caffeine is the most widely used central nervous system (CNS) stimulant in the
world. It has numerous pharmacological and physiological effects, including
cardiovascular, respiratory, renal, and smooth muscle effects, as well as effects on
mood, memory, alertness, and physical and cognitive performance .
Caffeine definitely should be considered in developing performance-enhancing
rations or ration components. Caffeine is safe as a component of food at doses
required to overcome sleep deprivation. It appears that doses of 300–600 mg/70
kg person will achieve the desired stimulus in those nonhabituated to caffeine;
additional research needs to be conducted to determine the effects of this level of
caffeine in those with higher habitual intakes. (IOM, 1994, p. 50). Caffeine (1,3,7-
trimethylxanthine) and the related methylxanthines, theobromine (3,7-
dimethylxanthine) and theophylline (1,3-dimethylxanthine), are widely
distributed in plants throughout the world.
TABLE 1–1Caffeine Content of Some Common U.S. Food Products
Item Average (mg) Range (mg)
Coffee (5-oz cup) a
Brewed, drip method 120 90–150
Percolated 90 64–124
Instant 75 30–120
Decaffeinated 3 1–5
Espresso (6-oz cup) 240 180–300
Teas (loose or bags, 5-oz cup) a
Item Average (mg) Range (mg)
1-minute brew 21 9–33
3-minute brew 33 20–46
Tea products
Instant (5-oz cup) 20 12–28
Iced (12-oz glass) 29 22–36
Carbonated beverages 24 20–40
Colas and pepper drinks (12 oz)
National brands, packaged 42 36–48
National brands, fountain 39 32–48
Store brands, packaged 18 5–29
Citrus drinks (12 oz)
National brands, packaged 52 43–56
Store brands, packaged 38 26–52
Chocolate products
Cocoa beverage (8 oz) 6 3–32
Item Average (mg) Range (mg)
Chocolate milk beverage (8 oz) 5 2–7
Milk chocolate (1 oz) 6 1–15
Dark chocolate, semisweet (1 20 5–35
oz)
Baker's chocolate (1 oz) 35 35
Chocolate-flavored syrup (1 oz) 4 4
The amount of caffeine in commonly consumed beverages and other products
varies a great deal (Table 1–1), from as little as 5 mg/8 oz of chocolate milk, to as
much as 300 mg/6 oz of strong espresso coffee. The reported signs and symptoms
include nervousness, anxiety, insomnia, irregular heartbeats, excess stomach acid,
and heartburn.
Caffeine (1,3,7-trimethylxanthine) is a plant alkaloid with a chemical structure of
C8H10N4O2 and a molecular weight of 194.19. In pure form, it is a bitter white
powder. Structurally, caffeine (and the other methylxanthines) resembles the
purines. The mean half-life of caffeine in plasma of healthy individuals is about 5
hours. However, caffeine's elimination half-life may range between 1.5 and 9.5
hours, while the total plasma clearance rate for caffeine is estimated to be 0.078
L/h/kg (Brachtel and Richter, 1992; Busto et al., 1989).
This wide range in the plasma mean half-life of caffeine is due to both innate
individual variation, and a variety of physiological and environmental
characteristics that influence caffeine metabolism (e.g., pregnancy, obesity, use of
oral contraceptives, smoking, altitude).
The fatal acute oral dose of caffeine in humans is estimated to be 10–14 g (150–
200 mg/kg body weight [BW]) (Hodgman, 1998).
Caffeine is rapidly and completely absorbed in humans, with 99 percent being
absorbed within 45 minutes of ingestion. When it is consumed in beverages (most
commonly coffee, tea, or soft drinks) caffeine is absorbed rapidly from the
gastrointestinal tract and distributed throughout body water. More rapid
absorption can be achieved by chewing caffeine-containing gum or other
preparations that allow absorption through the oral mucosa.
Peak plasma concentrations occur between 15 and 120 minutes after oral
ingestion. This wide variation in time may be due to variation in gastric emptying
time and the presence of other dietary constituents, such as fiber. Caffeine
metabolism occurs primarily in the liver, catalyzed by hepatic microsomal enzyme
systems. It is metabolized in the liver to dimethylxanthines, uric acids, di- and
trimethylallantoin, and uracil derivatives. In humans 3-ethyl demethylation to
paraxanthine is the primary route of metabolism. This first metabolic step
accounts for approximately 75–80 percent of caffeine metabolism and involves
cytochrome P4501A2. Paraxanthine is the dominant metabolite in humans, rising
in plasma to concentrations 10 times those of theophylline or theobromine.
Caffeine is cleared more quickly than paraxanthine, so 8 to 10 hours after caffeine
ingestion, paraxanthine levels exceed caffeine levels in plasma
. The fact that the human body converts 70–80 percent of caffeine into
paraxanthine with no apparent toxic effects following caffeine doses of 300–500
mg/day suggests that paraxanthine's toxicological potency is low. Formation of
paraxanthine and its excretion in the urine appears to be the major pathway for
caffeine metabolism
Caffeine is primarily metabolised in the liver by cytochrome P450 enzymes, which
are responsible for more than 90% of caffeine clearance19. The enzyme
responsible for metabolism of caffeine is coded for by the gene CYP1A2.
The large variability of CYP1A2 activity influences the clearance of caffeine and
may be affected by factors such as gender, race, genetic polymorphisms, disease,
and exposure to inducers
However, a further study suggested that the daily consumption of at least 3 cups
of coffee increased CYP1A2 activity
FACTORS AFFECTING CAFFEINE METABOLISM
1. Caffeine metabolism is increased by smoking, an effect mediated by an
acceleration in its demethylation (it also increases xanthine oxidase activity)
2. Earlier studies suggested that elimination of caffeine may vary across the
menstrual cycle, with elimination being about 25 percent longer in the
luteal phase. Decreased paraxanthine or caffeine metabolic rates in healthy
postmenopausal women on estrogen replacement therapy suggest that
exogenous estrogen in older women may inhibit caffeine metabolism
through the P450 isozyme CYP1A2, an isozyme common to both estrogen
and caffeine [Link], it is known that oral contraceptive
use can double caffeine half-life
Diet
A number of dietary factors may also affect caffeine metabolism.
Grapefruit juice consumption decreases caffeine clearance by 23% and prolongs
half-life by 31%28,29.
Consumption of broccoli and brassica vegetables in general30 and absorption of
large quantities of vitamin C increase caffeine clearance31.
The flavonoid, quercetin, found widely in fruit and vegetables, affects the
metabolism of caffeine and paraxanthine and mainly decreases the urinary
excretion of the latter compound by 32%; it also changes the excretion of several
other Women’s health
During pregnancy, caffeine metabolism is reduced, particularly during the third
trimester33,34. This is associated with a reduction in the activity of the main
enzyme involved in caffeine metabolism, and a consequent increase in caffeine
half-life35. Caffeine metabolism returns to normal a few weeks after delivery 35.
The European Food Safety Authority (EFSA) advises that pregnant women limit
their caffeine intake to 200mg from all sources
Caffeine intakes
The ADORA2A genotype is associated with different amounts of caffeine intake.
Individuals with the ADORA2A 1976TT genotype are significantly more likely to
consume less caffeine44.
Since individual reactions to caffeine may differ according to genetic variability,
individuals tend to only consume the amount of caffeine they feel comfortable
with44.
The European Food Safety Authority (EFSA) advises that daily caffeine intakes of
up to 400mg and single doses of up to 200mg do not raise concerns when
consumed as part of a health balanced diet4. 400mg caffeine is equivalent to up
to 5 cups of coffee per day, as part of a healthy balanced diet and an active
lifestyle. EFSA recommends lower levels for pregnant women, who are advised to
limit caffeine intake to 200mg from all sources4.