Claire Coombes
BALPA Human Factors Scientist
To really understand how caffeine works, we first need to understand what happens in the brain when we get tired. Every moment you’re awake, the neurons in your brain are firing away and your internal energy stores are being used up – even on your most zonked-out of days, when you have not moved from the sofa or contemplated a crossword. As this happens, those internal energy stores – known as adenosine triphosphate or ATP, and brain glycogen – have to be broken down, which produces a natural by-product molecule called adenosine.

As the day wears on, adenosine molecules begin to accumulate in the brain, and other internal sleep-regulating substances build up in your body’s cerebrospinal fluid. Once certain levels of these substances are reached, the body begins to ‘power down’ and transitions into sleep. Adenosine binds to specially tailored receptors in the brain, activating a cascade of biochemical reactions that prevents the action of wakefulness-promoting neurons. In essence, adenosine acts like the sensible parent at a party, monitoring how much fun has been had until – when their patience has finally been worn thin and the other parents have arrived – they eventually call a halt to proceedings.

At this point, where adenosine receptors are sufficiently occupied by adenosine molecules, the body is sufficiently tired to be nudged into sleep. During this time, adenosine levels go back down to normal and the body’s energy stores are replenished. Those levels don’t quite get down to normal if you don’t get enough sleep, but more on that later.

Now for caffeine. In its molecular size and structure, caffeine is very similar to the adenosine molecule. This means it can fit into adenosine receptors and block adenosine molecules from binding and initiating sleep processes. In this way, caffeine is sometimes thought of as an ‘impersonator molecule’. Importantly, caffeine doesn’t ‘bind’ in the same way to adenosine receptors, but rather is just in the way, occupying the space, preventing the ‘parents’ from getting in the room.

In summary, caffeine works by inhibiting the sleep-inducing molecule adenosine, allowing wakefulness-promoting neurons to keep firing and, therefore, delaying the onset of sleep. As there are other receptors and compounds that can also impact energy levels in the brain, caffeine should be thought of as doing a reasonable job at delaying the inevitable in some arenas. However, its impact is more to disrupt the ‘go to sleep’ signals to the brain than to create a new internal state of energy and vitality.

Why we like it


Other than being safe to use and easily available, caffeine is known for its psychoactive properties. For most of us, it can help us feel alert, improve our focus and work output, and give a mood and energy boost. It is most beneficial when alertness is already reduced, and it can counteract some of the cognitive deficits brought about by rising tiredness. However, there is a bit of a caveat. Its ability to improve performance appears to be far greater for tasks that are straightforward, that do not primarily require novel, divergent thinking, or more complex types of cognition. The way it improves performance appears more in the domains of increased vigilance and attentional capacity in simple tasks, like concentrating on driving on a long motorway stretch, rather than increases in the quality or accuracy of complex decision-making. It is also known to significantly benefit athletic performance, particularly stamina. 

How caffeine affects you depends on some individual factors, such as genetics and physiology, your level of tolerance and other environmental factors. For example, the half-life of caffeine – the time taken for the body to eliminate one half of the caffeine ingested – is roughly five to six hours in a human body. This is subject to some individual differences and external factors, too. For example, pregnant women or women using contraceptive pills are up to twice as slow in processing caffeine. By contrast, smokers process caffeine more rapidly than non-smokers.

The main well-known difference is tolerance level. If your adenosine receptors are constantly filled up with caffeine over time, your brain responds by adapting to anticipate these influxes and creates additional adenosine receptors. This means that even where there is more circulating caffeine in your body, adenosine will still be able to have its impact and start signalling for the brain and body to go to sleep. For heavy caffeine users this means that ever greater amounts of caffeine are required to feel alert, as there are more adenosine receptors that need blocking.

Kicking the caffeine habit 


If you have an unholy need for a coffee in order to function in the morning, it is an indication you are experiencing withdrawal. Caffeine withdrawal occurs fairly rapidly, between 12 to 24 hours after last ingesting it. Your brain gets used to a particular balance of molecules and receptors, so any change to the status quo is fed back, in this case to tell you to get that first caffeinated beverage in. The good news is that such additional adenosine receptors can be organically ‘downregulated’ – effectively made to disappear – if you diminish your intake. For heavy caffeine users it may take a few days to a couple of weeks to occur, with some side effects such as headaches, fatigue and lethargy in the mix. However, the body is essentially pretty good at adapting to feeling alert without the routine espressos.

Even though it might be considered outrageous to suggest it, if you want to preserve the alerting boosts caffeine gives you, it’s worth considering reserving caffeinated beverages until you really need them. Heavy caffeine users are not likely to get the jolt they’re after from two cups of coffee when they are trying to stave off sleep in the middle of the night. By substituting with decaffeinated products for social and other occasions, their caffeine hits will become more effective.

How much Caffine is too much? 


At very high dosages, caffeine consumption can be problematic, leading to issues such as heart palpitations. But the Food and Drug Administration in the US suggests that for healthy adults, 400mg a day – roughly four or five cups of homebrewed coffee – does not seem to be associated with any dangerous or overly negative effects. Generally speaking, a daily dosage limit of 800mg should not be exceeded.

It is also important not to consume caffeine within four to five hours of wanting to go to sleep, as it will interfere with the quality and length of your sleep.

Posted on 29 October 2018

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