Caffeine

Systematic (IUPAC) name :- 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Clinical data :-

AHFS/[Link]

monograph

Pregnancy cat. :- B?(AU) B(US)

Legal status :- Unscheduled (AU) GSL (UK) OTC (US)

Routes :- Oral

Pharmacokinetic data

Bioavailability :- 99%

Protein binding :- 17% to 36%

Metabolism :- demethylation by CYP1A2

Half-life :- 5 hrs

Excretion :- urine

Identifiers

CAS number :- 58-08-2

ATC code :- N06BC01

PubChem :- CID 2519

DrugBank :- DB00201

ChemSpider :- 2424

UNII :- 3G6A5W338E
KEGG :- D00528

ChEBI :- CHEBI:27732

ChEMBL :- CHEMBL113

Chemical data

Formula :- C8H10N4O2

Mol. Mass :- 194.19

SMILES :- eMolecules& PubChem

Properties:

Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in
varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that
paralyzes and kills certain insects feeding on the plants. It is most commonly consumed by humans in
infusions extracted from the bean of the coffee plant and the leaves of the tea bush, as well as from
various foods and drinks containing products derived from the kola nut. Other sources include yerba
maté, guarana berries, guayusa, and the yaupon holly.

In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and
restoring alertness. It is the world's most widely consumed psychoactive drug, but, unlike many other
psychoactive substances, it is both legal and unregulated in nearly all parts of the world. Beverages
containing caffeine, such as coffee, tea, soft drinks, and energy drinks, enjoy great popularity; in North
America, 90% of adults consume caffeine daily.[4]

Caffeine is toxic at sufficiently high doses, but ordinary consumption poses few known health risks, even
when carried on for years — there may be a modest protective effect against some diseases, including
certain types of cancer. Some people experience sleep disruption if they consume caffeine, especially
during the evening hours, but others show little disturbance and the effect of caffeine on sleep is highly
variable.
Evidence a risk to pregnancy is equivocal, but some authorities have concluded that prudent advice is
for pregnant women to limit consumption to the equivalent of two cups of coffee per day or less.
Caffeine has diuretic properties when administered to people who are not used to it, but regular users
develop a tolerance to this effect, and studies have generally failed to support the common notion that
ordinary consumption contributes significantly to dehydration. With heavy use, strong tolerance
develops rapidly and caffeine can produce clinically significant physical and mental dependence.

Contents

1 Health effects 1.1 Stimulant effects

1.2 Physical effects

1.3 Psychological

1.4 Caffeine intoxication

1.5 Tolerance and withdrawal

1.6 In other animals

2 Sources and consumption

3 Chemical properties and biosynthesis

4 Pharmacology 4.1 Mechanism of action

4.2 Metabolism

5 Detection in biological fluids

6 Decaffeination

7 History 7.1 Discovery

8 Religion

9 References
10 External links

Health effects

Main article: Health effects of caffeine

Effects of moderate caffeine consumption[5]

Stimulant effects

Caffeine is a central nervous system and metabolic stimulant,[6] and is used both recreationally and
medically to reduce physical fatigue and to restore alertness when drowsiness occurs. It produces
increased wakefulness, faster and clearer flow of thought, increased focus, and better general body
coordination.[7] The amount of caffeine necessary to produce effects varies from person to person,
depending on body size and degree of tolerance. Effects begin less than an hour after consumption, and
a moderate dose usually wears off in about five hours.[7]

Caffeine has a number of effects on sleep, but does not affect all people in the same way. It improves
performance during sleep deprivation but may lead to subsequent insomnia.[8] In shift workers it leads
to fewer mistakes caused by tiredness.[9] In athletics, moderate doses of caffeine can improve sprint,
[10] endurance[11] and team sports performance,[12] but the improvements are not usually very large.
High doses of caffeine, however, can impair athletic performance by interfering with coordination.[13]
Evidence shows that, contrary to common advice, caffeine may be helpful at high altitude.[14]

Physical effects

Consumption of large amounts of caffeine — usually more than 250 mg per day — can lead to a
condition known as caffeinism. Caffeinism usually combines caffeine dependency with a wide range of
unpleasant physical and mental conditions including nervousness, irritability, restlessness, insomnia,
headaches, and heart palpitations after caffeine use.[15]
Coffee consumption is associated with a lower overall risk of cancer.[16] This is primarily due to a
decrease in the risks of hepatocellular and endometrial cancer, but it may also have a modest effect on
colorectal cancer.[17] There does not appear to be a significant protective effect against other types of
cancers, and heavy coffee consumption may increase the risk of bladder cancer.[17]

There is little or no evidence that caffeine consumption increases the risk of cardiovascular disease, and
it may somewhat reduce the risk of type 2 diabetes.[18] Drinking four or more cups of coffee per day
does not affect the risk of hypertension compared to drinking little or no coffee, however those who
drink 1-3 cups per day may be at a slightly increased risk.[19]

Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal
individuals.[20] It may protect people from liver cirrhosis.[21] There is no evidence that coffee stunts a
child's growth.[22] Caffeine may increase the effectiveness of some medications including ones used to
treat headaches.[23]

Caffeine consumption during pregnancy does not appear to increase the risk of congenital
malformations, miscarriage or growth retardation even when consumed in moderate to high amounts.
[24] However as the data supporting this conclusion is of poor quality some suggest limiting caffeine
consumption during pregnancy.[25][26] For example the UK Food Standards Agency has recommended
that pregnant women should limit their caffeine intake, out of prudence, to less than 200 mg of caffeine
a day—the equivalent of two cups of instant coffee, or one and a half to two cups of fresh coffee.[27]
Although the evidence that caffeine may be harmful during pregnancy is equivocal, there is clear
evidence that the hormonal changes associated with pregnancy slow the metabolic clearance of caffeine
from the system, causing a given dose to have longer-lasting effects (as long as 15 hours in the third
trimester).[28]

On the positive side, caffeine is the primary treatment of the breathing disorders apnea of
prematurity[29] and may also be effective in preventing bronchopulmonary dysplasia in premature
infants.[30] The only short-term risk associated with caffeine citrate treatment is a temporary reduction
in weight gain during the therapy,[31] and longer term studies (18 to 21 months) have shown lasting
benefits of treatment of premature infants with caffeine.[32] The possibility of subtle long-term
developmental problems cannot, however, entirely be ruled out.[33]

When doses of caffeine equivalent to 2-3 cups of coffee are administered to people who have not
consumed caffeine over the previous days, they produce a stimulation in urinary output.[34] Because of
this diuretic effect, some authorities have recommended that athletes or airline passengers avoid
caffeine in order to reduce the risk of dehydration.[34] Most people who consume caffeine, however,
ingest it daily. Regular users of caffeine have been shown to develop a strong tolerance to the diuretic
effect,[34] and studies have generally failed to support the notion that ordinary consumption of
caffeinated beverages contributes significantly to dehydration, even in athletes.[35][36][37]

Psychological

Four caffeine-induced disorders are recognized by the American Psychiatric Association (APA) including:
caffeine intoxication, caffeine-induced sleep disorder, caffeine-induced anxiety disorder and caffeine-
related disorder not otherwise specified (NOS).[38] In moderate doses it may reduce symptoms of
depression and lower suicide risk.[39] High doses may trigger anxiety and rarely mania and psychosis. As
of 2010 the effect of caffeine on people with ADHD is not known.[39] The DSM-IV defines caffeine-
induced sleep disorder, as an individual who regularly ingests high doses of caffeine sufficient to induce
a significant disturbance in his or her sleep, sufficiently severe to warrant clinical attention.[38]

Caffeine can have both positive and negative effects on anxiety disorders depending on the dose. At
high doses, typically greater than 300 mg, it can both cause and worsen anxiety.[40] At low doses it may
little effect or may reduce symptoms of anxiety. Caffeine withdrawal, on the other hand, can cause an
increase in anxiety level.[39] In moderate doses caffeine typically does not affect learning or memory.
[41] It does however improve cognitive function in people who are fatigued, due to its effect on
alertness. Some studies have however found a modest protective against Alzheimer disease, but the
evidence is inconclusive.[42][43][44]

Caffeine intoxication

Primary symptoms of caffeine intoxication[45]

Caffeine overdose can result in a state of central nervous system over-stimulation called caffeine
intoxication (DSM-IV 305.90),[38] or colloquially the "caffeine jitters". The symptoms of caffeine
intoxication are not unlike overdoses of other stimulants. It may include restlessness, fidgeting, anxiety,
excitement, insomnia, flushing of the face, increased urination, gastrointestinal disturbance, muscle
twitching, a rambling flow of thought and speech, irritability, irregular or rapid heart beat, and
psychomotor agitation.[45] In cases of much larger overdoses, mania, depression, lapses in judgment,
disorientation, disinhibition, delusions, hallucinations, or psychosis may occur, and rhabdomyolysis
(breakdown of skeletal muscle tissue) can be provoked.[46][47]

Extreme overdose can result in death.[48][49] The median lethal dose (LD50) given orally, is 192
milligrams per kilogram in rats. The LD50 of caffeine in humans is dependent on weight and individual
sensitivity and estimated to be about 150 to 200 milligrams per kilogram of body mass, roughly 80 to
100 cups of coffee for an average adult taken within a limited time frame that is dependent on half-life.
[3] Though achieving lethal dose with caffeine would be exceptionally difficult with regular coffee, there
have been reported deaths from overdosing on caffeine pills, with serious symptoms of overdose
requiring hospitalization occurring from as little as 2 grams of caffeine. An exception to this would be
taking a drug such as fluvoxamine or levofloxacin, which blocks the liver enzyme responsible for the
metabolism of caffeine, thus increasing the central effects and blood concentrations of caffeine five-fold.
[47][48][49][50] Death typically occurs due to ventricular fibrillation brought about by effects of caffeine
on the cardiovascular system.

Treatment of severe caffeine intoxication is generally supportive, providing treatment of the immediate
symptoms, but if the patient has very high serum levels of caffeine then peritoneal dialysis,
hemodialysis, or hemofiltration may be required.[45]

Tolerance and withdrawal

With repetitive use, the stimulatory effects of caffeine are substantially reduced over time, a
phenomenon known as a tolerance. Tolerance develops quickly to some (but not all) effects of caffeine,
especially among heavy coffee and energy drink consumers.[51] Some coffee drinkers develop tolerance
to its sleep-disrupting effects, but others apparently do not.[28] Withdrawal symptoms—including
headache, irritability, inability to concentrate, drowsiness, insomnia, and pain in the stomach, upper
body, and joints—may appear within 12 to 24 hours after discontinuation of caffeine intake, peak at
roughly 48 hours, and usually last from one to five days.[52]

In other animals

Caffeine has a significant effect on spiders, which is illustrated here in the erratic construction of their
webs.
See also: Effect of psychoactive drugs on animals

While safe in humans, caffeine is considerably toxic to various animals, such as dogs and birds.[53][54]

The increased toxicity of caffeine in some animals is at least partly due to a poorer ability to metabolize
the compound.[55]

Caffeine also has a pronounced effect on mollusks, various insects, and spiders.[56]

Sources and consumption

Product

Serving size

Caffeine per serving (mg)

Caffeine per liter (mg)

Caffeine Content in Select Food and Drugs[57][58][59]

Caffeine tablet (regular-strength)

1 tablet

100

Caffeine tablet (extra-strength)

1 tablet
200

Excedrin tablet

1 tablet

65

Hershey's Special Dark (45% cacao content)

1 bar (43 g; 1.5 oz)

31

Hershey's Milk Chocolate (11% cacao content)

1 bar (43 g; 1.5 oz)

10

Percolated coffee

207 mL (7 U.S. fl oz)

80–135

386–652

Drip coffee

207 mL (7 U.S. fl oz)

115–175
555–845

Coffee, decaffeinated

207 mL (7 U.S. fl oz)

5–15

24–72

Coffee, espresso

44–60 mL (1.5-2 U.S. fl oz)

100

1,691–2254

Black tea
177 mL (6 U.S. fl oz)

50

282

Green tea

177 mL (6 U.S. fl oz)

30

170

Guayakí yerba mate (loose leaf)

6 g (0.2 U.S. oz)

85[60]
358 about

Coca-Cola Classic

355 mL (12 U.S. fl oz)

34

96

Mountain Dew

355 mL (12 U.S. fl oz)

54

154

Guaraná Antarctica
350 mL (11 U.S. fl oz)

30

100

Jolt Cola

695 mL (23.5 U.S. fl oz)

280

403

Red Bull

250 mL (8.4 U.S. fl oz)

80
320

Global consumption of caffeine has been estimated at 120,000 tonnes per year, making it the world's
most popular psychoactive substance. This amounts to one serving of a caffeinated beverage for every
person every day.[61]

Caffeine is found in many plant species, where it acts as a natural pesticide, with high caffeine levels
being observed in seedlings still developing foliage but lacking mechanical protection;[62] caffeine
paralyzes and kills certain insects feeding upon the plant.[63] High caffeine levels have also been found
in the surrounding soil of coffee bean seedlings. Therefore, caffeine is understood to have a natural
function as both a natural pesticide and an inhibitor of seed germination of other nearby coffee
seedlings, thus giving it a better chance of survival.[64]

Common sources of caffeine are coffee, tea, and (to a lesser extent) chocolate derived from cocoa
beans.[65] Less commonly used sources of caffeine include the yerba maté, guarana and ilex guayusa
plants,[66] 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.[67][68]

The disparity in experience and effects between the various natural caffeine sources could be because
plant sources of caffeine also contain widely varying mixtures of other xanthine alkaloids, including the
cardiac stimulants theophylline and theobromine, and other substances such as polyphenols that can
form insoluble complexes with caffeine.[69]

One of the world's primary sources of caffeine is the coffee "bean" (which is the seed of the coffee
plant), from which coffee is brewed. Caffeine content in coffee varies widely depending on the type of
coffee bean and the method of preparation used;[70] even beans within a given bush can show
variations in concentration. In general, one serving of coffee ranges from 80–100 milligrams, for a single
shot (30 milliliters) of arabica-variety espresso, to approximately 100–125 milligrams for a cup (120
milliliters) of drip coffee.[71][72] Arabica coffee typically contains half the caffeine of the robusta
variety.[70]
In general, dark-roast coffee has very slightly less caffeine than lighter roasts because the roasting
process reduces a small amount of the bean's caffeine content.[71][72]

Tea is another common source of caffeine. Although tea contains more caffeine than coffee (by dry
weight), a typical serving contains much less, as tea is normally brewed much weaker. Besides strength
of the brew, growing conditions, processing techniques and other variables also affect caffeine content.
Certain types of tea may contain somewhat more caffeine than other teas.[73]

Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee.
Preparation and many other factors have a significant impact on tea, and color is a very poor indicator of
caffeine content. Teas like the pale Japanese green tea, gyokuro, for example, contain far more caffeine
than much darker teas like lapsang souchong, which has very little.[74]

No-Doz OTC 100 mg caffeine tablets.

Caffeine is also a common ingredient of soft drinks, such as cola, originally prepared from kola nuts. Soft
drinks typically contain about 10 to 50 milligrams of caffeine per serving. By contrast, energy drinks,
such as Red Bull, can start at 80 milligrams of caffeine per serving. The caffeine in these drinks either
originates from the ingredients used or is an additive derived from the product of decaffeination or from
chemical synthesis. Guarana, a prime ingredient of energy drinks, contains large amounts of caffeine
with small amounts of theobromine and theophylline in a naturally occurring slow-release excipient.[75]

Chocolate derived from cocoa beans contains a small amount of caffeine. The weak stimulant effect of
chocolate may be due to a combination of theobromine and theophylline, as well as caffeine.[76] A
typical 28-gram serving of a milk chocolate bar has about as much caffeine as a cup of decaffeinated
coffee, although some dark chocolate currently in production contains as much as 160 mg per 100g.[58]
Various manufacturers market caffeine tablets, claiming that using caffeine of pharmaceutical quality
improves mental alertness. These effects have been borne out by research that shows caffeine use
(whether in tablet form or not) results in decreased fatigue and increased attentiveness.[7]

These tablets are commonly used by students studying for their exams and by people who work or drive
for long hours.[77] One U.S. company is also marketing dissolving caffeine strips as an alternative to
energy drinks.[78] Another unusual intake route is SpazzStick, a caffeinated lip balm.[79]

Inhaled caffeine is a distribution method now under scrutiny of some U.S. lawmakers. [80].

[edit] Chemical properties and biosynthesis

Caffeine biosynthesis[81]

Caffeine laboratory synthesis[82][83]

Caffeine is an achiral molecule[84] without stereoisomers.[85]

The two amide groups of caffeine exist predominately as zwitterionic resonance structures where the
nitrogen and carbon atoms are double bonded to each other so that both of these nitrogen atoms are
essentially planar (in sp2 orbital hybridization). The fused ring system therefore contains a total of ten pi
electrons and hence according to Hückel's rule is aromatic.[citation needed]
Caffeine is synthesized in plants from the purine nucleotides AMP, GMP, and IMP. These in turn are
transformed into xanthosine and then theobromine, the latter being the penultimate precursor of
caffeine.[86]

Being readily available as a byproduct of decaffeination, caffeine is not usually synthesized chemically.
[87] If desired, it may be synthesized from dimethylurea and malonic acid.[82][83][88]

Pure anhydrous caffeine is a white colorless powder with a melting point of 227–228 °C. Caffeine is
moderately soluble in water at room temperature (2 g/100 mL), but very soluble in boiling water (66
g/100 mL).[89] It is also moderately soluble in ethanol (1.5 g/100 mL).[89] It is weakly basic (pKa = ~0.6)
requiring strong acid to protonate it.[2]

[edit] Pharmacology

Inside the body caffeine acts through several mechanisms, but its most important effect is to counteract
a substance called adenosine that naturally circulates at high levels throughout the body, and especially
in the nervous system. In the brain, adenosine plays a generally protective role, part of which is to
reduce neural activity levels — for example, there is some evidence that adenosine helps to induce
torpor in animals that seasonally hibernate.[90]

[edit] Mechanism of action

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

Because caffeine is both water-soluble and lipid-soluble, it readily crosses the blood–brain barrier that
separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action
is as a nonselective antagonist of adenosine receptors (in other words, an agent that reduces the effects
of adenosine). The caffeine molecule is structurally similar to adenosine, and is capable of binding to
adenosine receptors on the surface of cells without activating them, thereby acting as a competitive
inhibitor.[91]

Adenosine is found in every part of the body, because it plays a role in the fundamental ATP-related
energy producing mechanism and is also necessary for RNA synthesis, but it has additional functions in
the brain. The evidence indicates that brain adenosine acts to protect the brain by suppressing neural
activity and by increasing blood flow via receptors located on vascular smooth muscle.[92] Brain
adenosine levels are increased by various types of metabolic stress, including lack of oxygen and
interruption of blood flow. There is evidence that adenosine functions as a synaptically released
neurotransmitter in some parts of the brain; however, stress-related adenosine increases appear to be
produced mainly by extracellular metabolism of ATP. Unlike most neurotransmitters, adenosine does
not seem to be packaged into vesicles that are released in a voltage-controlled manner, but the
possibility of such a mechanism has not entirely been ruled out.[92]

Several classes of adenosine receptors have been described, with different anatomical distributions. A1
receptors are widely distributed, and act to inhibit calcium uptake. A2A receptors are heavily
concentrated in the basal ganglia, an area that plays a critical role in behavior control, but can be found
in other parts of the brain as well, in lower densities. There is evidence that A 2A receptors interact with
the dopamine system, which is involved in reward and arousal. (A2A receptors can also be found on
arterial walls and blood cell membranes.)[93]

Beyond its general neuroprotective effects, there are reasons to believe that adenosine may be more
specifically involved in control of the sleep-wake cycle. Robert McCarley and his colleagues have argued
that accumulation of adenosine may be a primary cause of the sensation of sleepiness that follows
prolonged mental activity, and that the effects may be mediated both by inhibition of wake-promoting
neurons via A1 receptors, and activation of sleep-promoting neurons via indirect effects on A2A
receptors.[93] More recent studies have provided additional evidence for the importance of A2A, but
not A1, receptors.[94]

A number of potential mechanisms have been proposed for the athletic performance-enhancing effects
of caffeine.[95] In the classic, or metabolic theory, caffeine may increase fat utilization and decrease
glycogen utilization. Caffeine mobilizes free fatty acids from fat and/or intramuscular triglycerides by
increasing circulating epinephrine levels. The increased availability of free fatty acids increases fat
oxidation and spares muscle glycogen, thereby enhancing endurance performance. In the nervous
system, caffeine may reduce the perception of effort by lowering the neuron activation threshold,
making it easier to recruit the muscles for exercise.[96]

[edit] Caffeine metabolites

Metabolites of caffeine also contribute to caffeine's effects. Paraxanthine is responsible for an increase
in the lipolysis process, which releases glycerol and fatty acids into the blood to be used as a source of
fuel by the muscles. Theobromine is a vasodilator that increases the amount of oxygen and nutrient flow
to the brain and muscles. Theophylline acts as a smooth muscle relaxant that chiefly affects bronchioles
and acts as a chronotrope and inotrope that increases heart rate and force of contraction.[97]

[edit] Metabolism

Caffeine is metabolized in the liver into three primary metabolites: paraxanthine (84%), theobromine
(12%), and theophylline (4%)

Caffeine from coffee or other beverages is absorbed by the small intestine within 45 minutes of
ingestion and then distributed throughout all tissues of the body.[98] Peak blood concentration is
reached within one hour.[99] It is eliminated by first-order kinetics.[100] Caffeine can also be absorbed
rectally, evidenced by the formulation of suppositories of ergotamine tartrate and caffeine (for the relief
of migraine)[101] and chlorobutanol and caffeine (for the treatment of hyperemesis).[102]

The biological half-life of caffeine—the time required for the body to eliminate one-half of the total
amount of caffeine—varies widely among individuals according to such factors as age, liver function,
pregnancy, some concurrent medications, and the level of enzymes in the liver needed for caffeine
metabolism. It can also be significantly altered by drugs or hormonal states. In healthy adults, caffeine's
half-life is approximately 4.9 hours.[103] Heavy cigarette smokers show a decrease in half-life of 30-50%,
oral contraceptives can double it, and pregnancy can raise it even more, to as much as 15 hours during
the last trimester. In newborn infants the half-life can be 80 hours or more; however it drops very
rapidly with age, possibly to less than the adult value by the age of 6 months.[28] The antidepressant
Fluvoxamine (Luvox) reduces the clearance of caffeine by more than 90%, and prolongs its elimination
half-life more than tenfold; from 4.9 hours to 56 hours.[103]

Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system (to be specific, the
1A2 isozyme) into three metabolic dimethylxanthines,[104] each of which has its own effects on the
body:

Paraxanthine (84%): Has the effect of increasing lipolysis, leading to elevated glycerol and free fatty acid
levels in the blood plasma.

Theobromine (12%): Dilates blood vessels and increases urine volume. Theobromine is also the
principal alkaloid in the cocoa bean, and therefore chocolate.

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

Each of these metabolites is further metabolized and then excreted in the urine. Caffeine can
accumulate in individuals with severe liver disease, increasing its half-life.[105]

Some quinolone antibiotics exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby
reducing clearance of caffeine and thus increasing blood levels.[106]

A 2011 analysis published by PLoS Genetics reviewed five studies covering more than 47,000 subjects of
European descent. Researchers determined that habitual caffeine intake is associated with variations in
two genes that regulate how quickly the body processes caffeine. Subjects who had a high-intake
mutation of either gene on both chromosomes consumed 40 mg more caffeine per day (equivalent to a
can of cola) than people who did not.[107]

[edit] Detection in biological fluids

Caffeine can be quantified in blood, plasma, or serum to monitor therapy in neonates, confirm a
diagnosis of poisoning, or facilitate a medicolegal death investigation. Plasma caffeine levels are usually
in the range of 2–10 mg/L in coffee drinkers, 12–36 mg/L in neonates receiving treatment for apnea, and
40–400 mg/L in victims of acute overdosage. Urinary caffeine concentration is frequently measured in
competitive sports programs, for which a level in excess of 15 mg/L is usually considered to represent
abuse.[108]

[edit] Decaffeination

Fibrous crystals of purified caffeine. Dark field light microscope image, the image covers an area of
approx. 11 by 7 mm.

Main article: Decaffeination

Extraction of caffeine from coffee, to produce decaffeinated coffee and caffeine, is an important
industrial process and can be performed using a number of different solvents. Benzene, chloroform,
trichloroethylene, and dichloromethane have all been used over the years but for reasons of safety,
environmental impact, cost, and flavor, they have been superseded by the following main methods:

Water extraction: Coffee beans are soaked in water. The water, which contains many other compounds
in addition to caffeine and contributes to the flavor of coffee, is then passed through activated charcoal,
which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving
decaffeinated coffee with its original flavor. Coffee manufacturers recover the caffeine and resell it for
use in soft drinks and over-the-counter caffeine tablets.[109]

Supercritical carbon dioxide extraction: Supercritical carbon dioxide is an excellent nonpolar solvent for
caffeine, and is safer than the organic solvents that are otherwise used. The extraction process is simple:
CO2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73
atm. Under these conditions, CO2 is in a "supercritical" state: It has gaslike properties that allow it to
penetrate deep into the beans but also liquid-like properties that dissolve 97–99% of the caffeine. The
caffeine-laden CO2 is then sprayed with high pressure water to remove the caffeine. The caffeine can
then be isolated by charcoal adsorption (as above) or by distillation, recrystallization, or reverse osmosis.
[109]
Extraction by organic solvents: Certain organic solvents such as ethyl acetate present much less health
and environmental hazard than previously used chlorinated and aromatic organic solvents. Another
method is to use triglyceride oils obtained from spent coffee grounds.[109]

[edit] History

Coffeehouse in Palestine, circa 1900

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

Caffeine was first isolated from coffee in 1820 by the German chemist Friedlieb Ferdinand Runge, and
then independently in 1821 by French chemists Pierre Robiquet, Pierre Pelletier, and Joseph Caventou.
Pelletier coined the word "cafeine" from the French word for coffee (café), and this term became the
English word "caffeine".

According to Chinese legend, the Chinese emperor Shennong, reputed to have reigned in about 3000
BCE, accidentally discovered tea when he noted that when certain leaves fell into boiling water, a
fragrant and restorative drink resulted.[110] Shennong is also mentioned in Lu Yu's Cha Jing, a famous
early work on the subject of tea.[111]

The history of coffee has been recorded as far back as the ninth century. During that time, coffee beans
were available only in their place of origin, Ethiopia. Legends trace the discovery of coffee either to a
Sufi dervish named Omar, or to a goatherder named Kaldi, who observed goats become elated and
sleepless at night after grazing on coffee shrubs and, upon trying the berries the goats had been eating,
experienced the same vitality.[112] The earliest literary mention of coffee may be a reference to
Bunchum in the works of the 9th-century Persian physician al-Razi.[112]:11 The first reliable record of
the use of coffee outside Ethiopia comes from Aden, in 1451.[112]:16 The appreciation of coffee as a
beverage in Europe dates from the 17th century. The first coffee house in Venice opened some time in
the late 1640s.[112]:127 In Britain, the first coffee house was opened in Oxford in 1650.[112]:41 They
soon became popular throughout Western Europe, and played a significant role in social relations in the
17th and 18th centuries.[113]

Use of the kola nut, like the coffee berry and tea leaf, appears to have ancient origins. It is chewed in
many West African cultures, individually or in a social setting, to restore vitality and ease hunger pangs.
In 1911, kola became the focus of one of the earliest documented health scares, when the US
government seized 40 barrels and 20 kegs of Coca-Cola syrup in Chattanooga, Tennessee, alleging the
caffeine in its drink was "injurious to health".[114] Although the judge ruled in favor of Coca-Cola, two
bills were introduced to the U.S. House of Representatives in 1912 to amend the Pure Food and Drug
Act, adding caffeine to the list of "habit-forming" and "deleterious" substances, which must be listed on
a product's label.[115]

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

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

The leaves and stems of the yaupon holly (Ilex vomitoria) were used by Native Americans to brew a tea
called asi or the "black drink".[116] Archaeologists have found evidence of this use stretch back far into
antiquity, possibly dating to Late Archaic times.[citation needed]

[edit] Discovery

In 1819, the German chemist Friedlieb Ferdinand Runge isolated relatively pure caffeine for the first
time; he called it "Kaffebase" (i.e., a base that exists in coffee).[117] In 1821, caffeine was isolated both
by French chemist Pierre Jean Robiquet and by another pair of French chemists, Pierre-Joseph Pelletier
and Joseph Bienaimé Caventou, according to Swedish chemist Jöns Jacob Berzelius in his yearly journal.
Furthermore, Berzelius stated the French chemists had made their discoveries independently of any
knowledge of Runge's or each other's work.[118]

Pelletier's article on caffeine was the first to use the term in print (in the French form Caféine).[119] It
corroborates Berzelius's account:

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

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

Robiquet was one of the first to isolate and describe the properties of pure caffeine[120] while Pelletier
was the first to perform an elemental analysis.[121]

Berzelius later acknowledged Runge's priority in the extraction of caffeine, stating:[122] "However, at
this point, it should not remain unmentioned that Runge (in his Phytochemical Discoveries, 1820, pages
146–147) specified the same method and described caffeine under the name Caffeebase a year earlier
than Robiquet, to whom the discovery of this substance is usually attributed, having made the first oral
announcement about it at a meeting of the Pharmacy Society in Paris.) According to Runge, he did this
at the behest of Johann Wolfgang von Goethe."[123] In 1827, M. Oudry isolated "theine" from tea,[124]
but it was later proved by Mulder[125] and by Carl Jobst[126] that theine was the same as caffeine.[123]
The structure of caffeine was elucidated near the end of the 19th century by Hermann Emil Fischer, who
was also the first to achieve its total synthesis. This was part of the work for which Fischer was awarded
the Nobel Prize in 1902.[127]
[edit] Religion

Some Seventh-day Adventists, Church of God (Restoration) adherents, and Christian Scientists do not
consume caffeine.[citation needed] Some from these religions believe that one is not supposed to
consume a non-medical, psychoactive substance, or believe that one is not supposed to consume a
substance that is addictive. The Church of Jesus Christ of Latter-day Saints has said the following with
regard to caffeinated beverages: "With reference to cola drinks, the Church has never officially taken a
position on this matter, but the leaders of the Church have advised, and we do now specifically advise,
against the use of any drink containing harmful drugs under circumstances that would result in acquiring
the habit. Any beverage that contains ingredients harmful to the body should be avoided."[128]

Gaudiya Vaishnavas 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.[citation needed]

In Islam the main rule on caffeine is that it is permissible. With regard to the caffeine in coffee, Imam
Shihab al-Din said: "it is halal (lawful) to drink, because all things are halal (lawful) except that which God
has made haraam (unlawful)".[129]

Coffee
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[hide]

v·

d·

Stimulants (N06B)

Adamantanes

Adaphenoxate • Adapromine • Amantadine • Bromantane • Chlodantane • Gludantane • Memantine •

Midantane
Adenosine antagonists

8-Chlorotheophylline • 8-Cyclopentyltheophylline • 8-Phenyltheophylline • Aminophylline • Caffeine •

CGS-15943 • Dimethazan • Paraxanthine • SCH-58261 • Theobromine • Theophylline

Alkylamines

Cyclopentamine • Cypenamine • Cyprodenate • Heptaminol • Isometheptene • Methylhexaneamine •

Octodrine • Propylhexedrine • Tuaminoheptane

Arylcyclohexylamines
Benocyclidine • Dieticyclidine • Esketamine • Eticyclidine • Gacyclidine • Ketamine • Phencyclamine •
Phencyclidine • Rolicyclidine • Tenocyclidine • Tiletamine

Benzazepines

6-Br-APB • SKF-77434 • SKF-81297 • SKF-82958

Cholinergics
A-84543 • A-366,833 • ABT-202 • ABT-418 • AR-R17779 • Altinicline • Anabasine • Arecoline • Cotinine
• Cytisine • Dianicline • Epibatidine • Epiboxidine • GTS-21 • Ispronicline • Nicotine • PHA-543,613 •
PNU-120,596 • PNU-282,987 • Pozanicline • Rivanicline • Sazetidine A • SIB-1553A • SSR-180,711 • TC-
1698 • TC-1827 • TC-2216 • TC-5619 • Tebanicline • UB-165 • Varenicline • WAY-317,538

Convulsants

Anatoxin-a • Bicuculline • DMCM • Flurothyl • Gabazine • Pentetrazol • Picrotoxin • Strychnine •

Thujone

Eugeroics
Adrafinil • Armodafinil • CRL-40941 • Modafinil

Oxazolines

4-Methylaminorex • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline •

Thozalinone

Phenethylamines
1-(4-Methylphenyl)-2-aminobutane • 1-Phenyl-2-(piperidin-1-yl)pentan-3-one • 1-Methylamino-1-(3,4-
methylenedioxyphenyl)propane • 2-Fluoroamphetamine • 2-Fluoromethamphetamine • 2-OH-PEA • 2-
Phenyl-3-aminobutane • 2-Phenyl-3-methylaminobutane • 2,3-MDA • 3-Fluoroamphetamine • 3-
Fluoroethamphetamine • 3-Fluoromethcathinone • 3-Methoxyamphetamine • 3-Methylamphetamine •
3,4-DMMC • 4-BMC • 4-Ethylamphetamine • 4-FA • 4-FMA • 4-MA • 4-MMA • 4-MTA • 6-FNE •
Alfetamine • α-Ethylphenethylamine • Amfecloral • Amfepentorex • Amfepramone • Amidephrine •
Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • Arbutamine • β-
Methylphenethylamine • β-Phenylmethamphetamine • Benfluorex • Benzedrone • Benzphetamine •
BDB (J) • BOH (Hydroxy-J) • BPAP • Buphedrone • Bupropion (Amfebutamone) • Butylone • Cathine •
Cathinone • Chlorphentermine • Cinnamedrine • Clenbuterol • Clobenzorex • Cloforex • Clortermine •
D-Deprenyl • Denopamine • Dimethoxyamphetamine • Dimethylamphetamine • Dimethylcathinone
(Dimethylpropion, Metamfepramone) • Dobutamine • DOPA (Dextrodopa, Levodopa) • Dopamine •
Dopexamine • Droxidopa • EBDB (Ethyl-J) • Ephedrine • Epinephrine (Adrenaline) • Epinine
(Deoxyepinephrine) • Etafedrine • Ethcathinone (Ethylpropion) • Ethylamphetamine (Etilamfetamine) •
Ethylnorepinephrine (Butanefrine) • Ethylone • Etilefrine • Famprofazone • Fenbutrazate • Fencamine •
Fenethylline • Fenfluramine (Dexfenfluramine) • Fenmetramide • Fenproporex • Flephedrone •
Fludorex • Furfenorex • Gepefrine • HMMA • Hordenine • Ibopamine • IMP • Indanylamphetamine •
Isoetarine • Isoethcathinone • Isoprenaline (Isoproterenol) • L-Deprenyl (Selegiline) • Lefetamine •
Lisdexamfetamine • Lophophine (Homomyristicylamine) • Manifaxine • MBDB (Methyl-J; "Eden") •
MDA (Tenamfetamine) • MDBU • MDEA ("Eve") • MDMA ("Ecstasy", "Adam") • MDMPEA
(Homarylamine) • MDOH • MDPR • MDPEA (Homopiperonylamine) • Mefenorex • Mephedrone •
Mephentermine • Metanephrine • Metaraminol • Methamphetamine (Desoxyephedrine, Methedrine;
Dextromethamphetamine, Levomethamphetamine) • Methoxamine • Methoxyphenamine • MMA •
Methcathinone (Methylpropion) • Methedrone • Methoxyphenamine • Methylone • MMDA • MMDMA
• MMMA • Morazone • N-Benzyl-1-phenethylamine • N,N-Dimethylphenethylamine •
Naphthylamphetamine • Nisoxetine • Norepinephrine (Noradrenaline) • Norfenefrine •
Norfenfluramine • Normetanephrine • Octopamine • Orciprenaline • Ortetamine • Oxilofrine •
Paredrine (Norpholedrine, Oxamphetamine, Mycadrine) • PBA • PCA • PHA • Pargyline • Pentorex
(Phenpentermine) • Pentylone • Phenatine • Phendimetrazine • Phenmetrazine • Phenpromethamine •
Phentermine • Phenylalanine • Phenylephrine (Neosynephrine) • Phenylpropanolamine • Pholedrine •
PIA • PMA • PMEA • PMMA • PPAP • Prenylamine • Propylamphetamine • Pseudoephedrine •
Radafaxine • Ropinirole • Salbutamol (Albuterol; Levosalbutamol) • Sibutramine • Synephrine
(Oxedrine) • Theodrenaline • Tiflorex (Flutiorex) • Tranylcypromine • Tyramine • Tyrosine • Xamoterol •
Xylopropamine • Zylofuramine
Piperazines

2C-B-BZP • BZP • CM156 • DBL-583 • GBR-12783 • GBR-12935 • GBR-13069 • GBR-13098 • GBR-13119

• MeOPP • MBZP • Vanoxerine

Piperidines

1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine • 1-(3,4-Dichlorophenyl)-1-(piperidin-2-yl)butane • 2-
Benzylpiperidine • 2-Methyl-3-phenylpiperidine • 3,4-Dichloromethylphenidate • 4-Benzylpiperidine •
4-Methylmethylphenidate • Desoxypipradrol • Difemetorex • Diphenylpyraline • Ethylphenidate •
Methylnaphthidate • Methylphenidate (Dexmethylphenidate) • N-Methyl-3β-propyl-4β-(4-
chlorophenyl)piperidine • Nocaine • Phacetoperane • Pipradrol • SCH-5472

Pyrrolidines

2-Diphenylmethylpyrrolidine • α-PPP • α-PBP • α-PVP • Diphenylprolinol • MDPPP • MDPBP • MDPV •

MPBP • MPHP • MPPP • MOPPP • Naphyrone • PEP • Prolintane • Pyrovalerone

Tropanes
3-CPMT • 3'-Chloro-3α-(diphenylmethoxy)tropane • 3-Pseudotropyl-4-fluorobenzoate • 4'-
Fluorococaine • AHN-1055 • Altropane (IACFT) • Brasofensine • CFT (WIN 35,428) • β-CIT (RTI-55) •
Cocaethylene • Cocaine • Dichloropane (RTI-111) • Difluoropine • FE-β-CPPIT • FP-β-CPPIT • Ioflupane
(123I) • Norcocaine • PIT • PTT • RTI-31 • RTI-32 • RTI-51 • RTI-105 • RTI-112 • RTI-113 • RTI-117 • RTI-
120 • RTI-121 (IPCIT) • RTI-126 • RTI-150 • RTI-154 • RTI-171 • RTI-177 • RTI-183 • RTI-193 • RTI-194 •
RTI-199 • RTI-202 • RTI-204 • RTI-229 • RTI-241 • RTI-336 • RTI-354 • RTI-371 • RTI-386 •
Salicylmethylecgonine • Tesofensine • Troparil (β-CPT, WIN 35,065-2) • Tropoxane • WF-23 • WF-33 •
WF-60

Others

1-(Thiophen-2-yl)-2-aminopropane • 2-Amino-1,2-dihydronaphthalene • 2-Aminoindane • 2-

Aminotetralin • 2-MDP • 2-Phenylcyclohexylamine • 2-Phenyl-3,6-dimethylmorpholine • 3-
Benzhydrylmorpholine • 3,3-Diphenylcyclobutanamine • 5-(2-Aminopropyl)indole • 5-Iodo-2-
aminoindane • AL-1095 • Amfonelic acid • Amineptine • Amiphenazole • Atipamezole • Atomoxetine
(Tomoxetine) • Bemegride • Benzydamine • BTQ • BTS 74,398 • Carphedon • Ciclazindol • Cilobamine •
Clofenciclan • Cropropamide • Crotetamide • Cypenamine • D-161 • Diclofensine • Dimethocaine •
Efaroxan • Etamivan • EXP-561 • Fencamfamine • Fenpentadiol • Feprosidnine • G-130 • Gamfexine •
Gilutensin • GSK1360707F • GYKI-52895 • Hexacyclonate • Idazoxan • Indanorex • Indatraline • JNJ-
7925476 • JZ-IV-10 • Lazabemide • Leptacline • Levopropylhexedrine • Lomevactone • LR-5182 •
Mazindol • Meclofenoxate • Medifoxamine • Mefexamide • Mesocarb • Methastyridone •
Methiopropamine • N-Methyl-3-phenylnorbornan-2-amine • Nefopam • Nikethamide • Nomifensine •
O-2172 • Oxaprotiline • Phthalimidopropiophenone • PNU-99,194 • Propylhexedrine • PRC200-SS •
Rasagiline • Rauwolscine • Rubidium chloride • Setazindol • Tametraline • Tandamine • Trazium • UH-
232 • Yohimbine
See also Sympathomimetic amines

[hide]

v·

d·

Psychostimulants, agents used for ADHD, and nootropics (N06B)

Centrally acting sympathomimetics

Amphetamine • Amphetaminil • Atomoxetine • Dexmethylphenidate • Dextroamphetamine •

Dextromethamphetamine • Fencamfamine • Fenethylline • Lisdexamfetamine • Methylphenidate •
Mesocarb • Pemoline • Pipradrol • Prolintane

Xanthine derivatives

Caffeine • Fenethylline

Glutamate receptor
Racetams

Aniracetam • Nefiracetam • Noopept • Oxiracetam • Phenylpiracetam • Piracetam • Pramiracetam

Ampakines

CX-516 • CX-546 • CX-614 • CX-691 • CX-717 • IDRA-21 • LY-404,187 • LY-503,430 • PEPA • S-18986 •
Sunifiram • Unifiram
Eugeroics / Benzhydryl compounds

Adrafinil • Armodafinil • Modafinil

Histamine H3 receptor antagonists

A-349,821 • ABT-239 • Ciproxifan • GSK-189,254

GABAA α5 inverse agonists

α5IA • L-655,708 • PWZ-029 • Suritozole • TB-21007 • ZK-93426

Dopamine D1 receptor agonists

A-77636 • Dihydrexidine • Dinapsoline • Doxanthrine • SKF-81297 • 6-Br-APB

α7 nicotinic agonists / PAMs

AR-R17779 • PNU-282,987 • SSR-180,711

Prolyl endopeptidase inhibitors

S-17092

Alpha-adrenergic agonists

Clonidine • Guanfacine

Other psychostimulants and nootropics

Acetylcarnitine • Adafenoxate • Bifemelane • Carbenoxolone • Citicoline • Cyprodenate • Ensaculin •
Idebenone • Ispronicline • Deanol • Dimebon • Fipexide • Leteprinim • Linopirdine • Meclofenoxate •
Nizofenone • P7C3 • Pirisudanol • Pyritinol • Rubidium • Sulbutiamine • Taltirelin •
Tricyanoaminopropene • Vinpocetine

M: PSO/PSI

mepr
dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)

[hide]

v·

d·

Adenosinergics
Receptor ligands

Agonists

2-(1-Hexynyl)-N-methyladenosine • 2-Cl-IB-MECA • 2'-MeCCPA • 5'-N-ethylcarboxamidoadenosine •

ATL-146e • BAY 60–6583 • CCPA • CGS-21680 • CP-532,903 • GR 79236 • LUF-5835 • LUF-5845 • N6-
Cyclopentyladenosine • Regadenoson • SDZ WAG 994 • UK-432,097

Antagonists
8-Phenyl-1,3-dipropylxanthine • Acefylline • Aminophylline • Bamifylline • Caffeine • CGS-15943 • 8-
Chlorotheophylline • CPX • CVT-6883 • Dimethazan • DPCPX • Fenethylline • Istradefylline • KF-26777 •
MRE3008F20 • MRS-1220 • MRS-1334 • MRS-1706 • MRS-1754 • MRS-3777 • Paraxanthine •
Pentoxifylline • Preladenant • Propentofylline • PSB-10 • PSB-11 • PSB 36 • PSB-603 • PSB-788 • PSB-
1115 • Rolofylline • SCH-442,416 • SCH-58261 • Theobromine • Theophylline • VUF-5574 • ZM-241,385

Reuptake inhibitors

Plasmalemmal

ENT inhibitors
Dilazep • Dipyridamole • Hexobendine • Pentoxifylline • Propentofylline

Vesicular

VNT inhibitors

What is caffeine?
There are few people who are not aware of the stimulating effect that caffeine provides. We have a
choice and choose caffeinated beverages for a reason. Caffeine is considered the most commonly used
psychoactive drug in the world. Approximately 90% of adults consume it on a daily basis, and research is
being done on its health benefits and consequences.

We may love our caffeine, but what exactly is it? Caffeine is the common name for 1,3,7-
trimethylxanthine. When purified, caffeine produces an intensely bitter white powder that provides a
distinctive taste in soft drinks. The word "caffeine" came from the German word kaffee and the French
word café, each meaning coffee. After ingesting caffeine, it is completely absorbed within 30 to 45
minutes, and its effects substantially diminish within about three hours. It is eventually excreted so
there is no accumulation in the body. Caffeine has been shown to affect mood, stamina, the cerebral
vascular system, and gastric and colonic activity. But caffeine may not be for everyone. This article will
discuss the health benefits and consequences of caffeine.

What are the sources of caffeine?

Caffeine is naturally found in certain leaves, beans, and fruits of over 60 plants worldwide. Its bitterness
acts as a deterrent to pests. The most common sources in our diet are coffee, tea leaves, cocoa beans,
cola, and energy drinks. Caffeine can also be produced synthetically and added to food, beverages,
supplements, and medications. Product labels are required to list caffeine in the ingredients but are not
required to list the actual amounts of the substance.

The U.S. Food and Drug Administration (FDA) and the American Medical Association (AMA) classify a
"moderate intake" of caffeine as "generally recognized as safe." This means that if you consume a
moderate amount it is generally safe for the people on whom it has been studied. Most of these studies
have been done on adults. Here is the definition of what is considered low, moderate, high, and heavy
amounts of caffeine intake:

a low to moderate intake is 130 mg-300 mg per day

a moderate is 200 mg-300 mg per day

high doses are above 400 mg per day

heavy caffeine consumption is more than 6,000 mg/day.

It is estimated that the average daily caffeine consumption among Americans is about 280 mg/day,
while 20%-30% consume more than 600 mg daily. The top three sources of caffeine in adults are coffee
(70%), soda (16%), and tea (12%).

One mistake that people make is assuming that decaffeinated means that there is no caffeine in the
food or beverage. Decaffeinating happens through a process. According to the site [Link],
decaffeinating coffee usually consists of soaking the beans in water to dissolve the caffeine, extracting
the caffeine with a solvent or activated carbon, and then re-soaking the beans in the decaffeinated
water to reabsorb the flavor compounds that were lost in the initial extract. A study published by the
Journal of Analytical Toxicology found that nine out of 10 tested cups of decaf coffee from coffee from
shops and restaurants contained 8.6 mg-13.9 mg of caffeine. It also found that decaffeinated espresso
shots contained 3 mg-16 mg of caffeine per shot. Another study done by Consumer Reports tested 36
cups of small decaf coffees from six locations. They found that more than half had less than 5 mg of
caffeine while the rest had a range from 20 mg-32 mg per cup. Depending on how much you consume in
a day, you can end up consuming more caffeine from decaffeinated drinks than you would in one cup of
coffee.

There is no way to know for sure exactly how much caffeine you consume so it's a good idea to put a
limit on the total amount caffeinated and decaffeinated products that you consume. You can also
choose products with lower caffeine contents. You won't find the content on the food labels, so refer to
this chart. Make sure that you check the serving size on the can, bottle, or cup and do the math based
on the serving size provided here:
Sources of caffeine

Caffeine content

Coffee

Plain, brewed 8 oz

135 mg (range 102-200)

Instant 8 oz
95 mg (range 27-173)

Espresso 1 oz

40 mg (range 30-90)

Plain, decaffeinated 8 oz

5 mg (range 3-12)

Tea

Tea, brewed
53 mg (range 40-120)

Green tea 8 oz

25-40 mg

Black tea 8 oz

40-70 mg

Soft drinks

Barq's Root Beer

22 mg
Coca-Cola Classic 12 oz

35 mg

Diet Coke 12 oz

47 mg

Dr. Pepper 12 oz

42 mg

Dr. Pepper, diet 12 oz

44 mg
Jolt Cola 12 oz

72 mg

Mountain Dew, regular or diet 12 oz

54 mg

Mountain Dew, MDX, regular or diet 12 oz

71 mg

Pepsi-Cola 12 oz

38 mg
Pepsi, diet 12 oz

36 mg

Sunkist Orange 12 oz

42 mg

Tab 12 oz

46.5 mg

Vault 12 oz

71 mg
Energy drink

Full Throttle 16 oz

144 mg

Monster Energy 16 oz

160 mg

Red Bull 8.5 oz

80 mg

Rip It 8 oz
100 mg

SoBe No Fear 8 oz

130 mg

Spike Shooter 8.4 oz

300 mg

Chocolate, candies, other

Candy, milk chocolate 1 bar (1.5 oz)

9 mg

Candy, sweet chocolate 1 bar (1.45 oz)

27 mg

Cocoa mix, powder 3 tsp

5 mg

Hershey's Special Dark Chocolate Bar 1.45 oz

31 mg

Hot cocoa 8 oz

9 mg (range 3-13 mg)

Jolt caffeinated gum 1 stick

33 mg

Puddings, chocolate, ready to eat 4 oz

9 mg

Frozen desserts

Ben & Jerry's Coffee Heath Bar Crunch 8 oz

84 mg
Ben & Jerry's Coffee Flavored ice cream 8 oz

68 mg

Häagen-Dazs Coffee ice cream 8 oz

58 mg

Häagen-Dazs Coffee frozen yogurt 8 oz

58 mg

Medicine: over the counter

Excedrin Extra Strength 1 tablet

65 mg

Bayer Select Maximum Strength

65.4 mg

Midol Menstrual Maximum Strength

60 mg

NoDoz Maximum Strength 1 tablet

200 mg
Pain Reliever Tablets

65 mg

Vivarin 1 tablet

200 mg