At one point or another, we’ve all been told that the burn we feel in our legs is lactic acid. If we wanted to get rid of that soreness the next day, we needed to clear the lactic acid out of our legs. That was the belief for decades – that lactic acid was a dead product we produce when we “go anaerobic,” and we need to do everything we can to prevent that lactic acid from building up.
This is the landscape a young Dr. George Brooks was facing when he proposed an alternative theory. For one thing, it’s lactate, not lactic acid. For another thing, it’s not a dead-end product that just makes us sore – it’s in fact a critical fuel we produce all the time. Not to mention, it’s needed by many of the tissues in our body.
To say Dr. Brooks was met with skepticism when he proposed these notions in the early 1980s would be an understatement. But in the decades since, his theories have been vindicated, and our understanding of this essential molecule has fundamentally changed.
In this episode, our hosts talk about several of Dr. Brook’s most critical papers dating back to his first paper published in 1983. That paper shows that production is not the issue. Elite and untrained athletes produce about the same amount of lactate at a given intensity – elite athletes are just far better at clearing it.
In a second review from 2000, Dr. Brooks explained the concept of a lactate shuttle that he introduced in 1984. It stated that lactate is in fact a critical source of fuel that transports or “shuttles” from cells and tissues that produce it to cells and tissues that can use it. Along the way, he proved that it is impossible to understand how our bodies produce energy without understanding lactate.
Finally, in recent years, Dr. Brooks has been working with a friend of the show, Dr. Iñigo San Millán, to uncover the role that lactate plays in cancer development. One hundred years ago it was discovered that cancer cells produce up to 70 times as much lactate as regular cells. This discovery, called the Warburg Effect, has gone unexplained ever since. Dr. Brooks theorizes that lactate is necessary for cancer development and that the over-production of lactate is the cancer cell’s way of ensuring its survival.
This raises a broader conversation about the role of lactate, our mitochondria, and diet in health – not just in cancer, but also heart disease and even neurodegeneration. It wasn’t planned, but our hosts decided to dive into this important discussion.
So, get ready to feel the burn, and let’s make you fast!
Episode Transcript
Rob Pickels 00:04
Hello, and welcome to Fast Talk your source for the science of endurance performance. I’m your host Rob Pickels here with Coach Conner.
Rob Pickels 00:12
At some point in our lives, we’ve all been told that the burn we feel in our legs is lactic acid and it was responsible for slowing us down. That was the common understanding when Dr. George Brooks proposed the lactate shuttle theory. His research led him to believe that lactate is not a dead end product that just makes us sore. It is in fact a critical fuel we produce all the time that is needed by many of the tissues in our body. When he proposed this theory in the 1980s, Dr. Brooks was met with strong skepticism. But, in the decades since we’ve come to understand that lactate is a very complex and beneficial molecule.
Rob Pickels 00:50
That’s why today’s episode is focused on Dr. Brooks and three seminal papers that he’s written on the topic of lactate. The first published in 1983 shows that excessive production of lactate is not the cause for its build up. Trained and untrained athletes produce similar amounts of lactate at a given intensity. However, trained athletes are just far better at clearing it. In a second review from 2000. Dr. Brooks further explains the lactate shuttle concept that he introduced in 1984. It states that lactate is in fact a critical source of fuel that transports or shuttles from cells and tissues that produce it to cells and tissues that can use it. Our last study centers around research Dr. Brooks has been conducting with Dr. Indigo San Milan, a voice you’ve heard many times on the show. They’re looking to understand the Warburg effect, the fact that cancer cells can produce 70 times as much lactate as normal cells. In the 100 years since it was proposed, we lacked an understanding of why this is, but Dr. Brooks and Dr. San Milan proposed that the overproduction of lactate is essential for cancer survival. Today we’ve got a big episode, so get ready to feel the burn and let’s make you fast.
Trevor Connor 02:04
Hey, listeners. If you’ve been listening to Fast Talk for a while, you’ve probably heard a few of my hot weather racing stories. Like the time I tricked a rival team and defeated me some of their water bottles. Stories like those show how critical it is to beat the heat and stay hydrated. In our new pathway we explore exercise in the heat. We show how to manage heat, dial in hydration and feel for performance in hot conditions. This new pathway taps Dr. Stephen Chung the internationally recognized expert in thermal physiology, and sports scientists Rob pickles. Lindsey Gulledge, Dr. Steven Siler, plus Ryan Kohler and myself, this pathway bust myths and reveals science based best practices for beating the heat. Topics include rider body types, mental strategies, sports drinks, salinity, drinking versus dowsing, muscle crap, which is one of my favorites, and you’ll learn why taking electrolytes might not make a difference. Plus, we talk about getting acclimated, drink to thirst and how heat affects sports nutrition. Take a look at our new exercise in the heat pathway at fast talk labs.com. Well, Rob, we’re here for another seminal episode. And this is a real big name. This is Dr. George Brooks, anything you want to say about him before we dive into a few studies? Yeah, you
Rob Pickels 03:25
know, I think the thing to point out with this is Trevor, you didn’t realize this, and I guess I didn’t even realize it at the time. But the three studies that I chose for today, kind of follow in arc in my life. The first study that we’re going to talk about is from 1983, which is about when I was born, I was born just before that, and that’s endurance training affects lactate clearance, not lactate production, so we got the beginning of my life. The second study we’re talking about today came out in 2000. Same year I graduated high school, and that’s intra and extracellular lactate shuttles. And then the last study we’re talking about today is from 2017. And that’s called RE examining cancer metabolism lactate production for carcinogenesis could be the purpose and explanation of the Warburg effect. Not only is that a long title, but Dr. Brooks wrote that with Indigo, Santa Milan and I was working with Dr. Sam Milan when this paper came out. So if you think about it, today’s episode mirrors my life.
Trevor Connor 04:29
All I could think about was you don’t want to know where I was in 1983 and 2000 a little bit different a place I’m trying to think of I was when I didn’t have high school in Canada but wait, you
Rob Pickels 04:42
didn’t go to Canada doesn’t have a school. We do you just shovel the school
Trevor Connor 04:46
I went to and you’re gonna laugh at the second part of this. It was the same school from grade three to grade 13
Rob Pickels 04:52
grade 13 Yeah, you can’t do it. Well,
Trevor Connor 04:55
no we –
Rob Pickels 04:56
do now and you start at three I don’t know man, you can eight Ian’s
Trevor Connor 05:00
now we started at one but basically I was at the same school for a very, very long time.
Rob Pickels 05:05
There you go. Well, Trevor, should we take this from?
Trevor Connor 05:08
Well, I’m gonna share one quick story because I think everybody in this please do. And it’s a little coffee.
Rob Pickels 05:15
It’s my second one.
Trevor Connor 05:16
Okay, there we go. I think everybody in exercise physiology has a doctor bookstore and my story is the first exercise phys class I ever took. It was an undergrad 200 level course. We had a textbook for the course that I can’t remember whose textbook it was, wasn’t great. And I remember the bookstore was having the sale unused books and there was a copy of Dr. Brooks’s exercise physiology textbooks, which for anybody who is in the Exercise Science World will tell you, that’s kind of the definitive exercise physiology textbook. So the whole time I was taking that class, I would actually skim through the textbook we were supposed to read. And then I went to the Dr. Brooks textbook to get the real meat of the subject. And boy, was it a heavy textbook, but it was fantastic.
06:08
I can imagine Yeah, guys are in Brooks, they wrote a lot together. Another one. While we’re on textbooks textbook of work physiology by a strand. That’s a really good one, too. If people are just looking to way down their shelves with books, those are two great ones to go out and get.
Trevor Connor 06:24
And as we all know, you put the books on the bookshelf behind wherever you take your zoom call and you never read. You just make sure everybody can really
06:31
you’re hanging credibility on the wall, right? I mean, you got to create an aura and ambiance
Trevor Connor 06:37
where you go, God, I am proud to say my Dr. Brooks book, you can tell the spine of it is well run down. Well, it was used. So the first person, I’m not
Trevor Connor 06:47
going to say who is the one who did that to the book, I’m just gonna say it’s clearly a well used textbook. And there you go love it. So let’s dive into this first one. That is she’s when you were born. endurance training affects lactate clearance, not lactate production. And I think before we dive into this, there is a bit of context who basically through this episode, we are going to be talking about lactate. This is the mark that Dr. Brooks has made. And it is a huge mark, because before he started doing his research, there was a very common belief accepted belief about what lactate was and how it functioned. And I think a lot of us who are old enough, remember our school gym, teachers yelling this at us. And we’re going to start there because this is basically what Dr. Brooks has disproved. But the belief at this time was that lactate was just a dead end product. It was something you didn’t want. And so what they said back then was you didn’t start producing lactate until you went anaerobic. And we just did an episode recently with Dr. Steven Siler who talked about the fact that this whole concept of being aerobic and being anaerobic, anaerobic, yeah, it’s an outdated concept. But back in the early 80s, that’s the way they spoke, you were either aerobic or your anaerobic. And when you are anaerobic, you are producing a ton of lactate. As a matter of fact, they probably talked more about lactic acid. And we did an episode on the fact that lactic acid actually doesn’t exist in the human body. Just feel the burn, Trevor. Yep. But it was lactic acid that caused that burn. And that’s what made you sore the next day, and it was just as dead end product. And you needed to clear that lactic acid out. And what you’re going to hear over the course of our discussing a few of these studies from Dr. Brooks, is you couldn’t be further from the truth.
Rob Pickels 08:40
Yeah, and I think the second study that we talked about the lactate shuttle really drives that point home. But what’s worth pointing out is this first study from 1983. Trevor that we’re going to start with it was a full 17 years prior to that. And so this is lactate has been one of those molecules that has been studied for such a long time throughout exercise physiology, but it is ultimately mal aligned. I’m pretty sure that’s a word that’s been thrown out there in terms of what its function, what its purpose, and ultimately what its value is within the human body. Because there is value here,
Trevor Connor 09:17
what we’re actually going to get to and we’ll talk about this particularly in the second study is that lactate is a critical fuel. And one of the best ways to transport energy from cell to cell. So let’s dive into this study. And I think we need to start with what was this study about? And what it’s trying to figure out? Is there is a lot of flux in lactate in our system when we’re exercising flux, meaning movement, change travels around. I’m trying to think of a really simple way of explaining that. But you see kind of a constant level in the blood when you’re at a steady state. And so he’s trying to figure out what’s responsible for that steady state? Is it production of lactate? Does production go up and down? Or is it clearance at the time, it was very much believed it was production. So in an untrained athlete, they produce a lot more lactate, because their system just isn’t prepared to really handle this sort of intensity. And a very trained athlete, production actually goes way down, they’re not producing a lot of lactate. Lactate levels stay low. And remember, at this time, there was a belief that you really only started producing lactate when you went anaerobic.
Rob Pickels 10:39
Yeah, Trevor, and if we think, you know, I’m sure a lot of people I can’t, because I’m not good at picturing things in your mind. But a lot of people can picture what a typical lactate curve looks like, right? That test involves somebody running or riding, ultimately doing increasing workloads. And in those very early workloads, when the individual isn’t working very hard, the lactate concentration, their blood is quite low, usually below two millimole, oftentimes closer to one, maybe even under one. But as that person works a little harder, a little harder, a little harder, that level typically stays low, low, low until it doesn’t. And then, and the thinking at the time was, Oh, they’re going in aerobic, and you begin to see lactate increase exponentially. A little increase in workload nets, a really big change in lactate. And suddenly that line is shooting out the top of the graph.
Trevor Connor 11:39
I think another really important thing to point out about this study, and the work that Dr. Brooks did is his genius and figuring out how to actually study this. Because think about it, you have somebody exercise him actually this study, they used rats, yep. But let’s say you’re trying to figure out where’s the lactate coming from? Where’s it going? How is it being used? You have somebody running on a treadmill? How are you going to say, Okay, I’m going to poke inside you try to see what’s going on in your cells, see what’s going on in your blood? And get an answer for where this is going, what muscle you know, what tissues are producing this all that it’s actually extraordinarily difficult to do. And he really came up with this method of essentially stamping little IDs on the lactate molecule. So they use this carbon 14, identifier to really see where it is that lactate ultimately ended up. Where’s it coming from, and what I found amazing in this study, and this is where you kind of go, this is Dr. Brooks, nobody else could get away with this. The discussion was extraordinarily long for the study. And I’d say about a page of it was him musing about the different methods of doing this carbon identification. And sorry, I know there’s these are none of the right terms and just trying to keep this simple. Using this way of identifying the lactate molecules and tracing it, where it’s going, what’s happening to it. He literally just muses about it, and the different methods and which is better and what the pros and cons are. And I could tell you, if I wrote a paper and wrote a page like that, and submitted it, they would go get rid of that. But this is Dr. Brooks, he wants to Muse a bit about the best methods. He’s going to get that published.
Rob Pickels 13:30
Yeah, Trevor. And I think that that’s an area also where, you know, we’ve talked about Professor John Hawley and his bio chemistry abilities. And that’s the same thing with Dr. Brooks here where there is a lot of thought that has gone into the procedures. And I think that that’s a difference that we have research back in the day back in the 1980s. When these techniques are being developed. Research is oftentimes about figuring out the best technique on how to study something. In this day and age, we figured a lot of those techniques out. Current papers oftentimes are not discussing this, because they’re citing these original, foundational seminal studies like the one that we’re talking about today. But oftentimes, the hardest work wasn’t necessarily getting the data, it was creating the test to get the data.
Trevor Connor 14:22
And what I’m amazed by him, as you point out, this is a study from 1983. There’s so much evolution since then, but I in my notes, this is something that that I wrote, I’m just reading it right here, page 85 has very specific co2 measures and calculations there above my head, and it’s all I wrote.
Rob Pickels 14:42
I skip that section. There’s no highlights on that page at all.
Trevor Connor 14:46
No, I tried and just went it would take me a day to even try to understand this. It’s it’s pretty amazing stuff, particularly for the time
Rob Pickels 14:55
Yeah, so Trevor, something interesting to point out as well as if they also used a label decal. glucose as well. And ultimately, this is what’s helping Dr. Brooks and his team determine is the lactate increase that you see in the blood? Is that because the muscle cells are producing more, or because there’s a clearance change that’s happening.
Trevor Connor 15:18
So let’s dive into it. What did they discover in this study? And I’m going to point out, I’m glad you picked this paper, because this was a very important paper at the time. Yeah,
Rob Pickels 15:29
certainly. Well, Trevor, to give the basics on the background here. They did, they used rats throughout this, those rats were endurance train, there was one control group, right. And one train group, train group was five days a week, they began at 10 minutes a day. And they went up to 120 minutes a day. And so I was like, Man, that volume increase and how quickly they trained these rats is incredible. But I guess rat lives are a little bit shorter. And so you got to do everything a little bit faster. They also looked at these rats in three conditions, right when they did the infusions, when they were doing the measurements with the control. And then the trained group, the three conditions were rest, easy work, and hard work. And for those that don’t know, you can relatively easy control the workload of a rat, because you put it in a box on a treadmill, and it basically has to go the speed. I don’t necessarily agree with some of these methods. Animal testing is a tough topic. But this is a lot of the foundational work that we’ve had in physiology and in other fields. Yeah, I
Trevor Connor 16:32
was actually thinking about those poor rats when he did a vo two Max desk is he said he took them to failure. Yeah, they’re not making that choice. They’re on a treadmill. So at some point, that rat is going flying off that tread.
Rob Pickels 16:44
Well, I think that they’re rolling on the treadmill. Head over heels when they can’t keep up. Yes. So yeah, Trevor, what do we what do we normally see in an exercise training, right, the VO two max of the rats that were endurance trained went up. 13%. Great. We know that they got a robic li fitter. And then between both groups, we also know this is common knowledge today, lactate goes up with metabolic rate. Rats run faster work harder, lactate in the blood goes up doesn’t matter if you’re trained or untrained.
Trevor Connor 17:16
So what was interesting about all this is they showed so when they were doing the high intensity work, a lot of the things that at the time, they expected to be different really weren’t different. You saw about the same oxygen consumption between the trained and the untrained rats, you saw about the same carbon dioxide production. So you weren’t seen a giant difference in their fuel source between carbohydrates and fats. And to me, there were two big take homes from the study. And the first one, which was the main point of this study was they found it was not production of lactate, they were producing about the same amount of lactate, whether they’re trained or untrained,
Rob Pickels 17:54
ever so slightly lower for train, but really not enough to account for the differences that we see. But the
Trevor Connor 18:00
big difference was in the clearance rates, the train were just much better as they were producing that lactate to say we got a place to send it, we got a place to use it.
Rob Pickels 18:11
Yep. And so when you looked at the metabolic clearance rate between the two different groups at rest, both the trained and the untrained rats cleared about the same amount of lactate, not a big deal. With the easy exercise, the untrained rats actually decreased their clearance a little bit. Even though they’re producing more lactate, their clearance is going down. Whereas in the trained rats at easy exercise, their clearance went up. So they produced more lactate, they were able to clear more lactate. And that’s probably why we see in those beginning stages of a lactate test, that that value stays nice and low. Sometimes it even lowers a little bit because that clearance is ramping up with metabolic activity. Now, when we go to the high intensity exercise, the untrained rats their clearance basically it fell through the floor it was essentially gone at that point. And there was another you know kind of a maintenance I’ll say of metabolic clearance rate in the trained rats that was very similar between hard and easy exercise. So the big take home from this is training increases your clearance rate were not training, your clearance rate falls through the floor as exercise intensity increases.
Trevor Connor 19:28
And one of the explanations they have for this that they do address in the study is blood flow in untrained, most of the blood is going to the working muscles, the blood is transporting that that lactate, it needs to take that lactate to tissues that can actually use it. And if all the bloods go into the working muscles, you’re kind of out of luck the working muscles can use some of it but not a lot of it. Were in the train. They can still shunt that blood to other tissues that can take up the the lactate and use it so well. was one other thing that I kind of went, wow, you know, this is a 1983 study. And I have either forgotten this, or I hadn’t thought about this. And it was really quite interesting to me. But the question is what when they’re clearing the lactate, how is it being used? What’s going on with that lactate. And there’s basically two ways that can be used. One is oxidized. So basically, a tissue takes it up and says, we’re going to use it for fuel. And you see, the majority of lactate is oxidized. But some of it will go to the liver, kidneys, and even a little bit in the muscles, and use for something called gluconeogenesis, where lactate is basically converted back to glucose. And then the glucose is sent back to the tissues that need it for fuel. What I found really fascinating about that is in the trained, you saw, they were better able to use more of the lactate for gluconeogenesis. And that’s important because we always talk about the fact that you have limited glucose supplies. And if you’re out exercising, if you’re training hard, or and you’re in a race, and you deplete your glycogen, you deplete your glucose, everybody’s had that experience where you bonk, you hit the wall. That’s because you’re now relying completely on fat, you just don’t have glucose left to kind of fuel you. And so what you’re seeing here is lactate is being used to spare glucose, or to at least keep glucose levels high.
Rob Pickels 21:30
Yeah, I find this really interesting because it’s the original recycling program, right, we all go and try to recycle our plastic and our aluminum and our glass, you know, they’re breaking down those compounds and making new plastic, aluminum and glass out of it. Well, that’s exactly the same thing that’s happening in the body where we’re breaking down glucose, we make lactate, and then we take some of that lactate, and we try to turn it back into glucose. And it’s this cycle that keeps on going fueling the body, which makes sense, right? Because we want to be able to have glucose in our body when we’re at a high level of lactate production, right, it’s kind of a feed forward positive feedback loop that hopefully helps extend the amount of time that you can maintain that particular intensity for.
Trevor Connor 22:20
And actually, you just raised an important point, I want to make sure we give all the explanations for anybody who’s very new to all this. So when you are using glucose for fuel, it’s broken down in some in a process called glycolysis. So that’s where glucose is converted into ATP, which is your immediate source of energy. The belief back in this time was that the end of glycolysis, there, there were one or two possible end products. One was pyruvate. And pyruvate, could then be used to help burn fat and produce energy using oxygen. And I won’t go into the terms there. The other one was lactate. And the belief was when you are in an anaerobic state, which again is outdated. Glycolysis would go to lactate, the lactate couldn’t be used. And so your body go, gotta get rid of this, do something with the pump it out in the blood causes burning, because they believed it was lactic acid. And then you shut down. Another thing they do point out in, I believe it was in this paper was that actually that’s not quite accurate. And you see that generally the end product of glycolysis, whether you’re going easy, whether you’re sitting on the couch, whether you are going really hard is actually lactate, and that I’m not 100% certain that was in the study, it was definitely in the next one that we’re going to talk about.
Rob Pickels 23:44
Yeah. And that’s, you know, that’s the funny part about looking back and being able to see the bulk of this work at one point in time. The paper that we’re talking about right now is ultimately one of the formative papers that created the lactate shuttle hypothesis, which is ultimately the movement of lactate within cells and also between cells. And so you can see the underlings of some of these ideas in their infancy show up in these early papers. But then, you know, 17 years later, they’re significantly more flushed out and much more solid on their evidence, because they’ve been able to do some study in that intervening 17 or so years. And to that
Trevor Connor 24:25
point, so the paper that we just talked about, was published in 1983. It was in 1984. The doctor Dr. Brooks introduced the lactate shuttle concept. Yep, yep. And so shall we shift over there. Robert, do we have anything left to talk about the other one? Well, actually,
Rob Pickels 24:39
we kind of jumped ahead a little bit. One thing I wanted to point out back when we were talking about gluconeogenesis, the creation of new glucose. The untrained rats had a decrease in their blood glucose throughout exercise, whereas the trained rats had relatively no change. So just going back to Some data supporting the benefit of that gluconeogenesis. That’s an actual empirical evidence that we can see there. Redpoint
Ryan Kohler 25:09
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Rob Pickels 25:33
You know, Trevor, something that I’m struggling with right now is the first and the second studies that we’re talking about today are ultimately so interlinked, right, that it’s hard to just talk about this first study and not talk about the second the lactate shuttle study, you know, so maybe what we should do is start, you know, so let’s start bringing in that second study a little bit, because the lactate shuttle ultimately is what’s explaining some of these changes that we’re seeing in this first lactate clearance study. They just didn’t necessarily know it at the time.
Trevor Connor 26:06
Yep. And Porton point, lactate shallow concept was introduced in 1984. The review that we’re about to talk about right now was actually written in 2000. So this is a little bit of Dr. Brooks, looking back on the introduction. And then what happened after that, and how this was ultimately proved. But it’s really important to understand, when Dr. Brooks introduced the concept of the lactate shuttle, it was in complete contradictions of the belief about lactic acid at the time, and it was not well received.
Rob Pickels 26:39
Yeah, it wasn’t well received at all, because you know, that that’s oftentimes how new concepts ultimately get introduced. Right. But you are right, Trevor, at the beginning of this paper began with an overview of the history. And there was even a state of the art of 1990, you know, section, a state of the art of 1996. And he really outlined the changes in thinking as new research was coming out, how did that affect the knowledge kind of throughout those intervening years? And I feel like there was a lot of change from 1980s until 2000. But following in the reason I picked this paper, I think following this 2000 paper, we saw a lot less change from 2000. Today, right. And so that was sort of the apex in terms of our understanding or learning about lactate.
Trevor Connor 27:31
Great point. And I think, unfortunately, I thought it was going to avoid it before. But I think in order to fully understand this lactate shuttle, we need to give a little bit of physiology here of how our metabolism works. And I’ll try to keep this I’ll try to use as few terms as possible and keep this simple. But I always remember back to when I took that first exercise physiology class, my final exam, had this question of, does the Krebs cycle occur inside the mitochondria are inside the cytosol? And I read that question, when you gotta be kidding me, that is just the most in the weeds, unimportant question ever. And it just showed my lack of knowledge at the time, because actually, that is one of the most important things to understand about our metabolism. So let me see if I can explain this using as few terms as possible. But we just talked about glycolysis. That’s where you break down sugars, glucose, to produce energy. And really important to understand glucose requires no oxygen. So when you go back billions of years, the little bacteria on the earth, this was how they produced energy because they weren’t oxygen consumers, they didn’t need to breathe.
Rob Pickels 28:47
And this is where the term an aerobic without oxygen came from.
Trevor Connor 28:51
Right? So glycolysis is anaerobic. And glycolysis happens in what’s called the cytosol of the cell, which is just basically the main part of the cell where you’ve got this fluid and everything floats around in it.
Rob Pickels 29:06
It’s like a swimming pool with pool noodles. And some your uncle Bob is floating on the raft over there.
Trevor Connor 29:13
But you have and anybody who’s been involved in endurance sports has heard of mitochondria, these are these little organelles inside your cells. And this is where oxygen is used to produce energy. And they’re called the powerhouse of the cell, because they can produce a lot of energy. So glycolysis when it breaks down, a glucose molecule only produces what is a six ATP. Those two well, it would be nice.
Rob Pickels 29:42
Well, yeah, it’s depending because the glucose is cleaved, right and so relatively few without going into more detail.
Trevor Connor 29:49
So inside the mitochondria, there’s what’s called oxidative phosphorylation. So first, you have the Krebs cycle and then oxidative phosphorylation. Don’t worry too much about those terms. Basically, that’s where your body or your cells pull in fat, and break down fat for fuel, and a fat molecule, depending on which particular fat, you can produce 30 plus 40 plus ATP, it produces a lot more ATP than a glucose molecule, it just runs slowly. So hence, when you’re going really hard, and you need energy fast, use less efficient glycolysis break down glucose, when you are going slower, and you just need a lot of energy. That’s where this what’s going on inside the mitochondria really ramps up. Now what’s important to understand here, they say in in physiology, that fat is burned on a glucose fire, because at the end of that glycolysis, after you break down glucose for fuel, there’s that end product and we were talking about the end product can be pyruvate, or lactate. Pyruvate is the first step of everything that goes on inside the mitochondria. So you need that pyruvate. And without that pyruvate, you can’t start burning fat for fuel. So you need glycolysis to be happening, and then it needs to deliver that pyruvate to the mitochondria. And then the mitochondria can do their stuff with it. But one of the things that I believe Dr. Brooks introduced was, well, you gotta get that end product across the membrane wall of the mitochondria into the mitochondria. And actually, you can’t transport pyruvate across that wall, it has to be transported across his lactate. So even if pyruvate is the end product of glycolysis, it has to be converted to lactate. That lactate then transports across the into the mitochondria, then it’s converted back to pyruvate. So hence, this is and Dr. Brooks definitely mentions it in this paper. Lactate is really the dominant end product of glycolysis. So even when you are going easy, even when you are on the side, this is why this is important. Even when you’re on the couch, you are producing lactate, you are not just producing it when you’re going hard.
Rob Pickels 32:14
Correct. And yeah, that was really emphasized in the first study that we talked about today where the rate of appearance and the rate of clearance we’re always producing and through markers we can see Yeah, we’re always producing lactate by marking the glucose. But then also, we’re always turning that over and oxidizing it or creating glucose from it, the levels just look low, because appearance and production are relatively equal at that point in time because we’re at relatively low state, so we’re able to manage that.
Trevor Connor 32:45
And so what Dr. Brooks gets at, and this is kind of on the brilliance of physiology, the value of lactate is lactate transports really well. It moves across membranes really well. And we have a lot of membranes, every cell has a membrane around it. But then within the cell, the mitochondria have a membrane around it, your body has a whole ton of membranes. And to transport energy that energy has to somehow get across those membranes. And this is this concept of the lactate shuttle is lactate transports really well across them. We have the any talks a lot in this study, we’re not going to go too deep into it into what are called MC T’s. What? I’m going to butcher the pronunciation. But actually, Rob, you want to save me on that one? No, thank you mono car box so late, that I get it lactate transporters.
Rob Pickels 33:44
Yeah. And this is where we’re getting into that new concept, right? We knew that you produced lactate. And we knew that lactate made it into the blood, obviously, because lactate in the blood goes up as you work harder. But what we’re now beginning to discuss is that lactate can actually cross membranes into other cells and into their mitochondria. And that’s where a lot of this new thinking is coming out. The first half was has been figured out for years and years and years prior we knew it got to the blood. But what the heck did it do when it got to the blood? Well, the new thinking with lactate shuttle hypothesis is that that lactate is able to go into other cells and be utilized as energy because we can convert between lactate and pyruvate as Trevor talked about before, so if we can get lactate into the blood, if we can get it into slow twitch or cardiac muscle tends to be really good at this. If we can get it into their mitochondria, then their mitochondria can actually use that lactate and produce a whole heck of a lot more ATP. And so we don’t have to think about lactate and anaerobic glycolysis. The first set of steps of glycolysis that’s only producing two With ATP, it’s actually producing a heck of a lot more, it’s just producing the rest of them in other cells.
Trevor Connor 35:06
And this is the brilliance of the physiology. Because here’s, here’s the way to think about this, when we talked about glycolysis, and then the mitochondria is ability to burn fat. Not all cells have equal ability to do glycolysis, nor equal volume of mitochondria to burn fat. And so this is the brilliance you have, for example, your fast twitch muscle fibers, huge ability to perform glycolysis, but very little mitochondria. So they’re doing all this glycolysis. And they’re ending up with this lactate accumulation go on, I can’t use this, I’m not really an oxygen using cells. So I got to dump this somewhere. So it turns it into lactate pumps it out of the cell, you have other cells in your body that are the big oxygen using cells, like your your type one muscle fibers, your your heart tissue, and they don’t have a lot of glycolysis. But they have a ton of mitochondria, they want to be burning fat, and they’re screaming out, I need that precursor, I need that thing that keeps driving my ability to burn fat, which is lactate and pyruvate. And so they’re calling out for it. So you have these glycolytic tissues that are pumping the lactate out. And then you have these other tissues that are big oxygen users saying, Great, thank you. I’m gonna pump this in, and I’m gonna use it.
Rob Pickels 36:30
Yeah, and all of this is occurring along a concentration gradient, right? If you look at the amount of lactate in this paper, they termed it white muscle, but ultimately fast twitch muscle fibers. If you didn’t know that when you’re eating white and dark meat and chicken, that fast and slow twitch dominant muscle fibers. The white muscle fiber, the fast twitch has a lot of lactate in it. Blood has the second most lactate one step down the concentration gradient. And then the red muscle as they call it, or the dark meat the slow twitch that has the least lactate. So we’re flowing like most things do from high concentration to low concentration. And this is something that’s important to point out is these transporters, the MC T’s move lactate and they also move a hydrogen ion. And that is where everybody associated lactate with this lactic acidosis, right? It’s not as if the lactate and the hydrogen are bound together. It’s more that the transporter. Without getting into the details, the transporter has to use a hydrogen ion so that it changes shape and allows that lactate through.
Trevor Connor 37:42
Yeah, and so for anybody who doesn’t understand knows about this, when you’re talking about acid, you’re basically always talking about hydrogen ions. And he sort of acid just releases these hydrogen ions, hydrogen ions are highly damaging, they break things down. And so that to me was the really funny contradiction as as you pointed out, cells when they transport the lactate out, they also transport a hydrogen ion out. And so everybody was going lactic lactic acid is this dead product because whenever you see an increase in lactate, you you see pH go down. So you go and it’s causing burning, it’s this horrible acid in your body. Actually, what’s going on is your cells are using lactate to get those hydrogen ions out of the cells so the cells can keep functioning. So lactate is actually fighting the acidosis not causing it.
Rob Pickels 38:35
Yeah. And interestingly, we see changes in these transporters, they’ll increase with chronic exercise, exercise day in and day out endurance training, your ability to transfer these molecules goes up. But we don’t necessarily see any changes with acute exercise. And sometimes there are changes that happened immediately today. In response to that bout of activity. We don’t necessarily see that with lactate transporters, it takes days and days, weeks and weeks, months and months of training.
Trevor Connor 39:05
So I gotta go back to your point about the white meat and the red meat. When I learned that it really made me depressed. Why? Because I love white meat. I hate red meat whenever we have turkey or chicken and I realized if you ever cooked me being an endurance animal I would not taste very good so you don’t love yourself I would not want to eat
Rob Pickels 39:32
that’s really funny Trevor
Trevor Connor 39:34
are horrifying that actually think about these things. Well, hey,
Rob Pickels 39:37
just think that that the acid that we’re talking about here makes things nice and tangy and flavor. So yeah, there you go.
Trevor Connor 39:44
So I’ve said this before. I just want to restate this. Lactic acid does not exist in the human body. It is lactate which is alkaline, not acidic. And if you hear a co OCE talking about you got to clear the lactic acid in the next day when you are sore. They’re saying that’s because you got lactic acid in your tissues. They need to go and read their physiology because that is an outdated concept. It is not true. Is this your soapbox? It is one of my biggest so far that and they were knee warmers.
Rob Pickels 40:21
Skateboarding is not a crime.
Trevor Connor 40:22
That’s yours. Rob has perpetually had a skateboard in his office. I don’t know if you’ve actually used it.
Rob Pickels 40:32
Yeah, yeah, no, I sneak out over lunch when nobody’s looking.
Trevor Connor 40:35
And go skateboard. Yeah. Okay. To wear your hat backwards?
Rob Pickels 40:39
No, they were slightly cocked to the right.
Trevor Connor 40:44
So think as we close up this study, you know, I just want to emphasize the importance of this lactate shuttle concept that took us from this idea that lactic acid was his dead product that you don’t want to an understanding that lactate is actually this amazing molecule, for transporting energy from tissues that can’t use it to tissues that can use it. And it’s his great way of conserving that energy. And as you pointed out, even in the liver and the kidneys, converting it back into glucose so that we can avoid running out of our glucose supply longer. So we can even dive into other roles for lactate. But this ability to conserve and maintain energy to make sure it’s going to where it needs to go on the body is extraordinary. And lactate is actually when you’re talking about energetics, one of the most important molecules in our body.
Rob Pickels 41:43
Yeah, no, certainly, I think another thing to point out too, is that when we discuss glycogen, our ability to store glucose, the liver is the only organ that really stores significant glycogen and glucose and can also send it throughout the body, the glycogen and glucose that’s stored within your muscle is locked in your muscle. So that glucose in your leg doesn’t do anything for your triceps when you’re rowing a canoe climbing a rope doing push ups or whatever else. But through this lactate shuttle, it’s ultimately a way that we’re able to feed the rest of our body because this lactate production is occurring in something like our legs and being sent elsewhere. So it ultimately is evening the energy distribution a little bit.
Trevor Connor 42:34
And this is where we have to give huge amount of credit to Dr. Brooks and why we’re doing this episode about him because he was the one that shifted this understanding. And without this shift, we really couldn’t understand how we produce energy, how energy is used in our body. This was very, very important research that has really shaped a lot of modern exercise physiology.
Rob Pickels 42:57
So Trevor, I think that you’re right in that Dr. Brooks has been hugely influential in our understanding of lactate. But something that’s also important. And the reason that this 2017 study was chosen is that we pretty much always associate lactate with exercise. But that might not actually be the case. And the work that Dr. Brooks and Dr. innego sand Milan, great friend of the show, they’ve been looking at lactates role in cancer in carcinogenesis, in tumor migration, in angiogenesis, and all of these different factors that are relating ultimately to cancer metabolism within our body. I just kind of
Trevor Connor 43:40
love the fact I mean, this is this is the brilliance of the man, he kind of hit a point in his career where I went, Well, I saw bioenergetics. So now let’s go cure cancer now. He is putting out some absolutely great research. I mean, this is this is absolute brilliance. But yes, lactate is highly involved in cancer. And we are not going to go into the weeds on this paper because it is a deep paper that covers a lot of terms, a lot of concepts.
Rob Pickels 44:08
It has all the acronyms that make Trevor happy. I was very happy with his paper. I
Trevor Connor 44:12
thoroughly enjoyed reading this. But it is important to point out well, I’m not going to go into the particulars. I don’t think Rob wants to go into the particulars either. As he’s explaining this, they are pointing to a whole lot of research, where when they use drugs that block lactate, that block lactate production that blocks some of the important elements in this whole lactate transport such as the the MCT transporters. You actually can see improvements in cancer.
Rob Pickels 44:47
Yeah, and so the initial link what I’ll say is that as brilliant as we’ve made our Dr. Brooks to be the initial link between cancer and lactate actually happened with a researcher back in 1920s 1923,
Trevor Connor 45:02
if I remember in 2003 was the introduction? Yeah, we are at the 100 year mark.
Rob Pickels 45:06
We are Wow. That’s incredible. And that was from a researcher named Otto Warburg. And he ultimately it was later coined the term the word, Bear. It’s hard to say this word. Warbreaker glad I’m not the only one. It’s like a weird like, roll roll of your mouth. Right? It’s too I don’t know, the Warburg effect. Thank you, Otto. How about Dr. Autos? effect? How about that? Can I rename it?
Trevor Connor 45:33
That sounds like a Bond villain.
Rob Pickels 45:35
Alright, fine. Dr. Otto is effect. Mr. Bong? Oh, till you see my lactate Zeis. Lactate is serious business. Yes, it isn’t. Ultimately, what we see is that if you look at the lactate going into blood vessels that feed cancer, it’s relatively low. But for some unknown reason, especially in 1920s, there was a ton of lactate coming out of cancer cells, like 40 to 70 times the amount that should have been coming out.
Trevor Connor 46:09
Yeah. 70 times is what he found. Yeah. Which is extraordinary. So we’ve talked about the importance of homeostasis in our body, when you are producing 70 times more lactate than normal, like every homeostatic alarm in the body is going full Rev.
Rob Pickels 46:29
Yeah. And at the time, they couldn’t necessarily understand it 1920s To even, I can’t even imagine discovering this in the 1920s. With, you know, the ability and the laboratory techniques that people had. So we talked a lot about how we were just learning things in the 1980s. Right, right. But to be thinking about this in the 1920s. Is, is mind blowing. To me,
Trevor Connor 46:50
it was interesting, some of the ways he did it. So my understanding was, and it’s been a bit since I’ve read this, he would take cancer cells out of the body, and put them in a glucose solution. And then see what sort of how much lactate they were producing?
Rob Pickels 47:07
Did he tasted glucose solution and see if it has a tangy, not sweet?
Trevor Connor 47:10
Back then they did that sort of stuff?
Rob Pickels 47:12
They did do that. So there’s
Trevor Connor 47:14
the name of it. There’s a chemistry manual. That’s been around for hundreds of years. And for the longest time, when it had the descriptions of all the properties of each chemical, it included tapes, and I want to know, who was the poor research assistant who had to try dioxin?
Rob Pickels 47:33
Yeah, I know, is it just like death? You know, like, has? Yeah, it’s like, you know, can’t taste due to death?
Trevor Connor 47:45
Yeah, that’s horrible. But I wonder if that actually happened.
Rob Pickels 47:49
Anyway, the the original thinking at the time before, Dr. Brooks and Dr. Sam Milan got their hands on it was that it was more about the glucose, that the cancer cell was trying to metabolize, and less about the lactate that was coming out the other end. And what they’re proposing in this paper is that it has nothing to do with the glucose and everything to do with lactate. And that the cancer cells are purposefully it’s a little bit of an anthropomorphic zation of a cell, but that they’re purposely producing lactate because lactate is beneficial to cancer proliferation through carcinogenesis and other negative processes.
Trevor Connor 48:35
Yeah, this is really important. We are 100 years out from the discovery of the Warburg effect, and still have not landed on here as a definitive explanation for why the Warburg effect exists. And as Rob just pointed out, this is what they’re proposing in this paper, Dr. Sol, Milan and Dr. Brooks are saying, we think we understand and it’s not what you thought it was. It’s actually that the cancer cells want to produce lactate, and they go into a lot of detail in the paper, about how lactate high lactate levels, create the environment that cancer cells need to proliferate
Rob Pickels 49:14
now. So we kind of maybe let’s just focus on the steps here. And we’ll we’ll figure out on the fly, how much depth we want to go into for each one. But ultimately, the suggestion is that through some disruptive DNA, right, we talked about this in our skin care episode, UV light damages DNA, and then that can cause you know, skin cancers, melanoma, so on and so forth. Well that disrupted DNA can occur anywhere within the body, and that that change in DNA ultimately creates a cell that’s more glycolytic in nature. That’s sort of the first step of that one particular cell.
Trevor Connor 49:56
But this is really important when you look at the mutations in cancer cells a lot lot of them are related to the mitochondria. And you see a breakdown of mitochondrial function in cancer cells. So cancer cells have a harder time or completely incapable of using oxygen using fat produce energy.
Rob Pickels 50:17
Yeah. And it even starts at the beginning where the cancer cell in the mutations that occur increase, actually the glucose transport into the cell as well. So not only is the mitochondria struggling to do things in an aerobic manner, the cell is being set up to work in a glycolytic manner by increasing its ability to pull glucose in,
Trevor Connor 50:39
right? There’s something they mentioned in the paper, which I found interesting is Why do cancer cells become reliant on glucose. And their explanation for this was because the body always provides a steady stream of glucose. And Porton thing to remember here, when you’re talking about cancer cells, the one of the main issues with cancer is most cells in our body. Think of them as selfless. They provide a function in the body. And cells do that function at some point, they actually have a programmed death. So cells are completely there for whatever’s best for the body as a whole. Cancer cells think of them as kind of selfish cells, they go, Yeah, I don’t want that. You’re not going to program my death, I want to proliferate, I want to grow, leave me alone, I’m going to do my own thing. And I don’t care if this helps the body. And a lot of what they describe in this paper is how lactate drives a lot of these functions that allow this cancer cell to be very selfish, that actually draws all this glucose to the cancer cells, that prevents apoptosis. So cellular death, prevents all these things that you normally see in other cells, and so that the cancer cell can sit there and keep growing and be quite happy on its own, even though it’s damaging the body. And they do point out something really interesting to that it’s, it’s not really the tumor, when people die of cancer, it’s not the tumor that kills you. It’s all the damage that these cancer cells are doing to the body demanding all this energy demanding all this glucose, making all these demands for itself at the cost of the body.
Rob Pickels 52:20
Yeah, Trevor, and what you’re talking about now, is the thread that they use to explain why we see this shift to a glycolytic energy production that as you mentioned earlier, only produces relatively few ATP energy molecules in the single digits compared to the oxidative the A robic that produces, you know, in the 30s, to 40s. And that is because, well, when the liver is acting like a liver, it’s not acting to help itself, it’s acting to help the rest of the body. But in the cancer cell, it doesn’t care about efficient energy production, it makes no difference because it doesn’t care about the rest of the body, it shifts the burden of energy production onto the host, right. And the cancer is ultimately surviving at the expense of the tissues, not in support of the tissues around it.
Trevor Connor 53:13
So we’re definitely going to talk about this more in future episodes. But I’m going to mention this now. And I’m gonna watch Rob’s face to see how much he grimaces. But I’m not sure I agree with us. I’m not sure I agree that the reason cancer cells shift to rely on glucose is because there’s a ready supply, because our other primary fuel is fat. And there’s a much more ready supply of fat in our body pretty much at all times. So I’m not sure I buy that my personal feeling for the reason cancer cells become reliant on glucose. And I except we’re actually going to talk about this in a future episode, we just talked about the cell cycle that is cells function to to serve the whole body and cells go through these natural cycles that starts with proliferation where cells grow, then a cell goes into what’s called cell cycle arrest. And it can go back and forth between these, these two phases, ultimately goes into apoptosis, which is cell death. This is what’s called the cell cycle. And it’s important for cells to go through all three of those stages. There’s recent research showing that glucose levels direct which stage a cell is in. And when glucose is readily available. The cell is in a proliferation phase, which is what a cancer cell always wants to be in. So I actually, my thought on this is the reason cancer cells shift to rely on glucose and create that environment where it’s demanding glucose from the body is because that keeps it in a perpetual proliferations phase and prevents it from ever going to dabba ptosis.
Rob Pickels 54:55
Yeah, and I think that that that particular theory is outside The discussion of this paper but I do believe that it’s ultimately in line with where they’re going, right? Because if we begin and I don’t want to unpack it all now, but if we begin to think about the processes that occur, that are driving that proliferation, then it also is paralleling the effects that lactate is having for the cancer cell, right. Where by up regulating lactate, we’re down regulating the immune activity within the body. Right. And so that immune activity isn’t able to go out the natural killer cells, the T cells are not able to stop those individual cancer cells from traveling throughout the body and ultimately metastasizing, re creating cancer and more of a global sense within the body. So I think that we’re talking about things in parallel, but it’s an interesting take on why this is happening from the very beginning.
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Trevor Connor 56:45
Well, so Rob, you said before we dived into this paper that I’m not allowed to talk about HIF one or p 53.
Rob Pickels 56:51
I didn’t say you weren’t allowed to I just said, We don’t want to put people to sleep.
Trevor Connor 56:56
They’ve had their coffee. I’m the only one here as another coffee.
Rob Pickels 56:58
Can I point out something in this paper? Actually, I really appreciated that there was a little table of acronyms, right, like, right, you know, because oftentimes, what happens in papers is that the first time a term is used, it’s spelled out. And then in parentheses is the acronym and from hence, after in the paper, it’s only the acronym then they never ever mentioned what the original terminology was. But only about 50% of the acronyms were in that summary. And so I had a great reference for 50% of them. And I had to actually read the paper to find the other 50%. So can I
Trevor Connor 57:39
just embarrassingly admit to you that even though I had read that HIFF stands for hypoxia inducible factor? At some point, I switched to calling it high altitude inducible factor? Well, that for two years, I think without even being aware, I had accidentally done that same same but different. Yep, that actually I like the high altitude inducible factor because it makes it clear. This is caused by altitude, lack of oxygen,
Rob Pickels 58:06
decreased pressure, Trevor, not lack concentration is the same bro. Same amount of pressure pushing it across the membrane or not. That’s another episode call me
Trevor Connor 58:15
the nerd. So without diving into all these things, and anybody who is interested in the biochemistry and dress in the physiology, this is a great paper to read. Because the end, it’s another one those papers that has what 200 References I’m going down in the paper, it’s not even loading. There’s so many references to keep keep scrolling 225 references. This is a massive paper that is very insightful on a lot of what’s going on in cancer cells. But Rob, what else do we want to share here except just making that point? That lactate is really important to the pathogenesis of cancer?
Rob Pickels 59:00
Yeah, I kind of I want to just sum up the steps that this goes through so that people have any takeaway, they can just kind of remember these these quick things here. And so the very beginning of this is increasing glucose uptake within the cell. When that occurs, then we have this great upregulation of glycolytic enzymes, our ability to use that glucose for energy. And Trevor, as you pointed out, a decrease in our mitochondrial activity, right. And so that cell is becoming very quote unquote, anaerobic, right. And they liken it to what happens in yeast and bacteria for their energy production, right. Typically, our energy production differs. So after that decreased mitochondrial respiration, that’s when we really see this greatly increased lactate production coming out of the cell. And as we pointed out in our first two papers about exercise, we typically would use mitochondria to oxidize that lactate into fuel, but we’re down regulating our mitochondria. And so we’re losing that ability to use the lactate as fuel, which ultimately means we got more lactate floating around. And because we have more lactate floating around, now we’re seeing changes in our immune system and other downstream effects because lactate can also act like a hormone, Dr. Similan loves to call it a lacked hormone, I believe in his Basque accent that I can’t possibly do. And that sets up an environment that allows the lactate cells to proliferate and travel within our body. And ultimately, that’s a big part of why lactate is important. So my question, Trevor, I’m not willing to really say this. But can we learn something from this about lactate, about cancer, about metabolism? Are you willing to make any statements
Trevor Connor 1:01:00
I am, if you want me to make and then this is where I’m putting on my nutritionist hat. And the statement that I’m going to make which I get the sense you kind of want, this is where you’re pushing me?
Rob Pickels 1:01:10
Well, I want it to be said, but I don’t want to be the person to say it. So I’m
Trevor Connor 1:01:13
going to say it but understand what the explanation we just gave. This isn’t going to fully make sense. There’s a lot more to this, and it is something we might dive into later on. But basically, what you just heard is cancer cells are giant glucose consumers.
Rob Pickels 1:01:33
The biggest, actually, for what it’s worth, when we’re looking for cancer within the body, the scan that they use, detects glucose metabolism. That’s actually what a PET scan does. It’s how you find the cancer in the body.
Trevor Connor 1:01:48
What we haven’t gotten into at all that, like I said, we might cover another time, but I’ve read plenty of research on this is excess glucose supply can potentially lead to this mechanism. So the argument that I’m going to make my take home here is if you are at risk of cancer, or you have been diagnosed with cancer, you need to be very careful about the simple sugars and the carbohydrates you are consuming. And I am not a doctor. So I have to be careful about what I say. But I would say personally, if I was ever diagnosed with cancer, well, I am not a supporter of the keto diet, I would probably go keto for many months,
Rob Pickels 1:02:31
you know, at least on the surface, it seems like it might have an effect. Now, again, I don’t want to be the person that says that because I don’t fully understand this enough. And maybe what we should do is look for researchers. And if anybody is aware of researchers on the other side of this, I’d love to have that well rounded conversation about because, hey, there could be downsides, you know, to reducing your carbohydrate intake. Right. And maybe that’s appropriate for more of a treatment sort of a I don’t know, I don’t even want to go there. But I think that it’s an interesting conversation, and in an area that more research really needs to be done. And I know that Dr. San Milan has been involved in some research that’s looking at how do you suppress this lactate production? And at this point, I believe they’re looking at what does that do to cancer cells in the laboratory in a petri dish? We’re not at human trials, but a new way of looking at cancer treatment that ultimately revolves around this Warburg effect. I said it correctly that time and lactase role in the metabolism.
Trevor Connor 1:03:42
And look, I agree, it’d be great to get a researcher on on this, I’ve actually been doing a lot of research myself out of interest on this. The short story is unfortunately, my sister in law’s father is dying of cancer. I’m also a physiology geek. And so she asked me if I could see if there was anything. So I’ve been researching into this. And this is why I would love to do a few more episodes on this, because there are some really fascinating, really exciting stuff out there. But if people are interested in this, I’m just gonna give the names of a couple studies that dive into this, that would be really good reads. One is revisiting the Warburg effect, diet based strategies for cancer prevention. That’s a 2020 study. And it goes into the effects of a ketogenic diet if you really address in that cutting sugar and does it help or does it not help? And again, this is all very new. So this study is 2022. And they even say, promising a lot more research needs to be done
Rob Pickels 1:04:36
and nothing is a panacea, right. Let’s be honest about that. But
Trevor Connor 1:04:39
this study is called could ketogenic diet, starve cancer, emerging evidence, couple more effects of obesity and calorie restriction on cancer development. So there’s also evidence again, because it puts you into that ketogenic state is the theory here is a 2023 study showing that doing some intermittent fasting and seems to have some benefits. Other really interesting things I’ve seen in this and part of the reason I’ve been diving even further into this research is there are common mechanisms. So I’ve been diagnosed with atrial fibrillation, and here’s as a title that you’re kind of going to go what the Warburg effect and new insight into atrial fibrillation. And they’re showing that actually the Warburg effect happens in atrial fibrillation as well
Rob Pickels 1:05:24
meaning cardiac cells are producing more lactate than they should or I haven’t read the paper, I’m not familiar with this at all, they are producing
Trevor Connor 1:05:32
more than they should. You’d mentioned him if one if one is highly involved in in atrial fibrillation, another one which they only touch on in in Dr. Brooks’s paper, but I think is very important to this whole mechanism is something called ANP K. and P k is basically the glucose sensor. It senses the level of glucose in your bloodstream and then sets off different reactions in your body depending on whether the glucose is elevated or low. And that’s been shown to to relate to atrial fibrillation. So again, I was talking about the cells cycle. And what you are seeing is a breakdown of the cell cycle and atrial fibrillation. There’s a lot of research on that. And take it even a step further, I could read off a bunch of studies to you right now, about neuro degeneration, where you’re seeing a similar mechanism there as well. There you go. So it’s a pretty exciting stuff. I think, what you’re what you’re seeing from this, Dr. Brooks, paper, and all these other studies, I mentioned is almost kind of a revolution and how we’re looking at these chronic diseases, and realizing that there are common mechanisms and all of them,
Rob Pickels 1:06:43
yeah, and just the, you know, the interconnectedness within the body exercise. And the molecules, the processes associated with exercise, are not necessarily just about exercise, they’re about what happens to our body at rest in our daily life. And Dr. Sam, Milan talks a lot about how increasing endurance training how improving your mitochondrial function, will that allow us a metabolic flexibility that allows you to use carbohydrates or fat as fuel. And not doing that not having that metabolic flexibility means that you’re just stuck utilizing carbohydrate all the time. And that can lead to a whole host of chronic diseases as well. And that’s why one of the reasons that we see improvements in quality of life and in wellness through exercise. So I love that we started today’s episode with these deep dives into exercise and exercise physiology, but that ultimately, we’re rounding it out with this conversation about health and longevity and disease process, using the same terms, the same molecules, the same transporters, and tying it all together.
Trevor Connor 1:07:56
Yep. And so the last message I will give here, because you touched on metabolic flexibility, I think you’ve touched on one of the most important things, and this is where I’m getting outside of what we’re talking about in this episode. And talking about all the research that I’ve been currently going through, and that metabolic flexibility that sometimes relying on carbohydrates, sometimes relying on on fat, is actually essential for health, because we talked about the cell cycle that cells needs to go through proliferation, it needs to go through cell cycle arrest. And the reason cell cycle arrest is so important is because that’s when your body or cells repair DNA, and they also need to go through apoptosis, what they’re showing is that metabolic flexibility is essential to go through all those cycles. If you are in a constant state of high glucose, you’re going to be in a constant state of cellular proliferation. And that’s not healthy for you. And that leads to things like cancer. Alternatively, you have a lot of people saying, oh, we need to be keto, all the time. keto is really healthy for us. Well, very low glucose levels drive towards apoptosis. And that’s actually in the I could name you a bunch of more studies they’ve been showing that actually speeds up aging. So there isn’t I haven’t seen a study that says yes, somebody on a long term ketogenic diet, ages faster, but there’s plenty of evidence pointing in that direction. So the message here is, you need to be metabolically flexible, you need to sometimes have lower glucose levels sometimes have higher glucose levels. And that’s going to keep yourself healthy and having going through all those cycles. And the last thing I’ll mention, I just read a study a couple of weeks ago, that was a wow study for me. And if you’re interested in what we’re just talking about, read this one. It’s a 2022 study that explains all this. And it’s called coordination of the ANP KAKT mTOR and p 53. Pathways under glucose starvation. Wow. And I went nerdy, I bawled.
Rob Pickels 1:09:52
My eyes glazed over. I apologize to everybody else. You know, Trevor, yeah, I think that we’re ending on a great point here. As with everything, even endurance training, you can’t just have one process occurring within the body. We know that that’s not healthy. We talk a lot about how the majority of your training needs to be at relatively low intensities, but we never talk about how it should only be at low intensities. And there has to be a mix of high and low intensity, there has to be a mix of carbohydrate and fat, there has to be a mix of pushing forward and pulling back. Right. And that is that variety is ultimately the spice of life, right? It makes us happy in our everyday life. It makes our bodies healthy and their metabolic life. And we need to be training our bodies to be able to do that.
Trevor Connor 1:10:40
Fantastic, great message ended on if anybody’s still with us and not asleep.
Rob Pickels 1:10:46
This was a riveting conversation and people can’t wait for more.
Trevor Connor 1:10:50
I hope so.
Rob Pickels 1:10:52
That was another episode of Fast Talk. Subscribe to Fast Talk wherever prefer to find your favorite podcast. Be sure to leave us a rating and a review. The thoughts and opinions expressed on Fast Talk are those of the individual. As always we love your feedback. Tweet us at Fast Talk Labs or join the conversation at forums.fasttalklabs.com For Trevor Connor. I’m Rob Pickels. Thanks for listening!
