Exercise Physiology | Acid production and removal during exercise (Part 10)
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Welcome everybody to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike Todorovic, and today I'm joined by a movie star, star of Boogie Nights, The Hangover, and Austin Powers, the spy who shagged me, Heather Graham. Welcome Heather to the studio.

I got a new stick of deodorant today. The instructions said remove cap and push up bottom. I can barely walk, but my farts smell lovely. They're getting worse, Matt. They're getting worse. Welcome, everybody. Last week you said it was best ever. Really? There was a low bar. You've set a low bar over the last couple of months. We are on. We're still on our special series. Second last one. Oh, second last one. Okay, cool, cool, cool. Looking at...

the human body and how certain organ systems functions have changed or change according to exercise. So what does exercise do to that body's structural function and vice versa? Today we're looking at acid-base balance. Very important concept. Matt, first question I'm going to throw to you. Oh dear. Straight off the top is why... Firstly, how are you? Yeah, look, I'm good.

I always think about at the start of these podcasts, should we have a quick chat about life? Do the listeners want to know who we are, what we do, a little bit about us? And the more emails I get about hating me, the less I feel like people want to know about me. No, no, no. I don't get any hate mail about me. Matt doesn't get any about him. But I'm good.

I, what have I been doing? Gardening. I've been doing a lot of gardening. That's very boring. Trying to think of something fun. I bought a whoop. I've got a whoop on my wrist right now. And so that's been spitting out all this physiological data. I opened my phone up, right? So I opened my phone. Tell me what a whoop is. So a whoop is, it's a company that creates wearable devices. This episode is not sponsored by whoop. However, whoop, if you want to sponsor us, let me know. Uh,

And it basically links to your phone and it spits out a bunch of data. Now, I didn't know what sort of data it spat out. However, it spits out information about your sleep, your recovery and your strain. Strain? Strain. Not Australian. Not strain. Not Australia. Not Australia. Australia. But it spits out things like your resting heart rate, your average. You want to know what my resting heart rate is? What, right now? 50. Oh, just averaged. So it takes my resting heart rate while I'm asleep.

So the average throughout sleep, it's 50 beats a minute there. During the wake phase of your day. Yeah, that's not as good. My average is 67.

But I'm on dexamphetamine for my ADHD. That bumps it up. And you are highly strung normally. That's very, very true. But you didn't need to tell the listeners about my signal anxiety. Everyone knows. Heart rate variability. So HRV, I recorded a YouTube video on heart rate variability. So this is quite relevant to the topic of exercise, right? So if our dear listeners want to listen to heart rate variability, that should be released by the time they...

Listen to this. Listen to this episode. So go to Dr. Matt and Dr. Mike YouTube channel and you'll see heart rate variability. I even go through how to calculate it. So if you've got your R to R values, which is an ECG, which a lot of people probably don't have access to, but I tell you how to calculate it if you're interested. So you get R to R values with a WHOOP?

It doesn't tell you the R to R, it just spits out the heart rate variability. Resting heart rate, respiratory rate, sleep. That's the main thing where I got it because my sleep is terrible. How do you sleep? You sleep well? Eyes shut. With your eyes closed. Oh, maybe that's what I'm doing wrong. I used to sleep so well. My wife used to get so annoyed when we'd both go to bed and I'd be asleep within the first 10 seconds. So that quick.

And now it's been the last couple of years, I suppose, since having kids. I wake up, my whoop tells me I wake up about 25 times a night. Really? 25 times is over the last four nights I've had the whoop for about four days. And how would it know that? Does it do movement? It does movement and also your heart rate spikes and so forth.

It's like arousals. Yes. And I have around about three hours of deep, what they call restorative sleep, which is REM and, and, uh, great band, very good band. Um, so yeah, look, it's, it's, it's,

It's been interesting, the whoop. I'm going to do more videos on what some of this data might mean. What's the wearable rings? Is that also a whoop? That's Aura. Oh, Aura. O-U-R-A, yeah. Also not sponsored by Aura. I've never worn an Aura ring. I think, again, look. We had a colleague that has one. Really? Remember in Sydney? We went to Sydney for that, our book.

Yes, we'll tell the listeners about our book more in the near future. But she has one and she raves about it. Was that the aura she was wearing? I thought she had a whoop. No, it was an aura. A ring. Yeah. Look, I think... I think she said, correct me if I'm wrong here, but...

Her friend also has one. Yeah. And he was about to go on an international flight and it picked up that he had AF or some arrhythmia the night before the trip. Yes, yes. Which then led to obviously the cancellation of the trip but then some kind of cardio...

Yeah. Intervention. So they can do that. So the, the version of the whoop that I got, I don't have the high, I didn't pay for the highest level, which spits out ECG data. Um, the reason why was because when I was doing it, it said that this is not available in your region. So I don't know if it's an Australian, you know, uh, uh, F FDA, like you're part of Brisbane pun. Oh no. Yeah. It's just Eden's. Oh, I don't want to, well, Eden's landing, which is where I live. Uh,

I was just going to say, I'm not going to say where I live, but it doesn't matter. Yeah, it's just that area. It doesn't work. No, it's Australia. And I think it's got to do with the way Australia approves devices that might be seen as medical. Maybe. I don't know. I didn't look into it, but I didn't purchase it. Anyway, we should jump into this episode, Matt. The listeners are probably going, Jesus, shut up. So let's talk about acid-base balance. This is important when it comes to exercise. Why? Why?

Why is it important when it comes to exercise? What does the listener need to know just from the front end? Well, balance. Your balance. Balance. Coordination. Vestibular system. No, balance suggests homeostasis and we know how important that is in the body. If we don't get that right, systems start to break down. Now, with acid base, so this essentially just means –

Sorry, I just turned your microphone down. Go on. The amount of hydrogen ions in a solution or in a tissue or in something, an environment. Yeah. This will impact cellular functions. Now, in a muscle, we know that muscles are filled with proteins, not only contractile proteins but also enzymatic proteins, and so not balancing the pH well is

or the acid versus base environment will impact structural and functional outcomes of those processes. Yeah, acid-base imbalances stop things from working, muscles contracting and so forth, and increases fatigue and all the things we don't want, reducing performance when it comes to exercise. So the problem is that when you exercise, you produce acid.

And so that production of acid needs to be balanced out, like you said, because if it's not, then you don't perform and you can't continue to contract those muscles. And not just the muscles, but it spills over into the bloodstream and then it can be nasty for the rest of the body. So we need to maintain and balance appropriate levels. But before we jump into that, we need to talk about what the hell pH is and what acids and bases are. A lot of our listeners probably already know.

But we have to go back through this stuff. We won't take a huge amount of time here. So the way I begin this, and I've done it in previous episodes before, but I'll do it again, is that when I talk to my students and say, all right, Matt, if I'm going to take your blood right now and measure the concentration of the ions in your- What's an ion? A charged atom or element. So like sodium, magnesium, chloride, potassium, and hydrogen-

I want to measure – So they can be positive or negative? Yeah, they can have an extra electron, so they're negatively charged, or they can have lost an electron, so they're positively charged. And they all have very – ions have important functions in the body, right? So sodium is important for electrical relay systems, calcium for contraction, bicarbonate for buffering, which we'll talk about. So they all play important roles, including hydrogen.

Now, if I were to take your blood and measure the concentration of those ions, what we'd find is that, for example, sodium, its concentration would be around about 142 millimolar. That's the unit of measurement. Per litre. Yeah. Well, millimolar is millimoles per litre, right? I'm just saying in a blood test, it's usually that unit, right? Yeah. So it'll either say millimoles per litre or it'll say millimolar, which is the same thing, right? Potassium would be about four millimolar.

But if I were to measure the hydrogen concentration in millimolar, it's going to be 0.00004 millimolar. That's a lot of zeros. And it's easy to make a mistake, lose a zero, add a zero, big problem. That's the difference between life and death. Correcto. So what smart people did was they said, let's get rid of the zeros. And we know that in maths, if you want to get rid of the zeros, you can take the base 10, right? So you take the log of something.

Now, if it's a really big number with a lot of zeros, you take the log to the base 10. If it's a very small number with a lot of zeros, like this one here, you take the negative log to the base 10. It's basically telling you, compared to the zeros, where is the decimal point? So if the decimal points all the way to the right, like in a very big number, like a million, you take the positive log 10, right?

And it would make that a smaller number. If you take a very small number, like 0.00004, you take the negative log, right? And so if you put into a calculator,

Now, here's the thing, right? 0.00004 millimolar, which is the hydrogen ion concentration, if we turn it into molar, which is now like a unit that we can convert, it ends up being 0.0000004 molar. So 0 point with seven zeros and then a four. Right. If you take the negative log of that number, it gives you 7.5.

Right? So 7.5 is basically saying, hey, that's the pH of our blood.

And so the pH is the power of hydrogen ions. Effectively, it's the negative log of the concentration of hydrogen ions in molar. Okay. Now, that might be confusing, but we've done episodes covering all that, and I've done YouTube videos looking at the details. So if you want to quickly pause and watch a YouTube video and I draw it out, feel free. Type in Dr. Mike pH, and you'll see it. But effectively, that's all pH is. It's just the concentration of hydrogen ions in a solution. Okay. So, Matt, in saying that...

What does it mean to have an acid then? It's where there's a molecule in the solution that is going to donate hydrogen ions to the solution. So give them up and liberate them, dissociate, and so hydrogen ions drop off into solutions and then are available.

Okay, then what's a base? The exact opposite. It soaks them up. Right. And so this is a question for you. When we look at something that's considered a strong acid, is that just where it dissociates the hydrogen ions into the solution easily or is it more completely?

Both. Both. Yeah. So a strong acid is going to be... So this is like hydrochloric acid, which is the acid that we would see in our stomach. So HCL. So if you drop that into pure water, let's say, it would dissociate straight away into a hydrogen ion and a chloronion. So is that a question or are you giving the answer? Well, both. Okay. Yes, then. Okay. So a strong acid then basically just means it dissociates from

from its original form into free hydrogens very quickly or completely. Yeah, it'll fully disassociate to release all of its held hydrogen ions. So if you've got a molar concentration of hydrochloric acid

that full molar should disassociate into hydrogen ions. But if you've got a weak acid, it means that it's less likely to release its hydrogen ions into the solution. Okay. And the same goes with bases. A strong base sucks them up quickly. Yep. And a weak base is less likely to suck them up. All happening at a particular pH. So it depends on the environment. I mean, it makes sense. Like if you're...

You know, if you're an acid and you're surrounded by hydrogen ions in the solution around you, you're less likely to release your hydrogen ion, right? You'll go, oh, there's already heaps. I'm going to hold on to it.

Or if you're surrounded by not many hydrogen ions, you'll be more likely to release your hydrogen ions. Yep. So that's an important concept to understand because that's effectively how what we'll talk about shortly, how bases work, how we – sorry, how buffers work. Buffers work, yeah. How we can sort of regulate the acid-base balance. So then just to ensure that we've illustrated this point completely, so if you have a beaker and you fill it with lots of hydrogen ions, as the concentration of hydrogen ions go up –

the concentration of hydrogen goes up, but the pH by number goes down. So it goes towards a zero, more towards a zero end. And that's because it's the negative log of hydrogen ions. So effectively, you know,

A pH of 7 is basically telling you how many decimal points the zeros are to the left of a 1, right? So if you've got 1.0 and you move that decimal point to the left 1, 2, 3, 4, 5, 6, 7 places, you end up having 0.0000001 molar, right?

concentration of hydranines. So a pH of 7 is equivalent to 0.0000001 molar hydranines. Now, if you go down to a pH of 6, you're only moving the decimal point six places towards the left. So it's 10 times more concentrated. And people might be thinking, what do you mean 10 times more? Well, let's go all the way down to something like 2, a pH of 2. A pH of 2, I take all

1.0 and move that two decimal places to left, one, two, it ends up being 0.01 molar. That is a more concentrated solution than the seven, which I said was 0.0000001. So that's why- Each step is like a 10 times order of magnitude more. Yeah, going from a six to a five is 10 times more hydronylons. Going from five to a four, 10 times more hydronylons. And if you go the opposite way from a six to a seven-

You've lost 90% of the hydrogen ions. Yes, or you could say 10 times less hydrogen ions. Exactly. So that's an important point because when you look at pH, the pH of your blood is between 7.35, 7.45, right? Hence why we say 7.4, right?

you might go, oh, that's not a big difference. But remember, going from a seven to a six is 10 times more different. So yeah, it is still quite a concept. So the range of hydrogen ions does change relatively, can change relatively significantly, but it's really important that it doesn't. And this is the next thing I want to talk about before we talk about producing it in the exercising muscle. Why do we care about hydrogen ions? Let me ask you it as a question. Okay, go. Okay.

All right. So if you've got sodium, which is a cation, a positively charged ion, and you maybe get a little bit more than you should in your extracellular fluid, we know it will play a role with, say, fluid retention and blood pressure and so forth. But it may – I've got to be careful how I word. I don't want to say –

therefore it's not going to kill you. Obviously it will if it's way out of balance. But in comparison to hydrogen, if you get that out of balance, to a small degree, it's really profound in its impact to the body. Why, if they're both positively charged, why is hydrogen so nasty? That's a good question. So sodium being Na plus and hydrogen being H plus, they're both atoms on the periodic table or elements. They both are missing an electron.

What's the difference? Well, it's got to do with a couple of things, but one major thing is hydrogen is the first atom on the periodic table. It's the smallest, made up of one proton, one electron. Now, if the hydrogen's missing its electron, it's just a proton, right? So it's H+, but it's just a proton. Because it's so small...

The charge to size ratio is huge, right? Okay. Compared to sodium where you've got hydrogen, helium, lithium, beryllium, boron, carbon, nitrogen, oxygen, fluorine, neon, sodium, 11th on the periodic table. It's way bigger, right? So it's got 11 protons and 11 electrons. It's missing one electron.

it still wants to find an electron, right? But because it's a lot bigger, that charge to size ratio is less. Right. So the hydrogen has a greater affinity to be able to pluck electrons off because it's really starving for it, right? Hence why it can be far more damaging within the body if the hydrogen ion levels get too imbalanced. Does that make sense? It does, yeah. So that's why we really don't want to kick it. No one really explains that. Interesting. Yeah. So now I think we can talk about –

We know what acids are. We know what bases are. Oh, another thing I want to ask you before we move forward is there's a couple of terms that we need to define in the front end, which is acidosis, alkalosis, but acidemia and alkalinia. So...

What is the, okay, define for us what acidosis and alkalosis is. Osis is a process. Osis is a process. Yeah. That's good. So it just means there's a process happening in the body which is pushing you or pushing that area towards an acid state or a...

a basic state or an alkalitic state. Yeah. So you've got acidosis, it's pushing towards too many free hydrogen ions. Yep. Alkalosis, too many, not enough free hydrogen ions. Okay. What about the emus? This just purely relates to blood. Emus is in the blood. That's right. To quote Chubby Emu.

Finger pointing in the air. If you don't know who Chubby Emu is, go on YouTube, type in Chubby Emu. He's a medico that does great videos like I drank 100 Red Bulls. This is what happened to my kidneys. Exactly. Watch him. He's brilliant. Based on real clinical presentations. Yeah, I think exaggerated though, aren't they? I don't think they're verbatim case studies.

No, but it's probably embellished. Yeah, I think he takes a case study and then extrapolates, but it's still brilliant. But he always says emia is presence in the blood. So acidemia is too many hydronines in the blood, alkalinia. I actually used one part of his case, one of his cases in one of my tutorials on melanoma where a farmer in America got this lesion on his forearm

And he just cut it out himself. And then years later he found like a pulsating –

under his armpit and then started to get neurological symptoms and that was... It had spread by that stage but... Because he cut his... And he just dropped cancerous cells into his bloodstream through the... Not necessarily because of that. He just didn't seek proper medical assistance and he could have possibly got it rectified before it spread everywhere else. Wait, are you telling us not to cut our own melanomas out? All right, so...

Let's now talk about how we, so this exercise, right? Exercising muscle. We're going to talk about what's happening in the muscle.

We perform exercise. We perform exercise. And that exercise is contraction and relaxation. And as a byproduct of this process, we produce hydrogen ions. So we create an acidic environment so we can develop an acidosis in the muscle tissue. But your blood could be fine. But your blood could be fine. There will be spillover though. It's not an acidemia.

Not necessarily. But it could be an acidosis in one part of your body. That's the important distinction. Absolutely. So let's talk about the three main methods that are proposed to produce hydrogen ions in the muscle. Go. What are the three? Well, I guess you'd say when you're exercising, we know the muscle itself requires a lot of energy. And you would hope when you're exercising –

In most cases, you're delivering enough oxygen to the muscle to generate as much ATP as it can possibly produce in the mitochondria. So that's oxidative phosphorylation. That's complete...

I guess from the glucose molecule, if you want to say glucose is a substrate, energy substrate, all the way to producing the maximum amount of ATP out of that molecule, you hope to bring it all the way through to the electron transport chain and complete it. That's the, you know, you're getting, what is it? 32 ATP molecules per glucose molecule. 32 to 36. So that's really efficient.

And as a result of that process, you're producing CO2, carbon dioxide. And if you put carbon dioxide into a solution or into our system,

into our cells. We know our cells are filled with water and that will immediately turn into an acid, a weak acid, carbonic acid. Okay, so what's the first one? So CO2. Okay, so CO2 can produce acid. But CO2 in the form of carbonic acid, a weak acid. All right, so what's the second way we can produce hydrogen ions?

Well, this is a hard one. Can I skip this one and come back to it because I know it's going to- Well, let's just name them and then we can dissect all three. Okay. I'm going to be controversial, but we're going to rectify this controversy. Lactic acid. Okay. Lactic acid in the contractive muscle. In the guise of anaerobic respiration. Okay. So this is respiration without oxygen. Yep.

Happy with that so far? Yeah, yeah. What's number three? Split in ATP in half. Okay, maybe not in half, but ATP hydrolysis. So snapping the phosphate off. Yeah, that's right. Okay, so the three are, three ways that the muscle produces acid or hydrolynes is through producing carbon dioxide, which creates carbonic acid.

By producing lactic acid, quote unquote, and finally through breaking ATP into ADP for energy that releases hydrogen ions. Okay. Let's go to the first one again. So carbon dioxide. We ingest three macronutrients. What are the three macronutrients?

Calor hydrates, fats, proteins. Okay. If you were to look at them just chemically, right? So the elements of the periodic table that make them up, what are the elements of the periodic table that make up proteins, fats, and carbs? Mostly carbon, hydrogen, oxygen.

You might say nitrogen in amino acids. Yep, exactly. So the nitrogen for amino acids, that gets popped off. We turn that via the urea cycle into urea. We pee it out. So ignore that because it's basically not functional for us. Yeah, substrate for metabolism. But carbon, hydrogen, oxygen, absolutely. And so in the process of metabolism, remember we've spoken about this so many times before, but when you – let's just take carbohydrates –

The carbohydrates that we ingest will ultimately be absorbed as glucose, which is C6H12O6. So six carbon, 12 oxygen, 6 hydrogen.

Sorry, yeah. Six carbon, 12 hydrogen, six oxygen, but it's carbon, hydrogen, oxygen. What happens in the process of glycolysis is effectively we rearrange that molecule to pluck off the hydrogens and hand those hydrogens off. Remember, hydrogen is a single proton and a single electron. We hand those hydrogens off to NAD+, which is a carrier molecule, and that turns into NADH. Yep.

and FADH, which is a carrier molecule, and that turns into FADH2. And they carry the hydrogens off to the electron transport chain of the mitochondria to do that process that you mentioned just before, which is using oxygen, produce a huge amount of ATP through the electron transport chain. Right. So if we're plucking hydrogens off, the carbons, hydrogens, and oxygens, what are we left with?

Carbon and oxygen. Yeah, which is carbon dioxide. So the point I'm trying to get here through a very verbose, circuitous route is that by plucking the hydrogens off to be used in the electron transport chain, we produce carbon dioxide as the byproduct. We don't use it in this instance.

So that carbon dioxide needs to be thrown to the lungs, but to do that, it needs to jump into the blood. Okay, I've got one for you, and this just comes to- Wait, and that turns into carbonic acid, which as an acid releases hydrogen ions. Now go. Now, this just came to me because I'm looking at you right now, and next to you on your right-hand side, you've got a bottle of soda water. Yeah. Which is what?

Water with carbon dioxide in it, right? Yeah. It's a carbonated beverage. There we go. So you could – we'll use this as the analogy. You've got – it started with water. Yeah. But to carbonate it, you've got to pump CO2 into it. Yeah. Okay. Now, this can only happen to a certain degree without pressure. Okay. So if you want to carbonate it to the extent where it's got those carbon dioxide bubbles in it,

you need to push it under high degree of pressure to get it into the fluid. And this, not to this degree, but this is kind of what is happening in the exercise muscle. As you're producing more CO2 because you're exercising more and more, still aerobically though,

you've got more CO2, therefore more CO2 made in water, therefore more carbonic acid, therefore the pH drops. And same goes with this bottle. If you had a pH meter in it and you were slowly pressurizing it, so this is the partial pressure of carbon dioxide,

in the amount the pH is dropping as you're doing so. So in a way, this is kind of what's happening in your muscles. Not to the point where it's got CO2 bubbles in your muscles, but just to illustrate there's more carbonic acid in there. Yeah, it becomes acidic. I mean, it's one of the reasons why they say limit your soda intake is because the acid can affect your teeth. Yeah, enamel. Obviously, also the sugar as well, but yes, but there's no sugar in the soda water. But yes, great point. So that's the first point is that

Hydrogen ions are produced as a byproduct of carbon dioxide production. So carbon dioxide, you could argue, is an acid, right? However, if you look at the molecule, it's just carbons and oxygens. How the hell can that be an acid when there's no hydrogens there? It's because it combines to make carbonic acid, which is H2CO3. With water. Yep. Which you would never run out of in your body. Absolutely. And carbonic acid is a weak acid, which means...

which means it will release the hydrogen ions into the solution. So that's important. So yes, through the process of metabolism, we produce hydrogen ions as a byproduct. So that's one way that the muscles will do it because they're going to undergo glycolysis to try and get energy, right? All right, let's go to the second one with lactic acid. Let's skip it. Like you said, we'll touch upon that last. The third one you said was the hydrolysis of ATP.

So ATP, adenosine. Try. Try what? Phosphate. Okay. It's got phosphates. They're high energy bonds from one phosphate to the next and next. It's like an arm of phosphates, right? The three of them. If you snap the end phosphate off, energy is released. Produces ADP because then you've got diphosphate and then you've got a free phosphate in the solution.

The thing is that this happens through the water. Water is required to snap that phosphate off. It's called hydrolysis, so hydrolysis, water splitting. Makes sense. So when you mix ATP with water, you actually produce ADP and hydrogen phosphate.

And hydrogen ions. So where would this be happening predominantly, do you think, in the muscle that's exercising? In the muscle tissue. So this is the cross-bridge cycle? Yes. But you could also say all the energy-requiring enzymes that...

happening from all the different reactions would also be doing this as well. Yes, but intracellularly. Yeah, that's right. All happening inside the cell. So simply as a product of ATP being used to make energy, we release hydrogen ions. So that's two ways, metabolism and ATP hydrolysis. The third way, lactic acid. Matt, where do we even begin with this conversation?

Well, this has been around for a long time, this term lactic acid. Okay. Again, I'll ask you a question. When you were at university, what was that, 45, 50 years ago, what did you learn about lactic acid? I'm trying to think back to biochemistry. I'm guessing it would have been – I feel like it – Take your time. Yeah, no, I'm just trying to think back.

Heather is a nurse practitioner from UnitedHealthcare. We meet patients wherever they live. During a house call, she found Jack had an issue. Jack's blood pressure was dangerously high. It was 217 over 110. So they got Jack to the hospital and got him the help he needed. He had had a stent placed in his heart, preventing a massive heart attack.

If it wasn't for my guardian angel, I wouldn't be here. Hear more stories like Jack's at UnitedHealthcare.com. Benefits, features, and or devices vary by plant area limitation and exclusions apply. You know that feeling when you clear your inbox or end a meeting early or finally check your pipeline and everything's actually under control? That's what Monday CRM feels like. It's fast, easy to use, and with built-in AI, it helps you move faster without the busy work.

Try it free at monday.com slash CRM because sales should feel this good. It's hard to know what's my own memory and then what I was taught. But I would say that we were told in biochemistry, metabolic biochemistry, that go through glycolysis, then glycolysis if there's oxygen.

The pyruvate, which is the end of glycolysis, will then go into the Krebs cycle, drive this cycle, which then moves on to the electron transport chain. Now, if you don't have enough oxygen in, what would you say, mammals? So like us, we have this system where we can move from pyruvate

and generate lactic acid, and that allows glycolysis to continue, but then we're producing this acid which starts to build up in our muscles, which is why you get that burn when you exercise at a high intensity.

Is this true? Whereas other organisms like... Here we go. Bringing the animals in. It's been a while. Like yeast, let's say. Oh, my God. Yeah. Everyone cares about yeast. Oh, you will in a second when I mention it. Oh, you're bringing some beer in. Yeah. So when you put a yeast in an anaerobic environment, it also goes through, I guess, glycolysis. Okay. And...

It doesn't produce lactic acid. It produces ethanol. Right. And so when you produce an alcohol... Yes, go on. ...beer, spirits or whatever... Mm-hmm.

The yeast that's in it, when you feed it the sugars, like grapes or barley or whatever your alcohol choice is. But limit its oxygen. So it doesn't have oxygen because it's floating around in the fluid. It will start to produce ethanol as its byproduct. Instead of what the textbook says, lactic acid. And that changes the pH but also changes the alcohol content in the solution.

Okay, okay. Well, I'm just going to burst your bubble, Matt, because humans don't produce lactic acid, at least not in appreciable amounts, that would have any effect in making the environment acidic. So just to recap what you said, but adding a couple of additional details, when you have glucose...

and we undergo glycolysis to make ATP, but also we produce NADH and FADH2 carrying those hydrogen, we ultimately produce, like you said, pyruvate. Now, if there is enough oxygen available, like you said, that pyruvate turns into acetyl-CoA, jumps into the Krebs cycle, makes more NADH and FADH2, and therefore all this NADH and FADH2 gets carried over to the mitochondria,

It releases the protons, releases the electrons. They go through the electron transport chain and they produce all this ATP. However, we need oxygen to be the final electron acceptor. Otherwise, these electrons will damage the system. That's right. It'll be a full explosion.

And so without the oxygen, it backs up, backs up the Krebs cycle and backs up to pyruvate. Pyruvate goes, I'm not jumping into this Krebs cycle. There's no oxygen. I can't do this. So then it shifts off, but it doesn't produce lactic acid. It produces lactate. So pyruvate directly turns into lactate. And the reason why, yes, Matt. So here's a question for you. Then do you think, because part of this acid-base buffering concept that we're going through

we are always told that wherever you see a weak acid, there's a conjugate base. Yep. So did we get to the point of thinking lactic acid exists because we knew lactate existed and that's the base? So we just assumed its conjugate acid was lactic?

lactic acid. Well, let's, I'll talk about that once I tell everyone what lactate is, right? So the pyruvate doesn't turn into lactic acid. It turns into lactate. And the reason why it turns into lactate is because the pyruvate, like I said, it can't jump into the Krebs. It needs, it goes, well, I can't make all this ATP by jumping into Krebs and producing NADH and FADH2. How can I make ATP for this contracting muscle?

I know we're just going to have to rely on what has happened, you know, behind me, higher up. Ten steps above. Yeah, which is the Krebs cycle. But the Krebs cycle is limited by how much NAD plus is available to pluck the hydrogens off.

The problem is if it's plucked the hydrogens off and has created NADH, but that NADH can't carry it to the electron transport chain because there's no oxygen, we just accumulate NADH. And then glycolysis stops as well. So pyruvate goes, I know, I'll take that hydrogen back off you from the NADH. And in doing so turns into lactate.

And it's regenerated NAD+, which can go back to glycolysis and it allows for glycolysis to keep going. Now, glycolysis doesn't produce as much ATP as aerobic respiration through the electron transport chain and Krebs cycle, but it is enough to some regard to maintain contracting muscle. For a while. For a while, but it keeps accumulating lactate. So lactate – now, this is your question –

You said that, well, lactate is a base, right? So we know that it is a base. And your question was, well, because we go from pyruvate to lactate and a base is produced, we also produce hydrogen ions at the same time, but it's not through this process. It's through those other two processes that we mentioned, ATP hydrolysis and carbon dioxide production. And so historically in

In the research, they were looking and they went, hey, it's becoming really acidic in this contracting muscle. Or just when there's no oxygen. Or when there's no oxygen. And look, this lactate level is going well up.

at the same rate pretty much as the hydrogen ions being produced, this must be the conjugate base for an acid. And I'm going to call that acid lactic acid. And so that's where the idea of lactic acid came from, that, oh, there's no oxygen, pyruvate turns to lactic acid, it doesn't last very long, it splits into pyruvate, it splits into lactate, sorry, and hydrogen ions. But what we now know is that lactic acid...

And I'm not being definitive here because it's biology. The lactic acid likely is not an intermediate. It just goes from pyruvate to lactate. And lactate being a base can actually mop up hydrogen ions. So it does the opposite. Lactate can actually help reduce the hydrogen ion concentration in the solution. And having all these additional hydrogen ions in the muscle will cause pain.

we do know that that happens to sensitized nerve receptors, right? Yes. Similar to what we have when a person has reduced oxygen in their heart muscle. This could be an angina all the way through to a heart attack. They do get chest pain and that pain associated with that experience, that hypoxia or ischemia or...

complete infarction would produce hydrogen ions, which would then cause pain, right? Yes. Yes, exactly. It's not the only thing that causes pain because as many chemicals are released during muscle contraction, depending on how hard you're contracting the muscle, you can get some tears within the muscle tissue that can cause inflammation. So it's the local milieu, cellular milieu within that environment.

So the point that I think we're trying to get across here is that lactic acid production isn't a considerably important contributor to hydrogen ion production.

within the contracting muscle. In actual fact, the lactate, which people are actually referring to, is a buffer and can actually mop up excess hydrodynons and can actually reduce. Now, final point, which is for those that aren't interested in exercise physiology but more just the medical science area. Medical.

There's a term called lactic acidosis. And so lactic acidosis, when does lactic acidosis occur, Matt? What sort of instances would you say? Again, with low oxygen, hypoxic environments. Yeah, so... So if this would be if you were in any kind of shock. Okay. Not... Not scared. No, not typically. Not when I see you naked. So this...

Neurogenic shock. So if you had your heart's not produced, so acute heart failure or septic shock or distribution shock, I guess you would sit a hypervolemic shock in that as well. Just where there's the cells of the body aren't being perfused adequately with blood, they would go into an

anaerobic situation. And that's just because they're not getting the oxygen that they need to undergo the electron transport chain. So effectively these tissues on mass are undergoing anaerobic respiration. So everything we just said, glycolysis is being ramped up. Pyruvate needs to turn into lactate at a fast rate, which means, uh,

The glycolysis is happening. The ATP that's being produced is being readily utilised because it's trying to maintain energy demands and the splitting of that and the carbon dioxide production is producing the acid in this environment. That's right. And so if you were to take blood levels of lactate, you would actually see it's going well beyond 4 millimoles per litre, which would be suggesting that you are once term lactate

Lactate acidosis or acidemia. Yes. Which is not really the case. No, it's not a lactic acid. If you want to be accurate, you probably call it a metabolic acidosis with elevated lactate. Yes. Okay, so that's just a little bit of an aside. So we know that predominantly we're producing the hydrogen ions through two major mechanisms.

ATP hydrolysis and carbon dioxide production. So let's now talk about the importance of regulating. How do we regulate these? So we do intense exercise. We produce the hydrogen ions predominantly through intense exercise. So heavy, very heavy or severe exercise is when we're going to be producing most of these hydrogen ions.

And that's just going to be a product of ATP usage, right? In a short period, heaps of ATP being used, heaps of carbon dioxide being produced in a short period of time. So you're basically dumping large amounts of hydronines in the muscle itself and

That's damaging. How do we, quote unquote, buffer it out? So a buffer is anything that resists drastic changes in pH, right? So it can absorb a hydrogen ion if needed or it can release a hydrogen ion if needed. This is the job of buffers. And one of the first experiments that was done on this to know that a buffer existed, I forget the scientist, but he,

Wanted to investigate this, this chemical phenomenon in his pet dog. Oh, see, you always bring this up. There's always an animal. You know, Matt's got a dog on his polo shirt at the moment. I do actually. Anyway, this is not remembrance of this particular experiment, but-

What he did was he got hydrochloric acid at a certain amount and injected it into the dog. Jesus, that's horrendous. But had already worked out what amount of plasma or let's just say water in the whole dog as a volume. And he...

And he had it outside the dog. What? What do you mean I had it outside the dog? So he had the dog. Yes. But then he had like a big bucket of water that represented the amount of water that the dog would have in it. Oh, it was equivalent. Equivalent. I interpret that as he took the fluid out of the dog and put it in a bucket. Okay. So interesting.

Got the dog and the dog has its own water volume. He took the same water volume and had it in a bucket next to the dog. And he injected a certain quantity of hydrochloric acid in the dog and the same amount into the bucket. Okay, what happened? Then he took the pH of the bucket and the pH of the blood. All right, okay. And he found it was noticeably different. So in the bucket, it was like one. Right. In the dog...

I don't know. Maybe let's say 6.9. Right, right. So he's like, how is this possible? So the bucket was way more acidic than the dog. That's right. There must be a buffering system in the dog. Nice, nice, nice. Okay, that's cool. I mean, it's not cool. It's horrendous that he did it, but the results were cool. So there are buffering systems within not just dogs, but exercising human beings? Yeah, yeah, that's right. There's buffering systems that are located in the cell.

And there's buffering systems that are located in extracellular and other physiological systems. Okay. So if we look at the intracellular buffers, there's like four intracellular buffers. These four intracellular buffers are, so I'm going to name them and then let's dissect them one by one, right? Bicarbonate buffer, phosphate buffers.

protein buffers, and histidine dipeptide buffers. So these are the four main types inside the muscle cell itself. So let's start with the bicarbonate buffer. We've alluded to it in our respiratory episode. We spoke about it. Talk to us a little bit again, very briefly about the bicarbonate buffer in the cell itself, in the cytosol. So if I've dumped hydrogen ions in the cell, the muscle cell, what does the bicarbonate buffer do?

Yeah, it just soaks them up. And I think it's a very strong base, so it's very good at soaking hydrogen ions up effectively. Now there is, I think, three-fold less...

ions available in the cell compared to extracellularly. So there's a lot less in the cell. So it only has a certain capacity to do this. And it's important to note that how effective a buffer system is, is a combination of the concentration or the amount that's available and how good it is of performing that particular buffering chemical process.

Let me talk a little bit about that. So is that related to the PKA? Yeah, PKA. So PKA is effectively the pH that – let's just take like a protein. If this protein is a buffer, right?

It's the pH that this buffer would be to be equal parts releasing its hydrogen ions and holding onto its hydrogen ions. So if I were to measure a solution that had this protein and I go, oh, half of them have released their hydrogen ions, half of them have held onto them.

that is the ph that we call the pka at that ph that's the pka okay that's important because it's basically like a seesaw right in which well if the environment around that protein is less acidic than the pka that protein will be more likely to release its protons right it's hydrogen ions and vice versa if it's the base yeah with the base if it's if it's uh

more basic in its environment, it's more likely to release the hydrogen ions. So effectively, you could argue that when the pH is low in the environment, so that's a high number of hydrogen ions, it's... So the pH is lower than the pKa, it's more likely to hold onto its hydrogen ions and vice versa. Now...

The best buffers are those that have a PKA closest to the environment. Physiological pH. Physiological pH. So the buffers that have a PKA closest to 7.45, 7.35 sort of, they're going to be the best physiological buffers. Yes, but that's an interesting point because that might be only good at maintaining homeostasis in a fairly...

controlled state but when you start to really burden the system by performing severe exercise it may go outside of ph range where it's no longer effective well i mean if you've got okay let's just say you've got a buffer where it's pka is 7.4 yep right

If the pH drops below 7.4, what that then means is that that buffer will not release any hydronylons. It will actually mop them up and hold on to them. But if the pH goes above the 7.4, it's going to be more likely to release the hydronylons. So it does make a good buffer at those above and below. But what can happen is if you've got a buffer, let's just say that its pKa is 6.8, right? Yeah.

it will only really contribute to mopping up hydrogen ions when the pH goes below that 6.8. So it only sort of kicks in at that point. And does it have a rate? Does it have a kind of an amount that then it becomes less effective with? So if it got down to six, does then it?

also diminishing its speed and the ability to mop up. Yeah. The further away that you get from it, it's well, it depends because if it's again, a buffer, a PK of 6.8 and you go down to a pH of six, which I don't think that's going to happen, but you had a pH of six, the pH is below the PKA. It's really not going to release protons. It's going to hold onto protons because it's below. Right. But again,

Again, listen to this. If this buffer is at 6.8 and the body's pH is at a 7, which is still too acidic for the body, right, but it's more basic than the pKa of this buffer,

This buffer is not going to be helpful to manage this problem. Does that make sense? Yeah, and that was just my point. That's why it's better to have a buffer that's closest to the pH, the pKa of the buffer, as close to physiological pH as possible. It will be a better contributing buffer. Yeah, and that was just my point because if you look at inside the muscle as what we're focusing on here,

If you're looking at the buffers that are working all the time, just because there's always going to be fluctuations, right? Even at rest. And there's no perfect buffer. That the buffers that work best at physiological pH, which is, you know, 7.4, let's say.

And that could be, they could handle the fluctuations that you would see at a very low intensity exercise even, say 25% VO2 max. But as you start work, and this is like a fraction of the day, just for two minutes, you start to approach a VO2 max of 75, 80, 90%. All of a sudden, the muscles pH goes down to 6.4, 6.3%.

Now these buffer systems that work better at physiological aren't so effective anymore and you may have other buffers that may work a little bit better in a more acidic environment. Yes, they will sort of kick in. And that's what I was meaning. Yes, if their PK is at that particular point. But they won't be helpful closer to physiological pHs. Yes, yes.

Okay, hopefully that wasn't confusing for people, but it's an important point to highlight because not all buffers are created equal. Now let's just go back. We spoke about, so we said the four intracellular buffers, bicarbonate, phosphate, proteins, histidine, dipeptides. So bicarbonate, if I were to dump hydrogen ions into the muscle cell, the hydrogen binds to the bicarbonate, that creates carbonic acid and that produces carbon dioxide and...

And water. Sorry, carbon dioxide and water, sorry. And that carbon dioxide needs to diffuse out of the muscle tissue, go into the blood, go to the lungs to be breathed out. But effectively, it's buffering, right? The phosphate buffers...

These are powerful intracellular buffers and effectively they are inorganic phosphates like hydrogen phosphate, products of ATP hydrolysis that can hold on to hydrogen ions to produce dihydrogen phosphate. Quite good buffers. So they could be byproducts of other chemical reactions that have taken place? Yeah, you can pull that hydrogen phosphate from bone. You can take it – I mean you can ingest phosphates through your diet. No, I just mean like even if you were to hydrolyse –

What's the word? Hydrolyze. Hydrolyze, there we go. ATP, like you mentioned before, what's one of the products that you said comes off the ATP? An inorganic phosphate, right? Yes. Well, that is the phosphate, yeah. So that arguably could be a buffer to a certain extent. Yeah, that's what I said. So inorganic phosphate simply just means it doesn't have a carbon. So it's H2PO4-H2PO4-H2PO4.

HPO4 negative, HPO4 2 negative, right? That's hydrogen phosphate. If that then mops up hydrogen ion, it's H2PO4 negative, right? So that's dihydrogen phosphate. So that's the buffer that tends to be predominant. That's just called inorganic phosphate simply because there's no carbon. That's all that that means. But that can be a product that's popped off the ATP. But you can get it, again, through diet, through other means. So that's a good intracellular buffer.

Proteins, because of their amino acid residues or amino acids, which have side chains, there's about 20 amino acids. Each have a different flavor, which is their side chain, their R group. Some are basic like histidine, and that's a very good buffer amino acid because it has a PKA that's close to physiological pH.

So it's likely to hold on to hydrogen ions if needed and release hydrogen ions if needed, depending on the pH. So histidine, very good protein buffer. And then there's histidine dipeptides, where if you snap two together, you effectively can create something called carnosine. And that basically does the job of histidine. Okay, so that's histidine as an amino acid snapped together with...

beta alanine, which we're going to come to in a second for potential supplementation. Or at least beta alanine turns to histidine, which can then turn to carnosine. I can't remember the process. I think the two, the dipeptide one is beta alanine, one is histidine. Okay, cool. But the rate limiting step here is the beta alanine. Right. Do you want to talk about that now or later on? We'll come back to it. Okay.

So these are the intracellular buffers. But the thing is, if the hydrogen ions continue to accumulate, we can also just say, let's get them out of the muscle, right? So how do we do that?

And is this because, so we need these transporters because as a charged molecule like hydrogen, it can't cross the membrane, the muscle membrane, the sarcolemma. Correct. So we need to have transporters. Yeah. Yeah. So there's two main transporters. There's an exchanger, which essentially throws the hydrogen out in exchange for sodium. So this is basically just a sodium hydrogen exchanger. It's a charge for charge, you know, throw a positive hydrogen out, swap a positive sodium in.

And then we have another carrier which is throwing both lactate out and hydrogen out. That's a symport and lactate is negative, so it's okay to throw a negative thing out with a positive thing. So you're hydrogen out with negative lactate. Okay. And I guess it's this process of throwing the lactate out which then we can measure in the blood as a proxy. Yes.

of suggesting that anaerobic respiration is increasing. Yeah, and we can have a look at lactate threshold, right? So we've been able to correlate lactate with VO2 max and you can say, oh, at certain VO2 levels, we have our lactate threshold and lactate threshold, basically, we can't recycle it fast enough. And it's not necessarily the level of lactate that's limiting our performance, but what corresponds with that, as we said earlier, which is the continued abundance of hydrogen ions.

Okay, so outside the cell though, so let's say we've thrown the hydrogen out. We're now starting to make the blood acidic, right? So muscle first, then blood. Or the extracellular environment. Yes, or the extracellular environment, that's true. So what extracellular buffers do we have? Well, you've got three times more bicarbonate out here in the extracellular fluid. So is that the most...

important buffer in the extracellular fluid? Yeah, you'd probably say so because this, again, as the hydrogen is building up, it would meet the bicarbonate, which then goes to the carbonic acid, which then would start shifting it towards more the water carbon dioxide end. And to try to get rid of that...

is to incorporate the respiratory system. But that will be something we'll talk about shortly. Yes, yes. So bicarbonate, important extracellular buffer, probably the most. There's also proteins in the extracellular fluid, but not a lot. So it's not a really strong extracellular buffer. But we've also got hemoglobin.

Yeah, so once you go into the blood, so this is a bit different to just the extracellular space. So even though blood plasma is extracellular, we're now in a vessel and we do have plasma proteins, which are probably more abundant than you would find in extracellular fluid or the interstitial fluid. Here, you do have some plasma proteins that can do buffering like albumin, but this wouldn't be anywhere near

sufficient to buffer in a high intensity severe level of exercise like you mentioned we do have the red blood cells and 45 percent of your blood are red blood cells the way that the red blood cells buffer the change in ph is they take in the carbon dioxide into the red blood cell

That again meets the water, makes carbonic acid, splits because it's driving from a high partial pressure of carbon dioxide in the tissue like the soda water. So we've got a lot of carbon dioxide. So we shift it in the red blood cell. Now the red blood cell has a high amount of carbonic acid which dissociates straight away into hydrogen. The hydrogen then gets put onto hemoglobin

in the proteins in the hemoglobin. So that's the buffering in that capacity. And now we're left with bicarbonate. The bicarbonate gets pushed back out of the red blood cell into the plasma, which I guess in its capacity can still do some buffering. Extracellularly. Extracellularly. And then you need to bring in chloride to ensure that the electrical charges equalize because a bicarbonate is a negative component.

anion, so you've got to bring another anion to balance that out. That's the chloride shift. Yes. All that makes sense because when you bind hydrogen ions to the hemoglobin of a red blood cell, it's more likely to do it in the deoxygenated hemoglobin state, which makes sense because you're at the tissue now. So effectively, when this happens, oxygen is more likely to bounce off

which makes sense because it's at the tissues, right? CO2 is high, O2 is low. Yeah, and so if you were to want to figure out exactly what's happening in the system while you're exercising, as you're approaching 50% to 60% VO2 max, you're going to see the muscle pH is getting somewhere between 6.5 pH. But if you were to take the person's blood...

At this particular level, they're at 7.2. So there's quite a big difference there. So the pH is changing to the same degree at the same... It's got a relationship. There's a relationship, but it's not the same. But it's offset. Yeah. Okay. Which tells you that buffering is taking place and fairly well extracellularly or in the blood. Okay.

Okay. Now- Can I just add something before that? So interestingly, type two fast twitch fibers, they're better at buffering than the type one fibers. That makes sense. Does. Because they undergo anaerobic respiration more than they undergo aerobic respiration. And so they're producing more hydrogen ions. So they've developed a greater capacity. So that's one thing. Another thing is that

you know, doing exercise itself makes you better at buffering. And so it seems to be, this is mainly because you start to produce more carnosine. So that's the histidine residues, right? To be able to buffer, but you also start to produce more of the transporters, the hydrogen lactate transporters as well. So,

So training makes you better at buffering. Yep. So what were you going to say, sorry? So as you're approaching, let's say 60% VO2 max, now you're getting to the point of the lactate threshold. So here, if you were taking the person's blood, you would all of a sudden see a big spike in lactate levels.

you know, approaching above 4 millimoles per litre. Yeah. Okay. Now at the same time you're seeing – you'd see a continual drop in bicarbonate. So the bicarbonate levels is now a drop in the blood. Which is telling you it's binding to the hydrogen ions and essentially disappearing. And the pH is starting to drop in the blood as well. Yes. Now this is an important point because now you're bringing in another –

physiological system to not so much buffering. I guess you'd say it's buffering. What is? Bringing in the respiratory system. Right. So let's just recap that. You said lactate goes up. Makes sense. It's a product of anaerobic respiration. pH is going down. That makes sense because you're using all this ATP and producing carbon dioxide. But the bicarbonate is going down as well. And people might think, wait a minute, if that's going down, shouldn't the pH go up?

But no, it's going down because it's trying to fix the pH. It's not overly successful. I mean, it is the best one we've got, but it is going down because it's being consumed in the process of trying to maintain the pH. But in doing so, the bicarbonate, when it,

Bind to the hydrogen ions, both disappear from the solution effectively because they're now turned into something else and that something else is ultimately carbon dioxide and water. And so that carbon dioxide and water needs to travel to the lungs and the carbon dioxide gets blown out. And that's what we call a volatile acid. So carbon dioxide is sometimes referred to as an acid even though it itself doesn't have any hydrogen ions.

That's right. And so by doing this, the system, our physiological system is picking up the change in pH or picking up the change in hydrogen ions and it's picking up in certain locations of the body, in the medulla,

the aortic arch and the carotid bodies. Yep. And as it's seen this with the chemoreceptors, it's telling the brainstem, the respiratory center, we need to increase our ventilation rate or our minute ventilation, which is expelling more CO2 out of the body. Right in depth. Yes, absolutely. So with that said then, we spoke about...

Chemical buffers. Yes. But we also spoke about respiratory system. Can we hack the system? Can we do some shortcuts? Yes. Now, before we jump into that, just super quick, just for completion's sake, in the muscle itself, histidine and carnosine, they tend to constitute 60% of the muscle's buffering capacity. Wow.

while bicarbonate in the muscle is 20% to 30%, and phosphate is about 10% to 20%. That's different when we jump out of the muscle cell into the extracellular, where it's by far the bicarbonate. So I just wanted to finish with that. Okay, can we hack the system? Are you saying is there anything we can take potentially to improve our body's buffering capacity to improve performance? Let me give you a sport. I'll give you a support. Give me support and then give me sport.

Let's say if you were to perform 100-meter sprint swimming or a 400-meter swim or a 400-meter run where let's just say it's predominantly an anaerobic exercise and you're going to produce a heap of lactate as a result just to kind of demonstrate you're in that.

Yeah, I'm hitting my... Yeah. Can you do something before the event? So could you take a huge amount of bicarbonate or some kind of base to do the buffering more effectively before you go and perform this exercise? BetterHelp Online Therapy bought this 30-second ad to remind you right now, wherever you are, to unclench your chock.

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can that help buffer the hydrogen ions being produced? The answer is no. It can change the pH of your blood ever so slightly. And urine. And urine, mainly urine, but because we've got all these buffers, blood not so much, but it doesn't help buffer and therefore doesn't help performance. The thought is that if you can buffer better, you perform better, right? So there's a lot of research out there looking particularly at some types of bicarbonate-based substances

oral supplements that you can take. So two include sodium bicarbonate and sodium citrate, which both effectively work the same way as the bicarbonate buffer system. That would be extracellular? That would be extracellular because when you ingest it, it jumps into your bloodstream, won't jump into the cell. So it's going to be buffering in the arterial system predominantly and maybe in the extracellular fluid surrounding your muscle, but not in the muscle itself.

Now, the evidence is, yeah, they can help. They can increase the body's ability to buffer by a little bit, by a few percentage points, and can increase an individual's performance, again, by a few percentage points.

But, you know, the side effects, particularly the fact that, you know, the quantity... So some of the evidence shows you need to take, for example, with sodium bicarbonate, like 0.3 grams per kilogram. So ingesting bicarbonate at that quantity, well, a couple of risks. One is that GI upset. It's a bit... Crap yourself. Vomiting, crap yourself, right? So having to change your pants constantly might be a side effect. But also...

You can cause alkalosis, right? So you can give yourself alkalosis and it can be severe and that can be life-threatening. And the problem with all this, Matt, is that if you're a trained individual, which we said just before, right? If you're trained, you have better buffering capacity. So these buffering supplements are,

are less effective for trained athletes who are probably the ones that need that additional few percentage points in performance, right? For untrained individuals, this is where most of the benefit seems to fit, but untrained people probably don't need these types of buffers

to add 3% on top of that. And all the risks of the side effects. Yeah. Cause the side effects again, aren't just the GIT. You can get headaches, you know, you can again, get alkalosis. That is, that is, and if you're untrained, you probably aren't as well managed at knowing your limits and what the doses should be for what you're performing. And so, so,

I mean, from my perspective, it's not probably worth doing. So that's for the sodium bicarbonate and sodium citrate. But there's another one which is called beta-alanine, which you alluded to. So you said beta-alanine, histidine helps produce carnosine, and we said that's a buffer.

So this is intracellular. Okay, so is there evidence for this? So you can take beta-alanine as a supplement. So this is an amino acid. It's considered a non-essential amino acid. So it would, I guess in definition, mean your body has the capacity to make it. But in this case, you could consume...

some of this as a supplement and in doing so, in theory, can increase the amount of carnosine produced within the muscle. Yes. So some studies showed that two to three grams per day of supplementation with beta alanine increased carnosine by 60 to 80%, circulating carnosine 60 to 80%. Now that led to a three to 5% increase in muscle buffering capacity.

So that is an increase in buffering capacity. But again, go on. I don't want to... The only thing I was going to add is there is also side effects. The side effects are slightly different here. They're more to do with neurological or skin sensation. So there's a feeling of pins and needles or paresthesia, which can result. So again, just need to be mindful that there are drawbacks, side effects, adverse effects that you need to consider.

And the bang kind of relationship is possibly a caveat you needed to think about. Yeah, exactly right. What else? Do you know, like from your years of experience in the gym, do you hear people take better alanine? Yeah, people take better alanine. I don't think they know why they take better alanine. I mean that's a lot of people. Are they in – like would that just be incorporated in a protein powder? Like they'll just have better alanine as –

Yeah. It'll probably be in a, in a, an amino acid supplement. Right. So you've got branch chain amino acids. Beta alanine isn't one of, isn't a, isn't a branch. Oh, am I, is it a branch chain amino acid? I don't think it is, but, um, but people take beta alanine, um,

as amino acid supplementation, but I don't know how many people know what it's doing. Right. Same with a lot of the supplements. People sort of know what creatine does. Yep. People sort of know what protein does, but everything else. Um, yeah. All right. So here's what I'm going to throw at you. What about, no, it's not a branched out amino acid. I didn't think it was.

Because it's not essential, of course. Okay. So if you, like we spoke about when you need to perform a severe level of activity or exercise, like 100-meter sprint in the pool or a 400-meter sprint around a racetrack, and you're going to go into a significant amount of anaerobic respiration. Yes. And you know you're going to be producing a lot of hydrogen ions in there before you may exceed your buffering capacity. Right.

Trying to hack the system like we spoke about with supplementation. What about if you just thought, okay, I might just hyperventilate before I start the activity. If I hyperventilate, I'm going to get rid of a lot of CO2. Therefore, I'm going to drop my – sorry, I'm going to increase my pH.

drop my hydrogen levels in my blood. Become more alkalinic. That's right. Just before I compete. So therefore there's more capacity for acid to be taken up and my pH to be kind of maintained. Is there, what do you think about that? No, I wouldn't think that that, again, I'm working on first principles here. It's not like I've jumped into the literature for this, but I would say. Or done it yourself. Or done it myself. This is the way I think about it, right Matty? That if you're,

So these supplements that we've said have shown some performance benefit, they have been supplements in which you are increasing your base load, right? Yeah.

hyperventilation is decreasing your volatile acid load. So carbon dioxide. So what you're doing is you're removing the acids, but you haven't increased your baseline base, right? So when you do the exercise, you're just going to regenerate that carbon dioxide again through exercise. Um,

And you've got the same amount of base to help manage it. So the same buffering capacity to manage it. So my thought would be, no, it wouldn't do anything for you because you'd need an increased base load to be able to manage it. So if it was to do anything, it'd be even more transient? It would be far more transient because my thought would be,

when you hyperventilate, you will probably, I don't know this, but I'm sure that your CO2 levels go back to normal when you stop hyperventilating within seconds to minutes, right? I assume. But also when you hyperventilate, you're,

We know carbon dioxide levels directly affect blood vessel diameters, so it narrows them in the brain. You might pass out. That's probably not good before a race. Get a headache. If you're unconscious when they say three, two, one, go, and you're on your back. But also you'd lose your respiratory drive for a time because you're- Well, that's true. That's how kids die in swimming pools, right? They hyperventilate to hold their breath for longer, but because carbon dioxide is the stimulus to take the next breath-

And when it's gone, you don't take the next breath and your O2 disappears and you pass out. So, yeah, I would say no. I wouldn't say that hyperventilating before an event is performance enhancing. If anything, it's probably the opposite. But again, I'm just working off first principles. What the hell do I know? I'm sure, you know, if it had a benefit, it would be done.

Agreed. Agreed. Is there anything else that you would like to chat about when it comes to acid-base balance of exercising muscle tissue before we say thank you to our dear audience? No, not really. I think just the take-home point really is that we know when a muscle is performing at a high intensity, it's going to be producing a lot more hydrogen ions. They are going to have

...a deleterious effect on processes within the muscle. But one thing I did forget to mention is also the hydrogen ion... ...that is concentrated in the muscle, it will compete with calcium... ...to the troponin. Oh, so reduces contraction through competition. That's right. So there's also an effect there with efficiency of muscle contraction as well. And so by having systems in place...

like the intrinsic. So we call it the first line of defense, a bit like the immune system, right? Where we have those buffers in place that the muscle can utilize to try and offset all this. They're available. And then we need to bring in the second line of fence, which is more of your extracellular, but also your physiological systems. One we didn't really talk about is the kidneys, the,

as well. Yeah. When we're performing really far, because a lot of this stuff we're talking about today when we talk about severe or high intensity, they're only lasting for minutes. We're not talking about the whole day, right? No, no, exactly right. So respiration should be sufficient to get rid of the CO2 to manage the acid base level. Whereas the kidney, that works at best

at best, hours, but really days. So if I were to have that bicarbonate buffer equation written up, on one end you get the CO2 and H2O, which the respiratory system manages, and on the other end you've got the hydronyms and the bicarbonate, and that's the end that the kidneys manage. But the kidneys, like I said, that's hours to days. So that's...

It goes outside of sort of the timeframe in which you need that. Yes. Effectively, the kidneys tend to kick in when you've got a more chronic acid-base imbalance. However, saying that, if you were to have kidney issues... Yes.

that would then mean you're starting at a baseline of poor buffering. So you may have issues where the kidneys aren't recycling bicarbonate well, so that is then likely to put you into an acidosis state, or conversely, it could be losing bicarbonate. So you're either not making new or you're not recycling, or same with...

acid, so you're not handling the acid-base environment well with your kidneys for whatever reason. And if that was a state you were in when you perform a high level of exercise, then your buffering capacity would already be lower than it normally would be, right? Absolutely. Absolutely. So I guess we've covered everything we need to. We've gone through a lot. We've gone through a lot. So hopefully that was helpful. You can contact us if you like, admin at drmattdermike.com.

dot com. I think so. Send us an email if you have a query or a suggestion. We've got some emails there that we need to read in a future Q&A shortly. Follow us on social media. So please, we're approaching our one millionth subscriber on our YouTube channel. Now, if you look at it, we're at about 955,000 subscribers. So we're 45,000 off. You might think that's ages, but we should get there at the current rate by the 1st of September, one million subscribers. So we're at about 955,000 subscribers.

But if you want to help us get there earlier, please go to our YouTube channel, click subscribe. If you want to watch some videos, like I said, I've done a video on heart rate variability that's going to be released this Wednesday. So that's going to be- Aspirin. I did one on aspirin. Did you know aspirin can- Yeah, no one cares about aspirin. Aspirin, well, aspirin in overdose can be both-

It can produce both a metabolic acidosis and a metabolic alkalosis. That's true. Yeah, very good. Very good, Matt. I didn't talk about that in the video though. Okay. So if you don't want to hear that, watch Matt's video. But I've also released a video on muscle fatigue. So all those factors including the hydronine increase causing muscle fatigue. So feel free, go to DrMattDrMike. Give us five-star review for this podcast. Send us an email. Tell your friends, your parents, tell your dog.

Not the dog that we mentioned in this broadcast. No, no, no, no, no. Definitely not that. Thank you, Maddy. Thank you.

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