Caffeine Curiosities 

Laiana Farias. July 22, 2022.

If you are anything like me (and the majority of the population of the world) you probably consume some amount of caffeine on a daily basis, let it be from a nice cup of coffee or tea or any other caffeine-containing substance. As a coffee lover, I am guilty of consuming at least a cup a day. During my peak caffeine addiction a few weeks ago when I became particularly interested in the science behind what makes a good cup of coffee and was tasting several highly rated specialty coffee cafes around Amsterdam, I was drinking roughly four cups daily, and, to no one’s surprise, I was really feeling its effects on my body. Consequently, I wanted to learn more about the influence of caffeine on the human body, and thus I decided to research the topic.  

Coffee was discovered around 1000 AD in Arabia, but it only arrived in Europe around the 16th century. Beforehand, Europeans used to consume a lot of weak beers and wines in order to get their water intake, as regular water tended to be contaminated and poor in taste. However, as you might have guessed, this substitution caused people to become rather tipsy. When coffee finally reached Europe around the 1500s, it quickly became highly consumed. People enjoyed working more energetically and its introduction assisted in the popularization of cafes where people would come together to share ideas over a cup of joe. The latter contributed to serious conversations and debates about current events, leading to a drastic development in the areas of philosophy, politics and sciences. As a matter of fact, it is strongly believed that without this, Western civilization would not be as well-developed in these areas as it is now. Nevertheless, it was only around the 1800s that, with the assistance of scientific advances, scientists were able to isolate and study the caffeine component of coffee. More recently, around the 1900s, scientists discovered how it influences sleepiness. 

Caffeine is the most widely consumed mind-altering substance worldwide and belongs to a class of compounds called methylxanthines, which are naturally found in coffee and tea plants. Although it is mainly consumed through coffee and tea, it can also be found in energy drinks, sodas, chocolates, caffeine pills, and, to a lesser degree, even decaf beverages. Anyone who drinks any caffeinated beverage has experienced its effects – increased heart rate and sense of alertness, stronger focus and better concentration, and a peak in energy levels and wakefulness. This is due to the influence of its stimulant properties on the nervous system, which helps to keep you awake by blocking sleep-inducing molecules found in your neurones. A more in-depth crash course on neurones and their functions can be found in one of my previous articles on erasing our memories, but as a super brief summary, neurones contain receptors for specific neurotransmitters which trigger specific reactions. 

As you know, your body requires energy in order to go about your day-to-day activities. It gets this energy through the breakdown of the ATP (adenosine triphosphate) molecule, which produces the byproduct molecule adenosine. While awake, your body constantly breaks down ATP and accumulates adenosine. This molecule is responsible for the activation of a cascade of biochemical reactions that promotes sleep by causing the neurones to function slower through its inhibition of their specific receptors found in the neurone’s membrane. Higher levels of adenosine signify higher brain activity, which causes tiredness and the need to rest. Adenosine receptors are responsible for managing sleep by triggering the release of GABA (gamma-aminobutyric acid) neurotransmitters, which in turn inhibit the neurones involved with wakefulness and thus promote sleep.  

Adenosine triphosphate (ATP) molecule. 
https://byjus.com/biology/energy-currency-of-the-cell/

Caffeine is an antagonist for the adenosine neurotransmitter – meaning that it works its magic by inhibiting the active site (the ‘indent’ where molecules fit in) of adenosine receptors. This happens because both molecules have a very similar structure, as you can see highlighted in red in the photo below. Adenosine is blocked from its receptor once caffeine binds to it, thus the receptor is not activated and cannot stimulate sleep. This is the general idea of how caffeine keeps us awake, but I want to dive a little deeper into the topic.

“Caffeine and Adenosine Receptors”. YouTube, uploaded by Medicurio, April 7th, 2017, https://www.youtube.com/watch?v=jOfquPE1cnU 

There are four different types of adenosine receptors, but the relevant ones for this article are the A1 and A2A receptors, which are located in your brain. These two play a significant role in controlling sleep, as the A1 is found on the wake-stimulating neurones (keeps us awake) and the A2A is on the sleep-stimulating neurone (initiates sleep). Basically, when adenosine attaches to A1 receptors, it lowers its activity and decreases wakefulness; when it attaches to A2A receptors, it increases its activity and triggers sleep. This combination is what causes you to start to power off and feel sleepy. Caffeine’s ability to promote wakefulness comes mainly from its effect on the A2A receptors, as it prevents them from becoming active and thus sleep-inducing. Furthermore, your heart and your kidneys also contain the A2A receptors. Adenosine decreases their activity, so it lowers your heart rate and causes your kidneys to filter less blood (and therefore decrease urine production). Caffeine has the opposite effect, hence why you have a higher heart rate and an increased need to urinate once it is consumed. 

Caffeine Nap, May 12, 2022. https://sleepopolis.com/education/caffeine-nap/. Accessed December 11, 2022. 

Daily intake of caffeine has also been proven to have several positive impacts on us. For starters, it works with the stimulation and production of other neurotransmitters and hormones. It triggers the production of adrenaline (fight or flight hormone), consequently increasing your heart rate and opening your airways. Caffeine also stimulates happiness due to its interaction with the neurotransmitter dopamine (responsible for the feelings of pleasure, satisfaction and motivation). When adenosine binds to its receptors, it causes a slight alteration to the active site of dopamine (found in the same receptor) which can result in dopamine’s inability to bind to the receptor. Caffeine does not have this effect; if caffeine binds to the receptor instead of adenosine, dopamine’s active site remains intact, and so dopamine can do its job and promote positive feelings. Additionally, although scientists do not fully understand how, caffeine consumption has been linked to reducing the risk of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, as well as some types of cancers. Finally, caffeine also has medicinal properties – it is commonly found mixed with NSAIDs (non-steroidal anti-inflammatory drugs) such as acetaminophen and aspirin as it enhances their painkilling characteristics. Again, scientists do not fully understand why it does so. 

If you are a (loyal) coffee drinker and/or enthusiast, you have probably experienced (or at the very least heard that) your body can get used to drinking coffee and eventually you need more of it in order to feel the same effect. The human body has the excellent ability to adapt to change, and so when it grows accustomed to a certain concentration of caffeine in its body, it begins to produce more adenosine receptors. In other words, your body will have a greater number of these receptors in comparison to the same concentration of caffeine, given you drink the same number of cups per day. Basically, caffeine can still bind to adenosine receptors, but the extra receptors enable adenosine to come back into play and signal your brain to power down. As a result, you will need a higher intake of caffeine to reach the same desirable effect, as then there will be more caffeine molecules to inhibit the new receptors. Furthermore, caffeine has a half-life of about six hours. This means that when you drink a standard cup of coffee, your body has about 150mg of caffeine surging through your blood system. After six hours, the concentration would halve to 75mg and you would only be feeling half of the effect. After another six hours, it would be 37.5mg, and so on. This is why you might reach for another cup of coffee once its concentration lowers – adenosine jumps back into action and you start to feel its influence once again. On the other hand, if you decide to reduce or stop drinking coffee altogether, you will be left with all of these extra receptors that your body has synthesized and adenosine will work overtime since it no longer has any competitors. Consequently, you feel all those unpleasant withdrawal side effects: drowsiness, fatigue, irritability, struggle to concentrate, and headaches (caffeine narrows the blood vessels in the brain, so without it, your blood vessels widen and the boost of blood flow results in headaches). These off-putting withdrawal symptoms only last about a week, however, because your body readjusts to the decreased or lack of caffeine by eliminating the extra receptors. 

Of course, exaggerated caffeine consumption can be harmful. It can increase anxiety levels, cause insomnia, shakiness, dehydration and restlessness, to name a few. Its consumption is not recommended for sufferers of glaucoma, overactive bladders, heart conditions, sleep disorders, and epilepsy. Children should not consume it, as it makes them extra jittery, masks hunger cues (may lead to malnutrition), cause upset stomachs, etc. Pregnant and/or breastfeeding women are also encouraged to reduce to avoid caffeine altogether, as it might lead to dehydration and increase the risk of miscarriage, premature labour and low birth weight. Caffeine consumption is even regulated in professional athletes, as it is believed that high levels of the stimulant can result in unfair advantages in sports. Interestingly, albeit practically impossible, you can even overdose on caffeine! The lethal dose would be roughly 150mg of caffeine per kilogram of your body. To put this into perspective: a cup of coffee has about 150mg of caffeine, therefore, a person who weighs 70kg would need to ingest about 70 cups of coffee (thus about 1400mg of caffeine) in order to reach the lethal dose. This is impossible due to several factors: first, they would need to drink those 70 cups all at once in order to overdose; second, no one can drink 70 cups of coffee as our stomachs cannot contain that amount of liquid for it would induce vomiting; thirdly, you would experience mania and hallucination before reaching a lethal dose, and any (in)sane person would stop at that point. 

Laiana Farias. August 10, 2022.

I’m the first to admit that one of my greatest pleasures nowadays is drinking a nice cup of oat milk cappuccino with a stunning latte art. I’ll happily pay four euros for my dopamine-inducing cup of coffee in my favourite cafes and go exploring new specialty coffee places with my friends. Although coffee is considered to cause only a mild dependency rather than a full-blown addiction (as it is not as life-ruining as other addictive substances) I recognise that I fall under that category of ‘coffee addict’. However, I have recently decreased my coffee intake to a maximum of two cups a day in order to prevent harsh withdrawal symptoms when I decide to go on a spontaneous caffeine detox every now and then. Personally, I think it’s particularly interesting to understand the effects of certain substances on our bodies and see how they impact our day-to-day lives. I believe that learning about these dependencies and addictions helps to guide us into making healthier decisions. As much as I absolutely love drinking coffee, it’s better appreciated in moderation – like all things in life. 

Written by Laiana Farias

Sources

“How Does Caffeine Keep Us Awake?”. YouTube, uploaded by Ted-Ed, 17 July 2017. https://www.youtube.com/watch?v=foLf5Bi9qXs 

“Caffeine and Adenosine Receptors”. YouTube, uploaded by Medicirio, 7 April 2017. https://www.youtube.com/watch?v=jOfquPE1cnU

“Your Brain On Coffee”. YouTube, uploaded by AsapSCIENCE, 28 August 2014. https://www.youtube.com/watch?v=4YOwEqGykDM

MacDowell, Rose. “Caffeine Nap.” Sleepopolis. 12 May 2022. https://sleepopolis.com/education/caffeine-nap/ 

Shabir, Akbar, et al. “The influence of caffeine expectancies on sport, exercise, and cognitive performance.” Nutrients 10.10 (2018):

1528. Wierzejska, Regina. “Caffeine–common ingredient in a diet and its influence on human health.” Roczniki Panstwowego Zakladu Higieny 63.2 (2012): 141-147.

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