bedtime or continuously throughout the day, sleep onset may be delayed, total sleep time reduced, normal stages of sleep altered, and...

, as an individual who regularly ingests high doses of caffeine sufficient to induce a significant disturbance in his or her sleep, sufficiently severe to warrant clinical attention.

Caffeine can have both positive and negative effects on anxiety disorders depending on the dose. At high doses, typically greater than 300 mg, it can both cause and worsen anxiety. At low doses it may reduce symptoms of anxiety. Caffeine withdrawal, on the other hand, can cause an increase in anxiety level. In moderate doses caffeine typically does not affect learning or memory
Effect of caffeine on memory
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a psychoactive stimulant drug. It can have both positive and negative effects on different aspects of memory.-Short-term memory:...

. It does however improve cognitive function in people who are fatigued, due to its effect on alertness. Some studies have however found a modest protective against Alzheimer disease, but the evidence is inconclusive.

Caffeine intoxication

Caffeine overdose can result in a state of central nervous system over-stimulation called caffeine intoxication (DSM-IV 305.90), or colloquially the "caffeine jitters". The symptoms of caffeine intoxication are not unlike overdoses of other stimulants. It may include restlessness, fidgeting, anxiety, 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
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

. In cases of much larger overdoses, mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

, lapses in judgment, disorientation, disinhibition
Disinhibition
Disinhibition is a term in psychology used to describe a lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive and perceptual aspects with signs and symptoms...

, delusions, hallucinations, or psychosis may occur, and rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...

 (breakdown of skeletal muscle tissue) can be provoked.

Extreme overdose can result in death. The median lethal dose (LD50) given orally, is 192 milligrams per kilogram in rats. 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 time frame 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. An exception to this would be taking a drug such as fluvoxamine
Fluvoxamine
Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...

 or levofloxacin
Levofloxacin
Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class and is used to treat severe or life-threatening bacterial infections or bacterial infections that have failed to respond to other antibiotic classes. It is sold under various brand names, such as Levaquin and...

, which blocks the liver enzyme responsible for the metabolism of caffeine, thus increasing the central effects and blood concentrations of caffeine five-fold. Death typically occurs due to ventricular fibrillation
Ventricular fibrillation
Ventricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...

 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
Peritoneal dialysis
Peritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...

, hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...

, or hemofiltration
Hemofiltration
In medicine, hemofiltration, also haemofiltration, is a renal replacement therapy similar to hemodialysis which is used almost exclusively in the intensive care setting...

 may be required.

Tolerance and withdrawal

With repetitive use, the stimulatory effects of caffeine are substantially reduced over time, a phenomenon known as a tolerance. Tolerance develops quickly to some (but not all) effects of caffeine, especially among heavy coffee and energy drink consumers. Some coffee drinkers develop tolerance to its sleep-disrupting effects, but others apparently do not. Withdrawal symptoms
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...

—including headache, irritability, inability to concentrate, drowsiness, insomnia, and pain in the stomach, upper body, and joints—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.

In other animals

While safe in humans, caffeine is considerably toxic to various animals, such as dogs and birds.

The increased toxicity of caffeine in some animals is at least partly due to a poorer ability to metabolize the compound.

Caffeine also has a pronounced effect on mollusks, various insects, and spiders.

Sources and consumption

Global consumption of caffeine has been estimated at 120,000 tonnes per year, making it the world's most popular psychoactive substance. This amounts to one serving of a caffeinated beverage for every person every day.

Caffeine is found in many plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

 species, where it acts as a natural pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...

, with high caffeine levels being observed in seedlings still developing foliage but lacking mechanical protection; caffeine paralyzes
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

 and kills certain insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...

s feeding upon the plant. High caffeine levels have also been found in the surrounding soil of coffee bean seedlings. Therefore, caffeine is understood to have a natural function as both a natural pesticide and an inhibitor of seed germination of other nearby coffee seedlings, thus giving it a better chance of survival.
Caffeine Content in Select Food and Drugs

Product Serving size Caffeine per serving (mg) Caffeine per liter
Litér
- External links :*...

 (mg)
Caffeine tablet (regular-strength) 1 tablet 100
Caffeine tablet (extra-strength) 1 tablet 200
Excedrin
Excedrin
Excedrin is an over-the-counter headache pain reliever, typically in the form of tablets or caplets. It contains acetaminophen , aspirin, and caffeine. Until late 2005 it was manufactured by Bristol-Myers Squibb, but in July 2005 it was purchased by Novartis, along with other products from BMS's...

 tablet
1 tablet 65
Hershey's Special Dark
Hershey's Special Dark
Hershey's Special Dark is a chocolate candy bar manufactured by The Hershey Company.Special Dark is similar to a normal Hershey bar, but is made with a dark variety of chocolate, and contains a higher percentage of cocoa solids, chocolate liquor, and cocoa butter than milk chocolate...

 (45% cacao content)
31
Hershey's Milk Chocolate (11% cacao content) 10
Percolated
Coffee percolator
A coffee percolator is a type of pot used to brew coffee. The name stems from the word "percolate" which means to cause to pass through a permeable substance especially for extracting a soluble constituent....

 coffee
Coffee
Coffee is a brewed beverage with a dark,init brooo acidic flavor prepared from the roasted seeds of the coffee plant, colloquially called coffee beans. The beans are found in coffee cherries, which grow on trees cultivated in over 70 countries, primarily in equatorial Latin America, Southeast Asia,...

80–135 386–652
Drip
Drip brew
Drip brewing, or filtered coffee, is a method for brewing coffee which involves pouring water over roasted, ground coffee beans contained in a filter. Water seeps through the coffee, absorbing its oils and essences, solely under gravity, then passes through the bottom of the filter...

 coffee
115–175 555–845
5–15 24–72
Coffee, espresso
Espresso
Espresso is a concentrated beverage brewed by forcing a small amount of nearly boiling water under pressure through finely ground coffee. Espresso is widely known throughout the world....

44–60 mL (1.5-2 U.S. fl oz) 100 1,691–2254
Black tea
Black tea
Black tea is a variety of tea that is more oxidized than the oolong, green, and white varieties.All four varieties are made from leaves of the shrub Camellia sinensis. Black tea is generally stronger in flavor and contains more caffeine than the less oxidized teas. Two principal varieties of the...

50 282
Green tea
Green tea
Green tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...

30 170
Guayakí yerba mate
Mate (beverage)
Mate , also known as chimarrão or cimarrón, is a traditional South American infused drink, particularly in Argentina, Uruguay, Paraguay, southern states of Brazil, south of Chile, the Bolivian Chaco, and to some extent, Syria and Lebanon...

 (loose leaf)
85 358 about
Coca-Cola
Coca-Cola
Coca-Cola is a carbonated soft drink sold in stores, restaurants, and vending machines in more than 200 countries. It is produced by The Coca-Cola Company of Atlanta, Georgia, and is often referred to simply as Coke...

 Classic
34 96
Mountain Dew
Mountain Dew
Mountain Dew is a citrus-flavored carbonated soft drink brand produced and owned by PepsiCo. The original formula was invented in the 1940s by Tennessee beverage bottlers Barney and Ally Hartman and was first marketed in Marion, VA, Knoxville and Johnson City, Tennessee. A revised formula was...

54 154
Guaraná Antarctica
Guaraná Antarctica
Guaraná Antarctica is the most popular guaraná-flavoured soft drink in Brazil, created in 1921 by Pedro Baptista de Andrade for Companhia Antarctica Paulista, now part of Anheuser-Busch InBev...

30 100
Jolt Cola
Jolt Cola
Jolt Cola was a carbonated soft drink produced by Wet Planet Beverages. It was created in 1985 by C. J. Rapp as a highly caffeinated cola. It is targeted towards students and young professionals, stressing its use as a stimulant in a similar manner as energy drinks...

280 403
Red Bull
Red Bull
Red Bull is an energy drink sold by the Austrian Red Bull GmbH, created in 1987 by the Austrian entrepreneur Dietrich Mateschitz. In terms of market share, Red Bull is the most popular energy drink in the world, with 3 billion cans sold each year. Dietrich Mateschitz was inspired by an already...

80 320


Common sources of caffeine are coffee, tea, and (to a lesser extent) chocolate derived from cocoa beans. Less commonly used sources of caffeine include the yerba maté
Yerba mate
Maté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...

, guarana
Guarana
Guarana , Paullinia cupana, syn. P. crysan, P. sorbilis) is a climbing plant in the maple family, Sapindaceae, native to the Amazon basin and especially common in Brazil. Guarana features large leaves and clusters of flowers, and is best known for its fruit, which is about the size of a coffee bean...

 and ilex guayusa
Ilex guayusa
Ilex guayusa is an Amazonian tree of the holly genus, native to the Ecuadorian Amazon Rainforest. One of three known caffeinated holly trees, the leaves of the guayusa tree are dried and brewed like a tea for their stimulative effects....

 plants, which are sometimes used in the preparation of teas and energy drinks. Two of caffeine's alternative names, mateine and guaranine, are derived from the names of these plants. The disparity in experience and effects between the various natural caffeine sources could be because plant sources of caffeine also contain widely varying mixtures of other xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....

 alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

s, including the cardiac stimulants theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...

 and theobromine
Theobromine
Theobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...

, and other substances such as polyphenol
Polyphenol
Polyphenols are a structural class of natural, synthetic, and semisynthetic organic chemicals characterized by the presence of large multiples of phenol structural units...

s that can form insoluble complexes with caffeine.

One of the world's primary sources of caffeine is the coffee "bean" (which is the seed of the coffee plant
Coffea
Coffea is a genus of flowering plants in the Rubiaceae family. They are shrubs or small trees native to tropical and southern Africa and tropical Asia. Seeds of several species are the source of the popular beverage coffee. Coffee ranks as one of the world's most valuable and widely traded...

), from which coffee is brewed. Caffeine content in coffee varies widely depending on the type of coffee bean
Coffee bean
A coffee bean is a seed of a coffee plant. It is the pit inside the red or purple fruit often referred to as a cherry. Even though they are seeds, they are referred to as 'beans' because of their resemblance to true beans. The fruits - coffee cherries or coffee berries - most commonly contain two...

 and the method of preparation used; even beans within a given bush can show variations in concentration. In general, one serving of coffee ranges from 80–100 milligrams, for a single shot (30 milliliters) of arabica-variety espresso
Espresso
Espresso is a concentrated beverage brewed by forcing a small amount of nearly boiling water under pressure through finely ground coffee. Espresso is widely known throughout the world....

, to approximately 100–125 milligrams for a cup (120 milliliters) of drip coffee. In general, dark-roast coffee has very slightly less caffeine than lighter roasts because the roasting process reduces a small amount of the bean's caffeine content. Arabica
Coffea arabica
Coffea arabica is a species of Coffea originally indigenous to the mountains of Yemen in the Arabian Peninsula, hence its name, and also from the southwestern highlands of Ethiopia and southeastern Sudan. It is also known as the "coffee shrub of Arabia", "mountain coffee" or "arabica coffee"...

 coffee normally contains significantly (+/-50%) less caffeine than the robusta
Coffea canephora
Robusta coffee is a variety of coffee which has its origins in central and western sub-Saharan Africa. It is a species of flowering plant in the Rubiaceae family. Though widely known as Coffea robusta, the plant is scientifically identified as Coffea canephora, which has two main varieties -...

 variety.
Tea is another common source of caffeine. Although tea contains more caffeine than coffee (by dry weight), a typical serving contains much less, as tea is normally brewed much weaker. Besides strength of the brew, growing conditions, processing techniques and other variables also affect caffeine content. Certain types of tea may contain somewhat more caffeine than other teas. Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee. Preparation and many other factors have a significant impact on tea, and color is a very poor indicator of caffeine content. Teas like the pale Japanese green tea
Green tea
Green tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...

, gyokuro
Gyokuro
Gyokuro is a fine and expensive type of green tea from Japan. It differs from the standard green tea known as sencha , because it is grown under the shade rather than the full sun. Another Japanese green tea that is shaded during growth is kabusecha , which differs from gyokuro in the length of...

, for example, contain far more caffeine than much darker teas like lapsang souchong
Lapsang souchong
Lapsang souchong is a black tea originally from the Wuyi region of the Chinese province of Fujian. It is sometimes referred to as smoked tea...

, which has very little.

Caffeine is also a common ingredient of soft drink
Soft drink
A soft drink is a non-alcoholic beverage that typically contains water , a sweetener, and a flavoring agent...

s, such as cola
Cola
Cola is a carbonated beverage that was typically flavored by the kola nut as well as vanilla and other flavorings, however, some colas are now flavored artificially. It became popular worldwide after druggist John Pemberton invented Coca-Cola in 1886...

, originally prepared from kola nut
Kola nut
Kola Nut is the nut of the kola tree, a genus of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae . It is related to the South American genus Theobroma, or cocoa...

s. Soft drinks typically contain about 10 to 50 milligrams of caffeine per serving. By contrast, energy drink
Energy drink
Energy drinks are beverages whose producers advertise that they "boost energy." These advertisements usually do not emphasize energy derived from the sugar and caffeine they contain but rather increased energy release due to a variety of stimulants and vitamins....

s, such as Red Bull
Red Bull
Red Bull is an energy drink sold by the Austrian Red Bull GmbH, created in 1987 by the Austrian entrepreneur Dietrich Mateschitz. In terms of market share, Red Bull is the most popular energy drink in the world, with 3 billion cans sold each year. Dietrich Mateschitz was inspired by an already...

, can start at 80 milligrams of caffeine per serving. The caffeine in these drinks either originates from the ingredients used or is an additive derived from the product of decaffeination
Decaffeination
Decaffeination is the act of removing caffeine from coffee beans, cocoa, tea leaves and other caffeine-containing materials. Despite removal of caffeine, many decaffeinated drinks still have around 1-2% of the...

 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
Slow-release
Slow-release is a strategy in material science in which a chemical compound is introduced into a system at a reduced speed. Slow-release is applied in fertilizers, pesticides and drugs....

 excipient
Excipient
An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or...

.

Chocolate
Chocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...

 derived from cocoa beans contains a small amount of caffeine. The weak stimulant effect of chocolate may be due to a combination of theobromine and theophylline, as well as caffeine. A typical 28-gram serving of a milk chocolate bar has about as much caffeine as a cup of decaffeinated coffee, although some dark chocolate currently in production contains as much as 160 mg per 100g.

Various manufacturers market caffeine tablets, claiming that using caffeine of pharmaceutical quality improves mental alertness. These effects have been borne out by research that shows caffeine use (whether in tablet form or not) results in decreased fatigue and increased attentiveness. These tablets are commonly used by students studying for their exams and by people who work or drive for long hours. One U.S. company is also marketing dissolving caffeine strips as an alternative to energy drinks. Another unusual intake route is SpazzStick
SpazzStick
SpazzStick claims to be the world's only caffeinated lip balm. It was created by Richie Holschen, the only cop in the remote Alaskan village of Kaktovik, who needed to protect his lips and remain alert in an area so cold that coffee freezes. When he first started making the product in 2004, he...

, a caffeinated lip balm
Lip balm
Lip balm or lip salve is a wax-like substance applied topically to the lips of the mouth to relieve chapped or dry lips, angular cheilitis, stomatitis, or cold sores. Lip balm often contains beeswax or carnauba wax, camphor, cetyl alcohol, lanolin, paraffin, and petrolatum, among other ingredients...

.

Chemical properties and biosynthesis

Caffeine is an achiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 molecule without stereoisomers.

The two amide groups of caffeine exist predominately as zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...

ic resonance structures
Resonance (chemistry)
In chemistry, resonance or mesomerism is a way of describing delocalized electrons within certain molecules or polyatomic ions where the bonding cannot be expressed by one single Lewis formula...

 where the nitrogen and carbon atoms are double bonded to each other so that both of these nitrogen atoms are essentially planar (in sp2 orbital hybridization). The fused ring system therefore contains a total of ten pi electrons
Pi bond
In chemistry, pi bonds are covalent chemical bonds where two lobes of one involved atomic orbital overlap two lobes of the other involved atomic orbital...

 and hence according to Hückel's rule
Hückel's rule
In organic chemistry, Hückel's rule estimates whether a planar ring molecule will have aromatic properties. The quantum mechanical basis for its formulation was first worked out by physical chemist Erich Hückel in 1931...

 is aromatic
Aromaticity
In organic chemistry, Aromaticity is a chemical property in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization stronger than would be expected by the stabilization of conjugation alone. The earliest use of the term was in an article by August...

.

Caffeine is synthesized in plants from the purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

s AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

, GMP
Guanosine monophosphate
Guanosine monophosphate, also known as 5'-guanidylic acid or guanylic acid and abbreviated GMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase...

, and IMP
Inosinic acid
Inosinic acid or inosine monophosphate is a nucleotide monophosphate. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine. It is formed by the deamination of adenosine monophosphate, and is hydrolysed...

. These in turn are transformed into xanthosine
Xanthosine
Xanthosine is a nucleoside derived from xanthine and ribose.-See also:* Xanthosine monophosphate* Xanthosine diphosphate* Xanthosine triphosphate...

 and then theobromine
Theobromine
Theobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...

, the latter being the penultimate precursor of caffeine.

Being readily available as a byproduct of decaffeination, caffeine is not usually synthesized
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...

 chemically. If desired, it may be synthesized from dimethylurea
Dimethylurea
Dimethylurea is a urea derivative and used as an intermediate in organic synthesis. It is a colorless crystalline powder with little toxicity.-Uses:...

 and malonic acid
Malonic acid
Malonic acid is a dicarboxylic acid with structure CH22. The ionised form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic acid's ethyl ester...

.

Pure anhydrous
Anhydrous
As a general term, a substance is said to be anhydrous if it contains no water. The way of achieving the anhydrous form differs from one substance to another...

 caffeine is a white colorless powder with a melting point of 227–228 °C. Caffeine is moderately soluble in water at room temperature (2 g/100 mL), but very soluble in boiling water (66 g/100 mL). It is also moderately soluble in ethanol (1.5 g/100 mL). It is weakly basic (pKa = ~0.6) requiring strong acid to protonate it.

Pharmacology

Inside the body caffeine acts through several mechanisms, but its most important effect is to counteract a substance called adenosine that naturally circulates at high levels throughout the body, and especially in the nervous system. In the brain, adenosine plays a generally protective role, part of which is to reduce neural activity levels — for example, there is some evidence that adenosine helps to induce torpor
Torpor
Torpor, sometimes called temporary hibernation is a state of decreased physiological activity in an animal, usually characterized by a reduced body temperature and rate of metabolism. Animals that go through torpor include birds and some mammals such as mice and bats...

 in animals that seasonally hibernate.

Mechanism of action

Because caffeine is both water-soluble and lipid-soluble, it readily crosses the blood–brain barrier that separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action is as a nonselective antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

 of adenosine receptor
Adenosine receptor
The adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...

s (in other words, an agent that reduces the effects of adenosine). The caffeine molecule is structurally similar to adenosine, and is capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive inhibitor.

Adenosine is found in every part of the body, because it plays a role in the fundamental ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

-related energy producing mechanism and is also necessary for RNA synthesis, but it has additional functions in the brain. The evidence indicates that brain adenosine acts to protect the brain by suppressing neural activity and by increasing blood flow via receptors located on vascular smooth muscle. Brain adenosine levels are increased by various types of metabolic stress, including lack of oxygen
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...

 and interruption of blood flow
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

. There is evidence that adenosine functions as a synaptically released neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 in some parts of the brain; however, stress-related adenosine increases appear to be produced mainly by extracellular metabolism of ATP. Unlike most neurotransmitters, adenosine does not seem to be packaged into vesicles that are released in a voltage-controlled manner, but the possibility of such a mechanism has not entirely been ruled out.

Several classes of adenosine receptors have been described, with different anatomical distributions. A1 receptors are widely distributed, and act to inhibit calcium uptake. A2A receptors are heavily concentrated in the basal ganglia, an area that plays a critical role in behavior control, but can be found in other parts of the brain as well, in lower densities. There is evidence that A 2A receptors interact with the dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 system, which is involved in reward and arousal. (A2A receptors can also be found on arterial walls and blood cell membranes.)

Beyond its general neuroprotective effects, there are reasons to believe that adenosine may be more specifically involved in control of the sleep-wake cycle. Robert McCarley
Robert McCarley
Robert W. McCarley, MD, is Chair and Professor of Psychiatry at Harvard Medical School and the VA Boston Healthcare System. He is also Director of the Laboratory of Neuroscience located at the Brockton VA Medical Center and the McLean Hospital...

 and his colleagues have argued that accumulation of adenosine may be a primary cause of the sensation of sleepiness that follows prolonged mental activity, and that the effects may be mediated both by inhibition of wake-promoting neurons via A1 receptors, and activation of sleep-promoting neurons via indirect effects on A2A receptors. More recent studies have provided additional evidence for the importance of A2A, but not A1, receptors.

A number of potential mechanisms have been proposed for the athletic performance-enhancing effects of caffeine. In the classic, or metabolic theory, caffeine may increase fat utilization and decrease glycogen utilization. Caffeine mobilizes free fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...

s from fat and/or intramuscular triglycerides by increasing circulating epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 levels. The increased availability of free fatty acids increases fat oxidation and spares muscle glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

, thereby enhancing endurance performance. In the nervous system, caffeine may reduce the perception of effort by lowering the neuron activation threshold, making it easier to recruit the muscles for exercise.

Caffeine metabolites

Metabolites of caffeine also contribute to caffeine's effects. Paraxanthine
Paraxanthine
Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system stimulant...

 is responsible for an increase in the lipolysis
Lipolysis
Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...

 process, which releases glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...

 and fatty acids into the blood to be used as a source of fuel by the muscles. Theobromine is a vasodilator
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...

 that increases the amount of oxygen and nutrient flow to the brain and muscles. Theophylline acts as a smooth muscle relaxant
Muscle relaxant
A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...

 that chiefly affects bronchiole
Bronchiole
The bronchioles or bronchioli are the first airway branches that no longer contain cartilage or glands in their submucosa. They are branches of the bronchi.The bronchioles terminate by entering the circular sacs called alveoli.- Structure :...

s and acts as a chronotrope
Chronotropic
Chronotropic effects are those that change the heart rate.Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node...

 and inotrope
Inotrope
An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions...

 that increases heart rate and force of contraction.

Metabolism

Caffeine from coffee or other beverages is absorbed by the small intestine within 45 minutes of ingestion and then distributed throughout all tissues of the body. Peak blood concentration is reached within one hour.
It is eliminated by first-order kinetics. Caffeine can also be absorbed rectally, evidenced by the formulation of suppositories of ergotamine tartrate
Tartrate
A tartrate is a salt or ester of the organic compound tartaric acid, a dicarboxylic acid. Its formula is O−OC-CH-CH-COO− or C4H4O62−.As food additives, tartrates are used as antioxidants, acidity regulators, and emulsifiers...

 and caffeine (for the relief of migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...

) and chlorobutanol
Chlorobutanol
Chlorobutanol, or trichloro-2-methyl-2-propanol, is a chemical preservative, sedative hypnotic and weak local anaesthetic similar in nature to chloral hydrate. It has antibacterial and antifungal properties...

 and caffeine (for the treatment of hyperemesis).

The biological half-life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...

 of caffeine—the time required for the body to eliminate one-half of the total amount of caffeine—varies widely among individuals according to such factors as age, liver function, pregnancy, some concurrent medications, and the level of enzymes in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 needed for caffeine metabolism. It can also be significantly altered by drugs or hormonal states. In healthy adults, caffeine's half-life is approximately 4.9 hours. Heavy cigarette smokers show a decrease in half-life of 30-50%, oral contraceptives can double it, and pregnancy can raise it even more, to as much as 15 hours during the last trimester. In newborn infants the half-life can be 80 hours or more; however it drops very rapidly with age, possibly to less than the adult value by the age of 6 months. The antidepressant Fluvoxamine
Fluvoxamine
Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...

 (Luvox) reduces the clearance of caffeine by more than 90%, and prolongs its elimination half-life more than tenfold; from 4.9 hours to 56 hours.

Caffeine is metabolized in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 by the cytochrome P450 oxidase
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...

 enzyme system (to be specific, the 1A2
CYP1A2
Cytochrome P450 1A2 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body...

 isozyme) into three metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 dimethylxanthines
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....

, each of which has its own effects on the body:
  • Paraxanthine
    Paraxanthine
    Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system stimulant...

     (84%): Has the effect of increasing lipolysis
    Lipolysis
    Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...

    , leading to elevated glycerol
    Glycerol
    Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...

     and free fatty acid
    Fatty acid
    In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...

     levels in the blood plasma
    Blood plasma
    Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

    .
  • Theobromine
    Theobromine
    Theobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...

     (12%): Dilates blood vessel
    Blood vessel
    The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

    s and increases urine
    Urine
    Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

     volume. Theobromine is also the principal alkaloid in the cocoa bean, and therefore chocolate
    Chocolate
    Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...

    .
  • Theophylline
    Theophylline
    Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...

     (4%): Relaxes smooth muscle
    Smooth muscle
    Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

    s of the bronchi
    Bronchus
    A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....

    , and is used to treat asthma
    Asthma
    Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

    . The therapeutic dose of theophylline, however, is many times greater than the levels attained from caffeine metabolism.


Each of these metabolites is further metabolized and then excreted in the urine. Caffeine can accumulate in individuals with severe liver disease
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...

, increasing its half-life.

Some quinolone
Quinolone
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....

 antibiotics exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby reducing clearance of caffeine and thus increasing blood levels.

A 2011 analysis published by PLoS
Public Library of Science
The Public Library of Science is a nonprofit open-access scientific publishing project aimed at creating a library of open access journals and other scientific literature under an open content license...

 Genetics
reviewed five studies covering more than 47,000 subjects of European descent. Researchers determined that habitual caffeine intake is associated with variations in two genes that regulate how quickly the body processes caffeine. Subjects who had a high-intake mutation of either gene on both chromosomes consumed 40 mg more caffeine per day (equivalent to a can of cola
Cola
Cola is a carbonated beverage that was typically flavored by the kola nut as well as vanilla and other flavorings, however, some colas are now flavored artificially. It became popular worldwide after druggist John Pemberton invented Coca-Cola in 1886...

) than people who did not.

Detection in biological fluids

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

Decaffeination

Extraction of caffeine from coffee, to produce decaffeinated coffee and caffeine, is an important industrial process and can be performed using a number of different solvents. Benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....

, chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...

, trichloroethylene
Trichloroethylene
The chemical compound trichloroethylene is a chlorinated hydrocarbon commonly used as an industrial solvent. It is a clear non-flammable liquid with a sweet smell. It should not be confused with the similar 1,1,1-trichloroethane, which is commonly known as chlorothene.The IUPAC name is...

, and dichloromethane
Dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...

 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 many other compounds in addition to caffeine and contributes to the flavor of coffee, is then passed through activated charcoal
    Activated carbon
    Activated carbon, also called activated charcoal, activated coal or carbo activatus, is a form of carbon that has been processed to make it extremely porous and thus to have a very large surface area available for adsorption or chemical reactions.The word activated in the name is sometimes replaced...

    , which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving decaffeinated coffee with its original flavor. Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter caffeine tablets.

  • Supercritical carbon dioxide extraction: Supercritical carbon dioxide
    Supercritical carbon dioxide
    Supercritical carbon dioxide is a fluid state of carbon dioxide where it is held at or above its critical temperature and critical pressure.Carbon dioxide usually behaves as a gas in air at STP or as a solid called dry ice when frozen...

     is an excellent nonpolar solvent for caffeine, and is safer than the organic solvents that are otherwise used. The extraction process is simple: CO2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73 atm
    Atmosphere (unit)
    The standard atmosphere is an international reference pressure defined as 101325 Pa and formerly used as unit of pressure. For practical purposes it has been replaced by the bar which is 105 Pa...

    . Under these conditions, CO2 is in a "supercritical
    Supercritical fluid
    A supercritical fluid is any substance at a temperature and pressure above its critical point, where distinct liquid and gas phases do not exist. It can effuse through solids like a gas, and dissolve materials like a liquid...

    " state
    Phase (matter)
    In the physical sciences, a phase is a region of space , throughout which all physical properties of a material are essentially uniform. Examples of physical properties include density, index of refraction, and chemical composition...

    : It has gaslike properties that allow it to penetrate deep into the beans but also liquid-like properties that dissolve 97–99% of the caffeine. The caffeine-laden CO2 is then sprayed with high pressure water to remove the caffeine. The caffeine can then be isolated by charcoal
    Activated carbon
    Activated carbon, also called activated charcoal, activated coal or carbo activatus, is a form of carbon that has been processed to make it extremely porous and thus to have a very large surface area available for adsorption or chemical reactions.The word activated in the name is sometimes replaced...

     adsorption
    Adsorption
    Adsorption is the adhesion of atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids to a surface. This process creates a film of the adsorbate on the surface of the adsorbent. It differs from absorption, in which a fluid permeates or is dissolved by a liquid or solid...

     (as above) or by distillation
    Distillation
    Distillation is a method of separating mixtures based on differences in volatilities of components in a boiling liquid mixture. Distillation is a unit operation, or a physical separation process, and not a chemical reaction....

    , recrystallization
    Recrystallization (chemistry)
    -Chemistry:In chemistry, recrystallization is a procedure for purifying compounds. The most typical situation is that a desired "compound A" is contaminated by a small amount of "impurity B". There are various methods of purification that may be attempted , which includes recrystallization...

    , or reverse osmosis
    Reverse osmosis
    Reverse osmosis is a membrane technical filtration method that removes many types of large molecules and ions from solutions by applying pressure to the solution when it is on one side of a selective membrane. The result is that the solute is retained on the pressurized side of the membrane and...

    .

  • Extraction by organic solvents: Certain organic solvents such as ethyl acetate
    Ethyl acetate
    Ethyl acetate is the organic compound with the formula CH3COOCH2CH3. This colorless liquid has a characteristic sweet smell and is used in glues, nail polish removers, and cigarettes...

     present much less health and environmental hazard than previously used chlorinated and aromatic organic solvents. Another method is to use triglyceride oils obtained from spent coffee grounds.

History

Caffeine was first isolated from coffee
Coffee
Coffee is a brewed beverage with a dark,init brooo acidic flavor prepared from the roasted seeds of the coffee plant, colloquially called coffee beans. The beans are found in coffee cherries, which grow on trees cultivated in over 70 countries, primarily in equatorial Latin America, Southeast Asia,...

 in 1820 by the German chemist Friedlieb Ferdinand Runge, and then independently in 1821 by French chemists Pierre Robiquet
Pierre Jean Robiquet
Pierre Jean Robiquet was a French chemist, who laid founding work in identifying amino acids, the fundamental bricks of proteins, through recognizing the first of them, asparagin, in 1806, in the take up of the industry of industrial dyes, with the identification of alizarin in 1826, and in the...

, Pierre Pelletier
Pierre Joseph Pelletier
Pierre-Joseph Pelletier was a French chemist who did notable research on vegetable alkaloids, and was the co-discoverer of quinine and strychnine.- Further reading :...

, and Joseph Caventou
Joseph Bienaimé Caventou
Joseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...

. Pelletier coined the word "cafeine" from the French word for coffee (café), and this term became the English word "caffeine".

According to Chinese legend, the Chinese emperor
Emperor of China
The Emperor of China refers to any sovereign of Imperial China reigning between the founding of Qin Dynasty of China, united by the King of Qin in 221 BCE, and the fall of Yuan Shikai's Empire of China in 1916. When referred to as the Son of Heaven , a title that predates the Qin unification, the...

 Shennong
Shennong
Shennong , which names mean "Divine Farmer", but also known as the Emperor of the Five Grains , was a legendary ruler of China and culture hero reputed to have lived some 5,000 years ago...

, reputed to have reigned in about 3000 BCE, accidentally discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted. Shennong is also mentioned in Lu Yu's Cha Jing, a famous early work on the subject of tea.

The history of coffee has been recorded as far back as the ninth century. During that time, coffee beans were available only in their place of origin, Ethiopia
Ethiopia
Ethiopia , officially known as the Federal Democratic Republic of Ethiopia, is a country located in the Horn of Africa. It is the second-most populous nation in Africa, with over 82 million inhabitants, and the tenth-largest by area, occupying 1,100,000 km2...

. Legends trace the discovery of coffee either to a Sufi dervish named Omar, or to a goatherder named Kaldi
Kaldi
According to legend, Kaldi was the Ethiopian goatherder who discovered the coffee plant.-Myth:Kaldi, noticing that when his flock nibbled on the bright red berries of a certain bush they became more energetic , chewed on the fruit himself. His exhilaration prompted him to bring the berries to an...

, who observed goats become elated and sleepless at night after grazing on coffee shrubs and, upon trying the berries 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
Persian people
The Persian people are part of the Iranian peoples who speak the modern Persian language and closely akin Iranian dialects and languages. The origin of the ethnic Iranian/Persian peoples are traced to the Ancient Iranian peoples, who were part of the ancient Indo-Iranians and themselves part of...

 physician al-Razi
Al-Razi
Muhammad ibn Zakariyā Rāzī , known as Rhazes or Rasis after medieval Latinists, was a Persian polymath,a prominent figure in Islamic Golden Age, physician, alchemist and chemist, philosopher, and scholar....

. The first reliable record of the use of coffee outside Ethiopia comes from Aden
Aden
Aden is a seaport city in Yemen, located by the eastern approach to the Red Sea , some 170 kilometres east of Bab-el-Mandeb. Its population is approximately 800,000. Aden's ancient, natural harbour lies in the crater of an extinct volcano which now forms a peninsula, joined to the mainland by a...

, in 1451. The appreciation of coffee as a beverage in Europe dates from the 17th century. The first coffee house in Venice opened some time in the late 1640s. In Britain, the first coffee house was opened in Oxford
Oxford
The city of Oxford is the county town of Oxfordshire, England. The city, made prominent by its medieval university, has a population of just under 165,000, with 153,900 living within the district boundary. It lies about 50 miles north-west of London. The rivers Cherwell and Thames run through...

 in 1650. They soon became popular throughout Western Europe
Western Europe
Western Europe is a loose term for the collection of countries in the western most region of the European continents, though this definition is context-dependent and carries cultural and political connotations. One definition describes Western Europe as a geographic entity—the region lying in the...

, and played a significant role in social relation
Social relation
In social science, a social relation or social interaction refers to a relationship between two , three or more individuals . Social relations, derived from individual agency, form the basis of the social structure. To this extent social relations are always the basic object of analysis for social...

s in the 17th and 18th centuries.

Use of the kola nut
Kola nut
Kola Nut is the nut of the kola tree, a genus of trees native to the tropical rainforests of Africa, classified in the family Malvaceae, subfamily Sterculioideae . It is related to the South American genus Theobroma, or cocoa...

, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in many West Africa
West Africa
West Africa or Western Africa is the westernmost region of the African continent. Geopolitically, the UN definition of Western Africa includes the following 16 countries and an area of approximately 5 million square km:-Flags of West Africa:...

n 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
Coca-Cola
Coca-Cola is a carbonated soft drink sold in stores, restaurants, and vending machines in more than 200 countries. It is produced by The Coca-Cola Company of Atlanta, Georgia, and is often referred to simply as Coke...

 syrup in Chattanooga
Chattanooga, Tennessee
Chattanooga is the fourth-largest city in the US state of Tennessee , with a population of 169,887. It is the seat of Hamilton County...

, Tennessee
Tennessee
Tennessee is a U.S. state located in the Southeastern United States. It has a population of 6,346,105, making it the nation's 17th-largest state by population, and covers , making it the 36th-largest by total land area...

, alleging the caffeine in its drink was "injurious to health". Although the judge ruled in favor of Coca-Cola, two bills were introduced to the U.S. House of Representatives
United States House of Representatives
The United States House of Representatives is one of the two Houses of the United States Congress, the bicameral legislature which also includes the Senate.The composition and powers of the House are established in Article One of the Constitution...

 in 1912 to amend the Pure Food and Drug Act
Pure Food and Drug Act
The Pure Food and Drug Act of June 30, 1906, is a United States federal law that provided federal inspection of meat products and forbade the manufacture, sale, or transportation of adulterated food products and poisonous patent medicines...

, 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 bean use comes from residue found in an ancient Mayan
Maya civilization
The Maya is a Mesoamerican civilization, noted for the only known fully developed written language of the pre-Columbian Americas, as well as for its art, architecture, and mathematical and astronomical systems. Initially established during the Pre-Classic period The Maya is a Mesoamerican...

 pot dated to 600 BCE. In the New World, chocolate was consumed in a bitter and spicy drink called xocolatl, often seasoned with vanilla
Vanilla
Vanilla is a flavoring derived from orchids of the genus Vanilla, primarily from the Mexican species, Flat-leaved Vanilla . The word vanilla derives from the Spanish word "", little pod...

, chile pepper, and achiote
Achiote
Achiote is a shrub or small tree from the tropical region of the Americas. The name derives from the Nahuatl word for the shrub, achiotl. It is also known as Aploppas, and its original Tupi name urucu. It is cultivated there and in Southeast Asia, where it was introduced by the Spanish in the...

. Xocolatl was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content. Chocolate was an important luxury good throughout pre-Columbian
Pre-Columbian
The pre-Columbian era incorporates all period subdivisions in the history and prehistory of the Americas before the appearance of significant European influences on the American continents, spanning the time of the original settlement in the Upper Paleolithic period to European colonization during...

 Mesoamerica
Mesoamerica
Mesoamerica is a region and culture area in the Americas, extending approximately from central Mexico to Belize, Guatemala, El Salvador, Honduras, Nicaragua, and Costa Rica, within which a number of pre-Columbian societies flourished before the Spanish colonization of the Americas in the 15th and...

, and cocoa beans were often used as currency.

Xocolatl was introduced to Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 by the Spaniards
Spanish people
The Spanish are citizens of the Kingdom of Spain. Within Spain, there are also a number of vigorous nationalisms and regionalisms, reflecting the country's complex history....

, and became a popular beverage by 1700. The Spaniards also introduced the cacao tree into the West Indies and the Philippines
Philippines
The Philippines , officially known as the Republic of the Philippines , is a country in Southeast Asia in the western Pacific Ocean. To its north across the Luzon Strait lies Taiwan. West across the South China Sea sits Vietnam...

. It was used in alchemical
Alchemy
Alchemy is an influential philosophical tradition whose early practitioners’ claims to profound powers were known from antiquity. The defining objectives of alchemy are varied; these include the creation of the fabled philosopher's stone possessing powers including the capability of turning base...

 processes, where it was known as "black bean".

The leaves and stems of the yaupon holly (Ilex vomitoria) were used by Native Americans
Indigenous peoples of the Americas
The indigenous peoples of the Americas are the pre-Columbian inhabitants of North and South America, their descendants and other ethnic groups who are identified with those peoples. Indigenous peoples are known in Canada as Aboriginal peoples, and in the United States as Native Americans...

 to brew a tea
Tea
Tea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...

 called asi or the "black drink
Black drink
Black drink was the name given by colonists to a ritual beverage called Asi, brewed by Native Americans in the Southeastern United States...

". Archaeologists have found evidence of this use stretch back far into antiquity, possibly dating to Late Archaic times.

Discovery

In 1819, the German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...

 chemist Friedlieb Ferdinand Runge isolated relatively pure caffeine for the first time; he called it "Kaffebase" (i.e., a base
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...

 that exists in coffee). In 1821, caffeine was isolated both by French chemist Pierre Jean Robiquet
Pierre Jean Robiquet
Pierre Jean Robiquet was a French chemist, who laid founding work in identifying amino acids, the fundamental bricks of proteins, through recognizing the first of them, asparagin, in 1806, in the take up of the industry of industrial dyes, with the identification of alizarin in 1826, and in the...

 and by another pair of French chemists, Pierre-Joseph Pelletier
Pierre Joseph Pelletier
Pierre-Joseph Pelletier was a French chemist who did notable research on vegetable alkaloids, and was the co-discoverer of quinine and strychnine.- Further reading :...

 and Joseph Bienaimé Caventou
Joseph Bienaimé Caventou
Joseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...

, according to Swedish chemist Jöns Jacob Berzelius in his yearly journal. Furthermore, Berzelius stated the French chemists had made their discoveries independently of any knowledge of Runge's or each other's work.

Pelletier's article on caffeine was the first to use the term in print (in the French form Caféine). It corroborates Berzelius's account:

German chemist Emil Fischer (1852-1919) first synthesized caffeine from raw materials in 1895 and two years later, he also derived the structural formula of the compound.

Robiquet was one of the first to isolate and describe the properties of pure caffeine while Pelletier was the first to perform an elemental analysis
Elemental analysis
Percent Composition is a process where a sample of some material is analyzed for its elemental and sometimes isotopic composition. Elemental analysis can be qualitative , and it can be quantitative...

.

Berzelius later acknowledged Runge's priority in the extraction of caffeine, stating: "However, at this point, it should not remain unmentioned that Runge (in his Phytochemical Discoveries, 1820, pages 146–147) specified the same method and described caffeine under the name Caffeebase a year earlier than Robiquet, to whom the discovery of this substance is usually attributed, having made the first oral announcement about it at a meeting of the Pharmacy Society in Paris.) According to Runge, he did this at the behest of Johann Wolfgang von Goethe
Johann Wolfgang von Goethe
Johann Wolfgang von Goethe was a German writer, pictorial artist, biologist, theoretical physicist, and polymath. He is considered the supreme genius of modern German literature. His works span the fields of poetry, drama, prose, philosophy, and science. His Faust has been called the greatest long...

." In 1827, M. Oudry isolated "theine" from tea, but it was later proved by Mulder
Gerardus Johannes Mulder
Gerardus Johannes Mulder was a Dutch organic and analytical chemist-Biography:Mulder was born in Utrecht, and earned a medical degree from Utrecht University....

 and by Carl Jobst that theine was the same as caffeine. The structure of caffeine was elucidated near the end of the 19th century by Hermann Emil Fischer
Hermann Emil Fischer
Hermann Emil Fischer, Emil Fischer was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He developed the Fischer projection, a symbolic way of drawing asymmetric carbon atoms.-Early years:Fischer was born in Euskirchen, near Cologne,...

, who was also the first to achieve its total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...

. This was part of the work for which Fischer was awarded the Nobel Prize
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...

 in 1902.

Religion

Some Seventh-day Adventists
Seventh-day Adventist Church
The Seventh-day Adventist Church is a Protestant Christian denomination distinguished by its observance of Saturday, the original seventh day of the Judeo-Christian week, as the Sabbath, and by its emphasis on the imminent second coming of Jesus Christ...

, Church of God (Restoration)
Church of God (Restoration)
The Church of God is a Christian denomination that was founded in the 1980s by Daniel Layne . In a booklet written by Mr. Layne in the early 1980s, he claimed to be an ex-heroin addict who spent years dealing drugs and living a life of crime and sin on the streets of San Francisco...

 adherents, and Christian Scientists do not consume caffeine. Some from these religions believe that one is not supposed to consume a non-medical, psychoactive substance, or believe that one is not supposed to consume a substance that is addictive. The Church of Jesus Christ of Latter-day Saints has said the following with regard to caffeinated beverages: "With reference to cola drinks, the Church has never officially taken a position on this matter, but the leaders of the Church have advised, and we do now specifically advise, against the use of any drink containing harmful drugs under circumstances that would result in acquiring the habit. Any beverage that contains ingredients harmful to the body should be avoided."

Gaudiya Vaishnavas
Gaudiya Vaishnavism
Gaudiya Vaishnavism is a Vaishnava religious movement founded by Chaitanya Mahaprabhu in India in the 16th century. "Gaudiya" refers to the Gauḍa region with Vaishnavism meaning "the worship of Vishnu"...

 generally also abstain from caffeine, as it is alleged to cloud the mind and over-stimulate the senses. To be initiated under a guru, one must have had no caffeine (along with alcohol, nicotine and other drugs) for at least a year.

In Islam the main rule on caffeine is that it is permissible. With regard to the caffeine in coffee, Imam Shihab al-Din said: "it is halal
Halal
Halal is a term designating any object or an action which is permissible to use or engage in, according to Islamic law. The term is used to designate food seen as permissible according to Islamic law...

(lawful) to drink, because all things are halal
Halal
Halal is a term designating any object or an action which is permissible to use or engage in, according to Islamic law. The term is used to designate food seen as permissible according to Islamic law...

(lawful) except that which God has made haraam
Haraam
Haraam is an Arabic term meaning "forbidden", or "sacred". In Islam it is used to refer to anything that is prohibited by the word of Allah in the Qur'an or the Hadith Qudsi. Haraam is the highest status of prohibition given to anything that would result in sin when a Muslim commits it...

(unlawful)".

External links

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