Fatigue: how it arises and how caffeine combats it


In order to understand this spell, let's first explain how fatigue occurs. We may noticea decrease in energy and an increase in drowsiness after a few hours of concentrated work. Let us now take a closer look at this situation. I mean very closely down to the molecular level.

When we work, we need a lot of energy to keep our brains functioning. There are alot of metabolic processes going on in our body that convert certain substances into others, and this is how the molecule ATP - adenosine triphosphate -is naturally formed in our body.


We can call it as "energy molecule" because energy is embedded in it. It is a kind of storehouse of energy obtained from the oxidation of nutrients by the cells of our body. The moment our body needs energy, for example to work, it can release it from this molecular store by hydrolyzing ATP.

This means that with the help of a water molecule, the ATP molecule is converted and releases the energy needed for our work. Another product of this transformation is the part of the ATP molecule, Adenosine. This nucleoside then influences certain processes in our body. Its effect on the body is mediated by receptors - Adenosine receptors.


We can think of receptors as something like cellular receivers that are tuned to specific substances. Adenosine receptors are therefore ready to pick up adenosine. They are found in different ways in our body but their highest concentration is in the CNS, specifically in the brain. Once adenosine is captured in these receptors, it begins to signal fatigue to the body via the adenosine receptor. When we fall asleep, the receptors are then naturally cleared of adenosine during sleep.

The body's self-cleaning ability of adenosine during sleep can also be harnessed during the day with a short nap and coffee. This trick of "biohackers" to get a big dose of energy is called a Caffeine nap.

Trapped adenosine depresses the nervous system, lowers blood pressure and heart rate, and promotes sleepiness. Adenosine receptors are differentiated into A1, A2A, A2B and A3 receptors. Specifically A1 and A2A receptors are located in the brain where caffeine can reach them, but more on that in a moment.


Let's summarize. So, at the moment when our body produces energy by hydrolyzing the ATP molecule, it also produces the fatigue bringing adenosine. This is picked up in special places - receptors, mainly in the brain. Once it is captured, it begins to signal the body to feel sleepy. This is how fatigue is created in us.

If we know where and how adenosine "puts our body to sleep", we can prevent fatigue by simplynot letting adenosine reach its receptors. This is where coffee and its main ingredient caffeine come in.


Caffeine'sstructure is very similar to adenosine, which gives it amazing power. The adenosine receptors also take it up and caffeine can take the place of the "tired" adenosine. It acts as an adenosine receptor antagonist. It does the opposite of adenosine receptor activation due to the removal of endogenous adenosinergic tone.

By taking up residence in adenosine receptors, caffeine affects not only sleepiness but also other brain functions such as cognition, learning and memory. The property of caffeine to be an antagonist of adenosine receptors also has an effect on the development and progression of some diseases, mainly neurodegenerative disorders such as Alzheimer's or Parkinson's disease, Huntington's disease, epilepsy, migraine, depression, schizophrenia.

On average, caffeine is still active in our body 4-6 hours after drinking coffee. We should take this factor into account and drink coffee sensibly and in accordance with circadian rhythms.


How is the stimulation of adenosine receptors by caffeine and their blockage for adenosine related to the following diseases? This is based on the way in which the substances adenosine and caffeine affect neurons. Diseases such as Alzheimer's disease are classified as neurodegenerative diseases. Adenosineacts as a depressant on neurons. Itreduces neuronal activity and the release of neurotransmitters.

Neurotransmitters in the brain include dopamine. A hormone we know as a pleasure and motivational substance. It is linked to the reward centre of the brain and because of its abilities can lead to addictive behaviour. As a neurotransmitter, it is responsible for transferring excitement between certain neurons in thebrain.

When dopamine levels are increased or decreased, health complications such as Alzheimer's or Parkinson's disease, depression or schizophrenia occur. Returning now to the effect of adenosine, we know that it can reduce the activity of the neurotransmitter dopamine. Caffeine, as an adenosine receptor antagonist, promotes dopaminergic transmission activity.


Caffeine's dopamine boost can turn coffee into a drug. Respectively, the chances of addiction to coffee, i.e. the caffeine in it, classifies coffee as a drug. This puts coffee at the top of the list of the world's most abused drugs. Apart from the possibility of forming a habit ,you can also develop a resistance to caffeine.

Our bodies are naturally very adaptable and this includes drinking coffee. We gradually increase our coffee intake to achieve the same stimulating effect. For adenosine, which cannot reach its receptors via caffeine, the body creates additional receptors. We, in order to block even these newly formed adenosine receptors, have to get more caffeine into the body. By increasing the dose of caffeine, we then encourage the development of coffee addiction.


Caffeine is not just a fatigue helper. It and other substances contained in coffee bring many benefitsto our health . They prevent not only the mentioned neurodegenerative and psychological diseases linked to the activity of neurons and neurotransmitters. Coffee also has certain anticarcinogenic effects and thus counteracts cancer of certain organs.

Overall, it helps our health to fight oxidative stress as an antioxidant. In the context of damage to thefunction of the HPA axis by overproduction of cortisol caused by civilization stress, it helps with correcting the feedback loop of the HPA axis and thus its proper functioning. Last but not least, coffee is also an aid in weight loss. In the right combination with dopamine function, it brings moments of happiness into our lives over a cup of coffee.