**3.3 Caffeine Consumption:**

Definition of caffeine

Chemical composition of caffeine

Sources of caffeine and average consumption per capita

Pharmacological effects of caffeine

Symptoms, signs and performance effects of excessive caffeine
consumption

Recommendations on caffeine consumption

Caffeine, (trimethyl xanthine, an alkaloid), is a purine molecule
similar to theophylline and theobromine and, like these two agents,
provides noradrenergic stimulation to the central nervous system.
Caffeine is found in coffee beans, cola nuts, cocoa beans, tea leaves
and other plant structures. Theophylline occurs naturally in tea;
theobromine may be found in cocoa, cola nuts and tea. Over the
centuries, many cultures have used food and beverage products made from
these plants in an atmosphere of pleasurable socialization, and some
informal institutions have grown up around their use (i.e., coffee
houses, tea parties).

Coffee, a common source of caffeine, is easily available in the world of
aviation. As in the world of medicine, the irregular hours and
unpredictably changing schedules of fliers make caffeine a useful
stimulant. When an accurate assessment of caffeine intake is medically
indicated, the history of its consumption should be taken in more detail
than, "How many cups of coffee do you drink per day?" Almost any private
or commercial airport has coffee pots brewing somewhere, and pilots may
easily fill and refill their cups during pre-flight and post-flight
activities. In addition, many mid-size or large private aircraft and
essentially all commercial aircraft have coffee pots aboard, and even
the smallest private aircraft or helicopter will accommodate a thermos
filled with the brew. Thus, aviators (like physicians) sometimes cannot
accurately describe their caffeine intake, since they may sip it all day
rather than consuming a countable number of cups---and coffee cups
sometimes are larger than six ounces. To further complicate the matter,
people may prepare coffee in differing concentrations or may reheat pots
of the brew, further concentrating its caffeine content through
evaporation of water. One should also inquire about consumption of tea,
soft drinks and chocolate. Such irregular intake factors make it
difficult to ascertain the actual amount of caffeine and other dietary
xanthines absorbed on a daily basis.

A person's perception of the effects of caffeine may suggest excessive
consumption. In addition to its mental stimulation, caffeine may produce
tachycardia, increased blood pressure, gastrointestinal irritation, and
a feeling of "jitters" or even frank fine tremors that interfere with
delicate motor function and can be demonstrated in the physician's
office. (To amplify tremors, have the patient extend his/her arms with
the palms down, and place a sheet of paper on the back of one hand.
Tremors will be easily visible.) A history of withdrawal symptoms,
particularly a severe headache, following sudden deprivation of
accustomed coffee intake, may indicate a habitual intake of over 400 mg
of caffeine per day.

When ingested, caffeine is rapidly absorbed through the walls of the
stomach and small intestine, and disseminates widely through the body,
reaching its peak blood levels in about an hour. Its biological
half-life varies with many factors, including age, and may be as short
as three hours in children and teenagers, but seven hours or more in
older adults. Caffeine increases the production of urine (diuresis),
stimulates cardiac muscle, and relaxes smooth muscle. The liver uses
xanthine oxidase, a cytochrome P450 enzyme, in its metabolism of
xanthines. Such medications as allopurinol, acetaminophen (Tylenol®),
warfarin (Coumadin®), and omeprazole (Prilosec®) may influence this
process. These drugs may either increase or decrease caffeine's effects,
depending on the nature of the interactions. Nicotine will also induce
xanthine oxidase.

Aviators should avoid the social custom of using coffee to counteract
the acute effects---or after-effects---of alcohol consumption. Caffeine
may heighten the wakefulness of someone with a significant blood alcohol
level ("a wide-awake drunk"), but will not diminish the cognitive
impairment. The diuretic effect of caffeine taken to aid "morning-after'
symptoms may increase alcohol-induced dehydration. Occasionally the
combination of post-alcohol effects, hypoglycemia from not eating due to
nausea, fatigue due to sleep deprivation, and excessive coffee
consumption may induce cardiac arrhythmias such as atrial tachycardia,
the so-called "holiday heart" syndrome.

A six-ounce cup of caffeinated coffee contains about 100 mg of caffeine,
a six-ounce cup of tea about 30 mg, and a twelve-ounce soft drink about
50 mg; the exact amount varies between brands. "Decaffeinated" coffee
provides about 3 mg per cup. Milk chocolate contains xanthines
equivalent to about 6 mg of caffeine per ounce. Caffeine easily
penetrates the blood-brain barrier. Central nervous system (CNS) effects
include increased cortical activities such as cognition and vigilance,
and decreased reaction time to various stimuli. Caffeine does not
increase knowledge or innate intellectual abilities.

Doses of 200-300 mg will temporarily diminish the adverse effects of
sleep deprivation and induce wakefulness; one may easily achieve such
dosages under social conditions. Current concepts of caffeine metabolism
indicate that its actions derive from non-competitive inhibition of
adenosine receptors in neural networks. Brain metabolism furnishes
energy to its neurons through dephosphorylation of adenosine
triphosphate (ATP), a process leading to increasing levels of adenosine
in the CNS. Animal studies have demonstrated the association of
sleepiness with adenosine bonding to cell surface receptors in two
areas, the cholinergic basal forebrain and the mesopontine cholinergic
nuclei. Compounds such as xanthines that block these receptors increase
alertness. Researchers have identified four types of adenosine
receptors; one, the A1 receptor, appears to have the greatest
relationship to sleep. Although A1 agonists can induce sleep, they also
cause side effects by their effects upon A1 receptors elsewhere in the
CNS and in the cardiovascular system. Adenosine receptors are scattered
throughout the brain and body, a dispersion that may explain the various
systematic reactions to caffeine.

Over-the-counter (OTC) medications intended to treat upper respiratory
illness, 'flu' and allergies may contain 15 to 30 mg of caffeine per
dose. Many commercial headache remedies include 65 mg of caffeine in a
tablet also containing aspirin and/or acetaminophen (today's version of
the old military favorite, APC---aspirin, phenacetin and caffeine).
Stimulants such as NoDoz® and Vivarin® contain 100 and 200 mg
respectively. The makers of Dexatrim® have replaced the banished
phenolpropanolamine (PPA) with 200 mg of caffeine for appetite
suppression. Some anti-migraine prescription medications include
caffeine (i.e., the 100 mg in Cafergot®), and lesser amounts may be
found in such pain relief drugs as Esgic® (40 mg) and Norgesic® (30 mg).
More ominously, some illicit drugs represented as being stimulants
(amphetamines or cocaine) may be diluted with, or entirely composed of,
very large amounts of caffeine.

Caffeine fulfills some of the criteria for addiction: habituation,
tolerance and withdrawal symptoms. However, unlike other drugs of
dependence, chronic use of caffeine does not lead to steadily increasing
doses. Tolerance develops when a person habitually consumes more than
300 mg of caffeine per day, although high doses will continue to produce
nervousness, irritability, anxiety, tremulousness, muscle twitching,
insomnia, palpitations, and hyperreflexia. Those consuming more than
this amount, instead of continuing to be stimulated by its use,
experience a tolerance and withdrawal syndrome if they decrease or stop
their consumption. Also, in contrast to drugs of dependence, a motivated
individual may discontinue using caffeine with relatively minor
difficulty. Typical withdrawal symptoms include fatigue, drowsiness, and
decreased alertness and some, especially if prone to migraine or other
vascular headaches, may experience unrelenting headaches for several
days. Individuals wishing to cut down on the overuse of coffee may
usually avoid these symptoms by slowly tapering caffeine intake instead
of stopping suddenly ("cold turkey"). Overdose symptoms seldom occur
simply from drinking coffee, since the acute fatal dose is about 10
grams (i.e., 100 cups of coffee).

References:

Website of the Society for Neuroscience:
www.sfn.org/content/Publications/BrainBriefings/adenosine.html

Antunano MJ, Mohler SR. [Caffeine Can Pick You Up or Let You
Down]{.underline}. Flight Safety Foundation Human Factors and Aviation
Medicine Bulletin. 35(2), March, April 1988.

Klassen, C.D., Toxicology, 5th Edition, McGraw-Hill, New York, 1996.