Caffeine: How Much is Too Much?
Science Vs podcast
Chapter 1: We love/hate caffeine
Hi I’m WZ and you’re listening to Science Vs, the show that pits facts against flat whites! On today’s show: caffeine. Should you quit it?
Caffeine is one of the most used drugs in the world. 85% of people in the US drink at least one caffeinated beverage each day. That includes kids[1]!
But yet, despite the fact that we are shoving this drink down our pie holes, there have always been these fears that caffeine is bad for our health…
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Your cup of coffee could soon come with a spoonful of cancer warning
My heart was racing.. I was super anxious…something was happening, I was having a panic attack
Could it all be a sign though of a serious problem?
A problem like caffeine addiction… ?
And our worries around caffeine have reached new heights when it comes to Energy Drinks
Just last year, a 17 year old from Texas died after drinking Alani Nu[2] …
A Texas family is filing a wrongful death lawsuit over an energy drink that they claimed killed a teenage girl
According to family lawyers, a coroner’s report shows that she died from an enlarged heart caused by stress and a large amount of caffeine from Alani energy drinks
The distributor being sued - denies the claims and the company that makes the drink says it’s labeled ‘not recommended for children.’[3]
But this is just the latest in a string of scary stories from the past several years of people, often younger people, dying soon after drinking energy drinks[4]...
Davis collapsed in the classroom of his high school in South Carolina
It wasn't a car crash that took his life, instead it was an energy drink
She drank two 24-oz energy drinks in less than 24 hours…
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…and it took her life
So today on the show what is this drug doing to our brains and bodies? Is it ruining our sleep, turning us into caffeine addicts… and potentially even killing us?
When it comes to caffeine, there's a lot of
My heart was racing
But then there’s science.
Science Vs Caffeine is coming up just after the break.
BREAK
WZ Welcome back. Today on the show we’re taking on caffeine and energy drinks to find out once and for all how bad this stuff is, what is it doing to our bodies and our brains.
And we first drank up the science on caffeine a few years ago when we first put down this episode…and back then, there was all this hubbub about the energy drink Prime… And that’s what got senior producer Rose Rimler interested in this topic in the first place.
RR Yeah, a lot of the talk was about how it’s got a crazy amount of caffeine. It’s bad for us. Energy drinks are bad for us. And sort of just this feeling that caffeine is bad for us. And I dunno about you but I have caffeine every day when I have my coffee. So it made me wonder like, is my caffeine habit something I should take a second look at? Or is caffeine just all hunky dory?
WZ Yes I love this question because caffeine has been a thing that I have actively said you know what? I’m not into meth but I’m gonna be fine with my caffeine use. I felt guilty about it and I do wanna know whether I need to. So where do we begin?
RR Let’s start with Astrid Nehlig, she’s a caffeine researcher, and she says she hears this idea about people feeling guilty all the time.
AN I meet somebody. And they ask me on what I work and I say, I work on coffee and people are very shy all of a sudden and withdrawing a bit and telling me, oh, it's very bad. I should probably not drink …
RR Astrid is an emeritus research director at France’s National Institute of Health and Medical Research[5]. And she has studied caffeine for decades. So with her help I’m gonna walk you through what caffeine is doing to your brain and your body.
WZ: Ok
RR So Wendy, I asked you to come prepared with your favorite caffeinated beverage. So what did you bring today?
WZ That’s right I have an oat cappuccino.
RR Ok. Take a sip.
WZ Should I do it like ASMR? Or if you have misophonia just tune out. <<SIP noise>>
RR Ok gonna tell you what it’s doing RIGHT NOW.
WZ: Ok
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Chapter 2: How coffee affects our gut
Scientists think that once the coffee gets to your stomach it’s gonna wake up your guts – it’s gonna get your stomach to produce more acid … and your liver to produce more bile[6].
AN So it's really an activator of digestion.
RR Is that why, um, not to be crude, but sometimes you have to go number two after you drink coffee.
AN Yeah. At least in some especially sensitive individuals yeah it’s like that
RR We know this because, thankfully, in the 80s scientists got permission to stick probes ...
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… up people’s buttholes and give them coffee to see what happens[7] …
And the reason they wanted to test it this way, is because they had given people a survey and said do any beverages make you have to poop? A third of the people in this hundred-person survey said yeah, actually coffee, makes me poo. So they got some of these people and some other nonresponders into the lab and put this probe up in the upper part of their rectum ... And so what they were looking for was is there an actual physical change in your lower intestines when you’ve had coffee …
WZ What did they find?
RR In people who said yes coffee does this to me, they could actually measure “increased rectal activity.”
WZ I’m clenching. Have you been clenching as you’ve been reading this research?
RR No I’m quite relaxed.
WZ As soon as you said increased rectal activity I was like oof.
RR I like thinking of this peristalsis of your butthole ... y’know
WZ: it's graceful
RR: How food gets down, and something has to make it come out[8] - and that increased in response to coffee for some people.
WZ Interesting
WZ OK I have a very important question. How quickly — how quickly does this activation happen? Because–
RR It can happen within minutes[9].
WZ OMG! I feel so validated. Wow! Because I, like, I will sometimes have just a few sips of coffee and need to do a shit. Sorry for the kids out there. Need to do a big crap. And I have come to believe that it’s just placebo at this point. Like surely it can’t be working that quickly but it can!
RR: It can..
WZ Like just so you know Rose, because this is my first coffee of the day …
RR If you have to run off I’ll know why
WZ No I don’t! Because I took a couple sips before our chat and I’m all sorted.
RR Took care of business? Laugh I appreciate that level of planning. Always come prepared.
WZ: That's me
Chapter 3: Coffee and our brains
RR Ok so that’s how coffee can affect the gut. And from there caffeine starts getting absorbed in your bloodstream.
WZ OK.
Depends on your body this takes around half an hour or an hour to peak[10] [11] [12] So caffeine is in your blood, gets to the blood-brain barrier – and just SAILS past[13]. I talked to Astrid about this
RR When I think of coffee entering our brain I just imagine my brain is a sponge that just soaks up the coffee. Is that, is that kind of right?
AN Yes. Yeah, why not? Yes, because, you know, you drink your coffee and all of a sudden, your whole body, including your brain, gets invaded by these caffeine molecules
RR In the brain it stimulates some neurotransmitters, including dopamine[14] and that gives us a bit of a mood boost[15]. But the big thing caffeine does in the brain is- of course- that it wakes you up.
WZ: Yes!
RR: Yes, yes Its claim to fame. And it does this because it basically barges into the brain and elbows out this molecule. Called adenosine[16][17]. From these special receptors. And what adenosine is, it’s like the sleepy molecule.
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So it binds to these receptors in our brain that basically turn on the feeling of sleepiness. So caffeine’s like outta my way, I’m comin in, I’m gonna bind to those adenosine receptors. And that means you don’t feel as sleepy.
WZ So just to get real nerdy here, it’s not that caffeine is binding on to these receptors and going LET’S GO brain get excited– it’s rather the lack of adenosine, the lack of sleepiness that wakes you up.
RR Yeah! And that’s what we like about caffeine right? That’s the whole point. That it wakes us up. And it's not just about being awake – we have a lot of evidence that caffeine helps us be more alert, more focused, and helps us to react to stuff faster[18][19]
AN This has been quite extensively studied.This is clear. So for, if I take a stupid example, but
RR Please
AN If you. If you are facing a lion… if you have been drinking caffeine, you will react faster and you will run away before,
RR It could save your life.
AN Yeah, of course, absolutely. Could make a difference and save your life.
RR Scientists have actually tested this. They gave free coffee to people visiting the zoo that day and then they opened the lion cage.
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WZ Amazing. And they got away? They got away??
RR Some got away some didn’t.
WZ That’s right, those in the placebo group were less likely to get away. WE ARE JOKING
RR No, there are no lions. But there is one small study that suggests that caffeine really could save your life. So in this study, researchers had people stay up really late and then drive a car on the highway in the middle of the night. This is a real car! Real highway.
WZ: omg
RR They had a driving instructor in the next seat who could take control of the car if things were getting bad. And the scientists were counting how many times people veered out of their lane when they had placebo versus when they had coffee. And it turns out coffee made a big difference. The number of times people veered over the lane went way down after people had coffee[20].
WZ Ok the powers of caffeine[21]
RR Yes right And then I found this study that made me laugh… because it’s such a funny concept. These scientists really wanted to find out if coffee can make us appreciate humour more…
WZ laugh
RR When we are sleep deprived, we kinda lose our sense of humor, it takes a hit. So the researchers were wondering would caffeine give us back our sense of humor, improve that. I dunno if you know this Wendy but there IS a scientific test of sense of humor.
WZ oh my gosh that was entirely my next question. What is THE joke that scientists ask that they’re like, if you find this funny you have a good sense of humor
RR Then you’re operating on full cylinders. Yeah so they would show them two different pictures, ask which picture is funnier, or more podcast-appropriate, they would have them read two different headlines. Fake news headlines. Ask which is funnier? Here’s an example. I’m curious if you’re gonna get it right.
WZ I feel very cocky about my sense of humor.
RR Ok so here's the example - which of these two headlines is funnier - “Veterinarian Investigates Failed Panda Mating” that’s headline one. Or —“Panda Mating Fails; Veterinarian Takes Over.” That’s headline two. Which one is funnier[22]?
WZ Headline two is funnier. It suggests… I mean… headline one isn’t funny at all. Right? Headline two suggests…
RR Suggests something really disturbing actually. And the third headline is “Veterinarian f***s Panda” laugh
WZ laugh
RR You’re right it is the second headline. According to science, that is objectively funnier which I guess it is.
WZ I’m so proud of them for being naughty.
RR Well it turns out the caffeine in this case did not help people.
WZ I totally forgot we were talking about caffeine. Laugh
RR laugh.
RR So bottomline, caffeine may not improve your humor. But we have lots of evidence to show it’s not a myth or a placebo effect, caffeine does help us wake up, stay up, stay alert.
Chapter 4: How does caffeine affect sleep?
So that brings us to something people worry about with caffeine. That it’s keeping you TOO awake. That it’s messing with your sleep.
WZ: Yes, I have worried about this too and in fact cut down on caffeine because I’ve been worried about this.
RR: So let’s meet Gregory Marcus
GM I’m just gonna move my dog. C’mon
He's a cardiologist and professor of medicine at UCSF[23].
RR If you could be any caffeinated product, which caffeinated product would you be?
GM Oh, cappuccino, no doubt
WZ I guess he sees himself as serious on the bottom but frothy and sweet on top?
RR He didn’t refer to himself that way, but based on my conversation with Greg, I would say that’s an accurate description of him.
GM Buttercup has been removed for the moment, heheh
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RR So Greg did this pretty unique study where he got people to either drink coffee or not drink coffee at random. And then he was able to precisely measure exactly how that affected their sleep.
WZ Ooooh Ok
RR So they recruited about 100 coffee drinkers in San Francisco. Put a bunch of stuff on them they wore a fitbit to measure how well they slept and their steps, and they wore a portable heart monitor.
GM So it's essentially like a very big band aid, and it, it goes on the chest to the left of the sternum, essentially,
Interestingly in the middle of the sticker, there’s this big button[24].
GM We instructed them, just push that button whenever you have a cup of coffee or a caffeinated drink.
RR So you have your coffee, hit your button
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And one way they made sure people were doing what they were supposed to do, yknow not drinking coffee if they weren’t supposed to that day, they had everyone in the study get this app on their phone that allowed the team to monitor their location. So the team could see if they visited coffee shops[25]. So if they went to a coffee shop on a day they weren’t supposed to have caffeine, that would be highly suspicious.
RR Would they get, would there be like a button goes off in your office? Like a, a flashing red light? Would they get an electric shock?
GM yeah, that's a good idea, interesting idea.
RR Laugh
WZ That’s exactly what I was thinking! Bzzzt!
RR Well luckily for the people in the study, we didn't design it. They did not get shocked.
WZ Nooo. OK I’m gonna go out on a limb here Rose and say that on average coffee DID affect people’s sleep.
RR Yes but the key question here is how much, cause there is this idea that coffee really robs you of your sleep. Well, in reality, Greg found…
GM on days where people were randomly assigned to consume coffee that evening, they on average slept 30 minutes less[26] [27].
WZ Dahh!!
RR Yeah so on average, if they were in the coffee drinking group - they had half an hour less sleep – and Greg could even dive into the research and figure out how much sleep each cup of coffee cost these people. And it turns out to be about 15 minutes of sleep.
WZ Ok so loosely for every shot of espresso or just like regular coffee you get around 15 minutes less sleep a day. Uh huh Ok. That’s not terrible
RR Yes - BUT!
WZ ah!
RR There is an important caveat. Which is that Greg found that this REALLY varied from person to person based on their genetics. So on top of all that other stuff, Greg also took saliva samples from people. And worked out if they had these genes that make them either a fast or slow metabolizer of caffeine[28][29][30]. And he found that the slow metabolizers lost close to an hour of sleep a night on average. While the fast metabolizers lost basically no sleep at all.
WZ: huh
GM So people who say, Oh, yeah, I can have a, you know, cup, cup of coffee at night. I go right to sleep. Uh, they may be really telling the truth.
WZ My mum proudly says she can drink coffee at dinner time and it will not affect her sleep. To the point where she will mock me when she wants a coffee at 4 PM, and I say too late for me! Mama Zuk, vindicated once more by a Science Vs episode.
RR You're both right She’s right that she can have a coffee late at night. You’re right that you can’t. You’re probably both right!
WZ: laugh OK. But you know who isn’t right? Are those people online, influencers, whatever we want to call them, who have these definitive statements about how much coffee you're allowed to drink, and you need to stop at 10 AM you’re only allowed to have two cups! Whatever they’re saying. Actually what the science is saying is that these are very dependent on genetics.[31], and those blanket statements are kinda bollocks…
RR Yeah. Ok so that's sleep.
Chapter 5: Coffee makes us go vroom vroom vroom!
But Greg's study looked at something else – that people don't necessarily associate with having a cup of coffee.. and that's exercise. On top of measuring sleep - he also measured how many steps they took every day… and?
GM On days randomly assigned to coffee participants on average, exhibited a thousand more steps on those days.
RR Wow, that's a lot.
GM It IS a lot. And in fact there’s other evidence that that magnitude of a difference may be meaningful in the long run in enhancing longevity.
WZ: Oh wow
RR: Yeah
For example, one study found that older women who take 5000 steps a day lived longer than similar women who took 4000 steps a day [32].
WZ Oh that’s cool.
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RR And it's not just step count… We actually have a lot of data showing that caffeine can help us athletically. So when people have caffeine before they exercise, they tend to go a little harder[33][34] [35] [36] [37]. So people will be able to run for longer or do more squats, for example. [38] One study looked at swimmers doing a 1500 meter race, so almost a mile. It found that having some caffeine beforehand shaved 23 seconds off their time compared to a placebo[39]. And having caffeine before exercise, is considered safe as long as you don’t overdo it– like the equivalent of one or two coffees before exercising[40].
WZ Wow
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So why is that happening?
RR: You know how caffeine can boost our dopamine? That might be putting us in a better mood so we can work harder[41]. Also we know caffeine can kind of turn the dial down on feelings of pain[42]--- that’s why some painkillers have caffeine in them. So maybe athletes aren’t feeling the burn quite as much[43]. And then finally - there’s some evidence that caffeine can actually increase the amount of calcium getting released by your cells, which could make your muscles work better [44]…
WZ Wow
RR So Wendy, do you still feel guilty about your coffee?
WZ Oh! No. Thus far, no. But at the same time we haven't really talked about risks yet…
RR Good point! So next we’re gonna talk about – is caffeine addictive? And what’s going on with the scary stories we hear about people dying after drinking energy drinks?
WZ And that’s coming up - after this quick coffee break!
BREAK
Chapter 6: Are We Caffeine Addicts?
Welcome back! Today on the show we are asking, should you quit caffeine? Should you spit out your coffee? Spill your tea on the floor - say goodbye to your energy drinks… Rose Rimler, senior producer at Science Vs, is telling us all about it. Hey, Rose!
RR Hey Wendy. So the next thing I want to dive into is this idea that you can get addicted to caffeine... I think a lot of that comes from the terrible withdrawal some people have when they stop it. ... Now Caffeine withdrawal is real[45] - People who quit coffee suddenly can feel sick– about half of them will get a headache.[46] [47] [48], this could be because caffeine restricts the blood flow to the brain, and then when we go off it, that blood whooshes back in[49].
WZ oh wow
RR Some people even feel like they have the flu and feel tired and crappy. So send them help. So pray for them
WZ: Do I need to pray for them? If the apocalypse hit and they couldn’t get their coffee, how bad would it be?
RR All those symptoms - they go away for most people go away somewhere between 2 to 9 days..
WZ: Ok - so if they can survive for 9 days, they’ll be back to normal.
RR: Yes … just hunker in your bunker and it'll play itself out but back to this addiction thing…so you know, you might reasonably call yourself dependent on caffeine if you feel sick without it. But that’s not the same thing as addiction. With addiction what experts point to - is that you are using a substance even though it's bad for you - it has negative consequences on your life[50][51]. Maybe you even really want to quit and you can't. And I think right now the general idea among scientists is that this is not a problem for most people, they don’t really see evidence of this negatively affecting people[52]
WZ Right, right for most people – and then what about tolerance?This idea that you need to have more and more caffeine to have the same effect?
RR Yeah we don’t typically see that with caffeine[53][54]. One reason is probably that at a high dose, caffeine starts to activate this other type of adenosine receptor in our brain that causes anxiety[55].
WZ OH this is why you get jittery and oo ooooh when you have too much caffeine
RR Yeah there’s a threshold you can cross from feeling alert, energetic, good. To oh now i feel anxious and jittery and weird. One researcher I spoke to said that for caffeine specifically there’s a “short window” between caffeine’s good effects and its bad effects. So you can kind of easily tip yourself over into that when you’ve had more caffeine anxious feeling. And if you start to feel that way many people would probably put down your third venti frappuccino of the day at that point. And so there’s kind of a natural cap for most people on how much caffeine we’re gonna drink every day.
WZ Yes. Recently I did– I was like fuck it I’m gonna just drink more coffee. And it did make me feel anxious, and so I was like, no no just go back to one or two cups. This isn’t– Go for a run instead or whatever.
RR Yeah it’s not worth it to most people at a certain point.
And this can be different if you’re mixing caffeine with other drugs, it can be more dangerous[56]. But bottomline– Caffeine is not considered a drug of abuse. There is no caffeine in the DSM, the big manual for psychiatric disorders. It’s been proposed. But right now it's not officially in there
WZ: Now we can say science says caffeine isn't really that addictive. Is that where we’re at?
RR: I think so, I think so..
WZ: So thus far orright it doesn’t, it really doesn’t seem like caffeine is that bad. And I'm trying to think why I thought caffeine was bad for you
RR: I actually might have an answer - in the 90s there was news that coffee was associated with bladder cancer[57]
WZ: Oh, really??
RR: But that has been debunked in more recent years[58]. Turns out it was not a real association. But even if you don't remember that stuff about bladder cancer - I think that percolated in the culture… and we haven't quite gotten over it. Plus there's a lot of fears around pregnancy and caffeine and that is something to think about because we know caffeine can cross the placenta and get to the fetus. So drinking a lot of caffeine when you're pregnant isn't recommended, but yknow health guidelines from around the world say you can have one or two cups of coffee a day if you’re pregnant.[59] [60] [61] [62]
WZ right right
RR overall, putting aside pregnancy…I walked away feeling pretty reassured about caffeine.
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Because - here’s something I thought was great. People who drink coffee have a lower risk of Parkinson’s Disease[63], depression[64][65], Type 2 diabetes[66][67], and heart disease[68] [69] [70] [71] and although we once thought coffee was carcinogenic - more recent studies have found that it actually might reduce your risk of some cancers[72] [73] [74] like liver[75] and breast cancer.[76]
WZ What! Are you kidding me? Are you serious?
RR Yeah And drinking coffee is associated with being less likely to die earlier[77] [78] [79]. So the biggest benefits are seen in people who drink two to three cups a day. But even at higher amounts, we still see people apparently getting some benefit.
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Like one study looked at people drinking as much as EIGHT CUPS OF COFFEE A DAY and found they still lived a little longer than people who didn’t drink any coffee[80].
WZ: What wow. Are you kidding me?
RR Yeah I mean there aren’t that many people that drink eight cups of coffee a day, smaller sample size. But the point stands that science suggests coffee is not actively harming you. And caffeinated tea also seems to be good for us[81][82].
WZ Are we sure? Are we sure about this? Why would caffeine, why would coffee and tea have these benefits?
RR Nobody totally knows. It could have something to do with the exercise boost you get from caffeine. Like we said earlier, walking more steps a day. But also could be that it's not really about the caffeine, it’s the other stuff in the plant. The coffee bean, the tea leaf[83]. There’s a lot of stuff in there that’s really good for us, is anti-inflammatory[84][85], has antioxidant potential[86].
WZ: Wow! I'm feeling very good about my coffee. I was not expecting this from science but thank you
RR: Any time.
WZ: SO then I don't want to crap all over this party… is that how this phrase goes?
RR yes
WZ: Rain on your parade?? hahaha
RR: hahahah… it's a visceral expression
WZ: haha …haha I don't know if I have a good sense of humour or I laugh so much at my own jokes
RR: I know a test you can take
WZ: hahha great… BUT BUT - what does that mean about the energy drinks issue?? To change the tune - to get quite serious.
Chapter 7: Are energy drinks dangerous?
There are these stories about energy drinks killing people? So what does this mean?
RR Which is the opposite of what I just told you about coffee. A lot of times what people say is the problem is that energy drinks are dangerous because they are packed WAY too full of caffeine. But the funny thing is– when you look at the labels– many of them really don’t have that much caffeine in them.
WZ: Oh. How much caffeine is in your average energy drink?
RR: So Chuck Schumer said that Prime Energy had an “eye popping” amount of caffeine[87]. So I looked up the label of Prime. It contains 200 mg of caffeine[88].
WZ What? 200? Like two shots of espresso? That’s it???
RR Two[89] or three,[90][91] depending on how you make them
WZ I love that you were like so I went deep undercover. I bought a Prime and I turned it around, and I looked at the label.
RR And of course you can overdose on caffeine[92] [93] – toxic effects are thought to start at 1200 mg, which is about 6 cans of Prime[94] . And there are case reports of people drinking a bunch of energy drinks and being hospitalised… [95] [96] [97] [98] But! Here’s where things get mysterious.
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There are reports of people, often younger people, dying after drinking less than that[99] [100] [101]-- Which suggests this isn't just about caffeine[102][103]. … And Professor Sachin Shah saw reports like that in the news and thought …
SS Hey there's something going on here
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RR It was actually a little bit sad at points talking to Sachin - because he's been in touch with the parents whose kids have died after drinking energy drinks…
SS We've had emails from other countries. One where somebody's like, I've kept the drink that my, my kid drank from the time when they drank it, just in case it helps future scientists. I'm happy to give you that drink.
WZ Oof, that’s heartbreaking.
RR Yes. So Sachin, who's a professor of pharmacy at the University of the Pacific in California, wants to know – why would anyone die after drinking a couple of energy drinks?
WZ Yeah, yeah
RR To get to the bottom of it - he did this study where he got people to drink a couple of energy drinks[104] .. and then looked at what their heart was doing.. Because… typically what we see in these cases is that someone’s heart stops beating shortly after drinking energy drinks[105] [106] [107]. So he got these volunteers to come into the lab, he hooked them up to an EKG
SS Many people see this on TV shows when they have somebody in the hospital, they're connected to this, uh, screen, they're lying in the hospital and they show this squiggly line, right, that's looking at, that's looking at your heart rhythm
WZ Beep beep beep, just to avoid us putting the sound effect in
RR Always thinking ahead
WZ So they’ve drunk the energy drinks
RR and he's monitoring them..
SS At one hour, two hours, four hours, six hours and 24 hours.
RR and was looking at this particular part of our heart’s rhythm… called the QT interval. Basically, it’s looking at how long it takes your ventricles to contract after every beat[108]. And if this takes longer than normal[109]… it can throw your heart into something called fibrillation[110] … which is like, instead of going squeeze squeeze squeeze … your heart starts quivering … like a nervous Chihuahua. And the problem with that is the heart isn’t actually pumping out any blood. And you can die.
WZ: Oh man. OK. So did the energy drinks muck up the QT interval?
SS So yeah, so you know what was interesting is in that first study, we found that energy drinks were prolonging the QT interval by 10 milliseconds[111].
RR: A follow-up study he did found this again – that energy drinks extended the QT interval - by this time[112] 6 milliseconds. And Sachin points out that several drugs have been pulled from the market for prolonging the QT interval by 6 milliseconds[113].
WZ Oh wow. So if I were to drink the equivalent caffeine from what he gave them but in coffee, would my QT interval be extended like that?
RR No. Studies have looked at this for caffeine and for coffee and don’t find the same thing.[114][115] And actually in one of Sachin’s studies they included a caffeinated control, and it didn’t do the same thing to people’s hearts[116].
WZ: So then if energy drinks are doing this… why aren't heaps of people getting heart attacks and dying after drinking energy drinks?? I mean, millions of people guzzling this stuff- and only a handful have died or so?
RR: Well yeah - like no one in Sachin's study was rushed to the hospital or anything either right?? And the thinking is that there are some people who are really vulnerable to this -- like people who have heartbeats that already have a long QT interval, and then the energy drinks extend it even more... that could tip you over into.. Chihuahua territory...
WZ right
RR One study actually gave energy drinks to people with a heart condition like that and found it extended QT interval in such a way it was actually dangerous[117]..
WZ Uh huh so then can we go back to this point that it wasn’t the caffeine that did it then what is it in energy drinks that’s causing this?
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RR Yeah I mean in Sachin's study he tested a couple brands, they both had caffeine, taurine, which is an amino acid, and a supplement called glu-cu-rono-lac-tone, which is found in a lot of energy drinks, like Red Bull.
WZ: So this is the ingredients, this is how we get wings?
RR: This is the wing recipe. So all this stuff together – seemed to extend the QT interval.. but then I found this one study that tried to really get to the bottom of which ingredient is the bad guy here[118]… they basically deconstructed a Red Bull and had people drink a few of the components one at a time while they were hooked up to an EKG. Just like Sachin, after drinking the Red bull, volunteers had a prolonged QT interval BUT. none of its individual components
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Did this.
WZ What??
RR And neither did the combination of caffeine and taurine together[119]…..I asked Sachin about this…
RR What do you think is in these energy drinks that causes these changes?
SS That's the million dollar question …
WZ SCIENCE!
RR hehe
WZ I was having coffee with my brother the other day, and he said there's always a point in a Science Vs episode where the scientist says, well, we don't really know what's going on, and I guess this is that point.
RR Yeah, we've arrived at that point in the episode…And of course it’s also really hard to say what’s going on when this is probably really rare. People drink energy drinks all the time and very few people land in the hospital.
[MUSIC IN]
WZ: Ok so here is what I think I have learned from this episode, Rose Rimler, tell me how I did and if I passed the test. I have a good sense of humor. Is that what we learned?
RR Yeah case closed.
WZ Caffeine truly does make me poo very quickly. It can affect your sleep but very much dependent on genetics. So dare I say listen to your body and not what people online might be telling you about what you should and shouldn’t do with caffeine. . And meanwhile it might reduce your risk of depression, if you’re drinking coffee and tea, what’d you say? Cancer, Parkinson’s?
RR: Diabetes
WZ Diabetes. And energy drinks, there is something weird about them. So if you are looking for a boost, it’s safer to go with tea or coffee.
[MUSIC OUT]
WZ How’d I do?
RR A-plus pupil. I’m not surprised. And as a prize I sent a case of Prime to your house. So don’t drink it all at once
WZ Excellent! Cheers, Rose?
RR Cheers.
CITATIONS
This episode was produced by Rose Rimler, with help from Wendy Zukerman, as well as Nick DelRose, Joel Werner, and Michelle Dang. We’re edited by Blythe Terrell. Fact checking by Sarah Baum. Mix and sound design by Bumi Hidaka. Music written by Bobby Lord, Bumi Hidaka, Emma Munger and Peter Leonard. Special thanks to all the researchers we spoke to for this episode – including Dr. Bryan Saunders, Dr. Sergi Ferré, Prof. Andreas Heinz, Prof. Christine Curran, Dr. Erikka Loftfield, Dr. Felix Oberhoffer, Dr. Alan Wayne Jones, and Dr. Vijay Yadav. Extra special thanks to Jason Vytlacil and the Zukerman family.
Science Vs is a Spotify Studios Original. Listen for free on Spotify or wherever you get your podcasts. We are everywhere that podcasts are! If you are listening on Spotify, follow us and tap the bell for episode notifications. And if you like us, give a five star review!
RR: Now it's not all fun stuff like rectal probes
WZ: Name of your sex tape?
RR: No the sex tape is called all fun and rectal probes
WZ: Hahahah
RR: We can't only talk about rectal probes in this episode, we also unfortunately have to talk about unpleasant stuff
[1] 2014, nationally representative sample: Results showed that 85% of the U.S. population consumes at least one caffeinated beverage per day. The mean (±SE) daily caffeine intake from all beverages was 165 ± 1 mg for all ages combined. Caffeine intake was highest in consumers aged 50–64 years (226 ± 2 mg/day). The 90th percentile intake was 380 mg/day for all ages combined. Coffee was the primary contributor to caffeine intakes in all age groups. Carbonated soft drinks and tea provided a greater percentage of caffeine in the younger (<18 years) age groups. The percentage of energy drink consumers across all age groups was low (⩽10%).
[2] Her death was caused by an enlarged heart, due to all the caffeine in her system. https://www.nbcnews.com/news/us-news/texas-teens-death-linked-caffeine-alani-nu-energy-drink-family-alleges-rcna267441
[3] Celsius Inc., which owns Alani Nu, said in a statement to NBC News that it is “saddened by this loss, and our thoughts are with the family. We take product safety seriously and believe consumers should have clear information about what they are drinking.” “Alani Nu energy drinks disclose 200mg of caffeine on the can, and the label states the product is not recommended for children, people sensitive to caffeine, pregnant women, or women who are nursing,” the statement said. “Our products comply with applicable federal labeling requirements, and our policy is not to market or sample to anyone under 18, consistent with those label warnings.”
[6] Coffee (via caffeine and other components, mainly polyphenols) stimulates the secretion and production of gastrin and hydrochloric acid…Regular coffee and decaffeinated coffee stimulate the secretion of cholecystokinin (CCK), a hormone that stimulates gallbladder function and contractility, and increases the production of bile.
[7] https://pubmed.ncbi.nlm.nih.gov/2338272/ Subjects were positioned on their left sides and a multilumen manometric probe was inserted into the rectosigmoid using a rigid sigmoidoscope.
[8] In another similar study, “Caffeinated coffee stimulates colonie motor activity. Its magnitude is similar to a meal, 60% stronger than water and 23% stronger than decaffeinated coffee.”
[9] The speed at which the response occurs (within four minutes after drinking the coffee) suggests an indirect action on the colon as it seems unlikely that coffee would reach the colon in this time either via the intestinal lumen or the blood stream. We suspect that coffee may induce a 'gastrocolonic response' by acting on epithelial receptors in the stomach or small bowel. Such a mechanism could be mediated by neural mechanisms or by gastrointestinal hormones. Coffee has been shown to promote release of Gastrin' which can increase colonic spike and motor activity.7 Cholecystokinin is another putative mediator of the 'gastrocolonic response'8 but there are no data on the effect of coffee on CCK release.
[10] In ten men: The oral absorption was very rapid, reaching a peak (Tp) plasma concentration after 29.8±8.1 min (mean±SEM). [sci hub]
[11] According to human studies, nearly 99% of caffeine is absorbed across the wall of the gastrointestinal (GI) tract within approximately 30–45 minutes.
[12] After caffeine dosing, plasma caffeine levels peaked at an average concentration of 3.2 % 1.5 mg/L 75 minutes after 2 mg/kg and 7.5 2 1.0 mg/L 75 minutes after 4 mg/kg doses."
[13] Caffeine is lipophilic enough to cross all cellular membranes, including the blood-brain barrier. [sci hub]
[14] The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptor
[15] The results showed that caffeine led to a more positive mood and improved performance on a number of tasks. [sci hub]
[16] The molecular structure of caffeine is similar to
that of adenosine, which allows caffeine to bind to
adenosine receptors, block adenosine, and inhibit
its effects ….
Accumulation of adenosine in the brain inhibits arousal and increases drowsiness. In moderate doses (40 to 300 mg), caffeine can antagonize
the effects of adenosine and reduce fatigue, increase
alertness, and reduce reaction time
[17] Caffeine —the most often consumed stimulant in the world—blocks adenosine receptors and normally attenuates the consequences of sleep deprivation on arousal, vigilance, and attention.
[18] Almost all tests demonstrate significant effects of various doses of caffeine on attention performance. Three tests that have been extensively used, namely the repeat digit detection, simple reaction time and a focused attention choice reaction time test, shown consistent effects of a range of doses
[19]Caffeine exerts its most reliable beneficial effects on vigilance tasks. Caffeine’s positive effects are present in rested individuals (Lieberman et al., 2010, Lieberman et al., 1987b, Lieberman et al., 1987a, Smith, 2005) and in sleep-deprived individuals (Lieberman et al., 2002, Smith, 2011, Weiss and Laties, 1962, Wesensten et al., 2002, Wesensten et al., 2004), and likely occur because caffeine reverses decrements in alertness associated with prolonged maintenance of attention. Caffeine also reliably enhances the fundamental cognitive processes that underlie all types of performance such as reaction time (Nehlig, 2010, Smith, 2002) and attention (Einother and Giesbrecht, 2013, Smith, 2011). The acute effects of caffeine on memory are less consistent and appear, among other things, to be influenced by whether or not the task is boring or engaging (Amendola et al., 1998, Anderson and Revelle, 1983).
[20] Nighttime driving performance was similar to daytime performance (0 to 1 line crossing) for 75% of participants after coffee (0 or 1 line crossing), for 66% after the nap (P 0.66 vs. coffee), and for only 13% after placebo (P 0.041 vs. nap; P 0.014 vs. coffee). [sci hub]
[21] After adjustment for potential confounders, drivers who consumed caffeinated substances for this purpose had a 63% reduced likelihood of crashing (odds ratio 0.37, 95% confidence interval 0.27 to 0.50) compared with drivers who did not take caffeinated substances.
[22] An example of a visual cartoon item is shown in Figure 1. An example of a verbal headline item is as follows: Headline 1—“Veterinarian Investigates Failed Panda Mating;” Headline 2—“Panda
Mating Fails; Veterinarian Takes Over.” Participants made a forced choice for each pair, deciding whether the stimulus on the right was funnier, the one on the left was funnier, or whether the 2 stimuli
were equally funny…The modafinil 400-mg group (mean = 55.86, SD = 12.65) demonstrated significantly better performance on the cartoon items than both the placebo group (mean = 39.97, SD = 12.62, p = .004) and the caffeine 600 mg group (mean = 41.58, SD = 12.62, p = .011). None of the other groups differed significantly. [sci hub]
[25] The participants downloaded the Eureka app (developed and maintained by investigators at the University of California, San Francisco) to their smartphones to continuously monitor their geolocation in order to track visits made to coffee shops.
[27] When randomized to coffee, participants slept about a half-hour less per night (36 fewer minutes, 95% CI 25 to −47, p < .001, Figure 2), and every additional coffee drink was associated with 14 min less sleep per night (95% CI 10−18 fewer minutes, p < .001). Coffee notoriously disrupts sleep, but to our knowledge, the relationship had not previously been characterized, nor quantified, among ambulatory patients in a randomized trial. Of interest, there was a statistically significant interaction with caffeine metabolism-related genetic variants: slower caffeine metabolizers experienced almost an hour less sleep on average, whereas the fastest caffeine metabolizers had no detectable difference in sleep duration when exposed to coffee.
[28] The CYP1A2 variant is associated with the inducibility of CYP1A2, such that CYP1A2 C allele carriers (∼32% of the European population) metabolize caffeine less effectively than AA carriers
[31]Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine."
[33]There is sound evidence that caffeine enhances endurance and provides a small but worthwhile enhancement of performance over a range of exercise protocols, with the traditional protocol involving a caffeine dose of ~6 mgkg–1 body mass taken 1 h pre-exercise.
[34] This 2020 review on caffeine and athletic performance says: “Synthesis of the currently available meta-analyses suggest that caffeine ingestion improves exercise performance in a broad range of exercise tasks. Ergogenic effects of caffeine on muscle endurance, muscle strength, anaerobic power and aerobic endurance were substantiated by moderate quality of evidence coming from moderate-to-high quality systematic reviews. For other outcomes, we found moderate quality reviews that presented evidence of very low or low quality. It seems that the magnitude of the effect of caffeine is generally greater for aerobic as compared with anaerobic exercise.” [sci hub]
[35] Aerobic endurance appears to be the form of exercise with the most consistent moderate-to-large benefits from caffeine use, although the magnitude of its effects differs between individuals.
[36] Synthesis of the currently available meta-analyses suggest that caffeine ingestion improves exercise performance in a broad range of exercise tasks. Ergogenic effects of caffeine on muscle endurance, muscle strength, anaerobic power and aerobic endurance were substantiated by moderate quality of evidence coming from moderate-to-high quality systematic reviews.
[37] A review published last year found that “The performance-enhancing effect of acute caffeine ingestion has been well established, with a number of meta-analysis demonstrating benefits for muscular strength and power [1,2,3,4], endurance performance [5,6,7,8], anaerobic power [9], sport-specific skills [10,11] and cognitive function [12].”
[38] Caffeine significantly improved squat (4.5 ± 1.9%, effect size [ES]: 0.25) and bench press 1RM (3.3 ± 1.4%, ES: 0.20), and squat (15.9 ± 17.9%, ES: 0.31) and bench press RTF (9.8 ± 13.6%, ES: 0.31), compared to placebo. MVC torque (4.6 ± 7.3%, ES: 0.26), CMJ height (7.6 ± 4.0%, ES: 0.50), and power (3.8 ± 2.2%, ES: 0.24) were also significantly increased with caffeine.
[40] The Panel notes that caffeine antagonises the vasodilator effect of adenosine and other A2A receptor agonists in the coronary arteries in a dose-dependent manner and this effect leads to a reduction of MBF and MFR during intense physical exercise, primarily in subjects with CAD, but also in healthy subjects to some degree. However, on the basis of the data available, the Panel considers that caffeine at doses of 200 mg consumed one to two hours prior to exercise does not induce clinically relevant reductions of the coronary flow reserve in healthy adult subjects under normal environmental conditions. The Panel notes that the effect of higher doses of caffeine has not been tested.
Our findings indicate that acute caffeine supplementation in trained subjects has positive effects on several psychophysiological mood variables and psychological responses, and on performance.
[42] Of the papers reviewed in Supplementary Tables 2–4, almost 80% reported positive findings during endurance exercise, whereas two-thirds reported ergogenic effects for measures of muscle strength and associated tests of muscular endurance or high-intensity exercise. Except for very short duration anaerobic exercise, there was also a common thread throughout these studies, regardless of the type of exercise, that caffeine reduced perception of effort and lowered sensations of pain.
[43] Cochrane says “The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.”
[44] “There is some evidence that the effects of caffeine on physical performance could be related to the release of calcium from the sarcoplasmic reticulum and inhibition of its reuptake, which subsequently increases nitric oxide via the activation of endothelial nitric oxide synthase (see Cappelletti et al., 2015). These actions may be associated with changes in neuromuscular function and increased contractile force in skeletal muscles that could be ergogenic (Tarnopolsky, 2008).”
[45] Caffeine withdrawal is a clinically significant cluster of symptoms, behaviours and/or physiological features, varying in degree of severity and duration, that occurs upon cessation or reduction of use of caffeine.
[46] 55% of a sample of people fasting for Ramadan got a caffeine withdrawal headache; it was worse for people who typically drank more coffee.
[47] Caffeine withdrawal could potentially trigger a migraine in people who get migraines routinely.
[48] 2004 review: Of 49 symptom categories identified, the following 10 fulfilled validity criteria: headache, fatigue, decreased energy/ activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories. In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%. Typically, onset of symptoms occurred 12–24 h after abstinence, with peak intensity at 20–51 h, and for a duration of 2–9 days. In general, the incidence or severity of symptoms increased with increases in daily dose; abstinence from doses as low as 100 mg/day produced symptoms.
[50]Addiction is defined as a chronic, relapsing disorder characterized by compulsive drug seeking and use despite adverse consequences.
[51] Addiction is defined as not having control over doing, taking or using something to the point where it could be harmful to you.
[53] NHANES study finds people consume caffeine based on circadian rhythms and generally stay within healthy amount
[54] Tolerance to some subjective effects of caffeine, namely
anxiety, jitteriness/nervousness, activity/stimulation/
energy, and the potency of caffeine effects might occur
(Evans and Griffiths, 1992). Tolerance to caffeine-induced
alertness and wakefulness is debated (for review, see
Nehlig, 2004). These effects are paralleled by the lack of
tolerance of cerebral glucose metabolism and brain function to caffeine. As shown in rodents, the acute administration of a low dose of caffeine leads to similar metabolic
increases whether the animals have been exposed for
15 days to daily chronic treatment of caffeine or saline.
[55] Nevertheless, in drug-discrimination studies in users of prototypical psychostimulants, low to intermediate doses of caffeine produce a profile of positive subjective effects similar to those of amphetamine and cocaine, while with high doses of caffeine the subjects report aversive subjective feelings of anxiety and nervousness
[56] While more clinical research needs to be done to determine if caffeine use disorder can adhere to the general scheme of SUD and about the real contribution of arousal/withdrawal reversal in caffeine use, there is at present no reasonable doubt in the literature about the fact that a rising real societal danger of caffeine is its association with other drugs that fulfill the DSM-5 criteria for SUD. …..By blocking the A2A receptor, caffeine counteracts the remaining brake that endogenous adenosine imposes on D2 receptor signaling, which results in a maximal D2 and minimal A2A receptor signaling: a maximal psychostimulant effect (Fig. 3C).
[57] 1991: On the basis of available data, the working group concluded that coffee is possibly carcinogenic to the human urinary bladder.
[58] 2019: In summary, findings from this large meta-analysis of prospective studies suggest that coffee consumption was not significantly associated with long-term risk of bladder cancer.
[59] Habitual caffeine consumption up to 200 mg per day by pregnant women does not give rise to safety concerns for the fetus.
[60]Caffeine passes the placental barrier freely; the fetus does not express the main enzymes that inactivate it [4,5], and caffeine metabolites have been found to accumulate in the fetal brain.
[61] WHO recommendations for pregnant women with high daily caffeine intake (more than 300 mg per day), lowering daily caffeine intake during pregnancy is recommended to reduce the risk of pregnancy loss and low birth weight neonates.
[62] You can have caffeine, but no more than 200mg per day. Regularly drinking more than this amount can increase your risk of pregnancy complications, such as low birthweight, and even miscarriage.
[63]A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. https://pubmed.ncbi.nlm.nih.gov/23879665/
[64] https://journals.sagepub.com/doi/abs/10.1177/0004867415603131 Coffee and caffeine consumption were significantly associated with decreased risk of depression.
[65] https://www.sciencedirect.com/science/article/abs/pii/S0165032719301442
Regardless of psychiatric problems such as depression or sleep problems, regular and moderate caffeine intake likely reduces suicide risk as well as depression in women.
[66] Available evidence indicates that coffee consumption is inversely associated with risk of T2D.
[67]"Prospective epidemiological studies concur in an association between habitual coffee consumption and a lower risk of type 2 diabetes." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066601/
[68] Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.
[69] Findings consistently indicate that consumption of up to 6 standard cups of filtered, caffeinated coffee per day, as compared with no coffee consumption, is not associated with an increased risk of these cardiovascular outcomes in the general population. [sci hub]
[70] In this large, prospective, population-based community cohort study of more than 300 000 participants, each additional daily cup of coffee was associated with a 3% reduced risk of developing an arrhythmia.
[71] Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval (95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3−4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day.
[72] Coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption.
[73] The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee and 4% for every 100 mg of caffeine intake per day.
[75] From this meta-analysis, the risk of HCC is reduced by 40% for any coffee consumption vs no consumption.
[76] Indeed, systematic reviews have found a protective effect of coffee on liver, hepatocellular, and breast cancers. However, coffee seems to increase the risk for lung cancer development, whereas the association of coffee with other cancers such as those of the pancreas, bladder, ovaries, and prostate is controversial.
[77] This large prospective cohort study of a half million people found inverse associations for coffee drinking with mortality, including among participants drinking 1 up to 8 or more cups per day.
[78] Consumption of caffeinated coffee and consumption of decaffeinated coffee were similarly associated with a reduced risk of death from any cause. [sci hub]
[79]These results confirm prior findings on the reduced risk of mortality associated with coffee drinking but additionally show that this relationship does not vary by country where coffee preparation and drinking habits may differ. The study also reports novel inverse relationships between coffee drinking and digestive disease mortality.
[80] In the very large UK Biobank cohort, coffee drinking was associated inversely with all-cause mortality, including in those drinking at least 8 cups per day, in both slow and fast metabolizers of caffeine, and in consumers of ground, instant, and decaffeinated coffee.
[81]Green and black tea: Relative to no tea drinking, the hazard ratios (95% CIs) for participants drinking 1 or fewer, 2 to 3, 4 to 5, 6 to 7, 8 to 9, and 10 or more cups per day were 0.95 (95% CI, 0.91 to 1.00), 0.87 (CI, 0.84 to 0.91), 0.88 (CI, 0.84 to 0.92), 0.88 (CI, 0.84 to 0.92), 0.91 (CI, 0.86 to 0.97), a https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623338/
[82]Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption.
[84] In this report, we examined the effects of caffeine and other well-known coffee components, such as quercetin, flavone, and chlorogenic acids (CGAs), on neuroinflammation and neurotoxicity mediated by toxic factors from activated microglia and astrocytes…..We found that CGA, flavone, quercetin, and caffeine reduced the release of proinflammatory cytokines such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) from lipopolysaccharide/interferon-γ (LPS/IFNγ)-stimulated microglia and THP-1 cells, as well as from IFNγ-stimulated astrocytes and U373 cells.
[85] Lower circulating levels of inflammatory markers among coffee drinkers may partially mediate previously observed associations of coffee with cancer and other chronic diseases.
[86] Black, green, and red tea are rich in polyphenols and flavonoids, namely catechins and their oxidated products. These and other bioactive compounds in tea have the potential to reduce oxidative stress and inflammation, which may promote carcinogenesis, and improve endothelial function
[87] Senate Majority Leader Chuck Schumer (D-NY) sent the following letter to FDA Commissioner, Dr. Robert Califf, regarding Prime Energy drink – a product marketed to kids and teens to quench thirst – which contains an eye-popping 200mg of caffeine.
[89] Ninety-seven espresso samples in Australia were analysed. The mean (±SD) quantity of caffeine was 106 ± 38
[90]Starbucks says 75 mg per shot of its espresso. Literature says 63 mg per ounce of espresso, and 12 oz brewed coffee is 235 mg.
[91] https://academic.oup.com/nutritionreviews/article/72/suppl_1/23/1929608
"In general, a serving of espresso (about 1 oz or 30 mL) provides 64 mg of caffeine, and an 8-oz cup (237 mL) of automatic drip coffee provides 145 mg of caffeine.41"
[92] Review of Caffeine-Related Fatalities along with Postmortem Blood Concentrations in 51 Poisoning Deaths
[93] Caffeine is a mild central nervous stimulant that occurs naturally in coffee beans, cocoa beans and tea leaves. In large doses, it can be profoundly toxic, resulting in arrhythmia, tachycardia, vomiting, convulsions, coma and death.
[94] Toxic effects (including tachycardia, ventricular arrhythmia, and seizures) are observed at approximately 1200 mg, or 1.2 grams (0.15 tablespoons of caffeine) (Ref 2, 3, 4, 5, 6). A life threatening dose of caffeine is typically estimated at between 10,000 and 14,000 mg, or 10 and 14 grams (g) (1.2 – 1.7 tablespoons of caffeine), although smaller doses can be life-threatening in certain individuals (such as children or other sensitive populations) (Ref 5, 14, 15, 16, 17).
[95]Prior to cardiac arrest [a 22-year old female] patient consumed six cans of a caffeinated energy drink within 4 hours."
[96] “An otherwise healthy 28-year-old man had a cardiac arrest after a day of motocross racing… he had consumed 7–8 cans of a caffeinated “energy drink” between 8 am and his collapse 7 hours later.
[97] We present the case of a 22-year-old male attended in the emergency department of a general hospital…he ingested 20 cans of 250 cc of an energy drink in 24 hours.
[98] In 2007, a man in Australia was reported to have suffered cardiac arrest after consuming seven to eight cans of an energy drink while taking part in vigorous physical activity (36). A Swedish study in 2006 identified a number of cases with severe symptoms and a number of deaths possibly linked to energy drinks (37). Iyadurai and Chung (38) reported on four cases in the US, where patients presented at emergency rooms after suffering new, adult-onset seizures and the only common finding was that all the patients had consumed large amounts of energy drinks. Once the patients abstained from consuming energy drinks, no further seizures were reported. Avci et al. (39) reported another case from the United States where a 28-year-old man consumed three 250 ml energy drink cans, 5 h before a basketball match. After playing for 30 min, he lost consciousness, suffered from cardiac arrest, and died 3 days later.
[99] Fourteen-year-old Anais Fournier downed two 24-ounce energy drinks on one December day, while hanging out with her friends at the mall. The next day, the Maryland teenager went into cardiac arrest -- and just six days later, she was dead.
[100] A South Carolina teenager who collapsed in a high school classroom last month died because he drank several highly caffeinated drinks too quickly, a coroner said on Monday…Davis Allen Cripe, 16, drank a latte from McDonald's, a large Mountain Dew soda, and a highly caffeinated energy drink in just under two hours, said Gary Watts, the coroner of Richland County, South Carolina.
[101] See Table 1 – estimated caffeine content from various case reports not at toxic level
[102] Typically, caffeine toxicity–related adverse events have only been observed in case studies where doses far exceed 400 mg.
[103] As for the constituents of the energy drinks themselves, the concentrations of caffeine seem to be comparable or even lower than many popular coffee drinks making the amount of caffeine itself an unlikely reason to not consume the products.
[104] Shah et al 2019. A randomized, double‐masked, placebo‐controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6‐day washout period in between.
[105] This 2023 review attempts to look at all the negative effects & some mechanisms. In particular, the analysis identified nine cases of cardiac arrest, three of which were fatal.
[106] Overall, the AERs indicate that the FDA received 276 reports of adverse events involving energy drinks between January 1, 2004, and March 10, 2014. Excluding a suicide, thirty-four of the incidents involved death, often as a result of heart failure.
[107] Acute consumption of ED can alter the ECG in certain risk populations, posing a risk whose magnitude is yet to be determined.
[108] QT interval represents the duration of ventricular electrical systole, which includes ventricular activation and recovery.
[109] The danger inherent in a prolonged QT is that excessive QT prolongation carries a risk of sudden cardiac death (SCD) due to polymorphic tachycardia, also known as TdP…. Irrespective of the mechanism, TdP usually does not sustain long and terminates spontaneously. However, if it happens successively, it can degenerate into ventricular fibrillation and SCD
[110] An arrhythmia that starts in your ventricle is called ventricular fibrillation. This occurs when the electrical signals that tell your heart muscle to pump cause your ventricles to quiver (fibrillate) instead.
[111] The change in corrected QT interval from baseline in the energy drink arm was significantly higher than the caffeine arm at 2 hours (0.44±18.4 ms versus −10.4±14.8 ms, respectively; P=0.02).
[112] The maximum change from baseline in Bazett's corrected QT interval for drinks A, B, and placebo were +17.9±13.9, +19.6±15.8, and +11.9±11.1 ms, respectively
[113] Drugs such as ranolazine and terfenadine carry warnings, or have been removed from the market because of prolongation of the mean QT/QTc by 6 ms.
[114] In a large sample representative of the general US population, we found no association between QT interval duration and coffee or tea intake, cigarette smoking, physical activity, or total alcohol intake, although binge drinking was associated with an increased QT duration particularly in men.
[115] https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-10-15 The QT interval corrected for heart rate did not significantly change following CC or DC ingestion.
[116] Fletcher et al 2017 is the one that had caffeinated placebo
[117] Caffeinated energy drinks have significant haemodynamic effects in patients with LQTS, specifically an acute increase in blood pressure. [sci hub]
[118] The QTc interval was shortened after 1 h compared to baseline by the administration of CP + C + T and CP + G (both P < 0.05). Compared to the CP, CP + C and CP + C + T induced increased BP parameters. CP + C + T and CP + G caused a shortened QTc interval compared to CP (both P < 0.05) and CP + C + T reduced HR compared to CP (P < 0.05).