Discovery of caffeine
Caffeine in the lab
Caffeine and plants
Students and Caffeine

Caffeine Action and Metabolism

Virtually everybody agrees that caffeine keeps you awake and improves your mood, indeed it would be hard to find someone who could not tell you what the effects of caffeine are. Thus it would be easy to assume that we understand caffeine. Surely if people on the street can tell you what it does, then the people in the labs must know how it does it? Not so. Despite being investigated more extensively than any other drug in history, scientists are still arguing over the answers.

Cartoons by Robert Thierrien Jr., better known as BADBOB, celebrating caffeine's place
in contemporary culture and conforming to common understanding of caffeine's effects.

The problem arises from the complexity of caffeine's actions on the body. The drug produces one (or more) effect on each of the cardiovascular, respiratory, renal, and central and peripheral nervous systems. Studies into the pharmacology of caffeine have yielded many theories, most inconclusive, a few now completely discredited, none entirely accepted.

Here we will look at only the latest theory, the adenosine blockade theory, formulated in the early 1970s.

Competitive blockade of adenosine receptors: the adenosine blockade theory
Adenosine is a neuromodulator (what's a neuromodulator?) with mood-depressing and sleep inducing effects. It decreases the rate of spontaneous nerve cell firing and inhibits the release of other neurotransmitters that control the excitability of central neurons. The latest theory is simply that caffeine competitively blocks the sites that are designed to accomplish the uptake of adenosine into the human nervous system. This behaviour is referred to as 'competitive antagonism'. Caffeine has the correct structure to mimic adenosine in the active sites and thus prevents the body from being affected by adenosine's depressing effects. In laymen's terms, we are unable to become tired because the neurological pathways that would have enabled this to happen are blocked.

Some elements of caffeine's action on the body are well understood. The following few paragraphs briefly discusses why caffeine is such a potent drug, and suggests that the primary metabolites also possess stimulant properties.

The Metabolism of Caffeine

Some elements of caffeine's action on the body are well understood. Caffeine can spread quickly around the body because it is water soluble and passes easily through all cell membranes. Not long after you have finished your cup, caffeine will be present in virtually every cell of your body. Caffeine's permeability means that all areas are equally targeted, an accomplishment that few other pharmacological agents could achieve. Even the blood-brain barrier, safeguarding the brain and central nervous system from unknown agents in the bloodstream, can be traversed as if it didn't exist.

Absorption of caffeine from tea and coffee is much faster than from soft drinks, and for the hot drinks caffeine levels are at their highest around one hour after consumption. After circulating the body, most caffeine will eventually end up in the liver, where it is metabolised. The dominant mechanism is the demethylation of caffeine, a trimethylxanthine, into dimethylxanthines and monomethylxanthines. This produces dimethylxanthines as the primary metabolites; paraxanthine, theophylline and theobromine. You can read more about the methylxanthines on the methylxanthines page, but to remind you, theophylline is found is tea and theobromine in chocolate; all three are credited with acting as stimulants in a similar fashion to caffeine. Paraxanthine is produced in the greatest concentrations, into which more than 70 percent of caffeine is converted. In this form, paraxanthine is a "second incarnation of caffeine".

The liver also accomplishes the biotransformation of caffeine by oxidisation and conversion to uric acids, and water soluble caffeine can also be lost directly in urine. There is no accumulation of caffeine in body fat or specific organs; the same permeability that enables caffeine to get into the cells also facilitates its rapid departure. In healthy adults, the half-life of caffeine has a mean value of 3.5 hours (the half-life is the time taken for the body to eliminate one half of a given amount of a compound).

One final fact, to make you look smart in your coffeehouses: caffeine metabolism in women is about twenty-five percent faster than in men. So for men, the buzz lasts longer.

Images used without permission from the following sources (left to right):
Just Say No To Decaf                   The World of Caffeine, Weinberg and Bealer, Routledge, 2001
I Need Coffee                     
Screaming Man on Caffeine           The Daily Telegraph, Arts and Books Supplement, 5th May 2001, p.A3

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Caffeine - Simon Tilling