Coffee and The Brain: The Surprising Science Behind Hot, Brown, Bean-Water

Author: Ryan Wardle 

Coffee - who doesn't love starting the day with a cup of the world's the most commonly used psychoactive drug? Whether we drink it or not every one knows about the magic brown liquid that gives an extra jolt of energy. We love it so much that Americans drink over 400 million cups of the stuff every day. That pick-me-up energetic feeling is due of course to the molecule that we've all come to know and love, caffeine. 

But what even is caffeine? And how does it work? Is it healthy? Or is it harmful? We'll find out the answers in today's installment of Remarkable Physiology as we explore the fascinating effects that caffeine has on our brains and bodies. So go pour yourself a nice cup of joe and we'll get into it. 

The Brain for Beginners

The brain, a.k.a. the noggin, a.k.a the noodle, a.k.a old thinky,  is a crazy complicated and wonderful organ located inside your head. It is where thinking, feeling, and the entire internal experience takes place. It is composed of billions of cells known as neurons, forming trillions of connections with each other. Each neuron is connected to other neurons via a long structure called the axon. The neurons convey messages from cell to cell by sending electrical impulses down the axons to the receiving end of the target cell where it is received into the dendrite. It's like the internet, except inside your head.

But here's the weird part: the axon and the dendrite never touch (Think middle schoolers dancing).  There is a gap, or synapse, between the two cells. When the electrical signal reaches the end of the axon it triggers the cell to release signaling chemicals, known as neurotransmitters,  into the synapse. Neurotransmitters then bind to receptors across the synapse on the dendrite of the receiving cell. And thus the message transfer is complete and the new cell generates an electrical signal to send off to another neuron. This pattern of changing electrical to chemical, back to electrical is going on constantly inside your brain and throughout your entire nervous system.

Each neurotransmitter has a specific receptor that it binds to, sort of like a lock and key. Or perhaps a more evocative example would be those things babies use to learn shapes where each block can only fit in to it's particular hole. Yah, neurotransmitters are like a microscopic version of that. When the right shaped transmitter binds to its receptor is causes a change in the receiving neuron that generates a new electrical impulse.

Your Brain on Coffee

The neurotransmitter that's relevant to us caffeine addicts is adenosine. Adenosine is a sleepy molecule. It is released and builds up in the brain throughout the day, and as it binds to its receptors in the synapses it causes us to feel tired. But we don't have time to be tired! There's too many meetings to attend and proposals to write. And that's why God in his infinite wisdom created caffeine. Caffeine closely resembles adenosine. Basically what caffeine does is mimic adenosine, and binds to its receptors. This jams the neuron signaling, and now the message of "tired" can't be received.

How do we know this is what's happening? Crazy you asked that, because here's how!
In the graph right (Fredholm, 1980) we can see the effect of caffeine on different neurotransmitter pathways. The x-axis is showing the level of caffeine, and the y-axis is showing how much effect that level has on different targets. Focus on the A1, A2 receptors as these are the adenosine receptors. Don't worry about what the other receptors are, just know they're other pathways that do stuff in the neurons. These receptors are effected after ingesting the dose of caffeine found in a single cup of coffee. The other pathways only become activated well after the dosage of caffeine becomes toxic - 20-40x higher than one cup! I know some coffee addicts, but even they can't drink 20-40 cups of coffee in one sitting. Also, in case you were wondering the lethal dose of caffeine is, it is estimated at 10g, or about 100 strong coffees (Ritchie, 1975).

From this experiment we can conclude that it is in fact the blockage of adenosine receptors by caffeine that is producing that energized feeling. But that feeling is a lie!

Caffeine isn't actually giving you any more energy, it's just preventing you from feeling how tired you actually are. It's sort of like if you leave the house wearing a terrible outfit, but your friend somehow convinces everyone to not make fun of you. You don't actually look good, you're just not hearing how bad you do look. And all that adenosine keeps building up in the synapses, so after the caffeine molecules are degraded and the stimulating effect wears off the receptors become flooded with adenosine and you "crash". That's why you may feel even more sluggish and tired than before. In this way caffeine is sort of like a credit card where you feel like you can spend the energy now, only to later find out you didn't have any to begin with. So the perceived effect of energy can be helpful, but it comes at a cost. Caffeine goes beyond stimulation however and has many other effects on the mind and body.

Can Coffee Prevent Alzheimers and Dementia?

If you didn't already think caffeine was a wonder drug you will now. It turns out that drinking coffee might be a great way to prevent the onset of dementia or Alzheimer's disease later in life. Eskelinen et al., (2009) found that moderate coffee consumption in mid-life could reduce the likelihood of dementia and Alzheimer's later in life by up to 70%. A long-term group study of 1409 participants found that those who drank 3-5 cups of coffee per day in middle-age had a 65-70% decreased risk of dementia and 62-64% decreased risk of Alzheimer's disease when followed up with 21 years later.

The proposed mechanisms for this effect include coffee decreasing the risk of type 2 diabetes, which is associated with dementia. Another idea is that the caffeine and adenosine A2a receptor molecules prevent cognitive deficits related to the Alzheimer's associated protein amyloid-beta. Also it may be due to the antioxidants found in coffee. But no one really knows!

This same protection did not hold true for tea. I like tea, but you know how we all have that one friend who only drinks tea and is always going off about how much better it is than coffee and why tea is so great, and yada yada yada? Well next time they go off, just show them this. That oughta shut them up.

So in addition to helping you feel awake and tasting delicious it turns out coffee might help prevent degenerative neurologic diseases as well. Remarkable!

The Dark Side of the Dark Roast: Negative Effects

Surely coffee can't be all warm cozy mugs of delicious, energizing, dementia-fighting roast nut water though, can it? There has to be some downsides. The two most commonly cited negative effects of coffee are anxiety and insomnia. When looking at anxiety there was no significant effect of caffeine consumption on anxiety in the US (Eaton and McLeod, 1984) or UK (Warburton and Thompson, 1994). This may not be telling the whole picture however, as people who are prone to anxiety often avoid caffeine. The same general trend is true for insomnia where there is no effect of caffeine intake on insomnia, yet likely due to the fact that people who suffer insomnia avoid caffeine.

Another concern people have is that caffeine raises blood pressure. This is true, but maybe not in a relevant way. It is raised by a very small amount that some doctors believe to be harmful, and others believe to be fine. Additionally, caffeine is feared to raise blood cholesterol. This effect is eliminated when using filtered, percolated, or instant coffee, and is only an issue with boiled or turkish coffee.

So really then are the downsides that bad? I was lead to believe by public opinion that coffee had serious negative health consequences. But now I'm not so sure, the science seems less condemning. I wouldn't be surprised to learn there are some minor consequences, but I am definitely surprised to learn about the potential benefits of fighting dementia and Alzheimer's. If nothing else I don't feel so bad when drinking coffee now. Thank you science for always being an enabler for our addictions!

Conclusions

To wrap this all up, caffeine is a pretty cool chemical with a fascinating method for disrupting neuron activity to make us feel energized. It also may have the power to protect our neurons and minds from debilitating diseases when consumed as coffee. And even the negatives don't sound so bad. I think this chemical is so wonderful that we should stop calling it caffeine and start calling it caffriend.

References

Eaton WW, McLeod J (1984) Consumption of coffee or tea and symptoms of anxiety. Am J Public         Health74:66–68

Eskelinen, M. H., Ngandu, T., Tuomilehto, J., Soininen, H., Kivipelto, M. (2009) Midlife Coffee and     Tea Drinking and the Risk of Late-Life Dementia: A Population-Based CAIDE StudyJournal of           Alzheimer's Disease 16: 85-91

Fredholm, BB (1980) Are methylxanthine effects due to antagonism of endogenous adenosine?           Trends Pharmacol Sci 1:129–132

Goodman LS, Gilman, A Ritchie JM (1975) The xanthines. in The Pharmacological Basis of           Therapeutics, (MacMillan, New York), pp 367–376.

Warburton DM, Thompson DH (1994) An evaluation of caffeine in terms of anxiety, depression and     headache in the general population. Pharmacopsychoecologia 7:55–62.