Sources of caffeine

Caffeine is a plant alkaloid, found in numerous plant varieties. The

most commonly used of which are coffee, tea, and to some extent
cocoa. Other, less commonly used, sources of caffeine include the
plants yerba mate and guaran, which are sometimes used in the
preparation of teas and, more recently, energy drinks. Two of caffeine's
alternative names, mateine and guaranine, are derived from the names
of these plants.

The world's primary source of caffeine is the bean of the coffee plant,
from which coffee is brewed. Caffeine content in coffee varies widely
depending on the variety of coffee bean and the method of preparation
used, but in general one serving of coffee ranges from about 40 mg for
a single shot of espresso to about 100 mg for strong drip coffee.
Generally, dark roast coffee has less caffeine than lighter roasts since
the roasting process reduces caffeine content of the bean.

Tea is another common source of caffeine in many cultures. Tea

generally contains somewhat less caffeine per serving than coffee,
usually about half as much, depending on the strength of the brew,
though certain types of tea, such as black and oolong, contain
somewhat more caffeine than most other teas.

Caffeine is also a common ingredient of soft drinks such as cola,

originally prepared from kola nuts. Soft drinks typically contain about
10 mg to 50 mg of caffeine per serving. By contrast, energy
drinks such as Red Bull contain as much as 80 mg of caffeine per
serving. The caffeine in these drinks originates either from the
ingredients used or is an additive derived from the product of
decaffeination or chemical synthesis.

Chocolate derived from cocoa is a weak stimulant, mostly due to its

content of theobromine and theophylline, but it also contains a small
amount of caffeine. [1]However, chocolate contains too little of these
compounds for a reasonable serving to create effects in humans that
are on par with coffee.

Finally, caffeine may also be purchased in most areas in the form of a

pill that containing from 50 mg to 200 mg. Caffeine pills are regulated
differently among various nations. For example, the European Union
requires that a warning be placed on the packaging of any food whose
caffeine exceeds 150 mg per litre. In many other countries, however,
caffeine is classified as a flavouring and is unregulated.

affeine molecule

affeine equivalents

In general, each of the following contains approximately 200 mg of

caffeine:

O ne 200 mg caffeine pill (in some countries these are 100 mg,
in the UK these are 50 mg)
O %4 1-fluid ounce shots of espresso from robusta beans (2 fluid
ounces (0,59 dl) total)
O %4 8-fluid ounce containers of regular coffee (16 fluid ounces
(4.73 dl) total)
O ive 8-fluid ounce cups of black tea (40 fluid ounces (1.18 l)
total)
O ive 12-fluid ounce cans of soda (60 fluid ounces total (1.77 l),
although these can vary widely in content)
O %en 8-fluid ounce cups of green tea (80 fluid ounces (2.36 l)
total)
O ne and a half pounds (0,68kg total) of milk chocolate
O ifty 8-fluid ounce cups of decaffeinated coffee (400 fluid ounces
(11.82 l) total)

istory of caffeine use

lthough tea has been consumed in China for thousands of years, the
first documented use of caffeine in a beverage for its pharmacological
effect was in the 15th century by the Sufis of Yemen, who used coffee
to stay awake during prayers. In the 16th century there were coffee
houses in Istanbul, Cairo and Mecca, and in the 17th century coffee
houses opened for the first time in Europe.

In 1819, relatively pure caffeine was isolated for the first time by the
German chemist Friedrich Ferdinand Runge. ccording to the legend,
he did this at the instigation of Johann Wolfgang von Goethe (Weinberg
& Bealer 2001).

affeine has a significant effect on spiders,

as you can see in the pictures above

ffects of caffeine

Caffeine is a central nervous system stimulant, and is used both

recreationally and medically to restore mental alertness when unusual
weakness or drowsiness occurs. It is important to note, however, that
caffeine cannot replace sleep, and should be used only occasionally as
an alertness aid.

Caffeine is sometimes administered in combination with medicines to

increase their effectiveness, such as with ergotamine in the treatment
of migraine and cluster headaches, or with certain pain relievers such
as aspirin or acetaminophen. Caffeine may also be used to overcome
the drowsiness caused by antihistamines. Breathing problems (apnea)
in premature infants are sometimes treated with citrated caffeine,
which is available only by prescription in many countries.

While relatively safe for humans, caffeine is considerably more toxic to

some other animals such as dogs, horses and parrots due to a much
poorer ability to metabolize this compound. Caffeine has a much more
significant effect on spiders, for example, than most other drugs do.

affeine metabolism

Caffeine is completely absorbed by the stomach and small intestine

within 45 minutes of ingestion. It is widely distributed in total body
water and is eliminated by apparent first-order kinetics that can be
described by a one-compartment open-model system. Continued
consumption of caffeine can lead to tolerance. Upon withdrawal, the
body becomes oversensitive to adenosine, causing the blood pressure
to drop dramatically, which causes headaches and other symptoms.

Caffeine is metabolized in the liver by the cytochrome P450 oxidase

enzyme system into three metabolic dimethylxanthines, which each
have their own effects on the body:
O Paraxanthine (84%) - Has the effect of increasing lipolysis,
leading to elevated glycerol and free fatty acid levels in the
blood plasma.
O Theobromine (12%) - Dilates blood vessels and increases urine
volume. Theobromine is also the principal alkaloid in cocoa, and
therefore chocolate.
O Theophylline (4%) - Relaxes smooth muscles of the bronchi,
and is used to treat asthma. The therapeutic dose of
theophylline is many times greater than the levels achieved
from caffeine metabolism, however.
Each of these metabolites is further metabolised and then excreted in
the urine.

echanism of Action

The caffeine molecule is structurally similar to adenosine, and binds to

adenosine receptors on the surface of cells without activating them.
This effect, called competitive inhibition, interrupts a pathway that
normally serves to regulate nerve conduction by suppressing post-
synaptic potentials. The result is an increase in the levels of
epinephrine (adrenaline) and norepinephrine released from the
pituitary gland. Epinephrine, the natural endocrine response to a
perceived threat, stimulates the sympathetic nervous system, leading
to an increased heart rate, blood pressure and blood flow to muscles, a
decreased blood flow to the skin and inner organs and a release of
glucose by the liver. [2]

Caffeine also a known competitive inhibitor of the enzyme cMP-

phosphodiesterase (cMP-PDE), which converts cyclic MP (cMP) in
cells to its noncyclic form, allowing cMP to build up in cells. Cyclic MP
participates in the messenging cascade produced by cells in response to
stimulation by epinephrine, so by blocking its removal caffeine
intensifies and prolongs the effects of epinephrine and epinephrine-like
drugs such as amphetamine, methamphetamine, or methylphenidate.

The metabolites of caffeine contribute to caffeine's effects.

Theobromine, is a vasodilator that increases the amount of oxygen and
nutrient flow to the brain and muscles. Theophylline, the second of the
three primary metabolites, acts as a smooth muscle relaxant that
chiefly affects bronchioles and acts as a chronotrope and inotrope that
increases heart rate and efficiency. The third metabolic derivative,
paraxanthine, is responsible for an increase in the lipolysis process,
which releases glycerol and fatty acids into the blood to be used as a
source of fuel by the muscles (Dews et al. 1984).

With these effects, caffeine is an ergogenic, increasing the capacity for

mental or physical labor. study conducted in 1979 showed a 7%
increase in distance cycled over a period of two hours in subjects who
consumed caffeine compared to control tests (Ivy et al. 1979). 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 (Graham & Spriet
1991). The extensive boost shown in the runners is not an isolated
case; additional studies have reported similar effects. nother study
found 5.5 milligrams of caffeine per kilogram of body mass resulted in
subjects cycling 29% longer during high intensity circuits (Trice &
Hayes 1995).

affeine molecule

Side effects of caffeine

The minimum lethal dose of caffeines ever reported is 3,200 mg,

administered intravenously. The LD
50
of caffeine is estimated between
13 and 19 grams for oral administration for an average adult. The
LD
50
of caffeine is dependent on weight and individual sensitivity and
estimated to be about 150 to 200 mg per kg of body mass, roughly 140
to 180 cups of coffee for an average adult taken within a limited
timeframe that is dependent on half-life. The half-life, or time it takes
for the amount of caffeine in the blood to decrease by 50%, ranges
from 3.5 to 10 hours.

In adults the half-life is generally around 5 hours. However,

contraceptive pills increase this to around 12 hours, and, for women
over 3 months pregnant, it varies from 10 to 18 hours. In infants and
young children, the half-life may be longer than in adults. With
common coffee and a very rare half-life of 100 hours, it would require 3
cups of coffee every hour for 100 hours just to reach LD
50
. Though
achieving lethal dose with coffee would be exceptionally difficult, there
have been many reported deaths from intentional overdosing on
caffeine pills.

Too much caffeine, especially over an extended period of time, can lead
to a number of physical and mental conditions. The iagn48tic and
Stati8tical Manual 4f Mental i84rder8 4urth Editi4n (SM-IV) states:
"The 4 caffeine-induced psychiatric disorders include caffeine
int4icati4n, caffeine-induced aniety di84rder, caffeine-induced 8leep
di84rder, and caffeine-related di84rder n4t 4theri8e 8pecified (NS)."

n overdose of caffeine can result in a state termed caffeine

int4icati4n orcaffeine p4i84ning. Its symptoms are both physiological
and psychological. Symptoms of caffeine intoxication include:
restlessness, nervousness, excitement, insomnia, flushed face, diuresis,
muscle twitching, rambling flow of thought and speech, paranoia,
cardiac arrhythmia or tachycardia, and psychomotor agitation,
gastrointestinal complaints, increased blood pressure, rapid pulse,
vasoconstriction (tightening or constricting of superficial blood vessels)
sometimes resulting in cold hands or fingers, increased amounts of
fatty acids in the blood, and an increased production of gastric acid. In
extreme cases mania, depression, lapses in judgment, disorientation,
loss of social inhibition, delusions, hallucinations and psychosis may
occur. [3]

It is commonly assumed that only a small proportion of people exposed

to caffeine develop symptoms of caffeine intoxication. However,
because it mimics organic mental disorders, such as panic disorder,
generalized anxiety disorder, bipolar disorder, and schizophrenia, a
growing number of medical professionals believe caffeine-intoxicated
people are routinely misdiagnosed and unnecessarily medicated.
Shannon et al (1998) point out that:

"Caffeine-induced psychosis, whether it be delirium, manic

depression, schizophrenia, or merely an anxiety syndrome, in
most cases will be hard to differentiate from other organic or
non-organic psychoses....The treatment for caffeine-induced
psychosis is to withhold further caffeine." study in theriti8h
J4urnal 4f Addicti4n declared that "although infrequently
diagnosed, caffeinism is thought to afflict as many as one
person in ten of the population" (JE James and KP Stirling,
1983).

Because caffeine increases the production of stomach acid, high usage

over time can lead to peptic ulcers, erosive esophagitis, and
gastroesophageal reflux disease.
[citati4n needed]
Furthermore, it can also
lead to nervousness, irritability, anxiety, tremulousness, muscle
twitching, insomnia, heart palpitations and hyperreflexia. [4]

ithdrawal

Individuals who consume caffeine regularly develop a reduction in

sensitivity to caffeine; when such individuals reduce their caffeine
intake, their body becomes oversensitive to adenosine, with the result
that blood pressure drops dramatically, leading to an excess of blood in
the head (though not necessarily on the brain), causing a headache.
Other symptoms may include nausea, fatigue, drowsiness, anxiety and
irritability; in extreme cases symptoms may include depression,
inability to concentrate and diminished motivation to initiate or to
complete daily tasks at home or at work.

Withdrawal symptoms may appear within 12 to 24 hours after

discontinuation of caffeine intake, peak at roughly 48 hours, and
usually lasts from one to five days. nalgesics, such as aspirin, can
relieve the pain symptoms, as can a small dose of caffeine.

ffects on fetuses and newborn children

There is some evidence that caffeine may be dangerous for fetuses and
newborn children. In animal studies, caffeine intake during pregnancy
has been demonstrated to have teratogenic effects and increase the
risk of learning problems and hyperactivity in rats and mice,
respectively. The applicability of these results to human infants is
disputed since the concentrations involved were high and rodents are
more susceptible to most mutagens. In a 1985 study conducted by
scientists of Carleton University, Canada, children born by mothers who
had consumed more than 300 mg/d caffeine (about 3 cups of coffee or
6 cups of tea) were found to have, on the average, lower birth weight
and head circumference than the children of mothers who had
consumed little or no caffeine. In addition, use of large amounts of
caffeine by the mother during pregnancy may cause problems with the
heart rhythm of the fetus. For these reasons, some doctors recommend
that women largely discontinue caffeine consumption during pregnancy
and possibly also after birth until the newborn child is weaned.

The negative effects of caffeine on the developing fetus can be

attributed to the ability of caffeine to inhibit two DN damage response
proteins known as taxia-Telangeictasia Mutated (TM) or TM-Rad50
Related (TR). These proteins control much of the cells ability to stop
cell cycle in the presence of DN damage, such as DN single/double
strand breaks and nucleotide dimerization. DN damage can occur
relatively frequently in actively dividing cells, such as those in the
developing fetus. Caffeine is used in laboratory setting as an inhibitor
to these proteins and it has been shown in a study by Lawson et al. in
2004, that women who use caffeine during pregnancy have a higher
likelyhood of miscarriage than those who do not. Since the dosage rate
of self-administration is difficult to control and the effects of caffeine on
the fetus are related to random occurrence (DN damage), a minimal
toxic dose to the fetus has yet to be established.

%he dangers of caffeine pills

Caffeine pills are often used by college students and shift workers as a
convenient way to fight sleep, and are often considered harmless.
However, like any medication, caffeine can be harmful or deadly in
sufficient quantities. Due to the amount of caffeine present in standard
pills, it is possible to consume a dangerous amount of caffeine in this
form.

Periodically, caffeine pills come under media fire in connection with the
death of a college student due to a large overdose of caffeine. One
example is the death of a North Carolina student, Jason llen, who
swallowed most of a bottle of 90 such pills, the equivalent of about 250
cups of coffee. few other deaths by caffeine overdose have been
known, almost always in the case of massive pill consumption.[5]

Anhydrous (dry) USP grade affeine

traction of pure caffeine

It is very difficult to know the exact amount of caffeine in a particular

drink that is not automatically prepared. The amount of caffeine in a
single serving of coffee varies considerably due to many variables.
Concentration can vary from bean to bean within a given bush;
preparation of the raw bean will affect concentration, as well as
multiple variables involved in brewing.

Extracting caffeine takes some time, about two hours, and requires
chemicals unavailable for everyday use and equipment for distillation
and sublimation. To extract caffeine, one must mix the beverage one
wants to extract the caffeine from with a solvent possessing a high
affinity for caffeine and a different density. Chloroform is known to
possess both these properties, however industry prefers using the
much less toxic ethyl acetate.

Caffeine will migrate to the solvent in which it is most soluble, and it is

more soluble in chloroform than water. Using a separating funnel, one
should take about 30 ml of chloroform and 200 ml of the beverage
from which one wants to extract the caffeine and agitate for about two
minutes. The bottom phase will be the chloroform and the caffeine, so
one will keep this phase. Repeating this step about five times should
ensure extraction of most of the caffeine.

The next step is a distillation using a standard distillation column where

one gets rid of most of the chloroform. Finally, one has to sublimate
the remaining chloroform under vacuum. If the result is a fine white
powder, one's extraction has succeeded.