This Podcast Will Kill You - Ep 54 Wake Up and Smell the Caffeine

Episode Date: July 21, 2020

Are you one of the billions of people around the world who starts your day with a freshly brewed and deliciously aromatic cup of coffee or tea or maybe even hot chocolate? Or are you caffeine-avoidant, looking on at your coffee-addicted friends with confusion and maybe even pity? In either case, this episode is for you. We are joined by the one and only Matt Candeias of In Defense of Plants to tackle the world’s most consumed psychoactive drug: caffeine. First we get a taste of the massive history of the most popular caffeine-containing beverages, then we trace what exactly caffeine does in your body after that first scrumptious sip. And finally, we explore what role this compound has for those many, many plants that produce it. We hope you find this episode as stimulating as its subject! See omnystudio.com/listener for privacy information.

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Terms and conditions apply. Visit blueapron.com slash terms for more information. I'm Amanda Knox, and in the new podcast, Doubt the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? Evidence has been made to fit. The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to book?

Oh, my God, I think she might be innocent. Listen to Doubt, the case of Lucy Letby, on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the Iheart Radio app, Apple Podcasts, or wherever you get your

podcasts. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And I'm Matt Kandais. And this is This Podcast Will Kill You, Crossover Edition. Within Defensive Plants. Yes. I'm so excited.

Really excited. We've been waiting a long time. I can't believe this is the first one we've done this season. No, we did ricin. When was that? That felt like forever ago, by the way. I think it was like seven years ago. Easily.

Much has changed in the meantime. I don't remember anything about ricin. I got to tell you. Come on, the umbrella like pellet. Oh, yeah. Okay. A bad seed. I thought about it yesterday when I was covered in ticks.

Oh, yeah. Okay, now I remember. Thank you for reminding me. There's so much. I feel like if somebody drew up a pop quiz of like facts I learned on TPWKY, I would fail. It'd be embarrassing. I had someone write me the other day and say, in one episode you said this, but then in another episode you contradicted your perception on that. I was like, I don't know, I changed my mind, I guess.

I don't even remember saying that. But cool. Thank you for paying attention. Well, what are we talking about on this very exciting crossover episode? We're talking about the thing keeping me alive right now, and that is caffeine. My heart just swells when you say it. I mean, how much when you guys were reading about this or researching this, how much were you craving coffee or tea or chocolate or whatever it was?

I have had no less than six cups of coffee in the last 36 hours, in which I have also had less than two hours of discontinuous sleep. That doesn't sound great, Erin. Ooh, yeah. Mental health. Take care of yourself. We can talk about why it works, though. It's going to be really exciting.

White works for now. Yep. Well, I did all my research in the morning while I was drinking coffee, so it was perfect. Oh, excellent. So to celebrate this wonderful thing to which we are all, I can assume addicted. Mm-hmm. What are we drinking?

What's our quarantini? It's the caffeine. Get it? Yeah. Oh, Aaron, what's in the caffeine? It's kind of like a take on a white Russian, so it's vodka, it's got Kalua, it's got chai tea syrup, cream, and then to make it even more caffeine-friendly, we're going to toss in like a swirl of chocolate syrup on top

and then garnish with like a cinnamon stick if you have one. I'm not sure that I do. I'm allergic to cinnamon, so no, no. Entirely? Yeah, it's tragedy. Pure tragedy. We'll post the full recipe for that quarantini as well as our non-alcoholic but still caffeine-friendly placebo

on our social media channels and our website. This podcast will kill you.com. We sure will. So we just did an awesome interview today. It was so much fun with Corey from OPP, which is other people's podcast. It's a podcast where he interviews other people about their podcasts. It's super fun. It's really fun. It was such a great experience. You guys should go check it out. Yeah. Thanks for having us on, Corey. It was so fun. All right. So now is that business done, taken care of? I think we took care of taking care of business. TCOB.

This is going to be a great episode. Well, I think we already need a short break, maybe. I definitely think so. All right. We'll do that, and then we'll come back with some caffeine. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients,

so there's no meal planning and no extra grocery trip. There, assemble and bake meals, take about five minutes of hands-on prep. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and that's it. And if there's truly no time to cook, dish by Blue Apron meals are fully prepared. Just heat them in the oven or microwave, and dinner is ready. And here's the exciting news. Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another

recurring charge. Order now at Blue Apron.com. Get 50% off your first two orders plus free shipping with code this podcast 50. Terms and conditions apply. Visit blue apron.com slash terms for more information. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something.

That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking.

It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keef's. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. In 2023, a story gripped the UK, evoking horror and disbelief. A nurse who should have been in charge of caring. for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended. A verdict? A villain.

A nurse named Lucy Letby. Lucy Letby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, doubt the case of Lucy Lettby, we follow the evidence and hear from the people that lived in. To ask what really happened. when the world decided who Lucy Lettby was.

No voicing of any skepticism or doubt. It'll cause so much harm at every single level of the British establishment of this is wrong. Listen to Doubt, the case of Lucy Lettby on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. Okay. The story of caffeine. So when I was preparing this, I was like, okay, I don't know if I should concentrate more on coffee, or tea or cacao or any of the other caffeine-containing plants or foods or beverages that we consume. And I'm sure, Matt, you'll talk about some of those other ones.

Yeah, a little. And then one thought that occurred to me was like, maybe I'll write out a different history for each of those. I'll do, I'll write out a thing for coffee. I'll write out a thing for tea and I'll write out a thing for cacao and I'll be like, you guys choose. They could choose your own adventure. Ooh. And then I was like, why would I do that to myself? Each one of those is a novel in and of itself. Yeah.

Yeah. This is why I struggled. So instead I decided to just do a very general overview of caffeine, mostly concentrating on the big hitters coffee and tea with a little bit of cacao thrown in there. Awesome. So I want to start by just going over a little bit of the origin stories, the best part of every superhero movie. So let's start with tea. So tea was supposedly discovered by Shen Nung, the mythical first emperor of China and the inventor of all kinds of things from animal husbandry to the plow to plant-based medicine and of course tea. And so the story goes a little something like this. One day, Shen Nung sat down under a shady shrub to escape the heat in a particularly hot day. And then he's

decided to cool off by building a fire. I don't understand how that would work. And then boiling some water to drink. Again, doesn't seem like a particularly cool-down experience. You know, the boiled water thing actually did make sense because he had noticed that people who boiled their water tended to get sick less often, which is pretty cool. But as he was building up his fire, by adding more branches, a few of the leaves on the shrub that he was sitting under, they They just like happened to fall into his pot of boiling water. And he was like, you know what? I'm not dipping my hand in there and scooping them out.

I'm just going to let them stay in the water. And then he drank it. And he was like, what is this? This is delicious. I want to drink more of this. I need to tell everyone about this. And of course, it was tea. Can I just say that story reminds me a lot of the willow story of the guy trying to take a rest behind a tree and then chewing on some bark and being like, ooh, my pain is

gone. Yep, yeah. Oh, how fun. Always these fortuitous discoveries that just somehow under trees. Under trees. If you're stumped, just you know where to sit. On a stump. That was so dorky. I liked it. I'm for it. Okay, so also in addition to being the discoverer of T, he also recognized a lot of the stimulatory, is that a word? properties of tea. So he actually kept track of his own medical records. So there are like hundreds of pages of his own like, this is what my bladder was like. This is what my temperature was, whatever. And this is what the bile was. But he wrote down in his records that tea was good for tumors or abscesses that come about the head or for ailments of the bladder. It dissipates heat caused by

phlegms or inflammation of the chest, it quenches thirst. It lessens the desire for sleep. It gladdens and cheers the heart. Also true. And so because of these amazing benefits of tea, this drink steadily grew in popularity in China and then it downright exploded during the Tang Dynasty between 600 and 900 CE. But outside of China, the first references to tea come from about 900 CE in writings by Arab traders. But no one in Europe or the New World or anywhere else really knew that much about tea or cared to investigate it further until the mid-1500s, despite the fact that there was, you know, ample trade going on.

But remember that date, mid-1500s. Okay. Okay. So now coffee. The coffee bush, as I'm sure you'll talk about maybe Matt, grows through. Throughout Africa, and that's probably where it originated, like Ethiopia area. Yeah, I've heard like sort of Middle Eastern Africa. Middle Eastern, like Yemen, Ethiopia areas.

But it doesn't seem that coffee was used by or even known to anyone in any of like the ancient world. So like ancient Greece, ancient Rome, ancient Middle East or ancient Africa. There is some evidence that in Ethiopia, coffee beans were first consumed by people. possibly as small balls consisting of like the ground fruit and then the bean itself and then packed together with lard to make like a little energy ball energy bites energy bites i mean nice i mean i have always loved eating like chocolate covered coffee beans and then i find myself being like why do why can't i sleep why do i feel so uh what's the word alert on edge on edge yeah my grandmother used to give him to me as a kid and she would call him goat turds she's like you want

some goat turds and eventually I learned that, yeah, I do. You're like, that's not going to put me off them. Yeah, welcome to my life. Well, and then there's the whole thing about like the civet and the most expensive coffee in the world is like the one that has been passed through a civet's intestines. Poop. Poop. Yeah. Anyway, okay.

And so there are some historical references to ancient documents or accounts of coffee drinking as early as the sixth century. but the earliest indisputable records puts that timing as no earlier than the middle of the 15th century in the Sufi monasteries of the Yemen in southern Arabia. And this story goes a little something like this. An Ethiopian goat herd named Caldeu was outherding his goats one day when he noticed his flock nibbling on some bright red berries on a certain bush. And they wouldn't come over when he called, but when he found them, They were all jumping and kind of like frantically and frenzied dancing around.

He was like, okay, it has to do something with these red berries on this bush. So what would happen if I tasted them? So he chewed on some of the berries himself and he liked what he tasted. So he's like, all right, I'm going to gather a handful of these and bring them to the nearby monastery. But the holy men of the monastery did not approve of these devilish red berries. and so they threw them into the fire, which then only led to the most delicious smelling aroma. And they were like, well, not so fast. So they dragged these beans from the ashes, ground them up, and then dissolved them in hot water,

leading to the first cup of coffee. What an interesting story. There's so many steps in there. I would have loved to see sort of the thought process. Back to the fire, you must go. So these, I mean, of course, this story, just as the one previous, might just be a story. Right. But somehow, somehow, the infusion of both tea leaves and coffee beans had led to this discovery that whatever the infusion was was delicious in some way, even though it's bitter and surprising that people found it that delicious.

but maybe that's just the power of caffeine. Okay. So now, cacao. Cacao was first cultivated not by Mayans, but by the Olmecs who lived in the lowlands of Mexico from around 1,500 to 500 BCE. And they use the cacao pods to make a chocolate drink. And there's even evidence on a pottery jar

from like 500 CE found in Guatemala that has hieroglyphs that indicate cacao and analysis, like an analysis of the contents of the pot showed traces of caffeine and theobromine. Nice. And the drink was called choccalado, of course. And then the Mayans after them, so the Mayans after the Olmex,

so around 1,000 BCE to 250 CE followed the Olmex in this, using cacao as currency often. And then after the Mayans, it was picked up by the Toltecs between the 10th and 12th centuries, and then finally by the Aztecs, from the 12th centuries until the span,

Spanish conquistadors arrived in the mid-1500s and had chocolate for the first time and then destroyed everything. Yeah. And so like also just a note on naming, when Cortez first arrived to, you know, start the fall of the Aztec Empire, he was given chocolate, you know, initially in this warm welcome. And he was like, this is so delicious. This is the drink of the gods, hence Theo Broma cacao. Wow. I don't think I ever put that together. Okay, so with tea, coffee, and chocolate, I stopped it around the mid-1500s because that was, in general, the time when each of those stopped being known to only the region they originated in. And that's when they began this worldwide tour of notoriety that would lead to caffeine consumption on a scale that has not only. never decreased. That is so interesting that all three kind of coalesced at the same time.

I think a lot of it has to do also with just the timing of like when long distance traveling was made more possible and when, you know, sort of as it coincided with, as we talked about in the scurvy episode, I think like there was all of a sudden a need to go trade more and the shipbuilding really increased in that technology for a traveling long distances increased. And then, of course, like, when you find something like this that is widely consumed in a certain area and found to be delicious, you are probably one of the things that first occurs to you is how can I make money off this? How can I profit off this? Of course. Yeah. And like, I mean, we all use it for productivity. Imagine when that started to

catch on among all of the already crazy economic progress, quote unquote, that was happening. Oh, yeah. Yeah. Yeah. Exactly. And so these, yeah, of course, began to be highly sought after, particularly in Europe and North America during the 1600s when colonialism was raging, of course. And these caffeinated beverages may have come along at just the right time. So temperance movements in Europe had happened before they had started and failed and started and failed, long before coffee and tea came onto the scene and they failed largely because the proponents of these movements didn't have an alternative beverage to suggest to replace alcohol. They were like, you need to stop drinking. And they were like,

all right, maybe I will, but what should I drink instead? Drink the poop infused water? Like, no, it's not good. And so when coffee and tea and hot chocolate came onto the scene, alcohol at that time was consumed at every meal, breakfast, lunch, dinner by every person in Europe, whether you're a child or someone who's working or someone who's elderly. It was ubiquitous. And, you know, in a way, alcohol was safer than the water because at least killed a lot of the germs. So when tea and coffee replaced the morning beer or the lunchtime poor, people saw a noticeable shift in the productivity and safety. of the workplace. I mean, go fake.

But like, I never even thought of it. And there's the fact that these beverages were boiled. And so that also reduced the chance of getting some sort of waterborne pathogen or parasite. What a massive cultural shift to go from being drunk all day to just drinking caffeine all day. That must have been huge. Huge. It's wild. And so these caffeine drinks, these caffeinated drinks, were credited or have been credited with shaping the entire European workforce and leading to a burst of creativity and ingenuity.

Eventually that paved the way for the Industrial Revolution. I mean, it's a bit of a, you know, maybe that's a stretch, but I don't know. It's not a stretch. Let's take it. Let's say it made an impact and then some. That is so cool. Isn't that amazing? And these beverages were also held to be indirectly responsible for other kinds of revolutions,

namely political ones. Oh, yeah. So tea houses, which had been popular in China since the 13th century CE, they started to become popular in Europe and in the New World as well. And coffee houses also sprung up and were incredibly widespread and popular. Like the amount of coffee houses per capita was like, like maybe only we now have reached it. Wow.

And so, and for instance, in England, they were given the name Penny Universities to describe how people and men were only allowed in the coffee houses at the time, how men would go to these coffee houses to talk about philosophy or politics or to hear music or poetry. So, like, in many ways, they still exist in the same capacity today, which I think is really interesting, like the open mic night at the coffee house. Yeah, it's like a gathering place, not just. Yeah.

Not just a play. And so like some of the documentaries that I watched was like, you know, would the same political discourse be held at a bar and the same actions be planned in like a logical way than they would be at a coffee house fueled by alcohol versus fueled by caffeine? Like when are you going to most get the ends that you're planning, I guess? I don't know. Fascinating. Interesting to think about.

There were still temperance movements, but this time against coffee primarily. and also tea, or it was like alternatively coffee and then tea. But yeah, so back on the revolution thing, in the British colonies of the new world, coffee houses in Boston were essentially the headquarters of the American Revolution. The Boston Tea Party was planned at a coffee house called the Green Dragon, and the first public reading of the Declaration of Independence was held at another Boston coffee house, the bunch of grapes. Nice.

That's funny. Kind of a fun name. And of course, tea itself, or rather the import, tax on tea and the British government allowing the East India company to also tax the import of tea on the colonists, that was all part of the reason for the American Revolution in the first place. And that also kind of brings me to the dark side of coffee and tea and chocolate. Yeah, always. There's always a dark side. There's always a dark side. So coffee and tea were both in incredibly high demand in European countries and in the British colonies and the new

world. But caffeine addiction was an expensive habit to pick up in those early days as the cultivation of the plants was pretty restricted. So anytime, for instance, that coffee beans were sent out from mocha, which is where they were primarily grown, they were made sure to not able to be germinated or to not be able to grow into any viable plants. And it's sort of like what we saw with the Sanchona bark in the malaria episode and restrictions on that plant being grown elsewhere. But eventually, where there's a will, there's a way. And so people did manage to smuggle out some coffee beans and a few tea seeds.

And so coffee was smuggled from mocha and planted in the Dutch control Java around 1616. And that was also found to be able to grow in many parts of the new world, which had the right humidity and temperature and so on for the growth. And of course, if you want to gather a lot of the coffee beans, you have to gather them by hand. And what did that take was a lot of hands. And so what did that lead to? But a lot of enslaved people being forced to labor under horrific working conditions on all these plantations in the new world. And, of course, as consumption and demand for coffee rose, so did the number of enslaved people.

And the popular habit of adding sugar to coffee and tea ensured that sugar plantations also had a reason to exist, right? Jeez, Louise. Capitalism. And while all this was happening, England was racking up a hefty debt to China in the tea trade. And so they saw an alternative way to save some money and to try to limit how much they were giving in terms of bringing the tea over from there. So they were like, well, why don't we get some tea?

tea seeds and start growing tea plants in our colony in India, which was all of India. And so Britain ruled over India at the time. And so they planted tons and tons and tons of tea plants. And they hired, you know, kind of putting hired in quotes because like literally paid them almost nothing in back-breaking conditions. And then at the same time, they also grew a bunch of opium and then smuggled that into China to then addict the whole country and drive them into ruin. I had no idea. There's a whole separate story of like the opium wars and like the East India Company is like,

it's just a massive story there. It's really fascinating. But read more about it. I don't have the information. But anyway, so then T, because of this, because of all of the things, because of all of the tea that had been able to grow in India, that flooded the market back in Britain and it toppled coffee as the preferred beverage. Wow.

So then, and then that also led to like afternoon tea and then eventually tea bags and, you know, all these different cultures around tea. And yeah. So anyway, okay, so the 1800s saw the continued popularity of these beverages and also 1819 saw the discovery of the caffeine molecule by a young physician named. Rung. Oh, wow. 1819. Okay. And then the next year, four other researchers were able to isolate the compound.

So it kind of happened all at once. But this discovery did not start the debate on the healthy or harmful effects of caffeine, but rather continue it. Like this debate has been going on for ages and still seems to be raging. Aaron, I'm sure you'll talk about that. Oh, yes. And there's just a little bit more of the history of caffeine that I want to touch on. So caffeine played a huge role in the wars. It was during the Civil War, during World War I, during World War II, given to soldiers, like unlimited rations of caffeine, whether in the form of caffeine powder,

whether in the form of unlimited tea, whether in the form of Coca-Cola. And it often was restricted to try to reduce the morale of whatever opposing side was there. for instance that happened during the American Civil War. And then, of course, the 20th century saw caffeine in many different products. So we see the rise of it in sodas and then energy drinks and then decaf and then advertising wars leading to basically the consumption and an entire world addicted to this compound, which is also, of course, what then started a ton and ton and ton of research over the safety of caffeine. But, you know, this was not a very well-done history or whole history, but hopefully what it has done is given you a little bit of the taste of just the massive impact that caffeine has had on the world's history and culture. And just to like, I want to wrap up a little bit by saying, like, there are some parallels between particularly coffee and tea.

So I just wanted to find some patterns in these histories. So number one, both of these were harvested as a leaf or a berry and used as a stimulant or medicine first. And they often held great significance for the culture where they were first used. Number two, each was only used as an infused drink relatively recently. So maybe starting in the 1500s. Number three, each was brought into the region that they are now associated with by religious devotees' return. from another country. Number four, their cultivation was protected. Number five, they were used as currency. So coffee beans were used as currency in Arabia, colanuts used as currency in Africa,

cacao pods and matte leaves in the Americas and tea leaf bricks in China. And I wanted to, the final point I wanted to make is that number six, and just as it has always been, in the present day, the people who are actually farming and producing these products see a minuscule fraction of the profit that eventually comes out of them. So for every $10 that you spend on a bag of coffee, for instance, the farmer who produced it sees maybe a dollar of that. And that's just how it is. There are some programs that seek to remedy that or seek to make it a little bit more fair. but it's debated whether they actually function. So anyway, that's my story.

Aaron, please tell us why we are so addicted to caffeine and why right now just talking about it makes me want to have a cup of tea or an afternoon coffee. I was just thinking, do we have decaf? I know, if I did have coffee right now, I wouldn't be able to sleep for sure. Oh, I'd be up all night, yeah. Do you guys want to know why?

Of course I do. Oh, good. Let's take a quick break and then I'll talk about it. Excellent. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's Working Hands hand cream is such a relief.

It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that, locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my

skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keef's. Just visit o'Keef's company.com slash this podcast and code this podcast at checkout. In 2023, a story gripped the UK, evoking horror and disbelief. The nurse who should have been in charge of caring for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended. A verdict?

A villain. A nurse named Lucy Letby. Lucy Letby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, doubt the case of Lucy Lettby, we follow the evidence and hear from the people that lived it. To ask what really happened when the world decided who Lucy Lettby.

was. No voicing of any skepticism or doubt. It'll cause so much harm at every single level of the British establishment of this is wrong. Listen to Doubt, the case of Lucy Lettby on the Iheart radio app, Apple Podcasts, or wherever you get your podcasts. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world. But in 2017, the FBI got inside. This is Special Agent Regal, Special Agent Bradley Hall. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast.

I now have several terabytes of an MSS officer, no doubt, no question, of his life. And that's the unicorn. No one had ever seen anything like that. It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Okay. So, Aaron, it's very interesting that you use the word addicted.

Because I think a lot of us think of caffeine as an addiction. I'm addicted to coffee. I'm addicted to coffee. And it's true that caffeine is the most widely used by far psychoactive substance, drug, in the world. I think over 85% of Americans, regardless of age, use caffeine. Wow. Wow. Right?

Dang. Regardless of age. Yeah, so like, so for adults, it's like a lot more than 85% and hopefully it's less kids, but. But there's like even, but I mean, because that includes soda, right? And like kids drink soda and chocolate. Which for a long time, soda companies, namely Coca-Cola was like, oh yeah, caffeine is a is a flavor additive. Like it's required to be there because it's a flavor additive. It adds bitterness. But in like double-blind studies, people couldn't detect the difference. it was like, are you just doing this to addict the children to caffeine to happen to a whole new market? But then there's sugar, so like, is that addictive? You know, whatever. Yeah, so there's no

like diagnosis of caffeine addiction. And so whether or not you consider caffeine to be something addictive kind of depends on what the definition of addictive is, which is a whole other debate that I'm not even going to get into. But it is true that caffeine has effects on your nervous system. such that with habitual use, if you stop using caffeine, you will experience things like withdrawal symptoms. And so that means you can become dependent on caffeine, which is something that's often part of a diagnosis of something like addiction. So let's talk a little bit more about the effects of caffeine on your brain. Okay? Yay. All right. We all drink caffeine. Is that correct? Yeah. Yes. Oh, yeah.

Okay. Tell me what it feels like when you drink a cup of coffee. What are your symptoms? I have to run to the bathroom really quick. Okay. Thank you for that honesty. No, euphoria, excitement, heartbeats go up. Okay. Alertness. I always feel like I kind of had like a beginning period of this feels great and awesome and I'm finally like where I need to be in my morning. and then my bones start to feel hollow and I get like, does that not a thing where I'm like,

I feel so like jittery and... Jittery, okay. But I also... Is it... Okay, I have so many questions that I'm getting ahead of myself. I'm like, but I don't eat breakfast, so does that have an impact? You know?

But mostly I feel like I'm talking right now, which is like a mile a minute. My brain's very focused. Okay, great. You guys are hitting on a lot of the effects of caffeine, okay? So it's a stimulant. So it has an effect on your central nervous system. So the reason that it's able to have an effect on your CNS is because when you ingest caffeine, generally we ingest it orally, right? So you drink a cup of coffee or you pop a caffeine pill or you sip a cup

of tea. And almost 100% of that caffeine becomes bioavailable. So you absorb it through your intestine and it goes into your bloodstream. Caffeine is a lipophilic molecule. So it can pass through lipid membranes, which means it can pass through your blood brain barrier and get into your central nervous system right away. And within like an hour of consuming caffeine, your blood levels and your plasma levels are almost equivalent. So it kind of like distributes equally throughout your tissues, including your brain. Okay. So we need. know that it's overall going to keep you awake. And now we know that it can get into your brain, so it's going to have some effect there. But the question is really like, what is it doing on a

molecular level? And this is really fun. And I'm going to keep it really pretty simple and basic because there's a lot of nitty gritty biochem here that I just, I don't have enough caffeine in me to get into that nitty-gritty detail. So what we need to know is that depending on the concentration of caffeine, when we look in like cell culture studies or animal model studies, we know that it can have a lot of different effects on cells, right? Like it interacts with cells and can cause a lot of different things when you look at them in an animal.

But when you ingest it like you're drinking a cup of coffee, the amount that you would ingest with that, there's really only one main receptor that caffeine is going to interact with. And that is with the adenosine receptors. So adenosine might sound familiar. Does it sound familiar to you guys? Mm-hmm. Why does it sound familiar? ATP? ATP? So adenosine trifosate or ATP is like the energy of all of our cells. Okay. So when your cells use a bunch of energy, like your brain, for example, if your brain is working really hard because you're thinking or your muscles are working hard because they're contracting, they use up ATP. And in using up ATP, they release or create essentially by taking off phosphate.

They release adenosine, which is the adenosine part of adenosine triphosphate ATP. When adenosine levels in your brain become high, they bind to a number of different adenosine receptors. There's a bunch of different subtypes. And they basically cause you to become sleepy. Because if you think about it, if your brain is working hard and using up a bunch of energy, then your brain probably needs a rest, right? So by using up ATP, you increase the levels of adenosine, which tells your brain, by binding to these receptors,

Hey, I'm tired. I need a rest. Let's take a break. Huh. Okay. Which is why at the end of the day, that buildup makes you fall asleep. Exactly. You get sleepy at the end of the day. It's not the only thing. Sleep is more complicated than that, but that's one thing. Okay. So, yes. So caffeine, as it turns out, is an antagonist of adenosine receptors, which means it blocks adenosine receptors. So if it blocks the thing that makes you sleepy, it makes you feel awake. Amazing.

Question. Okay. So if you plotted the adenosine throughout the day, like starting in the morning of like an average day, or you did this and you averaged it or whatever, in the morning would it also be high because you're just waking up and you're not quite there? Like, why does caffeine make you wake up in the morning? Like, I could see why it would throughout the day make you feel more awake as it blocked those receptors, but why in the morning does it help?

Great question. So I don't fully know the answer to that. I don't know if maybe there's just adenosine, like, leftover, residual, or if just by blocking those receptors, you prevent any adenosine from binding. But I have seen some studies that suggest that caffeine has greater effects. if you're already a little drowsy, right? So if you're already tired and then you drink caffeine, it has greater effects when they've done trials of like,

how alert are you, what's your response time, things like that? The effects are greater if you're already drowsy rather than if you're already alert, if that makes sense. So there's like a maximum alertness almost. And then, so like to get back to that maximum, you have to be a little bit. Like coffee will help you get to there? I don't know.

It's a little, it's complicated, and this is just the basics. It makes sense, though, because I feel like anymore today, caffeine in the morning just kind of levels me, whereas caffeine at like 2 p.m. floors me. I'm like, oh, let's get this done. So another interesting point is that, remember I said you can become dependent where you can have withdrawal symptoms? When you are a habitual user of caffeine, your body actually upregulates the number of adenosine receptors so that adenosine can still bind so that caffeine is actually less effective. effective, which we see with so many different compounds where you basically, like, create tolerance to it. Your body finds a way to get around this drug that you're giving it, right? How long does it take to build a dependence or, like, to actually see those physiological long-term changes?

Not very long, because you can have withdrawal symptoms after just maybe like three or four days of chronic caffeine use. but it usually only takes 48 hours to go through withdrawals. But for some people, it can take up to like nine days. Oh, wow. Caffeine's another thing that, like, the effects of caffeine are very greatly, depending on like, interpersonal differences in metabolism and things like that. So there's a huge amount of variation in, like, the effect that a single cup of coffee

is going to have on any given individual? I have a question. Oh, gosh. Okay. Okay. So in terms of talking about withdrawal, why do we see some of the symptoms we see? Like, when you have, let's view you have those, the excess of receptors,

like, I could see how you'd be sleepier than normal or it'd be more difficult to, like, wake up. But why do I get a massive headache? And I feel like killing everyone around me. Great question. Okay. So let's talk about some of the other effects. of caffeine to be able to understand that. Thanks for asking. I'm very excited. That's perfect. Okay.

So the alertness and awakeness, that aspect, right, it's like hypervigilance, increased alertness, which leads to things like faster response time, better driving, okay, if you're sleepy, caffeine does make you a better driver, things like that. Those we can kind of all explain from the whole adenosine receptor thing. But that's not the only place that we have adenosine receptors. It's not just in those parts of our brain that have to do with sleepiness. Okay. Adenosine has a lot of other effects on our body. For example, there are adenosine receptors in our heart that block electric signaling in our heart. So, for example, if someone in the hospital has what we call a superventricular tachycardia, so their heart is beating way, way, way, way too fast and out of proper rhythm, you give them

a denazine, it blocks all-electric conduction to their heart, stops their heart for a split second, and then they can restart in normal sinus rhythm. So if adenosine can stop and slow your heart rate, what do you think caffeine can do if it blocks those receptors? Increase that heart rate. Yeah. Okay. So that's an effect that you mentioned, Matt, right?

You feel your heart rate. Oh, yeah. Okay. So headaches. Adenosine has also effects not just on your heart, but on your vascular in your brain, adenosine can help vasodilate vessels to your brain, while in your peripheral blood vessels, it causes vasoconstriction. Don't ask me the details, please. Why? And it does. Do you that? That was my next question. Details. So caffeine does this. The opposite. Caffeine causes vasoconstriction of your cerebral blood vessels to your brain and vasodilation of your peripheral blood vessels. Vesoconstriction is what a lot of headache medications do because a lot of headaches are caused by vasodilation increased pressure in your brain,

right, from too much blood flowing there. So if you have caffeine and can vaso-constrict those blood vessels, caffeine is really helpful and it's in a lot of headache medication, right? Like, what do you call that stuff? Excedrin. Excedrin, yeah. Right. And there's been a lot of studies that show like inseds with caffeine are more effective than insides alone for a lot of headaches.

But on the flip side, if you then take away that caffeine that your brain is used to having, you're going to have increased blood flow to that brain. You're going to have a headache. Oh. A bone. Wow. That's pretty fun, right? What about my hollow bones?

Your hollow bones. You're a bird. Stop it. So I'm not sure this can fully explain the hollow bones necessarily, but the jitteriness, okay? So this one's really fun. Adenosine in your brain also has interactions with dopamine receptors and dopamine release. We've talked about dopamine a number of times on the podcast, but dopamine is really important both in mood, So more dopamine usually means more happier, but too much dopamine can also mean like psychosis.

So we think that things like schizophrenia have to do with too much dopamine. Wow. But dopamine is also really important in motor control, right? So Parkinson's, for example, is a problem where your basal ganglia doesn't produce dopamine properly or doesn't respond to dopamine properly. so you end up with slow movement and arresting tremor. Okay. So adenosine normally is an antagonist of dopamine. So it blocks the release of dopamine.

Caffeine is an antagonist of adenosine. So it increases the release of dopamine. So it can cause those like tremors. It can increase muscle contraction. So maybe that's part of it for you, Aaron, and your hollow bone. It's why some people think that caffeine is a performance enhancer in general, right? Like for athletic events. People used to use caffeine, they still do, I'm sure, for like, it's going to make me run faster.

There's not a ton of data that says it actually does. It really just delays exhaustion, most likely. But, you know, give it to them if it makes them feel good. I'm calling the Olympics. That's a performance-enhancing drug. You know, there used to be limits on how much caffeine you could have in your bloodstream as an Olympic athlete. How much could you have? Like, what was, I don't know.

That's like a question for you. History. That's so fascinating. And it makes so much sense. And it also can kind of get at Matt why you said caffeine makes you feel happy, right? Caffeine can also increase serotonin levels. in your brain. So some people think that it can maybe help with depression. There's not a ton of great evidence for that because we've kind of already talked about a lot of these symptoms, heart palpitations,

you know, feeling like you're jittery. That sounds a lot like an anxiety attack. Yeah. So caffeine can actually exacerbate anxiety, especially in people who already have anxiety or who are prone to panic attacks. I've definitely had periods of my life where I've had to avoid it for that reason. And when you were going through the history, I was like, I want to meet the first person to overdo it on coffee. Yeah. Yeah. Yeah. Somebody, I can't remember who it was used to drink. This isn't coffee, but they would drink around 50 cups of hot chocolate a day. Nope. Bad idea. Okay. I just got an indigestion thinking about that. Speaking of, why does coffee make you poop? Okay.

Please tell me. So poop and pee, right? So people will say caffeine's a diuretic. It makes you pee and it makes you poop. I saw some things that suggest that maybe it can have some like pro-motility effects on your bowels. But in general, my understanding is that that's mostly a timing association. Most people poop in the morning. Most people have coffee in the morning.

You know, anytime you eat something, that's going to kind of wake your bowels up, get them moving. so then you can have a poop. The diuretic effect, so making you pee, there is some evidence that at like very high levels, there might be some diuresis from caffeine ingestion, but in general, especially at levels that you would consume normally, it's really, it's a negligible effect. So it's really like, are you drinking a liquid,

then you'll have to pee. So the whole thing about like coffee dehydrating the heck out of you is probably blown out of proportion? Yeah. I think it's, again, with the tolerance thing, if you never drink caffeine ever, then maybe it might have a little bit more of a diuretic effect than if you drink coffee regularly. But in general, it doesn't really have as strong of a diuretic effect as we used to think. Man, I am shocked about it not having a direct link to pooping.

Yeah, there was only like one paper that I saw that even mentioned. its effects on GI. So I don't even know, like, how real. I think it's largely timing, you know, you eat something, you drink something that wakes up your bowels. Like your guts and sleep. I don't eat anything in the morning. Yeah. So even coffee has calories, right? And it's, it's, it's, sending the signals to your stomach. It's send, it's activating those stretch receptors. It's, it's got amino acids. It's got, I thought, I thought coffee didn't have calories. But it has stuff in there, right? It's not just like drinking water, right? There's, I don't know what else is coffee, oils, amino acids, other compounds that are going to stimulate your, plus also you drink it with half

and half Aaron, sometimes. It's also, it's got to be negligible because all like the fasting, intermittent fasting stuff is like, coffee's fine. Don't worry about coffee. Yeah, it's true. Yeah. Oh, you want to know a fun, um, Side note use of caffeine. I learned this while researching. I think it's fascinating. Caffeine is used in premature newborns to help prevent apnea. So like to make them breathe better, essentially.

Because it helps your diaphragm, it helps their diaphragm to be more active and prevent complications from not breathing properly. So not just caffeine, but another. So caffeine is in a class of compounds called methyl xanthines. And there's another methyl xanthine that we actually used to treat asthma called theophalin. Interesting. Yeah. That's amazing. I know.

So one of the things that I was always told growing up, because I loved coffee as a kid, was that it would stunt my growth. And then I grew up to be the shortest by far of everyone in my family. And so I've always won it. That's it. That's it, Aaron. No. It's just bad luck. There's no effect.

Excuse me. Oh, sorry. Wow. Your jeans are terrible and you have coffee to find. There's no association with short stature and caffeine intake. Okay. What about any of the other studies? Has there been any association between caffeine intake and negative outcome in anything or any positive outcome? So there's been a lot of talk about whether it has effects on your cardinal? cardiovascular disease or increased risk of death from cardiovascular disease. There's not really an association there. There's some people that say it can increase your blood pressure, which for someone who never drinks caffeine, if they drink caffeine, you can see maybe like a 10 point bump in their blood pressure transiently, but if you drink caffeine regularly, it has pretty negligible

effects overall on your blood pressure. Basically, all the things that we used to think caffeine is just so terrible. It has all these negative effects. It doesn't actually have a lot of association. A lot of the studies that used to show it, because the problem with caffeine is that most of our studies about caffeine are coffee drinkers, right? Which means they're dietary studies, which means they're really hard to do. There's a lot of different ways you can end up with biases, like recall bias. But then there's also a lot of interactions in terms of who drinks coffee. So in some cases, it's actually people who are generally healthier that are drinking more coffee because they have access to it and they can afford it. But on the flip side, there's also associations with things like smoking and increased coffee drink.

If you think about going out for a smoke break and a cup of coffee, etc. And so in the past, a lot of studies have kind of confounded, especially the effects of cigarette smoking and coffee. drinking, which is why for a while, I think a lot of it was like, coffee's terrible for you. And then it was like, coffee will save you. And now it's kind of just like, if coffee makes you feel more awake than have some coffee. What about the sleep impacts? So caffeine increases your sleep latency, which means it takes you longer to be able to fall asleep. And subjectively, people say that after drinking caffeine, they feel less rested when they

wake up. So they say that it interferes with their quality of their sleep. In terms of how long the effects of caffeine last in your body, it can vary quite a lot. But on average, the half life is like three to seven hours. So if you drink a cup of coffee in the morning, it should be well gone by the time you get to bedtime. But if you have a cup of coffee at like four in the afternoon, then yeah, you'll probably have still like half of that in your bloodstream by the time you go to bed. Okay. Yeah. My cutoff is three. Yeah. Yeah.

My cut off is like 10 a.m. Oh, geez. I could chug like a triple espresso and fall asleep right after. And that's the thing. There's a lot. Yeah. There is a lot of variation, individual variation in the metabolism of caffeine. And then, of course, there's tolerance effects on top of all that.

I think it is interesting. Like, there's still this association that we have with like, oh, I'm giving up caffeine. It's like a very puritanical kind of like glimpse of like this thing that, you know. Oh, another thing I'd like to say because I get this question a lot from like friends. Caffeine and pregnancy. For a long time, it was like, no, you can't have caffeine if you're pregnant. There's been really no good studies that show that small amounts of coffee like up to 300 milligrams of caffeine, which is about like two to three cups, depending on what size your cup is.

Don't really have any effects, adverse effects on fetus or mom or anything. So, yeah. So, however, in the third trimester of pregnancy, the half-life of caffeine is increased quite a lot longer, which is super interesting. And in newborns, it's super long, like 80 hours it can be where caffeine, like that's the half-life for caffeine, which is so interesting. Don't ask me why. livers. Ooh, man. I've also read that taking oral contraceptives increases the half-life of caffeine in the body. It makes sense because the, so caffeine is metabolized by your liver, and oral contraceptives, especially ones with estrogen, are going to also have a lot of interactions with your liver

and with the enzymes that potentially metabolize caffeine. So I don't know for sure, but I wouldn't be surprised if that's why your half-life of caffeine increases in third trimester pregnancy when your hormones are going wild. Hmm. Interesting. That's wild. That was fun, guys. I'm glad you asked me so many questions because my notes were not organized, but I feel

like that was fun. I got over-eager and I couldn't stop. I'm learning. And what's amazing is how much of this I've just kind of taken with me and held on like, oh, this is what caffeine does. never realized how on the fence at best some of this is. Yeah. Yeah.

Yeah. And it's also, I will say it's really, really difficult, too, because a lot of our data about caffeine comes from studies on coffee. And coffee is not just caffeine, right? There are so many other compounds in coffee beans. There's so many other compounds in tea leaves that are different from coffee beans. So it is really difficult to fully get a handle on the exact effects of caffeine. fiend per se on these various processes.

So, Matt, can you please tell us why on earth would plants make such a substance and what is it good for? IRL. Amazing question. I'm so happy to be here to talk about this. We'll take a quick break and then I want you to tell us all about it. Okay. All right, Matt, hit us with the good stuff. Yeah.

Yes. So yet another fascinating dive down the literature hole on this one, and it is never as simple as I ever expected to be. So thank you again for forcing me to look at this, especially considering how dependent, we'll say, I am on this product. So as Aaron established in the beginning, more than just coffee produces caffeine. I keep seeing this number around 60 different species tossed around, but I did that whole web of science thing and traced it back. And it's just something that someone threw out there, they cited like a very very vascular flora of the tropics and just kind of picked it out. And basically what we're going to come down to here is that certainly far more plants than just 60 species do this. But we generally only tend to look at things that interest or have it used to us in some way. So food, drink, medicine, caffeine, tea, chocolate, that sort of stuff. But again, as we have established, some of the most prominent ones are very familiar to us.

So the genus Kaffia, which is the coffee plant and all of its relatives. Theobroma, which is chocolate. Citrus actually produces a fair amount of caffeine. Camellia, which is the genus for tea. Cola, which is the genus for the cola tree, which has gone on to give us a lot of soft drink flavoring. I see it hand raised here. Yep, sorry. Does that mean like oranges?

Not within the orange itself. We'll circle back to that, though. Okay. All citrus do this on some level. Okay. So Guarana, which is the genus Polinia, and you'll notice Guarana is a common ingredient within a lot of energy drinks because there's other compounds related to caffeine that have stimulatory effects.

And then a lot of hollies, which if you've ever drank, you've both been in Central America, Yerba Matae, which comes from a holly. So there's other, again, other stimulants within that, but caffeine is a major component of it. And so those are just the ones that have economic use to us and that we study the most. But again, this is something that's prevalent in a lot of different plant families and within those, a lot of different species, which is amazing. And the coolest part about it is that there is actually more than one way to synthesize caffeine if you're a plant. All of it involves alkaloid chemistry, which caffeine is a type of alkaloid.

And it tends to rely on, as with any alkaloid production, high nitrogen in the soil. So you generally will find these sorts of species in rich soils because you need a lot of nitrogen to build alkaloids. And that's kind of cool. You can look at something about the habitat that has allowed. the evolution, or at least selection to work on the evolution of these compounds. So the question then becomes, why is it there? Nothing in nature is done wastefully. There's always some sort of function in there. Well, it just so happens that researchers at the University of Buffalo, which is my alma mater, were studying the genus Kaffia, and they found that there are multiple

genes involved in the synthesis of caffeine, and that they did not arise all at once. Hmm. What? Yeah. So genes duplicate a lot in the plant world. It is not nearly as detrimental to have ploidy events in plants as it is most animals, I would assume, at least on the vertebrate spectrum of things. So ploidy is essentially a copying or duplication of the chromosomes. So you can have diploity, which means there's double the amount of chromosomes, triploity, and so forth. And that's really common in plants, and it's a very important way in which plants evolve and speciate and, you know, go about doing all the amazing chemistry that they do. And within just coffee alone, the genus Kaffaa, the genes that are involved in the production of caffeine have duplicated multiple times throughout the history of this genus. And what's amazing is that, like, in the creationist literature, that the propaganda that goes out, they use this to say there's no.

way this could have happened because every step in the way is important. You can't have this irreducibly complex system without there being a creator. But when you actually look at every step, every gene duplication, every mutation that led to the process, every compound that is the end result of that has a function for the plant. It is always bitter and it's always stored in an area in which will prevent herbivory. I get so excited about things like this. Every step of the way, every precursor compound is bitter and toxic to the exact kind of animals that want to nibble on these plants. Oh my gosh.

It's, it's mind-blowing. Just to kind of see how, like, and you look at these papers and you do see these chemical, I just like looking at them. I don't understand them to save my life, but it is amazing that every one of these compounds, every step of the process, has an anti-herbervery function, which brings us to the main function of caffeine for plants. The primary function or role that it's playing is a defense against herbivory and pathogens, which shouldn't surprise you.

So many of the chemicals within the plant world that we like to utilize have their origins and keeping something from attacking or eating them. And so as Aaron already mentioned, there's a lot of methyl xanthanes. And the way that they've kind of come to this conclusion is that they're able to kind of turn these genes on or at least insert them into crop species like beets that don't normally produce caffeine. And every time they induce caffeine production in a crop species, it has significantly less herbivory than their relatives, the clones that do not have caffeine production. So are they inserted in, like, is that one of the strategies to create, like, you know, as like a

natural pesticide, GMO pesticide plant? It, that is totally the motivation for doing this. I think the complication then becomes is keeping it from being expressed in tissues you don't want it. So I don't want a beat that's going to keep me up all night, right? And so it's a cheap way to study this. But in terms of the motivation behind a lot of these studies, it is trying to figure out how to get, say, foliar genes to express caffeine production as a quick and easy way. Because even at low concentrations that you would find in nature, these have a pesticidal effect, which is pretty cool. Like, even at low doses, it's keeping these things from being eaten. Wow. So caffeine is in so many different plant species all over the tropics naturally.

So does that mean that it evolved separately or in these convergent evolution, basically, events? Is caffeine like a simple molecule or like a relatively simple molecule that it had? Like, why caffeine? Like why that one particular compound? You know what I mean? Do you know what I'm asking? No, great question. Yeah, yeah. And so, yes, to answer your question, it is independent evolution. I mean, even if we just look at the families that we have listed already, caffeine or coffee is in rubyacee.

We have chocolate, which is now malvacy. It's a mallow. We have the hollies, which is aquifoliaci. They're their own family. We have, you know, it's widespread and independent. In terms of the complexity, I think it's a pretty complex molecule. And I think it's one of those things that just as evolutionary, is working as selection against her bivory works on it, you just have instances where it's either

you just have some sort of byproduct where a mutation leads to it and it just happens to be more bitter. And I think it's sort of selection against, you know, insects are really good at acclimating and evolving. That's that evolutionary arms of H. This is why we have so many chemical pesticides within the plant community is just because insects are really good at adapting because their generation times are so low. So I think it's a complex molecule. And, And I think it's one of those things that just kind of gets refined depending on the selection pressures of that given environment. And of course, anything that's valuable to us and especially in terms of things that are tasty, we breed it to do way more than it normally would in the wild. Which I have a really cool episode that's involving THC coming out soon, which has similar conclusions in terms of our use versus natural background.

Interesting. Yes. That sounds like a fun episode. It is. and I'm really excited for it. But yeah, so at lower concentrations, at lower concentrations, these methyl xanthines, as Aaron already pointed out, are really good pesticides. And they activate something within the insects, which I actually wanted to ask Aaron about

this, is the identolate cyclase. They activate that. They made that, they put that out there, and we're just like, of course it does that. And I was like, what does that? Yeah, that's getting into the biochemistry of things that I'm not going to get into, But like the adenosine receptors, some of them increase cyclic AMP, some of them decrease cyclic AMP. So then caffeine. So it's all basically the same general compounds that it's going to affect in insects versus humans and other mammals, if that makes sense.

Like on a biomolecular level, it's the same basic stuff. Cool. So apparently it works that way. But again, plants have many ways in which they can defend themselves, and there's mechanical defenses, which are like the thorns and spines that, you know, you grab a rose, you pay for it royally. But it's also just having tough tissues. And what's cool is that in early development of leaves and stems and stuff, caffeine production is super high. But as the leaves mature and become more tough, they, you know, kind of reinforce their cell membranes.

Caffeine production actually goes down, which is why actually younger tea leaves are preferred. They have a higher, because they're soft. and more vulnerable, they need the chemical defenses before they can beef up their structural defenses, which if you think in terms of investment in defenses, making lots of chemicals is expensive, whereas just using and reinforcing that lasts a lot longer. Oh, that's really cool. That's really amazing. Wow.

Yeah. Okay, so caffeine is in the seedlings really early on, because, again, it's like those mechanical defenses. The seeds are small. They're really vulnerable to herbivore. as smaller stuff, especially like slugs and everything that wants to eat a small, tender seedling. So caffeine production for about the first eight weeks is super, super high. And then it eventually starts to decline, just like we see in leaves throughout the germination

process. And so as long as the seeds are small and have this uniform soft tissue, this accumulation of caffeine is just going to continue to increase, which is pretty amazing. But as soon as the seeds start to toughen up, that's when you start to see that decline, again, goes back to this idea that nothing is being done in sort of a wasteful sense, and that a lot of these productions of chemicals, any chemical compound within a plant, it can either be inducible or it's really during a short period of time of development because they're not doing this for us. They're not doing it because we want them to.

They're doing it to protect themselves. And within plants like tea, there's also a shift you'll see in sort of where the caffeine's being stored. So once those tea leaves really start to toughen up, they start really packing it into their vacuels, which whenever an insect bites into it, those burst, and that gets into their mouth. And that's where you start to see, again, that sort of protection effect, where it's just like, oh, God, this is disgusting. I got to stop eating it. But they also put it into their vascular bundles, which is the vascular tissue throughout the plant. And that's one of the main conduits by which

pathogenic fungi will attack. And any organic gardener knows that a lot of antimicrobial properties are within coffee grounds as long as you haven't boiled them. And so there's also a big component of keeping microbial pathogens away. So it's not just herbivory. It's protecting against fungal attacks as well. But that's cool because it's also kind of funneling it to the areas of the plant that are most vulnerable. That's super cool.

Plants are so smart. Yeah. So if the caffeine molecules act on insects in similar ways as they do on humans, why, and I don't know who I'm directing this question towards. or whom I'm directing this question towards, but why do humans become dependent and want more caffeine? And insects are like, ugh. Because, I mean, obviously we like the bitterness and there is obviously bitter taste.

And it's evolutionarily wise, I'll say, just for lack of vocabulary at this point in the day, to avoid the taste of bitter things because it tends to be, you know, poisonous or toxic. But are there insects or insects or animals? animals in general that like caffeine. Hmm. That's a really good question.

And I, so for instance, if this was alcohol, I would say, yeah, there's tons of evidence that animals are seeking it out and having similar issues with alcohol that even humans have. For caffeine, I don't know. I don't think so, although there is this evidence of like, you know, that we talked about the civets having to pass the beans and making the best cup of coffee. So I would say potentially, but that's a mammal of a larger body mass. I would assume, you know, for as anxiety-ridden as I can be after, like, two or three cups of coffee, a few bites on a leaf for an insect is probably really rough for that body mass.

Yeah. Yeah. And I don't want to say, like, that the effects of caffeine are the same in an insect as they are in a human. I just mean, like, on a molecular level, the, like, changes are probably going to be similar. Right, right. The mechanism of effect. Right. Yeah.

But that's a really interesting question. Yeah, I would be really curious to look at even just dispersal because you have to figure like those coffee seeds have to go somewhere, right? And the dispersals usually, and especially if it's a redberry aided by some sort of animal. And so I wonder if caffeine, which will actually get to in a little bit here, some other ways that maybe caffeine could work for animals and plants together. But first, I want to talk to you about competition because everyone thinks about plants is sort of a static, not really interacting with the world kind of organisms, and especially

not harming each other or working against each other. You know, the World Wide Web stuff came out, Kumbaya, everything's getting along. Well, actually, plants are competing all the time. That's the only reason we have tall plants at all is because they can shade each other out. They take up space where other routes could go. They're competing for nutrients, water, all of that sort of stuff. And so it makes sense that at some point, anti-competition mechanisms would evolve in some species. And there is a lot of evidence that caffeine can be involved, can be involved in anti-competition interactions among especially young plants. What?

So, they looked at putting coffee seeds into auger just to see what was going on with relative caffeine levels as plants germinate and grown. We already established that they will really ramp up production while the seedling itself is growing. But what they found out is that the seed coat will actually leach a considerable amount of caffeine, up to 22% of the caffeine within the coat itself, into its surrounding environment. And when they use different levels of caffeine, especially that reflect background natural levels of what we're seeing from the leaching of the seeds, it's actually been shown to inhibit germination and growth of the surrounding vegetation. How?

Yeah. So these seedlings are releasing a ton of caffeine into the soil. which will inhibit the germination of potential competitors that could overgrow them and steal light, water, and nutrients from them. So caffeine is actually also an anti-competition compound. It's allelopathy. It's plants using chemical warfare. I do not know the mechanisms of it, but I'm assuming it has something to do with the metabolism. Here's a plant that's producing it, harming other plants that might not be, or it could even just be within its own self.

you know, within its tissues, it's fine, but if it's in the soil, interacting with the root hairs, maybe even, you know, the fungi that they're partnering with, there's a lot of mechanisms with which allelopathy can work. And it's one of those areas of science that we're only really starting to get our heads wrapped around. And it's, it's difficult to study. So there's a lot of open-ended questions, but that's just call for more attention, call for more work. Coffee's really easy to germinate. So it's something you could do in a greenhouse study pretty much anywhere in the world. So, Hey, kids.

Science experiment. So what's amazing is we have this dual benefit here. We have an anti-erbivory antipathogen, really protecting plants as they grow. And then they're also involved in anti-competition, so keeping your space free of potential competitors. But going back to your question about citrus, there is also evidence that caffeine is highly involved for a lot of the plant species that produce it in pollination. And this is where things get really cool. Yeah. Yeah.

Yeah. So this is best studied in coffee and citrus, but again, with the amount of plant species that are known to do it and probably are still yet to be kind of described or discovered to be doing it, a lot of these plants pump small amounts of caffeine into their nectar. Small amounts. Not nearly enough to be at that level of sort of anti-urbivory or preventative. but when they looked at this, they started asking these questions, what is this anti-urbivory compound doing in nectar? You know, this is supposed to be the one place where a plant really wants an organism or at least an insect to interact with it. So they studied this in honeybees. And again, all of this is done in species that have been domesticated, have used to humans just because

of the funding, but it really has a lot of implications for what's going on out in the wild. nonetheless, caffeine concentrations in nectar were found to not exceed the bees' bitter taste threshold, and I really want to know how they decided where that was. They just asked, they're like, can you taste it now? And the bees are like, whiz. And they're like, can you taste it now? And they're like, biz, biz, biz. And then they're like, bleas, blues.

But the fact that the levels in the leaves and the levels in the nectar seem to be highly regulated for, uptick in production, but keeping below a threshold in the nectar implies that there is some sort of selection for pharmacological activity within the nectar that isn't supposed to function as a repellent. And what they found is that when researchers presented bees with naturalistic levels of caffeine in any sort of drink, the bees were able to not only remember, locate, and understand the floral scents much higher than in any situation in which, which there was no caffeine in the nectar. So it also increased their alertness and their productivity and their focus and their

desire to poop. No. Yep. They're just squirting little bee poops everywhere as they go. But the thought is that actually the plants have also co-opted a slight amount of caffeine in their nectar to enhance the memories of reward within their pollinators, which secures pollinator fidelity and improves the reproductive success of the plant overall. That is incredible. That is beautiful. It's mind-blowing. So you have, you have defense,

you have minimizing competition, and you've got your sex taken care of. This is hitting all three of the major instances of things that actually influence plants in all steps of their life. Some of the most basic things in life is surviving, not getting sick, and being able to reproduce and caffeine is involved apparently in all of those in the species that is producing it that are producing it. Wow. Wow. What a gorgeous story. Did you come across anywhere about like when it was estimated that caffeine first evolved, like when plants first started to produce caffeine? So I did, but it seems like one of those things that's like heavily debated because you do have gymnosperms that produce like ephedra is from, or ephedron is from ephedra, which is a gymnosperm

that's probably much older than most of the flowering plant lineages. And estimates put most conservative the evolution of flowering plants somewhere in the Cretaceous, so when T-Rex was roaming the landscape. And so, you know, some of these lineages can be dated back to the Miocene, the Eocene, you know, so 40, 50 million years ago, but some of these lineages go back much farther. There's fossil evidence for them. And the problem is is we just don't know. You can't look at a fossil and tell what kind of chemical constituents were being produced. All we can say is this is affiliated with this order. This order is known for producing a lot of it. Potentially it was there. Yeah. Yeah. And are they all,

are all of these plant species concentrated in the tropics and subtropics? So the major ones that we talked about today, yes. And there is a really interesting latitudinal gradient. If for anyone that's familiar with this, it's basically going from the poles to the equator, there's usually a really strong gradient of like spices, all of these antimicrobial, anti-erbivory compounds, they increase the closer you get to the equator, but so does biodiversity. So all of the pressures and the climate of like inducing microbial attacks, fungal attacks, those are all way worse in the tropics. So the idea that you would see a lot more plants potentially stumbling onto this evolutionary process in the tropics, it just makes biological sense in the long

run. The laws of thermodynamics probably play in there just as much as evolution does. Oh, my God. Yeah. I love these episodes. I was just going to say that. I love these episodes so much. These are the Horizon Expanding episodes for me because it's like I'm able to connect so many more dots afterwards.

It's so cool. It's so cool. Wow, plants are really incredible. We don't give them enough credit. I'm telling you. That's why I'm here. It's why we need to. Oh, that was so fun. Thank you so much. I learned. Oh, my gosh. Oh, my gosh. Yeah, thank you. So, thank you. I always walk away a more full person after this. So thank you very much. Oh, this was great. Now we just have to brainstorm our next one. Oh my gosh, yeah.

Any requests, anyone? Send them our way. Yeah, please. I guess do we do sources now? We should do sources, yeah. Okay. So, let me pull mine up. I drew heavily from a few different books that I'll mention.

One was called The World of Caffeine, the Science and Culture of the World's Most Popular Drug, by Weinberg and Beeler. And then I also read, I also listened to a book because it's only an audiobook, which is the first time I've encountered that, called Caffeine, How Caffeine Created the Modern World by Michael Pollan, and then finally by Mare and Ho, The True History of Tea.

And I watched a documentary that is on YouTube called Black Coffee, and it's a Canadian National Film Board documentary. It's like a three-parter. It's really interesting. But I will say that the last section is like a bit too much like a Starbucks episode for me to feel comfortable with. But the first two are great. Cool.

So, yeah, I pulled from a handful of papers that we, I guess we can link in the show notes or whatever you like to do. So the first one was caffeine and related methamothanthines, possible natural occurring pesticides by Nathan, 1984. Oh, Nathanson, 1984. The second one was purine, alkaloid formation, and buds and developing leaflets of kofia arabica expression of an optimal defense strategy by Frisch Knecht at all, 1986. Convergent evolution of caffeine in plants by co-option of exacted ancestral enzymes by Hoanga at all 2016 and the immunohistochemical localization of caffeine and young camellia senensis by Breta at all 2013. And then finally, caffeine in floral nectar enhances a pollinator's memory of reward by Wright at all 2013. Awesome.

Excellent. I had a number of articles. I don't want to read all of their titles. So suffice to say, we will post them all on our website. This podcast Will Kill You.com where you can find our sources for this episode and every single one of our episodes. There's some great ones, especially if you want to read more about, for example, the effects on dementia, whether or not it's a diuretic, the effects on your cardiovascular. health, et cetera, et cetera. I got papers for all those. And we'll also put all of these onto our bookshop.org affiliate page, as well as our

Goodreads book list. So if you want to read some books or listen to some books, check them out. Well, thank you again, Matt, so much for coming on. We love having you on this podcast. It's so much fun and we learn so much every episode. Thank you both so much for having me. It's always a blast. I'm you all so much and I can't wait until we can do this in person again. Oh my gosh, I know. I know. I was just thinking that and I was like, I can't even say it. It's too sad, but. I know. Sorry, I'm the downer. Someday. Well, hey, usually I'm the downer, so it works. And then when we do meet, we will

drink all the quarantinis. We'll just carry on and then have some caffeine for the next morning. I was going to say quarantines and coffee. We'll be upset. It's a bad. It's a bad. combo, by the way, but separate topic. You mean for loco is bad for you? Yeah. Mm-hmm. Yeah.

What? Oh, my God. Also, thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to you, listeners. We hope that you enjoyed this episode. Thanks so much for sticking around. Yes.

Thank you. Thank you. Thanks for listening. Wait, Matt, you should tell everyone where to listen to your stuff and where to find stuff. Indefensive Plants is on all the major podcatchers. Just Google it. So, you know, iTunes, Spotify, Stitcher, that sort of stuff. Indefensiveplants.com is the website, blog. A lot of really cool updates. That's where you're going to find them. Twitter, Instagram, please follow there. I've got a lot of cool stuff coming out in the next couple of months, some big announcements. So please stay tuned. If you enjoy these sorts of things, there's more to be found. So yeah, go check it out and say hi. Yes, yes, yes. Yeah, I can attest that the In Defensive Plants, Twitter, or Instagram is incredible.

Oh, thank you. I enjoy it. It's so great. I appreciate that. Great content. Okay, well, until next time, wash your hands. You filthy animals. I'm Amanda Knox, and in the new podcast, Doubt the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023.

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