Caffeine molecular structure
Caffeine, also known as coffeine, theine, mateine, guaranine, and methyltheobromine, is an alkaloid found naturally in such foods as coffee beans, tea, kola nuts, Yerba matÚ, guarana, and (in small amounts) cacao beans. It is added to some soft drinks such as colas, Irn-Bru and Mountain Dew.
Caffeine has a characteristically intense bitter taste. Its main pharmacological properties are: a stimulant action on the central nervous system with psychotropic effects and stimulation of respiration, a stimulation of the heart rate, and a mild diuretic effect. Caffeine consumption leads to pharmacologic tolerance with defined withdrawal symptoms.
Caffeine is an alkaloid of the methylxanthine family, which also includes the similar compounds theophylline and theobromine. In its pure state it is an intensely bitter white powder. Its chemical formula is C8H10N4O2, its systematic name is 1,3,7-trimethylxanthine or 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione, and its structure is shown above.
Pure caffeine occurs as odorless, white, fleecy masses, glistening needles or powder.
Boiling point: 178 ░C (sublimes)
- Melting point: 238 ░C
- Density: 1.2 g/cm³
- Volatility: 0.5%
Vapor pressure: 101 kPa @ 178 ░C
pH: 6.9 (1% solution)
- Solubility in water: 2.17%
- Vapor density: 6.7 g/m│
- Molecular weight: 194.19 g/mol
One common source of caffeine is the coffee plant, the beans from which are used to produce coffee.
One dose of caffeine is generally considered to be 100 mg. In theory, a single serving (5 fl oz / 150 ml) of drip coffee or one-half caffeine tablet would deliver this dose. In the real world, coffee varies considerably in caffeine content per serving, ranging from about 75 mg to 250 mg.
Tea is another common source of caffeine in many cultures. Black tea contains somewhat less caffeine per serving than coffee, (usually about half as much, depending on the strength of the brew), and green tea contains significantly less (usually about 10% as much, or 10mg / serving).
Soft drinks such as Cola are also common. Such drinks typically contain about 25 mg to 50 mg of caffeine per serving. Some "Energy drinks" such as Red Bull contain considerably more caffeine per serving, ranging from 100 to 400 mg.
Mateine and Guaranine are other names for caffeine. The names come from yerba matÚ and guarana respectively, caffeine-containing plants used for tea and other things. Many yerba mate enthusiasts insist that mateine is a stereoisomer of caffeine and thus a different substance altogether. However, this is impossible; caffeine is an achiral molecule with no chiral centers, and therefore has no stereoisomers. Similar claims are sometimes made of guaranine.
The amount of caffeine typically found in some common consumables is as follows:
Cocoa powder - 0.1% - 0.5%
Chocolate, bittersweet - 25 mg/oz (875 mg/kg)
Chocolate, milk - 3 to 6 mg/oz (100 to 210 mg/kg)
Cocoa - 0.5 mg/floz (17 mg/l)
Cocoa and chocolate contain larger amounts of the related but only weakly stimulating compounds theobromine and theophylline.
Coffee, brewed (drip) - 4 to 20 mg/floz (130 to 680 mg/litre) (40 to 170 mg per 5 fl oz cup)
- Coffee, decaffeinated - 0.4 to 0.6 mg/floz (13 to 20 mg/litre)
- Coffee, instant - 4 to 12 mg/floz (130 to 400 mg/litre)
Espresso - 100 mg/floz (3400 mg/litre)
Teas and other infusions
Black tea, brewed (USA) - 2.5 to 11 mg/floz (85 to 370 mg per litre)
- Black tea, brewed (other) - 3 to 14 mg/floz (100 to 470 mg/litre)
- Black tea, canned iced - 2 to 3 mg/floz (70 to 100 mg/litre)
- Black tea, instant - 3.5 mg/floz (120 mg/litre)
Oolong, 3.75 mg/floz (120 mg per litre) (12 to 55 mg per tea bag, i.e. one serving)
Green tea, 2.5 mg/floz (85 mg/litre) (8 to 30 mg per tea bag, i.e. one serving)
White tea, 2.0 mg/floz (68 mg/litre) (6 to 25 mg per tea bag, i.e. one serving)
- Decaf, 0.5 mg/oz (17 mg/litre) (1 to 4 mg per tea bag, i.e. one serving)
Caffeine is sometimes called theine when it is found in tea, as the caffeine in tea was once thought to be a separate compound to the caffeine found in coffee. But tea does contain another xanthine, theophylline whose chemical structure is C7H8N4O2 compared to caffeine's C8H10N4O2. This is similar to the naming problem with mateine and guaranine.
Tisanes (i.e. Herbal teas) - caffeine content depends on the herb, e.g. Chamomile and Rooibos "teas" have no caffeine while Yerba matÚ and Guarana do contain varying quantities. Many tea drinkers characterise herbal tea simply as that which, unlike black or green tea, contains no caffeine.
Energy drink - 10 mg/floz (340 mg/litre). Some countries limit the caffeine content at 135 mg/litre.
Soft drink (caffeinated) - 3 to 8 mg/floz (100 to 270 mg/litre)
- Pill (caffeine) - 200 mg (100 mg in many countries within EU)
Equivalents to 200 mg of caffeine
- One caffeine pill (Two in some countries where these are 100 mg)
- One shot of espresso (2 oz)
- ~2 cups (5 floz) of regular coffee
- ~1.3 L soft drink (these can vary widely in content)
- ~1 kg (~2 lb) of milk chocolate or ~0.25 kg of bittersweet chocolate (~0.5 lb)
- ~5 cups (8 floz) of black tea or ~10 cups (8 oz) of green tea
In the European Union, a warning must be placed on packaging if the caffeine content of any beverage exceeds 150 mg per litre. This includes caffeine from any source (including guarana, which is often found in energy drinks). In many countries, caffeine is classified as a flavouring.
Metabolism and toxicology
Caffeine is thought to act on the brain (and in fact, most cells of the body, since all cells have adenosine receptors) by blocking adenosine receptors (thereby blocking a pathway that leads to the breakdown of cyclic adenosine monophosphate, CAMP). Adenosine, when bound to receptors of nerve cells, slows down nerve cell activity; this happens, among other times, during sleep. The caffeine molecule, being similar to adenosine, binds to the same receptors but doesn't cause the cells to slow down; instead, the caffeine blocks the receptors and thereby the adenosine action. The resulting increased nerve activity causes the release of the hormone epinephrine (adrenaline), which in turn leads to several effects such as higher heart rate, increased blood pressure, increased blood flow to muscles, decreased blood flow to the skin and inner organs, and release of glucose by the liver. In addition, caffeine, similar to amphetamines, increases the levels of the neurotransmitter dopamine in the brain.
Caffeine is quickly and completely removed from the brain and, unlike other CNS stimulants or alcohol, its effects are short lived. In many people, caffeine does not negatively affect concentration or higher mental functions, and hence caffeinated drinks are often consumed in the course of work.
Continued consumption of caffeine can lead to tolerance. Upon withdrawal, the body becomes oversensitive to adenosine, causing the blood pressure to drop dramatically, leading to headache and other symptoms. Recent studies suggest that caffeine intake (in coffee) may decrease the risk of developing Parkinson's disease, but additional study is needed.
Too much caffeine can lead to caffeine intoxication. The symptoms of this disorder are restlessness, nervousness, excitement, insomnia, flushed face, diuresis, gastrointestinal complaints, even hallucinations. They can occur in some people after as little as 250 mg per day. More than 1,000 mg per day may result in muscle twitching, rambling flow of thought and speech, cardiac arrhythmia or tachycardia, and psychomotor agitation. Caffeine intoxication can lead to symptoms similar to panic disorder and generalized anxiety disorder.
The minimum lethal dose ever reported was 3,200 mg, intravenously. The LD50 of caffeine (that is the lethal dosage reported to kill 50% of the population) is estimated between 13-19 grams for oral administration for a average adult. The LD50 of caffeine is dependent on weight and estimated to be about 150-200 mg per kg of body mass, roughly 140-180 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 to metabolize 50% of the caffeine, ranges from 3.5 to 100 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 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 LD50. Though achieving lethal dose with coffee would be exceptionally difficult, there have been many reported deaths from intentional overdosing on caffeine pills.
While safe for humans, caffeine and its related compounds theobromine and theophylline are considerably more toxic to some other animals such as dogs, horses and parrots due to a much poorer ability to metabolize these compounds.
Intake of caffeine can up to halve a patient's risk of diabetes mellitus type 2. While this was originally noticed in patients who consumed high amounts (7 cups a day), the relationship has now been shown to be linear (Salazar-Martinez 2004).
Intravenous caffeine is often used medically to treat post-lumbar puncture ("spinal tap") headache.
Abuse and overdose
Caffeine, in its many forms, has been used for its stimulating effects. In modern times, though, the substance can be produced in much higher quantities, and has found its way into many products. Purer forms, such as those in caffeine pills, are easily available. These pills are sometimes used by college students and graveyard shift workers to last an entire night with no sleep.
Caffeine pills have been under media fire for recent and past deaths of students, usually take on the form of a caffeine overdose. One such example of this was the death of a North Carolina student, Jason Allen. He swallowed most of a bottle of 90 such pills . This was the equivalent of about 250 cups of coffee (or, alternatively, a gallon and a half (5 liters) of espresso, or 22 gallons (~150 liters) of Mountain Dew, though the soft drink is not caffeinated in all areas). Allen probably ingested about 18 grams of caffeine, since caffeine pills are restricted to 200 milligrams or less in the U.S., and most manufacturers make them in that size. A few other deaths by caffeine overdose have been known, almost always in the case of massive pill consumption on dares.
Excessive ingestion of caffeine can result in increased blood pressure and pulse, increased urine production, tightening or constricting of superficial blood vessels (sometimes resulting in cold hands or fingers), increased amounts of fatty acids in the blood, increased production of stomach acid.
Long periods of abuse can lead to detrimental effects on the esophagus (persons who consume high amounts of caffiene may have a risk for higher incidents of ulcers, erosive esophagitis, and Zollinger-Ellison Syndrome), heart problems, insomnia, chronic muscle tension and nervousness.
One dangerous form of caffeine use is to stay alert when one is under the influence of alcohol or in severe sleep debt. This tricks users into thinking they are more alert than they really are. Taking part in certain activities, such as driving, may be dangerous in such cases.
Caffeine was isolated by the German chemist Friedrich Ferdinand Runge in 1819. According to the legend, he did this at the instigation of Johann Wolfgang von Goethe (Weinberg & Bealer 2001).
- Salazar-Martinez E, Willet WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FB. "Coffee consumption and risk for type 2 diabetes mellitus." Ann Intern Med 2004;140:1-8.
- Weinberg BA, Bealer BK. The world of caffeine. New York & London: Routledge, 2001. ISBN 0-415-92722-6.
Last updated: 10-24-2005 01:49:39