Caffeine is a bitter, white crystalline
xanthineXanthine , , is a purine base found in most human body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
alkaloidAlkaloids are naturally occurring chemical compounds containing basic nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of...
that is a psychoactive
stimulantStimulants, also sometimes called psychostimulants, 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...
drugA drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
. Caffeine was discovered by a German chemist,
Friedrich Ferdinand RungeFriedrich Ferdinand Runge was a German analytical chemist....
, in 1819. He coined the term
kaffein, a chemical compound in
coffeeCoffee is a brewed beverage prepared from roasted seeds, commonly called coffee beans, of the coffee plant. They are seeds of "coffee cherries" that grow on trees in over 70 countries. It has been said that green coffee is the second most traded commodity in the world behind crude oil. Due to its...
, which in English became
caffeine. Caffeine is also part of the chemical mixtures and insoluble complexes
guaranine found in
guaranaGuarana Guarana Guarana 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...
,
mateine found in
mateMate , also known as chimarrão or cimarrón, is a traditional South American infused drink. It is prepared from steeping dried leaves of yerba mate in hot water...
, and
theine found in non-herbal
teaTea is the agricultural product of the leaves, leaf buds, and internodes of the Camellia sinensis plant, prepared and cured by various methods...
; all of which contain additional
alkaloidAlkaloids are naturally occurring chemical compounds containing basic nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of...
s such as the cardiac stimulants
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
and
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
, and often other chemicals such as polyphenols which can form insoluble complexes with caffeine.
Caffeine is found in varying quantities in the
beanBean is a common name for large plant seeds of several genera of the family Fabaceae used for human food or animal feed....
s,
leavesIn botany, a leaf is an above-ground plant organ specialized for photosynthesis. For this purpose, a leaf is typically flat and thin. There is continued debate about whether the flatness of leaves evolved to expose the chloroplasts to more light or to increase the absorption of carbon dioxide. In...
, and
fruitThe term fruit has different meanings dependent on context, and the term is not synonymous in food preparation and biology. Fruits are the means by which flowering plants disseminate seeds, and the presence of seeds indicates that a structure is most likely a fruit, though not all seeds come from...
of some plants, where it acts as a natural
pesticideA pesticide is a substance or mixture of substances used to kill a pest.A pesticide is any substance or mixture of substance intended for:- preventing, destroying, repelling or mitigating any pest....
that paralyzes and kills certain
insectInsects are arthropods, having a hard exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae. They are the most diverse group of animals on the planet and include more than a million species that are already described. Insects represent more than half of all...
s feeding on the plants. It is most commonly consumed by humans in infusions extracted from the
cherriesA coffee bean is the seed of the coffee plant . The fruits, coffee cherries or coffee berries, most commonly contain two stones with their flat sides together. Coffee beans consist mostly of endosperm that contains 0.8 - 2.5 % caffeine, which is one of the main reasons the plants are cultivated...
of the
coffee plantCoffea arabica is a species of coffee indigenous to Ethiopia and Yemen. It is also known as the "coffee shrub of Arabia", "mountain coffee" or "arabica coffee". Coffea arabica is believed to be the first species of coffee to be cultivated, being grown in southwest Arabia for well over 1,000 years...
and the leaves of the
tea bushCamellia sinensis is the species of plant whose leaves and leaf buds are used to produce 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 differently...
, as well as from various foods and drinks containing products derived from the
kola nutKola nut is a genus of about 125 species 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...
. Other sources include
yerba mateYerba mate or yerba-mate , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, eastern Paraguay and southern Brazil...
,
guaranaGuarana Guarana Guarana 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...
berries, and the
Yaupon HollyIlex vomitoria , is a species of holly native to southeastern North America, occurring in United States from Maryland south to Florida and west to Oklahoma and Texas, and in Mexico in Chiapas.It is an evergreen shrub or small tree reaching 5-9 m tall, with...
.
In humans, caffeine is a
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
(CNS)
stimulantStimulants, also sometimes called psychostimulants, 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...
, having the effect of temporarily warding off drowsiness and restoring alertness. Beverages containing caffeine, such as
coffeeCoffee is a brewed beverage prepared from roasted seeds, commonly called coffee beans, of the coffee plant. They are seeds of "coffee cherries" that grow on trees in over 70 countries. It has been said that green coffee is the second most traded commodity in the world behind crude oil. Due to its...
,
teaTea is the agricultural product of the leaves, leaf buds, and internodes of the Camellia sinensis plant, prepared and cured by various methods...
,
soft drinkA soft drink is a drink that does not contain alcohol . Soft drinks are often carbonated and commonly consumed while cold. The most common soft drinks are colas, flavored water, sparkling water, iced tea, sweet tea, lemonade, squash and fruit punch....
s, and
energy drinkEnergy drinks are soft drinks advertised as providing energy to improve physical activity of the drinker, as compared to a typical drink. Rather than providing food energy , these drinks are designed to increase a user's mental alertness and physical performance by the addition of caffeine,...
s enjoy great popularity. Caffeine is the world's most widely consumed psychoactive substance, but unlike many other psychoactive substances it is legal and unregulated in nearly all jurisdictions. In North America, 90% of adults consume caffeine daily. The U.S.
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
lists caffeine as a "multiple purpose
generally recognized as safeGenerally recognized as safe is an American Food and Drug Administration designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act food additive tolerance requirements.GRAS exemptions are granted...
food substance".
Caffeine has
diureticA diuretic is any drug that elevates the rate of urination and thus provides a means of forced diuresis. There are several categories of diuretics...
properties, at least when administered in sufficient doses to subjects who do not have a tolerance for it. Regular users, however, 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.
Occurrence
Caffeine is found in many
plantPlants are living organisms belonging to the kingdom Plantae. They include familiar organisms such as trees, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The scientific study of plants, known as botany, has identified about 350,000 extant species of plants, defined as seed plants,...
species, where it acts as a natural
pesticideA pesticide is a substance or mixture of substances used to kill a pest.A pesticide is any substance or mixture of substance intended for:- preventing, destroying, repelling or mitigating any pest....
, with high caffeine levels being reported in seedlings that are still developing foliages, but are lacking mechanical protection; caffeine
paralyzesParalysis is the complete loss of muscle function for one or more muscle groups. Paralysis can cause loss of feeling or loss of mobility in the affected area.-Causes:Paralysis is most often caused by damage to the nervous system, especially the spinal cord...
and kills certain
insectInsects are arthropods, having a hard exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae. They are the most diverse group of animals on the planet and include more than a million species that are already described. Insects represent more than half of all...
s feeding upon the plant. High caffeine levels have also been found in the surrounding soil of coffee bean seedlings. It is therefore understood that caffeine has a natural function as both a natural pesticide and as an inhibitor of seed germination of other nearby coffee seedlings thus giving it a better chance of survival.
The most commonly used sources of caffeine are
coffeeCoffee is a brewed beverage prepared from roasted seeds, commonly called coffee beans, of the coffee plant. They are seeds of "coffee cherries" that grow on trees in over 70 countries. It has been said that green coffee is the second most traded commodity in the world behind crude oil. Due to its...
,
teaTea is the agricultural product of the leaves, leaf buds, and internodes of the Camellia sinensis plant, prepared and cured by various methods...
, and to a lesser extent
cacaoCacao , or the cocoa plant, is a small evergreen tree in the family Sterculiaceae , native to the deep tropical region of the Americas. Its seeds are used to make cocoa and chocolate...
. Less commonly used sources of caffeine include the
yerba matéYerba mate or yerba-mate , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, eastern Paraguay and southern Brazil...
and
guaranaGuarana Guarana Guarana 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...
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. Some yerba mate enthusiasts assert that mateine is a stereoisomer of caffeine, which would make it a different substance altogether. This is not true because caffeine is an
achiralThe term chiral is used to describe an object that is non-superposable on its mirror image. Achiral objects are objects that are identical to their mirror image....
molecule, and therefore has no
enantiomerIn stereochemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are "non-superposable" , much as one's left and right hands are "the same" but opposite....
s; nor does it have other stereoisomers. The disparity in experience and effects between the various natural caffeine sources could be due to the fact that plant sources of caffeine also contain widely varying mixtures of other
xanthineXanthine , , is a purine base found in most human body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
alkaloidAlkaloids are naturally occurring chemical compounds containing basic nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of...
s, including the cardiac stimulants
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
and
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
and other substances such as polyphenols which 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 plantCoffea is a large genus of flowering plants in the family Rubiaceae. They are shrubs or small trees, native to subtropical Africa and southern Asia. Seeds of several species are the source of the popular beverage coffee. After their outer hull is removed, the seeds are commonly called "beans"...
), from which
coffeeCoffee is a brewed beverage prepared from roasted seeds, commonly called coffee beans, of the coffee plant. They are seeds of "coffee cherries" that grow on trees in over 70 countries. It has been said that green coffee is the second most traded commodity in the world behind crude oil. Due to its...
is brewed. Caffeine content in coffee varies widely depending on the type of
coffee beanA coffee bean is the seed of the coffee plant . The fruits, coffee cherries or coffee berries, most commonly contain two stones with their flat sides together. Coffee beans consist mostly of endosperm that contains 0.8 - 2.5 % caffeine, which is one of the main reasons the plants are cultivated...
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 40 milligrams, for a single shot (30 milliliters) of
arabica-variety
espressoCaffè espresso, espresso, is a concentrated coffee beverage brewed by forcing hot water under pressure through finely ground coffee....
, to about 100 milligrams for a cup (120 milliliters) of drip coffee. Generally, dark-roast coffee has less caffeine than lighter roasts because the roasting process reduces the bean's caffeine content.
ArabicaCoffea arabica is a species of coffee indigenous to Ethiopia and Yemen. It is also known as the "coffee shrub of Arabia", "mountain coffee" or "arabica coffee". Coffea arabica is believed to be the first species of coffee to be cultivated, being grown in southwest Arabia for well over 1,000 years...
coffee normally contains less caffeine than the
robustaCoffea canephora is a species of coffee which has its origins in western Africa. It is grown mostly in Africa and Brazil, where it is often called Conillon. It is also grown in Southeast Asia where French colonists introduced it in the late 19th century...
variety. Coffee also contains trace amounts of
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
, but no
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
.
TeaTea is the agricultural product of the leaves, leaf buds, and internodes of the Camellia sinensis plant, prepared and cured by various methods...
is another common source of caffeine. Although tea contains more caffeine than coffee, 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
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
and slightly higher levels of
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
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 teaGreen tea is a type of tea made solely with the leaves of Camellia sinensis that has undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures in Asia from Japan to the Middle East. Recently, it has become more widespread in the...
gyokuroGyokuro is a fine and expensive type of green tea from Japan. It differs from a green tea known as sencha , because it is grown under the shade rather than the full sun. The name translates as "jade dew" and refers to the pale green colour of the infusion...
, for example, contain far more caffeine than much darker teas like
lapsang souchongLapsang 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 content of select common food and drugs.
| Product |
Serving size |
Caffeine per serving (mg) |
Caffeine per litre The litre or liter is a unit of volume. There are two official symbols: the Latin letter L in lower and upper case . The lower case L is also often written as a cursive ℓ, though this symbol has no official approval by any international bureau...
(mg) |
| Caffeine tablet (regular strength) |
1 tablet |
100 |
— |
| Caffeine tablet (extra strength) |
1 tablet |
200 |
— |
| 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 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 cacao solids than milk chocolate.Hershey's Special Dark is available in a variety...
(45% cacao content) |
| 31 |
— |
| Hershey's Milk Chocolate (11% cacao content) |
| 10 |
— |
Percolated coffeeCoffee is a brewed beverage prepared from roasted seeds, commonly called coffee beans, of the coffee plant. They are seeds of "coffee cherries" that grow on trees in over 70 countries. It has been said that green coffee is the second most traded commodity in the world behind crude oil. Due to its...
|
| 80–135 |
386–652 |
| Drip coffee |
| 115–175 |
555–845 |
| Coffee, decaffeinated |
| 5-15 |
24-72 |
Coffee, espressoCaffè espresso, espresso, is a concentrated coffee beverage brewed by forcing hot water under pressure through finely ground coffee....
|
| 100 |
1691–2254 |
Coffee, StarbucksStarbucks Corporation is an international coffee and coffeehouse chain based in Seattle, Washington, United States. Starbucks is the largest coffeehouse company in the world, with 16,120 stores in 49 countries, including around 11,000 in the United States, followed by nearly 1,000 in Canada and...
|
| 240 |
650-700 |
Black teaBlack 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 Camellia sinensis. Black tea is generally stronger in flavor and contains more caffeine than the less oxidized teas. Two principal varieties of the species are...
|
| 50 |
282 |
| Green tea Green tea is a type of tea made solely with the leaves of Camellia sinensis that has undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures in Asia from Japan to the Middle East. Recently, it has become more widespread in the...
|
| 30 |
169 |
Coca-ColaCoca-Cola is a carbonated soft drink sold in stores, restaurants and vending machines internationally. The Coca-Cola Company claims that the beverage is sold in more than 200 countries...
Classic |
| 34 |
96 |
Mountain DewMountain Dew, stylized as Mtn Dew, is a soft drink manufactured and distributed by PepsiCo. Although its formula was invented in Knoxville, Tennessee, it was first marketed in Knoxville and Johnson City, TN through the 1940s. Then by Barney and Ally Hartman, in Fayetteville, North Carolina, and...
|
| 54.5 |
154 |
| Jolt Cola Jolt Cola is 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 |
402 |
Red BullRed Bull is an energy drink which is produced and sold by the Austrian company Red Bull GmbH. In 2006, more than 3 billion cans were sold in over 130 countries.The beverage's slogan is "It gives you Wings."- History :...
|
| 80 |
320 |
Caffeine is also a common ingredient of
soft drinkA soft drink is a drink that does not contain alcohol . Soft drinks are often carbonated and commonly consumed while cold. The most common soft drinks are colas, flavored water, sparkling water, iced tea, sweet tea, lemonade, squash and fruit punch....
s such as
colaCola is a beverage usually containing caramel coloring, caffeine, and a sweetener such as sugar or high fructose corn syrup.Originally invented by the druggist John Pemberton, it has become popular worldwide. Coca-Cola has become the major international brand, leading to the drink often being seen...
, originally prepared from
kola nutKola nut is a genus of about 125 species 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...
s. Soft drinks typically contain about 10 to 50 milligrams of caffeine per serving. By contrast,
energy drinkEnergy drinks are soft drinks advertised as providing energy to improve physical activity of the drinker, as compared to a typical drink. Rather than providing food energy , these drinks are designed to increase a user's mental alertness and physical performance by the addition of caffeine,...
s such as
Red BullRed Bull is an energy drink which is produced and sold by the Austrian company Red Bull GmbH. In 2006, more than 3 billion cans were sold in over 130 countries.The beverage's slogan is "It gives you Wings."- History :...
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
decaffeinationDecaffeination is the act of removing caffeine from coffee beans, mate, cocoa, tea leaves and other caffeine-containing materials. In the case of coffee, various methods can be used...
or from chemical synthesis.
GuaranaGuarana Guarana Guarana 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...
, a prime ingredient of energy drinks, contains large amounts of caffeine with small amounts of
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
and
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
in a naturally occurring
slow-releaseSlow-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....
excipientAn excipient is an 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 mixed with an excipient...
.
ChocolateChocolate comprises a number of raw and processed foods produced from the seed of the tropical cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America, with its earliest documented use around 1100 BC...
derived from
cocoaCocoa is the dried and fully fermented fatty seed of the cacao tree, from which chocolate is made. "Cocoa" can often also refer to the drink commonly known as hot chocolate; to cocoa powder, the dry powder made by grinding cocoa seeds and removing the cocoa butter from the dark, bitter cocoa...
contains a small amount of caffeine. The weak stimulant effect of chocolate may be due to a combination of
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
and
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
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.
In recent years various manufacturers have begun putting caffeine into shower products such as
shampooShampoo is a hair care product used for the removal of oils, dirt, skin particles, dandruff, environmental pollutants and other contaminant particles that gradually build up in hair...
and
soapSoap is an anionic surfactant used in conjunction with water for washing and cleaning, which historically comes either in solid bars or in the form of a viscous liquid....
, claiming that caffeine can be absorbed through the skin. However, the effectiveness of such products has not been proven, and they are likely to have little stimulatory effect on the central nervous system because caffeine is not readily absorbed through the skin.
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 that 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.
History
- Main articles: History of cocoa, History of coffee
The history of coffee has been recorded as far back as the ninth century. At first, coffee remained largely confined to Ethiopia, where its native beans were first cultivated by Ethiopian highlanders...
, Origin and history of tea
Humans have consumed caffeine since the
Stone AgeThe Stone Age is a broad prehistoric time period during which humans widely used stone for toolmaking.Stone tools were made from a variety of different sorts of stone. For example, flint and chert were shaped for use as cutting tools and weapons, while basalt and sandstone were used for ground...
. Early peoples found that chewing the seeds, bark, or leaves of certain plants had the effects of easing fatigue, stimulating awareness, and elevating one's mood. Only much later was it found that the effect of caffeine was increased by steeping such plants in hot water. Many cultures have legends that attribute the discovery of such plants to people living many thousands of years ago.
According to one popular Chinese legend, the
Emperor of ChinaThe Emperor of China refers to any sovereign of Imperial China reigning since the founding of China, united by Fu Xi in 2852 BCE until the fall of Yuan Shikai's Empire of China in 1916. When referred to as the Son of Heaven , a title created no later than Shang Dynasty, the Emperor was recognized...
ShennongShennong , also known as the Yan Emperor or the Emperor of the Five Grains , is a ruler of China and culture hero who lived some 5,000 years ago, and taught ancient China the practices of agriculture. Appropriately, his name means "the Divine Farmer"...
, reputed to have reigned in about 3000 BC, accidentally discovered that when some leaves fell into boiling water, a fragrant and restorative
drinkA caffeinated drink or caffeinated beverage is a drink which contains caffeine, a stimulant which is legal and popular in most developed countries.Caffeinated drinks are primarily coffee, tea, soft drinks, and energy drinks...
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 native habitat,
EthiopiaEthiopia , officially the Federal Democratic Republic of Ethiopia, is a landlocked country situated in the Horn of Africa. Ethiopia is bordered by Eritrea to the north, Sudan to the west, Kenya to the south, Somalia to the east and Djibouti to the northeast. Its size is 1,100,000 km² with an...
. A popular legend traces its discovery to a goatherder named
KaldiAccording to legend, Kaldi was the Ethiopian goatherder who discovered the coffee plant.The story is probably apocryphal, as it was first related by Antoine Faustus Nairon, a Maronite who became a Roman professor of Oriental languages and author of one of the first printed treatises devoted to...
, who apparently observed goats that became elated and sleepless at night after grazing on coffee shrubs and, upon trying the berries that the goats had been eating, experienced the same vitality. The earliest literary mention of coffee may be a reference to Bunchum in the works of the 9th century
PersianThe Persian people are the majority ethnic group in Iran. However, there are sub-groups who speak the Persian language as their mother tongue throughout the Iranian plateau. The term Persian has also a supra-ethnic significance and has been historically referred to a part of Iranian peoples...
physician
al-RaziAbū Bakr Muhammad ibn Zakariyā Rāzī , known as Rhazes or Rasis after medieval Latinists, was a Persian alchemist, chemist, physician, philosopher and scholar...
. In 1587,
Malaye JaziriMalaye Jaziri , was a Kurdish writer, poet and mystic.One of the most influential principalities in the history of Kurdistan was Botan with the capital Jazira , in present day Şırnak province in south-eastern Turkey. Because of its superior position Botan came to be an important centre of Kurdish...
compiled a work tracing the history and legal controversies of coffee, entitled "Undat al safwa fi hill al-qahwa". In this work, Jaziri recorded that one
SheikhSheikh, also rendered as Sheik, Shaykh, Shaikh, Cheikh, Šeih, Šejh and other variants , is a word or honorific term in the Arabic language that literally means "elder". It is commonly used to designate an elder of a tribe, a revered wise man, or an Islamic scholar...
, Jamal-al-Din al-Dhabhani,
muftiA mufti is an Islamic scholar who is an interpreter or expounder of Islamic law . A muftiat or diyanet is a council of muftis.-Qualifications:...
of
AdenAden is a city in Yemen, 170 kilometres east of Bab-el-Mandeb.Aden's ancient, natural harbour lies in the crater of an extinct volcano which now forms a peninsula, joined to the mainland by a low isthmus. This harbour, Front Bay, was first used by the ancient Kingdom of Awsan between the 5th and...
, was the first to adopt the use of coffee in 1454, and that in the 15th century the
SufisSufism or ' , also spelled as tasavvuf and tasavvof, is generally understood to be the inner, mystical dimension of Islam. A practitioner of this tradition is generally known as a ' , though some adherents of the tradition reserve this term only for those practitioners who have attained the goals...
of
YemenYemen , officially the Republic of Yemen is a country located on the Arabian Peninsula in Southwest Asia...
routinely used coffee to stay awake during prayers.
Towards the close of the 16th century, the use of coffee was recorded by a
EuropeEurope 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 water divide of the Ural Mountains, the Ural River, the Caspian Sea, the Caucasus Mountains , and the Black Sea to the southeast...
an resident in
EgyptEgypt , officially the Arab Republic of Egypt, is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Western Asia...
, and about this time it came into general use in the
Near EastNear East today is an ambiguous term that covers different countries for archeologists and historians, on one hand, and for political scientists, economists, and journalists, on the other...
. The appreciation of coffee as a beverage in Europe, where it was first known as "Arabian wine," dates from the 17th century. During this time "coffee houses" were established, the first being opened in
ConstantinopleConstantinople was the imperial capital of the Roman Empire , the Byzantine/Eastern Roman Empire , the Latin Empire , and the Ottoman Empire...
and
VeniceVenice is a city in northern Italy, the capital of the region Veneto, a population of 271,367 . Together with Padua, the city is included in the Padua-Venice Metropolitan Area . The city historically was an independent nation...
. In Britain, the first coffee houses were opened in
London[]London is the capital of England and the United Kingdom. It has been a major settlement for two millennia, and the history of London goes back to its founding by the Romans, when it was named Londinium. London's core, the ancient City of London, the 'square mile', retains its medieval boundaries...
in 1652, at St Michael's Alley, Cornhill. They soon became popular throughout
Western EuropeWestern Europe is the collection of countries in the westernmost region of Europe, though this definition is context-dependent and carries cultural and political connotations. One definition describes Western Europe as a cultural entity—the region lying west of Central Europe...
, and played a significant role in
social relationA Social relation is a concept in social science referring most generally to a relationship between two or more people, but that relationship can exist without those people actively and deliberately relating, communicating or associating with each other....
s in the 17th and 18th centuries.
The
kola nutKola nut is a genus of about 125 species 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...
, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in many
West AfricaWest Africa or Western Africa is the westernmost region of the African continent. Geopolitically, the UN definition of Western Africa includes the following 16 countries distributed over an area of approximately 5 million square km:*Benin...
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-ColaCoca-Cola is a carbonated soft drink sold in stores, restaurants and vending machines internationally. The Coca-Cola Company claims that the beverage is sold in more than 200 countries...
syrup in
ChattanoogaChattanooga is the fourth-largest city in Tennessee , and the seat of Hamilton County. Located in southeastern Tennessee on Chickamauga Lake and Nickajack Lake, which are both part of the Tennessee River, Chattanooga lies approximately 120 miles to the northwest of Atlanta, Georgia, about 135...
,
TennesseeTennessee is a state located in the Southeastern United States. According to the 2008 census, it has a population of 6,214,888, an increase of nearly 9.5% since 2000. Tennessee is the 14th fastest growing state in the US and is ranked 17th by population. It is ranked 36th by total land area. In...
, alleging that the caffeine in its drink was "injurious to health". On March 13, 1911, the government initiated
The United States v. Forty Barrels and Twenty Kegs of Coca-ColaUnited States v. Forty Barrels and Twenty Kegs of Coca-Cola, 241 U.S. 265 , was a case under the 1906 Pure Food and Drug Act. At issue was whether the Coca-Cola company had adulterated the product by adding artificial caffeine, and whether Coca-Cola was misbranded because both coca and cola,...
, hoping to force Coca-Cola to remove caffeine from its formula by making claims, such as that the excessive use of Coca-Cola at one girls' school led to "wild nocturnal freaks, violations of college rules and female proprieties, and even immoralities." Although the judge ruled in favor of Coca-Cola, two bills were introduced to the
U.S. House of RepresentativesThe United States House of Representatives, commonly referred to as the "House," is the lower house of the bicameral United States Congress, the upper house being the United States Senate. The composition and powers of the House and the Senate are established in Article One of the Constitution...
in 1912 to amend the
Pure Food and Drug ActThe 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
cocoaCocoa is the dried and fully fermented fatty seed of the cacao tree, from which chocolate is made. "Cocoa" can often also refer to the drink commonly known as hot chocolate; to cocoa powder, the dry powder made by grinding cocoa seeds and removing the cocoa butter from the dark, bitter cocoa...
use comes from residue found in an
ancient MayanThe Maya is a Mesoamerican civilization, noted for the only known fully developed written language of the pre-Columbian Americas, as well as its art, architecture, and mathematical and astronomical systems. Initially established during the Preclassic period , many Maya cities reached their highest...
pot dated to 600 BC. In the New World, chocolate was consumed in a bitter and spicy drink called
xocoatl, often seasoned with
vanillaVanilla is a flavoring derived from orchids of the genus Vanilla native to Mexico. Etymologically, vanilla derives from the Spanish word "", little pod. Originally cultivated by Pre-Columbian Mesoamerican peoples, Spanish conquistador Hernán Cortés is credited with introducing both the spice and...
, chile pepper, and
achioteAchiote is a shrub or small tree from the tropical region of the American continent. 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...
. Xocoatl was believed to fight fatigue, a belief that is probably attributable to the
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
and caffeine content. Chocolate was an important luxury good throughout
pre-ColumbianThe 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 to European colonization during the...
MesoamericaMesoamerica or Meso-America is a region and culture area in the Americas, extending approximately from central Mexico to Honduras and Nicaragua, within which a number of pre-Columbian societies flourished before the Spanish colonization of the Americas in the 15th and 16th centuries...
, and cocoa beans were often used as currency.
Xocoatl was introduced to
EuropeEurope 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 water divide of the Ural Mountains, the Ural River, the Caspian Sea, the Caucasus Mountains , and the Black Sea to the southeast...
by the
SpaniardsSpanish people or Spaniards constitute the nationality and ethnic group of natives of Spain, a European country in the Iberian Peninsula, in southwestern Europe. The Spanish nationality is in essence made up of regional nationalities, reflecting the complex history of Spain...
and became a popular beverage by 1700. They also introduced the
cacaoCacao , or the cocoa plant, is a small evergreen tree in the family Sterculiaceae , native to the deep tropical region of the Americas. Its seeds are used to make cocoa and chocolate...
tree into the West Indies and the
PhilippinesThe Philippines officially known as the Republic of the Philippines, is a country in Southeast Asia with Manila as its capital city. It comprises 7,107 islands in the western Pacific Ocean....
. It was used in
alchemicalAlchemy is both a philosophy and a practice with an aim of achieving ultimate wisdom as well as immortality, involving the improvement of the alchemist as well as the making of several substances described as possessing unusual properties...
processes, where it was known as Black Bean.
The leaves and stems of the Yaupon Holly (Ilex vomitoria) were used by
Native AmericansThe indigenous peoples of the Americas are the pre-Columbian inhabitants of the Americas, their descendants, and many ethnic groups who identify with those peoples...
to brew a
teaTea is the agricultural product of the leaves, leaf buds, and internodes of the Camellia sinensis plant, prepared and cured by various methods...
called
AsiBlack drink was the name given by colonists to a ritual beverage called Asi, brewed by Native Americans in the Southeastern United States. It was prepared from the roasted leaves and stems of the Yaupon Holly , native to the Atlantic and Gulf Coasts...
or the
Black DrinkBlack drink was the name given by colonists to a ritual beverage called Asi, brewed by Native Americans in the Southeastern United States. It was prepared from the roasted leaves and stems of the Yaupon Holly , native to the Atlantic and Gulf Coasts...
the use of which among Native American groups archaeologists have demonstrated to stretch back far into antiquity, possibly dating to Late Archaic times.
Synthesis and properties
In 1819, the
GermanGermany , officially the Federal Republic of Germany , is a country in Central Europe. It is bordered to the north by the North Sea, Denmark, and the Baltic Sea; to the east by Poland and the Czech Republic; to the south by Austria and Switzerland; and to the west by France, Luxembourg, Belgium,...
chemist
Friedrich Ferdinand RungeFriedrich Ferdinand Runge was a German analytical chemist....
isolated relatively pure caffeine for the first time. According to Runge, he did this at the behest of
Johann Wolfgang von GoetheJohann Wolfgang von Goethe was a German writer and polymath. Goethe's works span the fields of poetry, drama, literature, theology, philosophy, humanism and science. Goethe's magnum opus, lauded as one of the peaks of world literature, is the two-part drama Faust...
. In 1827, Oudry isolated "theine" from tea, but it was later proved by
MulderGerardus Johannes Mulder was a Dutch organic chemist who described the chemical composition of proteins and was the first to use this name coined by Jöns Jakob Berzelius in a publication, his paper 'On the composition of some animal substances'...
and Jobat that theine was the same as caffeine. The structure of caffeine was elucidated near the end of the 19th century by
Hermann Emil FischerHermann Emil Fischer was a German chemist and recipient of the Nobel Prize for Chemistry in 1902.-Early years:...
, who was also the first to achieve its
total synthesisIn principle a total synthesis is the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes....
. This was part of the work for which Fischer was awarded the Nobel Prize in 1902.
The nitrogen atoms are all essentially planar (in sp
2 orbital hybridisationIn chemistry, hybridisation is the concept of mixing atomic orbitals within an atom to form new hybrid orbitals. It is an integral part of the valence bond theory.Hybridisation of orbitals will change the shape of the atom...
), resulting in the caffeine molecule having
aromaticIn organic chemistry, the structures of some rings of atoms are unexpectedly stable. 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...
character.
Being readily available as a byproduct of decaffeination, caffeine is not usually
synthesizedIn 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...
. If desired, it may be synthesized from
dimethylureaDimethylurea is a urea derivative and used as an intermediate in organic synthesis. It is a colorless crystalline powder with little toxicity.-Uses:...
and
malonic acidMalonic acid is a dicarboxylic acid with structure CH
22. 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...
.
Pharmacology
Global consumption of caffeine has been estimated at 120,000 tonnes per year, making it the world's most popular psychoactive substance. This number equates to one serving of a caffeine beverage for every person, per day. Caffeine is a
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
and metabolic stimulant, and is used both recreationally and medically to reduce physical fatigue and restore mental alertness when unusual weakness or drowsiness occurs. Caffeine and other methylxanthine derivatives are also used on newborns to treat
apneaApnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
and correct irregular heartbeats. Caffeine stimulates the central nervous system first at the higher levels, resulting in increased alertness and wakefulness, faster and clearer flow of thought, increased focus, and better general body coordination, and later at the spinal cord level at higher doses. Once inside the body, it has a complex chemistry, and acts through several mechanisms as described below.
Metabolism and half-life
Caffeine from coffee or other beverages is absorbed by the stomach and small intestine within 45 minutes of ingestion and then distributed throughout all tissues of the body. It is eliminated by
first-order kineticsThe rate law or rate equation for a chemical reaction is an equation which links the reaction rate with concentrations or pressures of reactants and constant parameters . To determine the rate equation for a particular system one combines the reaction rate with a mass balance for the system...
. Caffeine can also be ingested rectally, evidenced by the formulation of suppositories of ergotamine tartrate and caffeine (for the relief of migraine) and chlorobutanol and caffeine (for the treatment of hyperemesis).
The
half-lifeThe 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
liverThe 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. In healthy adults, caffeine's half-life is approximately 4.9 hours. In women taking oral contraceptives this is increased to 5–10 hours, and in pregnant women the half-life is roughly 9–11 hours. Caffeine can accumulate in individuals with severe
liver diseaseLiver disease is a broad term describing any single number of diseases affecting the liver. Many are accompanied by jaundice caused by increased levels of bilirubin in the system...
, increasing its half-life up to 96 hours. In infants and young children, the half-life may be longer than in adults; half-life in a newborn baby may be as long as 30 hours. Other factors such as smoking can shorten caffeine's half-life.
FluvoxamineFluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor and is predominantly used to treat obsessive–compulsive disorder.-History:...
reduced the apparent oral clearance of caffeine by 91.3%, and prolonged its elimination half-life by 11.4-fold (from 4.9 hours to 56 hours).
Caffeine is metabolized in the
liverThe 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 oxidaseCytochrome P450 is a very large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions...
enzyme system (specifically, the
1A2Cytochrome P450 1A2 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body.Expression of CYP1A2 appears to be induced by various dietary constituents....
isozyme) into three
metabolicMetabolism is the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter,...
dimethylxanthinesXanthine , , is a purine base found in most human body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
, which each have their own effects on the body:
- 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 lipolysisLipolysis is the breakdown of fat stored in fat cells. During this process, free fatty acids are released into the bloodstream and circulate throughout the body. Ketones are produced, and are found in large quantities in ketosis...
, leading to elevated glycerolGlycerol is an organic compound, also commonly called glycerin or glycerine. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydrophilic hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. ...
and free fatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid often with a long unbranched aliphatic tail , which is either saturated or unsaturated...
levels in the blood plasmaBlood plasma is the yellow liquid component of blood, in which the blood cells in whole blood would normally be suspended. It makes up about 55% of the total blood volume. It is mostly water and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide...
.
- Theobromine
Theobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
(12%): Dilates blood vesselThe blood vessels are the part of the circulatory system that transport 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 urineUrine is a liquid waste product of the body secreted by the kidneys by a process of filtration from blood called urination and excreted through the urethra. Cellular metabolism generates numerous waste compounds, many rich in nitrogen, that require elimination from the bloodstream...
volume. Theobromine is also the principal alkaloid in cocoaCocoa is the dried and fully fermented fatty seed of the cacao tree, from which chocolate is made. "Cocoa" can often also refer to the drink commonly known as hot chocolate; to cocoa powder, the dry powder made by grinding cocoa seeds and removing the cocoa butter from the dark, bitter cocoa...
, and therefore chocolateChocolate comprises a number of raw and processed foods produced from the seed of the tropical cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America, with its earliest documented use around 1100 BC...
.
- Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it...
(4%): Relaxes smooth muscleSmooth muscle is an involuntary non-striated muscle, found within the tunica media layer of large and small arteries and veins, the bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, arrector pili of skin, the ciliary muscle, and iris of...
s of the bronchiA bronchus is a passage of airway in the respiratory tract that conducts air into the lungs.No gas exchange takes place in this part of the lungs.-Anatomy:...
, and is used to treat asthmaAsthma is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. Asthma affects 7% of the population of the United States, and 300 million worldwide...
. 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.
Mechanism of action
Caffeine 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 an
antagonistA 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 receptorThe adenosine receptors are a class of purinergic receptors, G-protein coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
s. The caffeine molecule is structurally similar to
adenosineAdenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule moiety via a β-N
9-glycosidic bond....
, and binds to adenosine receptors on the surface of cells without activating them (an "antagonist" mechanism of action). Therefore, caffeine acts as a competitive inhibitor.
Adenosine is found in every part of the body, because it plays a role in the fundamental
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
-related energy metabolism, but it has special functions in the brain. There is a great deal of evidence that concentrations of brain adenosine are increased by various types of metabolic stress including
anoxiaThe term anoxia means a total decrease in the level of oxygen, an extreme form of hypoxia or "low oxygen". The terms anoxia and hypoxia are used in various contexts:* Anoxic waters* Anoxic event* Dead zone or hypoxic zones* Hypoxia...
and
ischemiaIn medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue...
. The evidence also indicates that brain adenosine acts to protect the brain by suppressing neural activity and also by increasing blood flow through A2A and A2B receptors located on vascular smooth muscle. By counteracting adenosine, caffeine reduces resting cerebral blood flow between 22% and 30%. Caffeine also has a generally disinhibitory effect on neural activity. It has not been shown, however, how these effects cause increases in arousal and alertness.
Adenosine is released in the brain through a complex mechanism. There is evidence that adenosine functions as a synaptically released neurotransmitter in some cases, but stress-related adenosine increases appear to be produced mainly by extracellular metabolism of ATP. It is not likely that adenosine is the primary neurotransmitter for any group of neurons, but rather that it is released together with other transmitters by a number of neuron types. 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 been completely ruled out.
Several classes of adenosine receptors have been described, with different anatomical distributions. A
1 receptors are widely distributed, and act to inhibit calcium uptake. A
2A 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
dopamineDopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
system, which is involved in reward and arousal. (A
2A 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 McCarleyRobert 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 A
1 receptors, and activation of sleep-promoting neurons via indirect effects on A
2A receptors. More recent studies have provided additional evidence for the importance of A
2A, but not A
1, receptors.
Some of the secondary effects of caffeine are probably caused by actions unrelated to adenosine. Caffeine is known to be a competitive inhibitor of the enzyme
cAMP-phosphodiesteraseA phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
(cAMP-PDE), which converts
cyclic AMPCyclic adenosine monophosphate is a second messenger important in many biological processes...
(cAMP) in cells to its noncyclic form, thus allowing cAMP to build up in cells. Cyclic AMP participates in activation of protein kinase A (PKA) to begin the phosphorylation of specific enzymes used in glucose synthesis. By blocking its removal caffeine intensifies and prolongs the effects of
epinephrineEpinephrine is a hormone and neurotransmitter that participates in the "fight or flight" response of the sympathetic nervous system...
and epinephrine-like drugs such as
amphetamineAmphetamine is a psychostimulant drug that is known to produce increased wakefulness and focus in association with decreased fatigue and appetite. Amphetamine is related to drugs such as methamphetamine and dextroamphetamine, which are a group of potent drugs that act by increasing levels of...
,
methamphetamineMethamphetamine also known as metamfetamine , dextromethamphetamine, methylamphetamine, N-methylamphetamine, and desoxyephedrine) is a psychostimulant and sympathomimetic drug. Methamphetamine enters the brain and triggers a cascading release of dopamine, serotonin and norepinephrine...
, or
methylphenidateMethylphenidate is the most commonly prescribed psychostimulant and is indicated in the treatment of attention-deficit hyperactivity disorder, Postural Orthostatic Tachycardia Syndrome and narcolepsy, although off-label uses include treating lethargy, depression, neural insult, and obesity.In...
. Increased concentrations of cAMP in
parietal cellParietal cells, or oxyntic cells, are the stomach epithelium cells that secrete gastric acid and intrinsic factor.- Acid production :...
s causes an increased activation of
protein kinase Aprotein kinase A refers to a family of enzymes whose activity is dependent on the level of cyclic AMP in the cell, in cell biology. PKA is also known as cAMP-dependent protein kinase ). Protein kinase A has several functions in the cell, including regulation of glycogen, sugar, and lipid...
(PKA) which in turn increases activation of
H+/K+ ATPaseGastric hydrogen potassium ATPase is also known as H+/K+ ATPase- Function and location :The gastric hydrogen potassium ATPase or H+/K+ ATPase is the proton pump of the stomach and, as such, is the enzyme primarily responsible for the acidification of the...
, resulting finally in increased
gastric acidGastric acid is a secretion produced in the stomach. It is one of the main ditotonic solutions secreted, together with several enzymes and intrinsic factors...
secretion by the cell. Cyclic AMP also increases the activity of the
funny currentFunny current refers to a specific current in the heart....
, which directly increases heart rate. Caffeine is also a structural analogue of
strychnineStrychnine is a very toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion. The most common source is from the seeds of the...
and like it (though much less potent) a competitive antagonist at ionotropic
glycine receptorThe glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory...
s.
Metabolites of caffeine also contribute to caffeine's effects.
ParaxanthineParaxanthine, 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
lipolysisLipolysis is the breakdown of fat stored in fat cells. During this process, free fatty acids are released into the bloodstream and circulate throughout the body. Ketones are produced, and are found in large quantities in ketosis...
process, which releases
glycerolGlycerol is an organic compound, also commonly called glycerin or glycerine. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydrophilic hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. ...
and fatty acids into the blood to be used as a source of fuel by the muscles. Theobromine is a
vasodilatorVasodilation 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 relaxantA 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
bronchioleThe bronchioles or bronchioli are the first airway branches that no longer contain cartilage. They are branches of the bronchi, and are smaller than one millimeter in diameter....
s and acts as a
chronotropeChronotropic 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
inotropeAn inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction....
that increases heart rate and efficiency.
Effects when taken in moderation
The precise amount of caffeine necessary to produce effects varies from person to person depending on body size and degree of tolerance to caffeine. It takes less than an hour for caffeine to begin affecting the body and a mild dose wears off in three to four hours. Consumption of caffeine does not eliminate the need for sleep, it only temporarily reduces the sensation of being tired throughout the day. In general, 25 to 50 milligrams of caffeine is sufficient for most people to report increased alertness and arousal as well as subjectively lower levels of fatigue.
With these effects, caffeine is an
ergogenicErgogenic aids are any external influences that can be determined to enhance performance. These include mechanical aids, pharmacological aids, physiological aids, nutritional aids, and psychological aids....
, increasing a person's capability for mental or physical labor. A study conducted in 1979 showed a 7% increase in distance cycled over a period of two hours in subjects who consumed caffeine compared to control subjects. Other studies attained much more dramatic results; one particular study of trained runners showed a 44% increase in "race-pace" endurance, as well as a 51% increase in cycling endurance, after a dosage of 9 milligrams of caffeine per kilogram of body weight. Additional studies have reported similar effects. Another study found 5.5 milligrams of caffeine per kilogram of body mass resulted in subjects cycling 29% longer during high intensity circuits.
Caffeine citrateCaffeine 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...
has proven to be of short and long term benefit in treating the breathing disorders of
apnea of prematurityApnea 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 bronchopulmonary dysplasia in
prematureIn humans, preterm birth refers to the birth of a baby of less than 37 weeks gestational age. Premature birth, commonly used as a synonym for preterm birth, refers to the birth of a premature infant. Because it is by far the most common cause of prematurity, preterm birth is the major cause of...
infants. The only short term risk associated with caffeine citrate 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.
Caffeine relaxes the
internal anal sphincter musclesThe Sphincter ani internus is a muscular ring which surrounds about 2.5 cm of the anal canal; its inferior border is in contact with, but quite separate from, the Sphincter ani externus....
and thus should be avoided by those with
fecal incontinenceFecal incontinence is the loss of regular control of the bowels. Involuntary excretion and leaking are common occurrences for those affected.Subjects relating to defecation are often socially unacceptable, thus those affected may be beset by feelings of shame and humiliation. Some do not seek...
.
While relatively safe for humans, caffeine is considerably more toxic to some other animals such as dogs, horses, and parrots due to a much poorer ability to metabolize this compound. Caffeine has also a pronounced effect on mollusks and various insects as well as
spiderSpiders are air-breathing chelicerate arthropods that have eight legs, and chelicerae modified into fangs that inject venom. They are the largest order of arachnids and rank seventh in total species diversity among all other groups of organisms...
s.
Tolerance and withdrawal
Because caffeine is primarily an
antagonistA 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 the central nervous system's receptors for the
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
adenosineAdenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule moiety via a β-N
9-glycosidic bond....
, the bodies of individuals who regularly consume caffeine adapt to the continual presence of the drug by substantially increasing the number of
adenosine receptorThe adenosine receptors are a class of purinergic receptors, G-protein coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
s in the central nervous system. This increase in the number of the adenosine receptors makes the body much more sensitive to adenosine, with two primary consequences. First, the stimulatory effects of caffeine are substantially reduced, a phenomenon known as a tolerance adaptation. Second, because these adaptive responses to caffeine make individuals much more sensitive to adenosine, a reduction in caffeine intake will effectively increase the normal physiological effects of adenosine, resulting in unwelcome withdrawal symptoms in tolerant users.
Other research questions the idea that up-regulation of adenosine receptors is responsible for tolerance to the locomotor stimulant effects of caffeine, noting, among other things, that this tolerance is insurmountable by higher doses of caffeine (it should be surmountable if tolerance was due to an increase in receptors), and that the increase in adenosine receptor number is modest and does not explain the large tolerance which develops to caffeine.
Caffeine tolerance develops very quickly, especially among heavy coffee and energy drink consumers. Complete tolerance to sleep disruption effects of caffeine develops after consuming 400 mg of caffeine 3 times a day for 7 days. Complete tolerance to subjective effects of caffeine was observed to develop after consuming 300 mg 3 times per day for 18 days, and possibly even earlier. In another experiment, complete tolerance of caffeine was observed when the subject consumed 750–1200 mg per day while incomplete tolerance to caffeine has been observed in those that consume more average doses of caffeine.
Because adenosine, in part, serves to regulate blood pressure by causing
vasodilationVasodilation 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...
, the increased effects of adenosine due to caffeine withdrawal cause the blood vessels of the head to dilate, leading to an excess of blood in the head and causing a
headacheIn medicine a headache or cephalalgia is a symptom of a number of different conditions of the head. Some of the causes are benign while others are medical emergencies.There are a number of different classification systems for headaches...
and
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
. Reduced
catecholamineCatecholamines are sympathomimetic "fight-or-flight" hormones that are released by the adrenal glands in response to stress. They are part of the sympathetic nervous system....
activity may cause feelings of
fatigueFatigue is a state of awareness. It can describe a range of afflictions, varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles. It can be both physical and mental...
and drowsiness. A reduction in
serotoninSerotonin is a monoamine neurotransmitter. It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements...
levels when caffeine use is stopped can cause anxiety, irritability, inability to concentrate and diminished motivation to initiate or to complete daily tasks; in extreme cases it may cause mild
depressionIn psychology and psychiatry, depression is a state of low mood and aversion to activity. While most often described as a disease or dysfunction, there are also strong arguments for seeing depression as an adaptive defense mechanism....
. Together, these effects have come to be known as a "crash".
WithdrawalWithdrawal 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/or alcohol...
symptoms—possibly including headache, irritability, an 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, representing the time required for the number of adenosine receptors in the brain to revert to "normal" levels, uninfluenced by caffeine consumption.
AnalgesicAn analgesic is any member of the diverse group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos...
s, such as
aspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
, can relieve the pain symptoms, as can a small dose of caffeine. Most effective is a combination of both an analgesic and a small amount of caffeine.
This is not the only case where caffeine increases the effectiveness of a drug. Caffeine makes pain relievers 40% more effective in relieving headaches and helps the body absorb headache medications more quickly, bringing faster relief. For this reason, many over-the-counter headache drugs include caffeine in their formula. It is also used with
ergotamineErgotamine is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor...
in the treatment of
migraineMigraine is a neurological syndrome characterized by altered bodily perceptions, severe headaches, and nausea. Physiologically, the migraine headache is a neurological condition more common to women than to men. The word migraine was borrowed from Old French migraigne...
and cluster headaches as well as to overcome the drowsiness caused by
antihistamineAn H
1 antagonist is a histamine antagonist of the H
1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
s.
Overuse
In large amounts, and especially over extended periods of time, caffeine can lead to a condition known as
caffeinism. Caffeinism usually combines caffeine
dependencyAccording to the current Diagnostic and Statistical Manual of Mental Disorders , substance dependence is defined as:Substance dependence can be diagnosed with physiological dependence, evidence of tolerance or withdrawal, or without physiological dependence.The related concept of drug addiction has...
with a wide range of unpleasant physical and mental conditions including
nervousnessAnxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry....
,
irritabilityIrritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli....
,
anxietyAnxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry....
,
tremulousnessA tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, head, face, vocal cords, trunk, and legs. Most tremors occur in the hands. In some people,...
, muscle twitching (
hyperreflexiaHyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies, which are indicative of upper motor neuron disease as well as the lessening or loss of control ordinarily exerted by higher brain centers of lower neural pathways...
),
insomniaInsomnia is a symptom of any of several sleep disorders, characterized by persistent difficulty falling asleep or staying asleep despite the opportunity. Insomnia is a symptom, not a stand-alone diagnosis or a disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both"...
, headaches,
respiratory alkalosisRespiratory alkalosis is a medical condition in which increased respiration elevates the blood pH . It is one of four basic categories of disruption of acid-base homeostasis.-Types:...
, and heart palpitations. Furthermore, because caffeine increases the production of stomach acid, high usage over time can lead to
peptic ulcerA peptic ulcer, also known as ulcus pepticum, PUD or peptic ulcer disease, is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful...
s, erosive
esophagitis- Causes :* The most common cause is gastroesophageal reflux disease . If caused by GERD, the diseases is also called reflux esophagitis....
, and
gastroesophageal reflux diseaseGastroesophageal reflux disease ', gastro-oesophageal reflux disease ', gastric reflux disease, or acid reflux disease is defined as chronic symptoms or mucosal damage produced by the abnormal reflux inthe esophagus....
.
There are four caffeine-induced psychiatric disorders recognized by the
Diagnostic and Statistical Manual of Mental DisordersThe Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides diagnostic criteria for mental disorders...
, Fourth Edition: caffeine intoxication, caffeine-induced anxiety disorder,
caffeine-induced sleep disorderCaffeine-induced sleep disorder is a psychiatric disorder that results from overconsumption of the stimulant caffeine. The specific criteria for this disorder in the fourth axis of the Diagnostic and Statistical Manual of Mental Disorders include that there must be a significant inability to sleep...
, and caffeine-related disorder not otherwise specified (NOS).
Caffeine intoxication
An acute overdose of caffeine, usually in excess of about 300 milligrams, dependent on body weight and level of caffeine tolerance, 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, nervousness, excitement, insomnia, flushing of the face,
increased urinationDiuresis is the increased production of urine by the kidney.-Types and causes:The kidney normally produces up to 180 L of "pro-urine" per day, but reabsorbs most of this before entering the calyx of the kidney. No more reabsorption takes place past this point.Polyuria is increased diuresis...
,
gastrointestinalThe human gastrointestinal tract , digestive tract, guts or gut is the system of organs within humans that takes in food, digests it to extract energy and nutrients, and expels the remaining matter...
disturbance,
muscle twitchingA fasciculation is a small, local, involuntary muscle contraction visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
, a rambling flow of thought and speech, irritability,
irregularCardiac arrhythmia is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular....
or
rapid heart beatTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heartrate...
, and
psychomotor agitationPsychomotor 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,
maniaMania is a severe medical condition characterized by extremely elevated mood, energy, unusual thought patterns and sometimes psychosis...
,
depressionIn psychology and psychiatry, depression is a state of low mood and aversion to activity. While most often described as a disease or dysfunction, there are also strong arguments for seeing depression as an adaptive defense mechanism....
, lapses in judgment, disorientation,
disinhibitionDisinhibition 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, and
psychosisPsychosis literally 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"...
may occur, and
rhabdomyolysisRhabdomyolysis is the rapid breakdown of skeletal muscle due to injury to muscle tissue. The muscle damage may be caused by physical , chemical, or biological factors...
(breakdown of skeletal muscle tissue) can be provoked.
In cases of extreme overdose, death can result. The median lethal dose (
LD50In toxicology, the median lethal dose, LD50 , LC50 or LCt50 of a toxic substance or radiation is the dose required to kill half the members of a tested population...
) given orally, is 192 milligrams per kilogram in rats. The LD
50 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
fluvoxamineFluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor and is predominantly used to treat obsessive–compulsive disorder.-History:...
which blocks the liver enzyme responsible for the metabolism of caffeine, thus increasing the central effects and blood concentrations of caffeine dramatically at 5-fold. It is not contraindicated, but highly advisable to minimize the intake of caffeinated beverages, as drinking one cup of coffee will have the same effect as drinking five under normal conditions. Death typically occurs due to
ventricular fibrillationVentricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them tremble rather than contract properly...
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 dialysisPeritoneal dialysis is a treatment for patients with severe chronic kidney failure. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...
,
hemodialysisIn medicine, hemodialysis is a method for removing waste products such as potassium 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
hemofiltrationIn 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.
Anxiety and sleep disorders
Two infrequently diagnosed caffeine-induced disorders that are recognized by the
American Psychological AssociationThe American Psychological Association is a professional organization representing psychologists in the U.S., with around 150,000 members and an annual budget of around $70m...
(APA) are
caffeine-induced sleep disorder and
caffeine-induced anxiety disorder, which can result from long-term excessive caffeine intake.
In the case of
caffeine-induced sleep disorderCaffeine-induced sleep disorder is a psychiatric disorder that results from overconsumption of the stimulant caffeine. The specific criteria for this disorder in the fourth axis of the Diagnostic and Statistical Manual of Mental Disorders include that there must be a significant inability to sleep...
, an individual regularly ingests high doses of caffeine sufficient to induce a significant disturbance in his or her sleep, sufficiently severe to warrant clinical attention.
In some individuals, the large amounts of caffeine can induce
anxietyAnxiety is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components. These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear, or worry....
severe enough to necessitate clinical attention. This caffeine-induced
anxiety disorderAnxiety disorder is a blanket term covering several different forms of abnormal and pathological fears and anxieties which only came under the aegis of psychiatry at the very end of the 19th century. Current psychiatric diagnostic criteria recognize a wide variety of anxiety disorders...
can take many forms, from
generalized anxietyGeneralized anxiety disorder is an anxiety disorder that is characterized by excessive, uncontrollable and often irrational worry about everyday things that is disproportionate to the actual source of worry...
to
panic attackPanic attacks are very sudden, discrete periods of intense anxiety, mounting physiological arousal, fear, stomach problems and discomfort that are associated with a variety of somatic and cognitive symptoms. The onset of these episodes is typically abrupt, and may have no obvious triggers...
s, obsessive-compulsive symptoms, or even
phobic symptomsA phobia , is an irrational, intense, persistent fear of certain situations, activities, things, or people. The main symptom of this disorder is the excessive, unreasonable desire to avoid the feared subject...
. Because this condition can mimic organic mental disorders, such as
panic disorderPanic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
, generalized anxiety disorder,
bipolar disorderBipolar disorder, also known as manic depressive disorder, manic depression or bipolar affective disorder, is a serious mental disorder that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if...
, or even
schizophreniaSchizophrenia , from the Greek roots skhizein and phrēn, phren- is a psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality...
, a number of medical professionals believe caffeine-intoxicated people are routinely misdiagnosed and unnecessarily medicated when the treatment for caffeine-induced psychosis would simply be to stop further caffeine intake. A study in the
British Journal of Addiction concluded that caffeinism, although infrequently diagnosed, may afflict as many as one person in ten of the population. Co administration of
theanineTheanine is a glutamic acid analog or amino acid derivative commonly found in tea , and also in the basidiomycete mushroom Boletus badius. In 1950 the Tea laboratory of Kyoto successfully separated theanine from Gyokuro leaf, which has the highest theanine content among all teas...
was shown to greatly reduce this caffeine-induced anxiety.
Effects on memory and learning
An array of studies found that caffeine could have
nootropicNootropics, also referred to as smart drugs, memory enhancers, and cognitive enhancers, are drugs, supplements, nutraceuticals, and functional foods that are purported to improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration. The word nootropic...
effects, inducing certain changes in memory and learning. However, the tests performed contradict one another and the results have proven inconsistent and inconclusive.
Researchers have found that long-term consumption of low dose caffeine slowed
hippocampusThe hippocampus is a major component of the brains of humans and other mammals. It belongs to the limbic system and plays important roles in long-term memory and spatial navigation. Like the cerebral cortex, with which it is closely associated, it is a paired structure, with mirror-image halves in...
-dependent learning and impaired long-term memory in mice. Caffeine consumption for 4 weeks also significantly reduced hippocampal
neurogenesisNeurogenesis is the process by which neurons are generated. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain.-Adult neurogenesis:...
compared to controls during the experiment. The conclusion was that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis..
In another study, caffeine was added to rat neurons
in vitroA procedure performed in vitro is performed not in a living organism but in a controlled environment, such as in a test tube or Petri dish...
. The
dendritic spineA dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from a single synapse of an axon. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body...
s (a part of the brain cell used in forming connections between neurons) taken from the
hippocampusThe hippocampus is a major component of the brains of humans and other mammals. It belongs to the limbic system and plays important roles in long-term memory and spatial navigation. Like the cerebral cortex, with which it is closely associated, it is a paired structure, with mirror-image halves in...
(a part of the brain associated with memory) grew by 33% and new spines formed. After an hour or two, however, these cells returned to their original shape.
Another study showed that human subjects—after receiving 100 milligrams of caffeine—had increased activity in brain regions located in the frontal lobe, where a part of the working memory network is located, and the
anterior cingulate cortexThe Anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain....
, a part of the brain that controls attention. The caffeinated subjects also performed better on the memory tasks.
However, a different study showed that caffeine could impair short term memory and increase the likelihood of the
tip of the tongueThe tip of the tongue phenomenon is an instance of knowing something that cannot immediately be recalled. TOT is an experience with memory recollection involving difficulty retrieving a well-known word or familiar name. When experiencing TOT, people feel that the blocked word is on the verge of...
phenomenon. The study allowed the researchers to suggest that caffeine could aid short-term memory when the information to be recalled is related to the current
train of thoughtThe train of thought, stream of thought, or chain of thought refers to the interconnection in the sequence of ideas expressed during a connected discourse or thought, as well as to the sequence itself, especially in discussion how this sequence leads from one idea to another.When a reader or...
, but also to hypothesize that caffeine hinders short-term memory when the train of thought is unrelated. In essence, caffeine consumption increases mental performance related to focused thought while it may decrease broad-range thinking abilities.
Effects on the heart
Caffeine binds to receptors on the surface of heart muscle cells which leads to an increase in the level of
cAMPCyclic adenosine monophosphate is a second messenger important in many biological processes...
inside the cells (by blocking the enzyme that degrades cAMP), mimicking the effects of
epinephrineEpinephrine is a hormone and neurotransmitter that participates in the "fight or flight" response of the sympathetic nervous system...
(which binds to receptors on the cell that activate cAMP production). cAMP acts as a "second messenger," and activates a large number of protein kinase A (PKA;
cAMP-dependent protein kinaseprotein kinase A refers to a family of enzymes whose activity is dependent on the level of cyclic AMP in the cell, in cell biology. PKA is also known as cAMP-dependent protein kinase ). Protein kinase A has several functions in the cell, including regulation of glycogen, sugar, and lipid...
). This has the overall effect of increasing the rate of
glycolysisGlycolysis is the metabolic pathway that converts glucose, C
6H
12O
6, into pyruvate, C
3H
6O
3-...
and increases the amount of
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
available for muscle contraction and relaxation. According to one study, caffeine in the form of coffee, significantly reduces the risk of
heart diseaseHeart disease or cardiopathy is an umbrella term for a variety for different diseases affecting the heart. As of 2007, it is the leading cause of death in the United States, England, Canada and Wales, killing one person every 34 seconds in the United States alone.-Coronary heart disease:Coronary...
in epidemiological studies. However, the protective effect was found only in participants who were not severely hypertensive (i.e. patients that are not suffering from a very high blood pressure). Furthermore, no significant protective effect was found in participants aged less than 65 years or in
cerebrovascular diseaseCerebrovascular disease is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. Hypertension is the most important cause; it damages the blood vessel lining, endothelium, exposing the underlying collagen where platelets aggregate to initiate a repairing process...
mortality for those aged equal or more than 65 years.
Effects on children
It is a common myth that caffeine causes stunted growth in children because scientific studies have disproved the belief. Children experience the same effects from caffeine as adults.
Energy drinks, most of which containing high amounts of caffeine, have been banned in many schools throughout the world.
Caffeine intake during pregnancy
Despite its widespread use and the conventional view that it is a safe substance, a 2008 study suggested that pregnant women who consume 200 milligrams or more of caffeine per day have about twice the miscarriage risk as women who consume none. However, another 2008 study found no correlation between miscarriage and caffeine consumption. The UK
Food Standards AgencyThe 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 an appointed board that is intended to act in the public interest...
has recommended that pregnant women should limit their caffeine intake to less than 200 mg of caffeine a day – the equivalent of two cups of instant coffee or a half to two cups of fresh coffee. The FSA noted that the design of the studies made it impossible to be certain that the differences were due to caffeine per se, instead of other lifestyle differences possibly associated with high levels of caffeine consumption, but judged the advice to be prudent.
Dr De-Kun Li of Kaiser Permanente Division of Research, writing in the American Journal of Obstetrics and Gynecology, concluded that an intake of 200 milligrams or more per day, representing two or more cups, "significantly increases the risk of miscarriage". However, Dr. David Savitz, a professor in community and preventive medicine at New York's Mount Sinai School of Medicine and lead author of the other new study on the subject published in the January issue of Epidemiology, found no link between miscarriage and caffeine consumption.
Genetics and caffeine metabolism
A 2006 study by Dr. Ahmed El-Sohemy at the University of Toronto discovered a link between a gene affecting caffeine metabolism and the effects of coffee on health.
Some people metabolize caffeine more slowly than the general population due to variations in a specific cytochrome P450 gene, and there is evidence people with this gene may be at a higher risk of myocardial infarction when consuming large amounts of coffee. For rapid metabolizers, however, coffee seemed to have a preventative effect. Slow and fast metabolizers are comparably common in the general population, and this has been blamed for the wide variation in studies of the health effects of caffeine.
Intraocular Pressure and caffeine
Recent data has suggested that caffeine consumption can raise intraocular pressure . This may be a significant consideration for those with open angle glaucoma .
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.
BenzeneBenzene, or benzol, is an organic chemical compound with the molecular formula C6H6. It is sometimes abbreviated Ph–H. Benzene is a colorless and highly flammable liquid with a sweet smell and a relatively high melting point...
,
chloroformChloroform is the organic compound with formula CHCl
3. This colourless, sweet-smelling, dense liquid is a trihalomethane. It is also considered somewhat hazardous...
,
trichloroethyleneThe chemical compound trichloroethylene is a chlorinated hydrocarbon commonly used as an industrial solvent. It is a clear non-flammable liquid with a sweet smell....
and
dichloromethaneDichloromethane is the organic compound with the formula CH
2Cl
2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. More than 500,000 tons were produced in 1991. Although it is not miscible with water, it is miscible with many organic...
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 charcoalActivated carbon, also called activated charcoal or activated coal, 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....
, which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving decaffeinated coffee with a good flavor. Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter
caffeine tabletsCaffeine tablets contain between 50 mg and 200 mg of caffeine and can be purchased without prescription in Australia and the USA. A typical cup of coffee contains 100 mg of caffeine....
.
Supercritical carbon dioxide extraction
Supercritical carbon dioxideSupercritical carbon dioxide refers to carbon dioxide that is in a fluid state while also being at or above both its critical temperature and pressure, yielding rather uncommon properties. 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: CO
2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73
atmThe standard atmosphere is an international reference pressure defined as 101,325 Pa and formerly used as unit of pressure . For practical purposes it has been replaced by the bar which is 100,000 Pa...
. Under these conditions, CO
2 is in a "
supercriticalA supercritical fluid is any substance at a temperature and pressure above its critical point. It can diffuse through solids like a gas, and dissolve materials like a liquid. In addition, close to the critical point, small changes in pressure or temperature result in large changes in density,...
"
stateIn 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 which allow it to penetrate deep into the beans but also liquid-like properties which dissolve 97–99% of the caffeine. The caffeine-laden CO
2 is then sprayed with high pressure water to remove the caffeine. The caffeine can then be isolated by
charcoalActivated carbon, also called activated charcoal or activated coal, 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....
adsorptionAdsorption is the accumulation of atoms or molecules on the surface of a material. This process creates a film of the adsorbate on the adsorbent's surface. It is different from absorption, in which a substance diffuses into a liquid or solid to form a solution...
(as above) or by
distillationDistillation is a method of separating mixtures based on differences in their volatilities in a boiling liquid mixture. Distillation is a unit operation, or a physical separation process, and not a chemical reaction....
,
recrystallizationRecrystallization may refer to:*Recrystallization *Recrystallization *Recrystallization...
, or
reverse osmosisReverse osmosis is similar to the membrane filtration treatment process. However there are key differences between reverse osmosis and filtration...
.
Extraction by organic solvents
Organic solvents such as
ethyl acetateEthyl acetate is the organic compound with the formula CH3COOCH2CH3. This colorless liquid has a characteristic sweet smell like certain glues or nail polish removers, in which it is used...
present much less health and environmental hazard than previously used chlorinated and aromatic solvents. Another method is to use triglyceride oils obtained from spent coffee grounds.
Religion
Some Latter-day Saints (Mormons),
Seventh-day AdventistsThe Seventh-day Adventist Church is a Christian denomination which is 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. It is the eighth largest international body of...
,
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. A few followers 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.” (Priesthood Bulletin, Feb. 1972, p. 4.)
See also Word of Wisdom.
Gaudiya Vaishnava HindusGaudiya Vaishnavism is a Vaishnava religious movement founded by Chaitanya Mahaprabhu in India in the 16th century. "Gaudiya" refers to 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, however it is worth noting that it should not be over used and cause severe harm to one's body. With regard to the caffeine in coffee, Imam Shihab al-Din said: 'it is
halalHalal is an Arabic term designating any object or an action which is permissible to use or engage in, according to Islamic law. It is the opposite of haraam. The term is widely used to designate food seen as permissible according to Islamic law...
(lawful) to drink, because all things are
halalHalal is an Arabic term designating any object or an action which is permissible to use or engage in, according to Islamic law. It is the opposite of haraam. The term is widely used to designate food seen as permissible according to Islamic law...
(lawful) except that which God has made
haraamHaraam is an Arabic term meaning "forbidden". In Islam it is used to refer to anything that is prohibited by the faith...
(unlawful)'.
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