CAFFEINE JUMP TO:

Introduction

Chemical Information

Decaffeination

Caffeine in Food and Drink

Caffeine and Your Metabolism

Pregnancy and Caffeine

Deadly Dosage of Caffeine

Medicinal Uses

Side Effects of Caffeine

Mixing Caffeine with Other Substances

Introduction to Caffeine and Your Body

Caffeine as a CNS Stimulant

Caffeine and Neurotransmission

Caffeine’s Psychoactive Properties

Caffeine Dependency

Metabolism of Caffeine by the Body Part 2

INTRODUCTION TO CAFFEINE

85% of the United States population consumes a caffeinated

beverage daily, if not more (1) . The most common method of

consumption was through coffee with tea and soda not far behind for

citizens under the age of 18. While scientists have found that 400 mg

per day have no adverse health effects, high caffeine intakes have

been seen to correlate with “anxiety, headaches, nausea, and

restlessness.” Because of these, and many other factors, caffeine

has become the most researched “food component.” Its effects,

positive and negative, and uses are widespread (1).

CHEMICAL INFORMATION

Physical Properties-

Caffeine is a white powder with a very bitter taste in its most common

form (See Figure 2) . It can also be found as a group of “white

glistening needles (2).” Caffeine’s molecular weight is 194.2 g/mole.

The nitrogen and oxygen atoms are highly electronegative and

therefore attracts the hydrogen atom. This results in caffeine being

soluble in water as these hydrogen bonds can be created in six

places on the molecule (3). The melting point of caffeine is 235°C

and the boiling point is 178°C (4). No natural isomers of caffeine

exist. Isomers are molecules that have different molecular structures

but the same chemical formula. Caffeine has no stereoisomers as

there are no tetrahedral structures, with all different substituents,

preventing a chiral center (See Figure 1).

Figure 1-

The figure above is the 3D molecular structure of caffeine. The

model shows hydrogen atoms (white), Nitrogen atoms (blue), Carbon

atoms (green) and oxygen atoms (red) bonded together. All but one

of the nitrogen atoms are trigonal planar, meaning they have 3

substituents around the atom.

Figure 2-

The figure above shows Caffeine in its pure, extracted form. Caffeine

can be formed in this powdery substance or can be crystalized and

maintained both at room temperature.

The Intermolecular Forces - Intermolecular forces are the “various

forces of attraction that may exist between the atoms and molecules

of a substance (5).” The weakest of these forces are the London

Dispersion forces. London

Dispersion forces are the result of the constant motion of the

electrons in the atom or molecule. This force creates two types of

dipoles: an instantaneous dipole, when the electrons are distributed

asymmetrically, an induced dipole, a dipole which distorts the

electrons of a neighboring atom or molecule. The strongest force

occurring in the caffeine molecule is the Dipole-Dipole force. The

Dipole-Dipole attraction is the “electrostatic force between the

partially positive end of one polar molecule and the partially negative

end of another (5).” These charged ends of the molecules are

attracted to one another and, therefore, create the intermolecular

force that occurs between the molecules.

Polarity - We know caffeine is polar as polar molecules dissolve in

polar substances, and, as stated earlier, caffeine dissolves in the

polar molecule water. However, we also know that caffeine is polar

because of its structure. The Carbon atom have a weaker dipole then

the Nitrogen and Oxygen atoms. Therefore, they will move the

electrons toward the stronger bonds. Increasing electrons near the

Nitrogen and Oxygen molecules increases the negative charge

around these bonds and decreasing the negativity around the carbon

molecules. This results in the polar molecule caffeine.

DECAFFEINATION

Caffeine is a xanthine alkaloid that is mostly found in the leaves and

beans of the coffee tree, tea and cocoa. Caffeine can also be found

in yerba mate, guarana berries. the kola nut and the Yaupon holly

(6). Because caffeine is found in plants, to obtain pure caffeine it

must be extracted from the plants. This pure caffeine is artificially

placed in foods, drinks, and medication. Caffeine is an alkaloid,

meaning it is mostly made up nitrogen. There are multiple means

through which the extraction of caffeine can occur, the first method

being the solution method. The plant is processed to “obtain aqueous

solutions of the alkaloids.” The alkaloids are removed and the

solutions and the pure substance is extracted(7). The coffee beans

are steamed and soaked to remove the caffeine. The solvents most

commonly used for this process are ethyl acetate or methylene

chloride because they are more efficient and have a lower toxicity.

The next method, differs slightly from the first. The water process hot

water to soak the coffee beans. This water, now filled with coffee

flavor and caffeine molecules is passed through carbon filters to

collect the caffeine molecules. The water which passes through is

now caffeine free. This process is the most common for organic

coffee beans. This process is natural however it isn’t specifically

designed for caffeine therefore “it only removes 94 to 96 percent of

the caffeine (8).” Lastly, the least used method: The Supercritical

Carbon Dioxide Method. This method uses carbon dioxide under

high temperatures and pressures. This causes the CO2 to act like a

gas and a liquid. It goes into the beans as a gas but the “dissolves

[the] caffeine like a liquid.” Because it is exposed to the supercritical

CO2 for hours at a time, the decaffeinated CO2 evaporates and the

beans are left caffeinated with all the flavor intact (9) .

CAFFEINE IN FOOD AND DRINK

Originally, caffeine was only available in its organic form, plants that

contained the alkaloid. As science evolved, scientists found a way to

add caffeine to all types of food and drinks. Scientists have now

added this molecule to over 800 products for consumption (See

Table 1) . Caffeine is FDA regulated and does have a lethal dose;

however, the lethal doses of the most common sources of caffeine

would be difficult to reach without intention. To find just how much

caffeine is safe or even healthy in the most common products there

are calculators based on your weight and the content of caffeine.

Other factors can influence this amount. These factors include “ a

person’s tolerance, sensitivity, weight, age and health history (10) .”

(To find your lethal and safe doses by weight, visit this calculator.)

Table 1-

Product Caffeine Content

Brewed Coffee 163 mg

Baking Chocolate 23.2 mg

Excedrin Migraine 65mg

Lipton Tea 55mg

Coca-Cola 34mg

Red Bull 80mg

The table above was produced using Caffeine Informers lethal dose

calculator. The products were chosen as they make up the most

common products through which caffeine is consumed. 300-400 mg

is the average safe daily intake for healthy adults.

CAFFEINE AND YOUR METABOLISM

Caffeine metabolizes in the body due to the cytochrome P450

enzyme in the liver, where factors like genetics, diet and habits can

affect the activity of this enzyme and the half life of the caffeine itself.

When initially synthesizing the protein, a person’s genetic code

decides how much of the enzyme is made. Increased production of

this protein increases clearance of caffeine from a person’s system,

meaning the effects of caffeine do not last as long. Consumption of

grapefruit juice prolongs the half life of caffeine and decreases the

clearance of the substance, while consumption of foods high in

Vitamin C increase the clearance rate of caffeine from the body

through stimulation of the P450 enzyme. Finally, smoking doubles

the rate of clearance of caffeine in the body. Oral contraceptives,

namely birth control, nearly doubles the half-life of caffeine,

decreasing the effectiveness of the ‘buzz’ a person achieves while

consuming it. Pregnancy also affects the metabolism of caffeine, as

the P450 enzyme is less active in clearing the substance from the

body, particularly during the third trimester. The half life of caffeine

also increases, but metabolism of the substance will return to normal

a few weeks after delivery when bodily hormones and chemicals

level out [11].

PREGNANCY AND CAFFEINE: MOSTLY A NO-NO

Caffeine consumption is typically frowned upon when a woman

is pregnant. Associations between low birth weight (being defined as

a weight of less than 2,500 grams) and consumption of caffeine were

found, and that the risk of a baby having low birth weight increases

linearly as caffeine consumption increases [12]. Another study found

that increases of 100 milligrams per day of caffeine were associated

with a 13% higher risk of low birth weight [13]. Caffeine has structure

that is similar to that of the purine molecules in DNA, which has the

potential to affect cell division and metabolism, since the enzymes

necessary for the digestion of caffeine do not manifest until several

days after birth [25]. Other side effects of caffeine consumption

include an increased risks of birth defects and miscarriages [14,15].

Maybe just switch to decaf coffee and lay off the Red Bulls if you’re

expecting.

DEADLY DOSAGE OF CAFFEINE

Finals got you down? Be careful with the amount of caffeine

you ingest. Caffeine overdose is rare, as your body will stop you from

eating or drinking the amount of food or drink that it would take to

reach the deadly level. However, if taking solid caffeine, in the form

of powder or pill, overdosing is very possible. A lethal dose of

caffeine is considered to be around 10 grams (which varies from

person to person) according to healthline.com [16], but according to

the Material Safety Data Sheet (MSDS) for

caffeine, the lethal dose for 50% of the test

group (LD50) of caffeine is considered to be

194 milligrams for every kilogram weighed

[15]. The typical way of death by caffeine is when cardiac arrest

occurs from overconsumption [17], as caffeine increases heart rate,

increases blood pressure, and affects the flow of blood, which all

lead to cardiac related problems.

MEDICINAL USES

Caffeine is used in conjunction with painkillers like aspirin or

acetaminophen to treat headaches and migraines. During a

migraine, blood vessels in the brain enlarge. Caffeine counteracts

this, as it contains vasoconstrictive properties. When used in

conjunction with painkillers, it increases the effectiveness of the

medication [18]. Caffeine is also a diuretic,

though not enough research has been done to

fully explain its mechanisms. It is postulated that

caffeine blocks the reabsorption of sodium in the

kidneys and that it increases the filtration rate in

the kidneys by contradicting the instated vasoconstriction [19].

Caffeine is also used in premature babies who suffer from apnea, or

the cessation of breathing for longer than 15 seconds. This treatment

reduced the episodes for shortness of breath in infants [20,21].

Caffeine can also be used to treat asthma, exhaustion, and other

types of pain. It is also effective for reducing the risk of developing

Parkinson’s disease, gallbladder disease, and type 2 diabetes.

SIDE EFFECTS OF CAFFEINE

Consumption of caffeine can cause pupil dilation, increase in

rate of breathing, increased heart rate, constriction of blood vessels

which causes a decrease of blood flow to cuts and increases the flow

of blood to muscles, increased blood pressure, decreased blood flow

to stomach which causes slower digestion, a release of sugar from

the liver causing an increase in energy, and tightening of muscles

[22].

MIXING CAFFEINE WITH OTHER SUBSTANCES

When mixing caffeine with alcohol, caffeine masks the

depressant effects of the alcohol, causing the consumer to feel more

alert than they actually are and the consumer may consume more

alcohol and increase impairment as a result. The effects of mixing

caffeine and alcohol are not completely understood.

However, it is known that both alcohol and caffeine

interact with adenosine neurotransmission, and interfere

with one another [26]. Caffeine does not actually sober you up when

consumed (sorry to disappoint) [23].

Mixing caffeine and marijuana actually increases the

effectiveness of the drug, as both THC, also known as

Tetrahydrocannabinol, and caffeine release dopamine in the brain.

Though this may sound like a good, hold your stoner horses.

Caffeine also increases the risk of addiction to weed when the

substances are combined, or rather increases the risk of being

addicted to the feeling of being high [24].

INTRODUCTION TO CAFFEINE AND YOUR BODY

Caffeine is found in a massive variety of everyday products,

including coffee, soda, chocolate, and even medications, such as for

headache relief. Because of the ubiquity of caffeine-containing

products in our society, it is important to understand how these

myriad products use the effects of caffeine on our bodies to bring

about their intended results.

CAFFEINE AS A CNS STIMULANT

Caffeine is a central nervous system (CNS) stimulant, meaning

that it increases activity of the CNS [28][29]. This stimulation

manifests itself in the form of heightened alertness, elevated heart

rate, and increased blood pressure, among other physiological side

effects. These effects are what most people experience after having

a few cups of coffee or soda. Although most people know what kinds

of effects caffeine has on the body, fewer know how caffeine causes

these physiological changes.

To understand how caffeine specifically stimulates the CNS,

one must first understand the basis of the nervous system. Nerve

cells, called neurons, are comprised of several key regions: cell body

(A.K.A. soma), dendrites, axon, and axon terminals. The cell body

houses the nucleus and other organelles important for the neuron’s

survival. The dendrites are branched protrusions from the cell body

that connect the cell body of one neuron to the axon terminals of

another neuron. The axon is a long, slender structure along which

an action potential is transmitted from the cell body to the axon

terminals. An action potential is essentially just an electrochemical

potential that can move from one neuron to another along axons,

chiefly used to transmit information across the whole body. The

axon terminals are structurally similar to dendrites in that they are

branched protrusions that connect neurons. However, axon

terminals have an especially important function: They release

neurotransmitters packaged in vesicles—small, membrane-bound

sacs—into the synaptic cleft, a small space between one neuron’s

axon terminals and another’s dendrites. The neurotransmitters are

then absorbed by the dendrites of the next neuron, which triggers the

start of an action potential down the next neuron’s axon, and so forth.

This basic system is how the nervous system acts as a line of

communication throughout the entire body using electrochemical

messages in the form of neurotransmitters.

CAFFEINE AND NEUROTRANSMISSION

With caffeine, specifically, the release of antagonists, which are

substances that bind to a receptor and block agonistic binding or

activation, to A1 and A2A adenosine receptors is triggered as it is

digested and absorbed, which promotes the neurotransmitter release

of acetylcholine [30]. This antagonism with adenosine is responsible

for the wakefulness experienced after consumption of caffeine, as it

stops adenosine from binding to its receptors, which typically causes

sleepiness as a part of one’s normal circadian rhythm

[31]. Additionally, the release of acetylcholine causes stimulation of

neuromuscular junctions, which can cause those who consume

caffeine to feel jittery or hyperactive. Thus, the primary effect of

caffeine consumption with which most people are very familiar has

an interesting biochemical and physiological reason behind it!

CAFFEINE’S PSYCHOACTIVE PROPERTIES

In addition to its properties as a CNS stimulant, caffeine is also

a psychoactive substance, meaning that it primarily affects the CNS

by changing brain function [32][33]. It has variable effects on a

person’s memory and ability to learn and can either improve or

decrease one’s capability to retain information. Due to its properties

as a stimulant, caffeine can contribute to significantly augmented

concentration, coordination, dexterity, and reaction time. These

changes in one’s alertness and wakefulness are why many people

will grab a cup of coffee every morning to help brush away any

lingering sleepiness. However, it is critical that more people

understand the potentially adverse effects that consumption of large

amounts of caffeine might have because of how widespread

caffeine-containing products are all around the world.

CAFFEINE DEPENDENCY

Caffeine, as a CNS stimulant, when used regularly can

produce a mild physical dependence in users. The development of

such a dependence happens because of chemical reactions in one’s

brain, known as the reward system. “When exposed to a rewarding

stimulus, the brain responds by increasing release of the

neurotransmitter dopamine” [34]. This influx of dopamine causes

positive, happy sensations in the person. Repeated use of stimuli

that activate the reward system can lead to psychological

dependence on said stimuli and even full-blown addiction if the

effects of the stimulus is potent enough. In the case of caffeine,

addiction is much less grave than for more addictive stimuli like

nicotine or opiates, although mild dependences are fairly common in

instances where people often consume caffeine, which can cause

the repeated release of dopamine to reinforce the positive

physiological effects of that stimulus. If a person who has built up a

dependence on caffeine goes without it for a long period of time, he

or she might experience headache, fatigue, anxiety, irritability,

depressed mood, or difficulty concentrating [35]. But because of the

relatively mild consequences of caffeine withdrawal, most experts

consider caffeine addiction to be not serious.

METABOLISM OF CAFFEINE BY THE BODY PART 2

Caffeine is metabolized exceptionally well by the human body,

with 99% of caffeine being absorbed within 45 minutes of

consumption [36]. Because of this very rapid metabolism, it takes

very large amounts of caffeine to be consumed before seriously

adverse effects come about, typically on the order of whole grams of

caffeine. Also because of the rapid metabolism of caffeine in the

body, its effects as a CNS stimulant are fairly immediate. This is

easily observable when a person who is feeling groggy after just

having woken up drinks a cup of coffee and quickly perks up, ready

for the coming day.

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