Caffeine is a bitter, white crystalline
xanthine alkaloid that is a
psychoactive stimulant drug. Caffeine was
discovered by a German chemist,
Friedrich Ferdinand Runge, in
1819. He coined the term
kaffein, a chemical compound in
coffee, which in English became
caffeine. Caffeine is also part of the chemical mixtures
and insoluble complexes
guaranine found in
guarana,
mateine found in
mate, and
theine
found in non-herbal
tea; all of which contain
additional
alkaloids such as the
cardiac stimulants
theophylline and
theobromine, and often other chemicals such as
polyphenols which can form
insoluble complexes with caffeine.
Caffeine is found in varying quantities in the
beans,
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
cherries 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 mate,
guarana berries, and the
Yaupon Holly.
In humans, caffeine is a
central
nervous system (CNS)
stimulant, having
the effect of temporarily warding off
drowsiness and restoring alertness. Beverages
containing caffeine, such as
coffee,
tea,
soft drinks, and
energy drinks enjoy great popularity. Caffeine
is the world's most widely consumed
psychoactive substance, but unlike
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 Administration
lists caffeine as a "multiple purpose
generally recognized as safe
food substance".
Caffeine has
diuretic 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
Roasted coffee beans, a common source
of caffeine
Caffeine is found in many
plant species, where
it acts as a natural
pesticide, with high
caffeine levels being reported in seedlings that are still
developing foliages, but are lacking mechanical protection;
caffeine
paralyzes and kills certain
insects 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
coffee,
tea, and to a lesser
extent
cacao. Less commonly used sources of
caffeine include the
yerba maté and
guarana 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
achiral molecule, and therefore has no
enantiomers; 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
xanthine alkaloids, including the
cardiac stimulants
theophylline and
theobromine 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 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;
even beans within a given bush can show variations in
concentration. In general, one serving of coffee ranges from 40
milligrams, for a single shot (30 milliliters) of
arabica-variety
espresso, to about
100 milligrams for a cup (120 milliliters) of drip coffee.
Generally, dark-roast coffee has less caffeine than lighter roasts
because the roasting process reduces the bean's caffeine content.
Arabica coffee normally
contains less caffeine than the
robusta variety. Coffee also
contains trace amounts of
theophylline,
but no
theobromine.
Tea 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
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.
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.
Chocolate derived from
cocoa contains a small amount of caffeine. The weak
stimulant effect of chocolate may be due to a combination of
theobromine and
theophylline as well as caffeine. 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
shampoo and
soap, 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
A coffeehouse in Palestine, circa
1900
- Main articles: History of
cocoa, History of coffee,
Origin and history of
tea
Humans have consumed caffeine since the
Stone
Age. 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 China Shennong, reputed to have reigned in about 3000 BC,
accidentally discovered that when some leaves fell into boiling
water, a fragrant and restorative
drink resulted. Shennong is also mentioned
in Lu Yu's
Cha Jing, a famous
early work on the subject of tea.The history of coffee has been
recorded as far back as the ninth century.
During that time,
coffee beans were available only in their native habitat, Ethiopia
. A
popular legend traces its discovery to a
goatherder named
Kaldi, who
apparently observed goats that became elated and sleepless at night
after 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
Persian physician
al-Razi. In 1587,
Malaye
Jaziri 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
Sheikh, Jamal-al-Din al-Dhabhani, mufti of Aden
, was the
first to adopt the use of coffee in 1454, and that in the 15th
century the Sufis of Yemen
routinely
used coffee to stay awake during prayers.
Towards
the close of the 16th century, the use of coffee was recorded by a
European resident in Egypt
, and about
this time it came into general use in the Near
East. The appreciation of coffee as a beverage in
Europe, where it was first known as "Arabian wine," dates from the
17th century. A legend states that after the Ottoman Turks
retreated from the walls of Vienna after losing a battle for the
city, many sacks of coffee beans were found among their baggage.
Europeans didn't know what to do with all the coffee beans, being
unfamiliar with them. So Franz George Kolschitzky, a Pole who had
actually worked for the Turks, offered to take them. He
subsequently taught the Viennese how to make coffee, and the first
coffee house in the Western world was opened in Vienna, thus
starting a long tradition of coffee appreciation.
In Britain, the first
coffee houses were opened in London
in 1652, at
St Michael's Alley, Cornhill
. They
soon became popular throughout
Western
Europe, and played a significant role in
social relations in the 17th and 18th
centuries.
The
kola nut, like the coffee berry and tea
leaf, appears to have ancient origins. It is chewed in many
West African cultures, individually or
in a social setting, to restore vitality and ease hunger pangs.
In 1911,
kola became the focus of one of the earliest documented health
scares when the US government seized 40 barrels and 20 kegs of
Coca-Cola syrup in Chattanooga
, Tennessee
, alleging that the caffeine in its drink was
"injurious to health". On March 13, 1911, the government
initiated
The United
States v. Forty
Barrels and Twenty Kegs of Coca-Cola, hoping to force
Coca-Cola to remove caffeine from its formula by making claims,
such as that the excessive use of Coca-Cola at one girls' school
led to "wild nocturnal freaks, violations of college rules and
female proprieties, and even immoralities." Although the judge
ruled in favor of Coca-Cola, two bills were introduced to the
U.S. House of
Representatives in 1912 to amend the
Pure Food and Drug Act, adding
caffeine to the list of "habit-forming" and "deleterious"
substances which must be listed on a product's label.
The earliest evidence of
cocoa use comes from
residue found in an
ancient Mayan
pot dated to 600 BC. In the New World, chocolate was consumed in a
bitter and spicy drink called
xocoatl, often seasoned with
vanilla,
chile
pepper, and
achiote. Xocoatl was
believed to fight fatigue, a belief that is probably attributable
to the
theobromine and caffeine content.
Chocolate was an important luxury good throughout
pre-Columbian Mesoamerica, and cocoa beans were often used as
currency.
Xocoatl was introduced to
Europe by the
Spaniards and became a popular
beverage by 1700.
They also introduced the cacao tree into the West Indies
and the Philippines
. It was used in
alchemical processes, where it was known as Black
Bean.
The leaves and stems of the
Yaupon
Holly were used by
Native Americans to brew
a
tea called
Asi or
the
Black Drink 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 German
chemist
Friedrich Ferdinand Runge
isolated relatively pure caffeine for the first time.
According to Runge, he did this at the behest of
Johann Wolfgang von Goethe. In
1827, Oudry isolated "theine" from tea, but it was later proved by
Mulder 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 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.The nitrogen atoms are all
essentially planar (in sp
2 orbital hybridization), resulting in
the caffeine molecule having
aromatic
character.Being readily available as a byproduct of decaffeination,
caffeine is not usually
synthesized. If desired, it may be
synthesized from
dimethylurea and
malonic acid.
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 system 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
apnea 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
[[Image:Caffeine metabolites.svg|thumb|right|350px|Caffeine is
metabolized in the liver into three primary metabolites:
paraxanthine (84%),
theobromine (12%), and
theophylline (4%)|alt=A diagram featuring 4
skeletal chemical formulas. Top (caffeine) relates to similar
compounds paraxanthine, theobromine and theophylline.]]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 kinetics. 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-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. 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 disease, 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.
Fluvoxamine reduced the
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
liver by the
cytochrome P450 oxidase
enzyme system (specifically, the
1A2 isozyme)
into three
metabolic dimethylxanthines, which each have their own
effects on the body:
Each of these metabolites is further metabolized and then excreted
in the urine.
Mechanism of action
Caffeine 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
antagonist of
adenosine receptors. The caffeine
molecule is structurally similar to
adenosine, and binds to adenosine receptors on the
surface of cells without activating them (an "antagonist" mechanism
of action). Therefore, caffeine acts as a
competitive inhibitor.
Adenosine is found in every part of the body, because it plays a
role in the fundamental
ATP-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
anoxia and
ischemia. 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
dopamine 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
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
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-phosphodiesterase (cAMP-PDE), which
converts
cyclic AMP
(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
epinephrine and epinephrine-like
drugs such as
amphetamine,
methamphetamine, or
methylphenidate. Increased concentrations of
cAMP in
parietal cells causes an
increased activation of
protein kinase A (PKA) which
in turn increases activation of
H+/K+ ATPase, resulting finally in
increased
gastric acid secretion by the
cell. Cyclic AMP also increases the activity of the
funny current, which directly increases heart
rate. Caffeine is also a structural analogue of
strychnine and like it (though much less potent)
a competitive antagonist at ionotropic
glycine receptors.
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
efficiency.
Effects when taken in moderation
Overview of the more common side
effects of caffeine, possibly appearing even at levels below
overdose.
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
ergogenic, 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 citrate has proven to be
of short and long term benefit in treating the breathing disorders
of
apnea of prematurity and
bronchopulmonary dysplasia in
premature 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
muscles and thus should be avoided by those with
fecal incontinence.
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
spiders.
Tolerance and withdrawal
Because caffeine is primarily an
antagonist of the central nervous
system's receptors for the
neurotransmitter adenosine, the bodies of individuals who regularly
consume caffeine adapt to the continual presence of the drug by
substantially increasing the number of
adenosine receptors in the central
nervous system. This increase in the number of the adenosine
receptors makes the body much more sensitive to adenosine, with two
primary consequences. 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
vasodilation, the increased
effects of adenosine due to caffeine withdrawal cause the blood
vessels of the head to dilate, leading to an excess of blood in the
head and causing a
headache and
nausea. Reduced
catecholamine activity may cause feelings of
fatigue and drowsiness. A
reduction in
serotonin levels when
caffeine use is stopped can cause anxiety, irritability, inability
to concentrate and diminished motivation to initiate or to complete
daily tasks; in extreme cases it may cause mild
depression. Together, these effects have
come to be known as a "crash".
Withdrawal 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.
Analgesics, such
as
aspirin, 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
ergotamine
in the treatment of
migraine and
cluster headaches as well as to overcome
the drowsiness caused by
antihistamines.
Overuse
In large amounts, and especially over extended periods of time,
caffeine can lead to a condition known as
caffeinism.
Caffeinism usually combines caffeine
dependency with a wide range of
unpleasant physical and mental conditions including
nervousness,
irritability,
anxiety,
tremulousness,
muscle twitching (
hyperreflexia),
insomnia,
headaches,
respiratory alkalosis, and
heart palpitations. Furthermore,
because caffeine increases the production of stomach acid, high
usage over time can lead to
peptic
ulcers, erosive
esophagitis, and
gastroesophageal reflux
disease.
There are four caffeine-induced psychiatric disorders recognized by
the
Diagnostic
and Statistical Manual of Mental Disorders, Fourth
Edition: caffeine intoxication, caffeine-induced anxiety
disorder,
caffeine-induced sleep
disorder, and caffeine-related disorder not otherwise specified
(NOS).
Caffeine intoxication
Main symptoms of 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 urination,
gastrointestinal disturbance,
muscle twitching, a rambling flow of
thought and speech, irritability,
irregular or
rapid
heart beat, and
psychomotor
agitation. In cases of much larger overdoses,
mania,
depression,
lapses in judgment,
disorientation,
disinhibition,
delusions,
hallucinations, and
psychosis may occur, and
rhabdomyolysis (breakdown of skeletal muscle
tissue) can be provoked.
In cases of extreme overdose, death can result. The median lethal
dose (
LD50) 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
fluvoxamine 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 fibrillation brought
about by effects of caffeine on the
cardiovascular system.
Treatment of severe caffeine intoxication is generally supportive,
providing treatment of the immediate symptoms, but if the patient
has very high serum levels of caffeine then
peritoneal dialysis,
hemodialysis, or
hemofiltration may be required.
Anxiety and sleep disorders
Two infrequently diagnosed caffeine-induced disorders that are
recognized by the
American Psychological
Association (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
disorder, an individual regularly ingests high doses of
caffeine sufficient to induce a significant disturbance in his or
her sleep, sufficiently severe to warrant clinical attention.
In some individuals, the large amounts of caffeine can induce
anxiety severe enough to necessitate
clinical attention. This caffeine-induced
anxiety disorder can take many forms, from
generalized anxiety to
panic attacks,
obsessive-compulsive symptoms, or even
phobic symptoms. Because this condition can
mimic organic mental disorders, such as
panic disorder,
generalized anxiety disorder,
bipolar disorder, or even
schizophrenia, a number of medical
professionals believe caffeine-intoxicated people are routinely
misdiagnosed and unnecessarily medicated when the treatment for
caffeine-induced psychosis would simply be to 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
theanine was shown to
greatly reduce this caffeine-induced anxiety.
Effects on memory and learning
Anhydrous caffeine
An array of studies found that caffeine could have
nootropic effects, inducing certain changes in
memory and learning.
Researchers have found that long-term consumption of low dose
caffeine slowed
hippocampus-dependent
learning and impaired long-term memory in mice. Caffeine
consumption for 4 weeks also significantly reduced hippocampal
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 vitro. The
dendritic spines (a part of the brain cell
used in forming connections between neurons) taken from the
hippocampus (a part of the brain
associated with memory) grew by 33% and new spines formed. After an
hour or two, however, these cells returned to their original
shape.
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 cortex, 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 tongue phenomenon. The study
allowed the researchers to suggest that caffeine could aid
short-term memory when the information to be recalled is related to
the current
train of thought, but
also to hypothesize that caffeine hinders short-term memory when
the train of thought is unrelated. 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
cAMP inside the cells (by
blocking the enzyme that degrades cAMP), mimicking the effects of
epinephrine (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
kinase). This has the overall effect of increasing the rate of
glycolysis and increases the amount of
ATP available for muscle
contraction and relaxation. According to one study, caffeine in the
form of coffee, significantly reduces the risk of
heart disease in epidemiological studies.
However, the protective effect was found only in participants who
were not severely
hypertensive (i.e.
patients that are not suffering from a very high blood pressure).
Furthermore, no significant protective effect was found in
participants aged less than 65 years or in
cerebrovascular disease mortality
for those aged equal or more than 65 years.
Effects on children
It is a common myth that caffeine causes stunted growth in children
but 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
Agency 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.
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 a good flavor.
Coffee manufacturers recover the caffeine and resell it for use in
soft drinks and over-the-counter
caffeine tablets.
Supercritical carbon dioxide extraction
Supercritical carbon
dioxide 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
atm. Under these
conditions, CO
2 is in a "
supercritical"
state: it has gaslike properties which allow
it to penetrate deep into the beans but also liquid-like properties
which dissolve 97–99% of the caffeine. The caffeine-laden
CO
2 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.
Extraction by organic solvents
Organic solvents such as
ethyl acetate
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 Adventists,
Church of God 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 Hindus
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
halal (lawful) to drink,
because all things are
halal (lawful)
except that which God has made
haraam (unlawful)'.
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