265. Tyler LeBaron: Hydrogen Water, Mitochondrial Health, Selective Antioxidants, & Longevity

22:19Gary Brecka:Yes. Yeah, 7.35, 7.45 is kind of what we say. And you know that when you just hold your breath, for example, that urge to breathe, it actually comes because you start to build up acidity. You start to build hydrogen ions. And so you want to excel out because people can try this. Take a straw, for example, and blow into water with pH drops. And you can see that the pH starts to go down because CO2 dissolves in the blood to create carbonic acid. And that makes hydrogen ions. So in the same way, like when you exercise, you break down your carbohydrates and fats into CO2. The CO2 dissolves into your blood and lowers the pH.

22:58So by you exhaling, you remove that CO2 and the pH is able to help to maintain. That's also why sometimes when you're in shock, for example, people will start to hyperventilate and you exhale so much CO2, the blood pH starts to go up a little bit too high and now people can start actually tweaking their arms or going like these contortions, you start to raise the pH so high that you start to ionize various proteins and now that the cell membrane potential reaches threshold easier. For example, you start to get muscle contractions. Your alpha motor neurons activate your skeletal muscles. So you get these contractions, for example.

23:36Gary Brecka:And just those small changes in pH. Is that why they have you breathe into a bag? Yeah, exactly. Because you're breathing in a bag and you're reabsorbing the CO2. You're keeping that CO2 level so you don't raise that up higher. So point is, even if you subscribe to the benefits that we need to maintain an alkaline body or something, you can't do with alkaline water. Breathing is much more effective, right? And even when you look at like say pH of 10, a pH of 10 is, although it's alkaline, it's not really a buffer. That's why just a drop or two of lemon juice brings the pH right down. In contrast to say baking soda, which is a pH of 8.1, that could neutralize thousands of liters of alkaline, of acidic water, but it would take thousands of liters of alkaline water to neutralize the same amount of acid because of the buffering effect.

24:21Gary Brecka:Right. Okay. So then the first paper that you were involved in, was this the paper that was looking at alkaline water? Yeah, that's one of the early ones. We actually looked at, it was an animal study in NAFLD, and we found that we first did an experiment where we were using alkaline ionized water. This is a collaboration that I was doing with a group out of Israel. And there was no benefit. And they were surprised. And I was like, well, what's the hydrogen gas concentration? And they're like, we've got to figure out how to do that. So they measured the concentration and it was pretty low. It was like 0.3 milligram per liter or so.

25:01And it's like, I think the concentration needs to be higher because the other studies were using higher concentration. so now they can measure hydrogen it took a long time to do this this was like a several year experiment that we were involved in increase the concentration of hydrogen using different methods and then we were able to do two different groups where we could do a higher and a lower concentration the low concentration again no benefits at all even though it had like a negative ORP it was an alkaline pH all the same properties, no benefits the higher concentration did have obvious benefits so that was published back in 2018, 2019 or so, but we worked on it since like 2014 for quite a while.

25:40Actually, earlier than that. But the main article is this comprehensive review article. You can look it up. It's called Electrolyzed Reduced Water Review 1. And there's two reviews. There's review 1 and review 2. And there's this comprehensive review to go through any question or any thought you've ever had about this area. It goes through the water, microclustering claims, alkaline pH, negative ORP aspects. It just systematically goes through every one of them and conclusively demonstrates that molecular hydrogen is the key to any of the benefits, if there are any, to alkaline ionized water.

26:15Gary Brecka:Right. So you also authored a paper, I think, which may be, in my opinion, the most impactful paper that you've ever authored or co-authored, and that was understanding the exact mechanism by which hydrogen acts inside the mitochondria. And I don't think most people absorb what it means to be a selective antioxidant versus an antioxidant. So maybe we could talk about what makes something an antioxidant. What is oxidative stress? And why do you not want to over-suppress it? And why could that be dangerous? And what's unique about hydrogen that it restores this redox homeostasis versus just over-suppressing oxidative free radicals?

27:00So let's do this. So let's go through some history, okay? Okay. We're going to start with that Nature Medicine publication, and then we're going to talk about the benefits and problems with antioxidants in general, and that'll lead us to this target of hygiene that we recently published, and that explains everything. I can tell you're so proud of it. You smile when you say it, dude.

27:18Gary Brecka:You're proud of that one. I read it too. It was very well-authored. Well, and again, I'm just one of the authors. I was happy to be involved with that paper, but really the heart of research belongs to the other authors. and I was just grateful to be part of it. Because when I was in Japan, back in 2013, is when I proposed this concept. And we stayed in communication, you know, talking about it and working on it for a long time. That's why I'm happy because it's over 10 years of work. A lot of effort went into this. But let's talk about some background information to understand why this is so important.

27:55If you remember with that Nature Medicine publication, It talked about how hydrogen acts as a selective antioxidant. And that's a key word about that selectivity. Because we don't want just more antioxidants. Because antioxidants aren't necessarily a good thing. And the research has shown that over and over again. And that's because it turns out we actually need free radicals. So let's just break this down and maybe a step back. We know that too much oxidation is bad. So if you take like an apple and you cut it in half, it's going to turn brown, right? An avocado turns brown. You have rusting.

28:29All that is literally oxidation, right? We are breathing right now and that oxygen going into our bodies is oxidizing. It's oxidizing our cells. It's also what's driving life. That's how our metabolism works. It's oxygen at the complex four of the electron transport chain, literally consuming the electrons from our foods, making metabolic water. That process is oxidation. But see, sometimes during that process in an electron transport chain, that oxygen gets consumed prematurely by electrons. It gets electrons prematurely and that creates free radicals. Okay, this is going to be really important.

29:06So I just want to set this up a little bit more in the mitochondria. This is where we're at. We're going deep into the cell, into the mitochondria, and you have what's called the electron transport chain, right? And there's four main complexes. Complex one, two, three, and four. and basically you get electrons that are passed from complex 1 and then those get passed to CoQ10, actually, ubiquinol, and then they go to complex 3. Electrons from complex 2 also go there, they go to complex 3. So complex 3 is very important. They're seeing all these electrons. We're going to come back to this. It's going to be important.

29:39So remember, complex 2 is very important. Then the electrons go from complex 3, one electron at a time, a little bit dangerous, one electron at a time, through cytochrome C, go to complex four. At complex four, those electrons typically will combine with oxygen and two hydrogen ions and you make water.

29:58Gary Brecka:So you make water inside the mitochondria. Exactly, right? During this process, you make what's known as the proton gradient, hydrogen ion gradient. So in the inner membrane space of the mitochondria, you put a whole bunch of protons there, pumping against its concentration gradient, and then those hydrogen ions are able to go through the ATP synthase enzyme, sometimes called complex five, but it goes through this enzyme and he makes ATP. Turns out lots of ATP. Now, as I said, oxygen is a strong oxidizer. So you inhale, the oxygen is going to bind onto your hemoglobin. It has some, the iron, right, on your hemoglobin.

30:33So it can bind there. And that's important because you want to kind of sequester oxygen as much as you can in the blood. You don't want to have a whole bunch of oxygen floating freely all over the place all the time. The hemoglobin goes down, goes into like your muscle cells and the pH is lower, which is actually going to cause the hemoglobin to slightly shift its conformation. It's going to allow oxygen to leave the hemoglobin easier. As soon as that oxygen diffuses out, it's immediately gets sucked up by the mitochondria and complex four and converts into water. That way there's like hardly any oxygen at any time in the cells because that oxygen, if it goes in the cell membranes, it's going to cause oxidation.

31:10It's going to cause, in a cytosol, oxidation, free radicals, damage, right? As it goes in the mitochondria, there's electrons in the electron transport chain are being transported. But sometimes that oxygen could actually consume those electrons, say, at complex 1 or sometimes at complex 3 or through the simoyquinone radical that was created. CoQ10, that enzyme, ubiquinol, can be a ubiquinone radical, for example. and oxygen can get reduced, receive an electron. When oxygen gets a one electron reduction, it's called a superoxide anion radical. Now, that radical, it turns out, it's beneficial and harmful.

31:51Gary Brecka:So beneficial to a certain level, harmful at a certain level. Yes. Like a lot of species, hydrogen peroxide. Yes, that's another one. Very necessary, but it can also be very damaging. What happens, because hydrogen peroxide comes next, what happens is it's actually a certain signaling effect that superoxide can do. And then this enzyme, superoxide dismutase, can convert superoxide to hydroperoxide, let's say, or to water. And then hydroperoxide also has certain signaling effects it can do. And then there's even a specific aquaporin or protein channel for aquaporin to transverse to do further signaling.

32:25And then say like catalase, glutathione peroxidase can get rid of that. So these free radicals are literally produced for specific signaling effects that our bodies literally need in order to have normal mitochondrial function. So the mitochondria regulates our entire redox homeostasis. That's the main area. There's other enzymes like the NADPH oxidase or these NOX enzymes and a number of other enzymes that make free radicals. But the mitochondria is very crucial and plays the largest role in making free radicals. But see, our body has developed in ways to create a small amount of free radicals when needed and to do specific signaling.

33:07So when we exercise, we're breathing more oxygen. We're using more oxygen. So what happens to the free radicals? They increase. that increase in free radicals in turn signals our body to make more mitochondria to make our muscles work better to do a whole bunch of signaling effects that hormetic stress it's a

33:27Gary Brecka:hormetic stress exactly you have a positive response so is it fair to say that we actually don't want to over suppress that's that's the point right that's exactly right you've used this term redox homeostasis i want to pause on that for a second because redox homeostasis is this balance between oxidation and reduction, right? And ideally, we want it to be in balance. We don't want to over-suppress oxidation. We also don't want to over, we don't have too much inflammation or oxidation either. And with antioxidants, you really don't know if you're over-suppressing it or if you, maybe you just inadvertently hit the target.

34:06Gary Brecka:But, you know, if you're piling a bunch of vitamin C or beta carotene or something like that into the body. Yes, it's an antioxidant, but I think there's a prevailing thought that, well, oxidation's bad, more antioxidants must be good. Yeah. You hit the nail on the head. And the only technicality is technically we don't really want to balance. We want homeostasis. And the difference is that balance would mean they're equal and that's dead, right? So we can't say that oxidation is just bad. In the same way, you can't say reduction is just bad. You need to have both of them. And that's why I like the term redox because redox means oxidation and reduction.

34:43And you want to have that homeostasis. So our body, I was going through that whole transport chain because we want to see that we are designed to make free radicals, to do certain signaling effects, and then our body naturally gets rid of them through our body's natural antioxidants. Now what happens though with aging, with environmental toxins and whatever have you, or just - Exercise, yeah. Yeah, or if you're not exercising, inactivity, then your natural body's ability to produce antioxidants goes down. Your mitochondria become dysfunctional as well. You start to increase more free radicals.

35:20You increase free radicals to the point you are now suffering from oxidative stress, right? That's a bad thing. You don't want the stress. You want a hormetic type of effect, but not an excessive amount. And so maintaining, again, maintaining a redox homeostasis is why it's so important. So our body contains our own antioxidants, right? Glutathione, we mentioned these, right? There's a whole bunch of them. And all plants do the same thing. That's why if you have like your apples, for example, if they're on the tree, they're not turning brown because they also have antioxidants in them. And that's why when we eat, say, the apples or the carrots or what have you, we get those antioxidants inside of us.

35:59these are polyphenols that can scavenge some of the oxidants, right? Now, it turns out, though, that when you basically isolate these potent antioxidants, all of the cells, or you have synthetic forms, and you just ingest high amounts of them, well, that's going to be problematic, kind of what you pointed out, because now we're potentially blunting those free radicals that our body specifically produced so that we could have improved mitochondrial function or mitochondrial biogenesis. So when we look at these studies, we can clearly see that if you're eating a healthy diet of fruits and vegetables and so on, then you have your antioxidant homeostasis, your redox homeostasis, everything is good.

36:41It's healthy.

36:42Gary Brecka:But when you start to perturb that, either by doing things that are very oxidatively harmful, like say smoking or environmental toxins, or you have low physical activity because low physical activity will result in lower levels of your body's natural antioxidants. Then you have oxidative stress. Also, if you start taking high doses of say synthetic antioxidants, then you start to cause a disequilibrium. Blunting, yeah. Yeah, you blunt those benefits. So you can actually see a number of, especially in animal studies, but clinical studies as well, a number of them have actually shown that antioxidants might actually blunt exercise training adaptations.

37:23Gary Brecka:Wow. So you don't get mitochondrial biogenesis. You don't get improved, say, insulin sensitivity, or if you're blunting the inflammatory response, right? We need these things. We need to maintain the homeostasis. And so that's why we don't want to just take a bunch of antioxidants. And that's why hydrogen is so different than any other antioxidant. And I want to talk about this for just a second. This is just basic chemistry, actually. But the reason why it's selective is because hydrogen gas does not react with the beneficial free radicals. It only reacts with the harmful ones. That is so incredible that word selective means it's reacting with the harmful free radicals like the hydroxyl free radicals and not interacting with the beneficial free radicals and allowing the body to just perform that function on its own.

38:13Gary Brecka:Because, I mean, there's nothing more intelligent than our own innate system. That electron transport chain was designed for a reason. It innately knows what it's doing. And it's right there in that same Nature Medicine publication. Again, it's such a landmark paper. They took, say, nitric oxide, superoxide, hydrogen peroxide, and hydroxyl radical formation through the fenton reaction. And they added vitamin C or hydrogen gas. And you can see that vitamin C neutralized everything. The good, the bad, everything. So vitamin C is great. It's going to get rid of the bad, but high amounts could also get rid of the good.

38:50Hydrogen gas. When you put that with, say, superoxide or these other free radicals, there was no reaction. That's so awesome. It's thermodynamically possible, but it's kinetically infeasible based upon these rate constants. See, the hydroxyl radical is so reactive that it'll react with anything.

39:09Gary Brecka:Yeah. Anything that's in its vicinity. And that's really the only free radical that I'm aware of that has no known benefit in the body. Pretty much. Right, I mean, it's, I mean. Maybe by accident. Okay, because ostensibly, we'd want to take that as close to zero as possible. Yeah, absolutely, yeah. Okay. Yeah, exactly. Yeah. It's just because it reacts so quickly with anything and that's going to cause, you know, DNA damage and all sorts of problems. All the other ones can kind of be regulated and your body have a natural detoxification systems for that, like the superoxidus mutase enzyme, right?

39:39And all the other ones. So we're going through some of this history. We first see the hydrogen is selected because it can only react with the most oxidative or strongest radicals and most harmful ones, right? And it's small enough, it can actually get into the mitochondria. Whereas again, these other larger antioxidants, maybe like vitamin E, which is larger, but it's also more lipophilic. So maybe it can't easily transfuse into the cytosol and then go into the mitochondria or different areas. Hygiene gas can do that, where vitamin C is more water-soluble, so it's going to have a harder time going through the cell membrane.

40:18It has to go through a transporter protein. Hygiene gas, again, there's no problem. It can diffuse very easily into the mitochondria and there it can help with these free radicals and selective antioxidation. There are three ways that hydrogen is helping with this antioxidative process. And that's one of them is it's only gonna react with the most toxic hydroxyl radicals if it reacts with them at all.

40:43Gary Brecka:Yeah, I hope people are picking up on the fact that that, you know, how profound that is because it is the only selective antioxidant that I've ever been able to find in any kind of research. which antioxidants are abundant, but selective antioxidants, the mechanism that hydrogen uses to leave the body's production of free radicals, necessary free radicals alone, reduce the harmful free radicals that we don't need, and allow this cellular homeostasis to return. I mean, you just can't overemphasize how unique hydrogen is in that way. And that's actually, as cool as that is, that's a minor mechanism by which it exerts these antioxidant effects.

41:32The other big one is because it's able to regulate your body's innate or natural antioxidant defense mechanisms.

41:40Gary Brecka:Wow. So it can even bring redox up. That's right, yeah. Wow. So you have your natural antioxidants, right? Glutathione, superoxidant mutase. These are all regulated by this transcription factor, the NRF2 pathway, the NRF2 keep one pathway. What happens, this is a protein that's in the cytosol. And when you get oxidative stress that's happening, then you get oxidation of this keep one factor basically, and then the NRF2 can diffuse into the nucleus. They're biased to the DNA. And then you get this basically just transcription of your body's natural antioxidants. So it's trying to protect itself.

42:16Exactly. Catalase, glutathione. They all start to increase. Yeah, NRF2 regulates over 200 different cytoprotective proteins and enzymes. Wow. And this is the other cool thing. So intelligent.

42:26Gary Brecka:It's just mind-numbing. Hydrogen is only going to upregulate NRF2 when the cell needs it. So if you have a cell, and we've published studies on this, demonstrating that hydrogen can upregulate NRF2, but only if there was a stress. Wow. So if you take hydrogen gas, you put it in a cell culture, and you measure NRF2 levels from a healthy cell, you don't see any nrf2 protein changes you might see some changes in mrna but just because you see something mrna doesn't mean it's actually at the protein level but but in general you don't see any you don't see any real changes at the protein level but if you were to add say environmental toxin some stressor or something that would normally uh cause oxidative damage in the cell and then you administer hydrogen gas that's when you see the rescuing effect of hydrogen wow so Hydrogen is able to go to the individual cells, knock on the door, and say, okay, how are you doing?

43:23How's your redox homeostasis? What do you need? Do you need the NRF2 upregulated or not? It's only going to basically upregulate the NRF2 pathway in the cells that are suffering from not having enough NRF2, where you want to bring those glutathione levels up higher. This is a key mechanism because, again, yes, superoxide, hydrogen peroxide, These are all good, but again, only if you have it at the right concentration in the right location for the right duration. If you start making too many of these because you have a hyperactivated, say, NOX enzyme system or certain complex of the mitochondria, that's when it becomes problematic.

44:02Hydrogen is able to regulate our body's natural antioxidants so our body can naturally detoxify these oxidants before they get too high

44:11Gary Brecka:and to help clear them. It's actually using the innate intelligence of the DNA to regulate that system instead of circumventing the DNA and just suppressing it on its own. Yeah, exactly. It's regulating everything. That's fascinating. And then there's a third way. I said there's three ways. We've talked about two so far. The third way is that hydrogen, because it's signaling effects, it can actually help to suppress excess oxidation that's occurring. It's more of a modulator because in some cases, hydrogen is able to... If there's an excessive amount of free radical that are being produced, like say a complex one of the mitochondria or NADPH oxidase enzymes, these NOX enzymes, or neuronal nitric oxide synthase where you're getting too much nitric oxide in the brain that's causing a nitric state of stress.

45:06Gary Brecka:It happens in Alzheimer's patients. It happens in autistic patients, ostensibly because of gut dysbiosis. But you see very high levels of nitric oxide, which most people think just has a vasodilation effect, which it does, but it can also be a toxic gas. Yes, it is a free radical. It can be very toxic when you have dysregulation. And that's another key area that hydrogen helps to regulate. See, hydrogen gas doesn't react. I'm so glad I take hydrogen water every day, dude. If you're not convinced halfway through this podcast, I'm going to take some right now. Well, I mean, the mechanisms are very interesting, but we're still looking at the clinical evidence on this, and the preliminary evidence looks very exciting.

45:48But the nitric oxide one is very interesting because, again, nitric oxide hydrogen gas don't react, but hydrogen gas can regulate its production. And so these different enzymes, if they get too high, like for example, you have superoxide that's produced from the NOx enzyme, and you have high levels of nitric oxide, if those levels get high, they immediately react. I mean, the only thing that slows the reaction is the rate of diffusion. And when they do react, you form perioxydant nitrite, which is a strong oxidative molecule. So hydrogen is essentially preventing that formation because it's able to decrease the amount of free radicals that were produced in the first place.

46:26So you have prevention. But it's not more than just prevention because, as I said earlier, our bodies need free radicals. so sometimes the cells need a little boost and so in a number of studies including our own that we'll talk about here in just a second we can see that hydrogen gas can transiently increase small levels of free radicals so it can increase say superoxide production for just a little bit it's a small transient level that's kind of a hormetic stressor my point is think about what hydrogen is going to do go to this cell and this is not really accurate but I'm just trying to explain this as a layman idea because we can look at the cell culture studies on this.

47:08So hygiene gas goes to this cell. Oh, you're not producing enough free radicals to have the hormetic stress, right? So we increase your superoxide production. Now that could in turn activate NRF2 and now you can have higher levels of endogenous antioxidant self-defense system.

47:24Gary Brecka:Like glutathione, catalyze, all these other drugs. So that's that cell. The same body. We're talking about the same human. And now we go to the other cell, a different organ or an adjacent cell, who knows. And this one says, oh, you know what? You are suffering from oxidative stress. I'm going to decrease the amount of oxidation that's occurring. I'm going to help suppress or down-regulate NADPH oxidase system. I'm going to help decrease the amount of free radicals that are being produced. And then it can go to another cell and it can say, oh, you know, I'm going to modulate your entire free radical production so you have a better homeostasis, right?

48:03Or maybe it's going to go into another cell and it's just going crazy. Eschemia or perfusion, you have hydroxyl radicals being produced just like crazy. And hydrogen gases, if it's there, it can react with the hydroxyl radicals and form water.

48:14Gary Brecka:Yeah. So you have - Completely neutralizing the worst free radical in the body. Wow. I mean, I hope mechanistically people are really grasping how incredibly unique that is. It's almost like an intelligent molecule, right? I mean, it sort of arrives and then assesses and can shift its impact based on really what that redox homeostatic environment needs, an improvement in redox, a reduction in oxidation. And that's just so fascinating because I think very often we just have, you know, take these blanket approaches. And I did for years too. I just thought, man, more vitamin C IVs, more, you know, more antioxidants, less free radicals, that's a good thing.

49:04Gary Brecka:But really years ago when I started stumbling upon a lot of your research, talking to you, getting to know you, really going down the rabbit hole of how unique hydrogen is, it's not only a part of my routine every day. I mean, I take it either immediately before or right after I do every hyperbaric session because I realized that in hyperbarics, that excess oxygen, that oxygen singlet could be creating oxidative stress. Yeah. And it does. And that's how HBOT tends to work. You literally create a hormetic stressor just like exercise. And you want to get the benefits and negate some of the negative effects.

49:42So taking hydrogen therapy, there's some research on this, at least in cell cold studies, some very interesting research helping prevent oxygen toxicity. So you're able to get some of these benefits. Oxygen is a much stronger molecule, like ozone therapy that people do or hydrogen peroxide. There's a number of things out there that are pretty strong and have serious side effects potentially. Like HBOT, going too high, going for too long. Oxygen toxicity is a very well-known thing. Hydrogen seems to help negate, negate is probably a strong word, but help to reduce some of those excess side effects so you can still get those benefits because to your point, you need to have this, I want to say balance colloquially, but really this homeostasis of oxidation and reduction.

50:28And so that's really where the research is, I would say, converging in terms of aging and disease conditions and so on. It's not about oxidative stress or the free radical theory of aging. It's all about redox dysregulation. And as you get older, as you age, as you have environmental toxins and so on, you get a redox dysregulation. And the problem is that redox dysregulation can happen not only in the same individual, but even in the same organ, even in the same cell. So you can have like one portion of your cell, say the cytosol, that is suffering from an oxidative stress or say in the mitochondria, an oxidative stress that's going on.

51:10There's too many free radicals that are being produced. but yet another area you're actually lacking reductive potential say like in the endoplasmic reticulum or something you're not able to fold your proteins correctly if you can't do that then you can't protein structure dictates function you need to have the correct redox homeostasis and so you can imagine if the cell itself is suffering from a redox dysregulation how would it be possible that taking a conventional antioxidant that only is unidirectional, it's just an electron donor basically, is going to help that?

51:47Gary Brecka:Well, there have actually been cancer studies with beta carotene, I think, where they showed that it went the opposite direction. Yeah, unfortunately, that's exactly right. They found people who smoked a lot when they ate carrots, there's a correlation, they tended to maybe live longer and be better. And it just makes sense. Well, yeah, smoking causes a lot of free radicals, carrots have a lot of beta carotene, That's an antioxidant, so they're going to neutralize those. But when they decided to do the study, hey, let's really determine this, they found that those taking the beta carotene started dying faster and getting cancer faster than those on the placebo group.

52:24Gary Brecka:Wow. And maybe we could talk about the mechanism quite a bit, but maybe it's because, again, you're not able to directly address the redox homeostasis, the dysregulation, right? because you're just providing a bunch of antioxidants, but you could still be suffering from a reductive stress in different areas, whereas hydrogen is totally different. You don't have that same concern. But that study actually, it's another maybe critical thing for us to think about just logically as well because on the surface, it can make total sense mechanistically like, hey, carrots rich in beta carotene, antioxidants, smoking, oxidative stress, we should take it.

53:05And that's why we have to be careful when we focus too much on mechanisms, like, oh, this is the mechanism, this is the mechanism, that. Because just because we can find a mechanism to support something doesn't necessarily mean that that's going to be the clinical outcome. Because the clinical outcome is going to be a summation of a whole bunch of the mechanisms all together.

53:25Gary Brecka:Yeah, yeah, yeah, yeah, yeah. You know, I think some of the worst research we do is when we study things in isolation, we look how something behaves in a laboratory and we assume when we put it back into the human body, it's going to behave the same way. And very often, nothing could be further from the truth. That's exactly right. And that's also some of my skepticism, even with this area of hydrogen research. Like I'm talking about this because I'm passionate about this area, and the mechanisms are, I love biochemistry. I love this area. Clearly you love biochemistry. Yeah, I'm going to pull us out of the weeds here in a second because I want to get into some of the more practical applications.

54:02Gary Brecka:Yeah. Right. I mean, which I know is what people want to hear. And we'll do our best to do that. But it goes to my saying, I also have to be cautious because I don't want to be the hypocrite. Like, oh, this is all the things happening in the cell. Yeah. And then what we really want to know, OK, what's the end point? What are the clinical studies actually show? Right. Right. That's really what matters. If you want protein to build lean muscle, but without the caloric impact or need to cut, you need perfect amino. It's pure essential amino acids, the building blocks of proteins in a precise form and ratio that allows for near 100 % utilization in building lean muscle and no caloric impact.

54:40Gary Brecka:So we build protein six times as much as whey, but without the excess body fat we normally get during bulking. This is the new era of protein supplementation, and it's real. If you want to build lean muscle without having to cut, you need Perfect Amino. Now let's get back to the Ultimate Human podcast. Because, you know, anecdotally and observationally, what I have seen from bathing clients of mine in hydrogen gas, by using hydrogen gas myself during intense exercise, like what we did this morning, trying to keep up with my son, his performance in distance racing, you know, he just did 100-mile race.

55:21Gary Brecka:I truly believe if he wasn't powered by hydrogen water, he wouldn't have completed the seven marathons, seven continents in seven days because he had never run a marathon. I've read some of the published research on delayed onset muscle soreness, on lactate thresholds. And again, mechanistically, it makes sense, but also practically in the host, it's also making sense. So maybe we, eventually I want to get to how should people take it? How much should they take? is it safe for everybody to take a hydrogen tablet first thing in the morning, maybe another one in the afternoon or take additional hydrogen if you're exercising intensely, certainly if you're using hyperbarics.

56:07Gary Brecka:But where are the broad applications? Does hydrogen water help with hormones and women's health specifically? And how does hydrogen water impact athletic performance? So I want to finish the mitochondria story briefly because I'm going to refer back to that as I digest all of these things. And the summation of everything is back to the mitochondria, the mechanism, and to that paper that you mentioned. We published a paper in Redox Biology with my collaborators in Japan. Again, the real researchers behind this, I'm just happy that I was involved since 2013 actually on this project. But Redox Biology is a top journal, But what we found was that hydrogen specifically targets a specific protein in complex three of the mitochondria.

56:59Remember with the electron transport chain? In complex three is a specific protein called the risque iron sulfur protein or the RISP protein. And it transfers an electron, one electron at a time. Ubiquinol comes in, gives an electron, then one goes to the risque iron sulfur protein pathway. When hydrogen gas targets this protein, it actually... It stops it from working. Basically, it causes a change in this protein that stops from working. This is a stress. Because you're not able to transfer the proteins. The mitochondria quickly recognizes the stress and you start to see increases in some superoxide levels.

57:37So a slight transit increase in superoxide production. You have an initial drop in ATP levels. that quickly causes the mitochondria to respond to regenerate and rejuvenate its mitochondrial function. And then the RISP or the RISC-AR protein levels, they come back up even higher than they were. ATP levels go back. Follow that with exercise. As soon as you start exercising, what's the first thing that happens? You start producing free radicals. Your ATP levels drop immediately, just very quickly. because the creatine phosphate kicks in very quickly, right? All these similar things start happening.

58:17And then later, you start having an increase in everything. So you get the mitochondria biogenesis, right? So one of the main targets of hydrogen gas seems to be this risque iron sulfur protein in complex three of the mitochondria. So mitochondria is a prime target of hydrogen. And based upon that, we can understand why hydrogen is able to regulate redox homeostasis, produce some free radicals when needed, suppress free radicals in other cases, activate the Nrf2 pathway, increase mitochondrial regeneration, rejuvenation, ATP production, all the cellular things that are needed right there in the mitochondria.

58:53And now we have one of the mechanisms of how hydrogen specifically does this. Wow. So now let's go to these practical applications because I want to refer back to that target and we can understand how hydrogen gas would be doing some of this based upon understanding of the mechanism.

59:10Gary Brecka:Yeah, so maybe we start with athletic performance, right? Because, you know, the vast majority of my audience is exercising on a regular basis, and they're either taking hydrogen, water, or they're not. I take hydrogen for all my exercise. Yeah, so do I. And I absolutely, unequivocally notice a benefit. So does my son, and so does every athlete that I work with. So there's a couple points. The first one I want to point out is when it comes to athletic performance, We call it an ergogenic effect. Whatever we do, we first don't want to make things worse. And that is a major concern that a lot of new emerging technology supplements, fad concepts come in where they could potentially negate some of the exercise benefits.

1:00:01We talked about earlier how some studies show that taking antioxidants can actually blunt exercise performance because maybe you're blunting those free radicals that you need. Taking NSAIDs, anti-inflammatories, same thing. That could potentially blunt exercise benefits.

1:00:17Gary Brecka:Cold water immersion immediately after strength training. Yeah, that's another good one. Yep, exactly. So when it comes to hygiene therapy, we can very confidently say actually that hygiene at least does not negate exercise benefits. It doesn't impair exercise performance. So that's number one. If there's a question, maybe you should really be cautious before you try to do any intervention. Hygiene doesn't do that. And we can think about the mechanisms. It doesn't react with other free radicals at all. It can't do it. It's only going to regulate the NR2 pathway when there's a serious problem going on.

1:00:53It actually can increase superoxide production similar to exercise. And then we look at the studies. If we look at the animal studies, for example, with exercise, So combinational studies, we actually see that during the control, of course, there's no increase in mitochondrial biogenesis. We look at a marker, PGC1-alpha. There's a peroxisome proliferator active receptor coactivator 1-alpha. That was a mouthful. There's going to be a test on this later, so I hope that everybody got that. But this is a master target we want to activate. Things like AMPK can activate this, which AMPK gets activated.

1:01:28You break ATP down, you get some AMP levels. that AMP can activate AMPK. Calcium is another one that can activate this. But you want to activate PGC-1-alpha and exercise does that really well. PGC-1-alpha in turn can increase things like mitochondrial biogenesis and vascular industrial growth factor and a number of other things. So hydrogen, when you do exercise and you combine it with hydrogen, you see PGC-1-alpha levels increase. Actually, they increase even more than exercise alone. Wow. When you do the same exercise with vitamin C, you see PG-1 alpha levels decrease.

1:02:06Gary Brecka:Yeah. This is critical to understand. This means that hygiene is not impairing exercise performance. And if anything, it might act as an exercise memetic to help to improve exercise performance, especially over the long run, because you see increases in PG-1 alpha. Wow. So this is animal studies, and it makes mechanistic sense based upon the mechanisms I just talked about in vitro studies, soul culture. Now we look at the clinical studies. There's a breadth of studies on exercise performance. I've read them in swimmers, elite swimmers. I want to say another one in elite soccer players. Yeah, that's right.

1:02:46Gary Brecka:So I've read some of this research and more discussed like delayed onset muscle soreness, but it also discussed performance, recovery. I don't remember if we went into specific mechanisms but I mean, I don't know that I have read a negative research publication on hydrogen. I'll just put it that way. It depends on the definition of negative. There are a number of papers that show there are no benefit. We published an article, one of my first articles actually when I was doing my master's is we, there's a lot of people are saying that their VO2 max was increasing when they're taking hydrogen water and you know, it was a simple study because we know exactly how to measure VO2 max.

1:03:28It's a little more complicated. We'll say VO2 peak for those who are exercise physiologists. But we looked at this and we found that there was no increase in the VO2 peak following acute supplementation with hydrogen. And mechanistically, that wouldn't be expected. But in that case, it would be like a negative study. However, we did a sub-analysis of some of the, like the exercise, look at the exercise in heart rate at lower exercise intensities, we can see that the heart rate was a little bit lower. And there's changes like in the respiratory quotient or the respiratory exchange ratio and the number of other changes.

1:04:07And other people have reported on this too, showing that actually hygiene, even an acute dose of hygiene water might be able to help with some of the athletic performance, whether hygiene water or hygiene inhalation.

1:04:19Gary Brecka:It did in the swimmers and it did in the soccer players. Yes, exactly. And some of the soccer players, they took it for like a week, but they was not at a VO2 max, it was on a max effort. So we're probably not going to see a change if you just take one dose of hydrogen and you go for a peak performance. Right. But you might see even just one dose of hydrogen and you can see at kind of a lactate threshold, a pretty high intensity, you can maybe exercise for a longer period of time, maybe do more bouts of exercise. and probably those benefits are going to be more significant when you do a longer dosing protocol because again, just like exercise, it takes time to activate mitochondrial biogenesis.

1:05:01So by taking hydrogen water, you want to recover quickly because that's like the number one thing that comes to athletes is you want to recover fast. Why? So you can train again, right? It's volume dependent and the volume is limited by how quickly you can recover. And so by taking hydrogen water, if we can improve the inflammatory response, we actually can see that an acute dose of hydrogen often will increase superoxid production and inflammatory markers like interleukin-6, for example. And then it goes back to baseline faster and lowers that chronic low-grade inflammation, lowers that chronic oxidative stress.

1:05:35Gary Brecka:Which is why it has a positive effect on delayed onset muscle soreness. Yeah, there's a lot of potential mechanisms that could be going on with that. And more research need to be done A lot of those studies are still pretty small, right? But we can see, though, in the studies that have been done where hydrogen doesn't seem to exert like an anti-fatigue effect, right? They're able to exercise, let's say... Yeah, there was a scale where they rated the... Yeah, the Borg's effect or the RPE. Yeah, yeah, where they rated the actual level of intensity, level of perceived effort. Yeah, the perceived exertion.

1:06:10Gary Brecka:Perceived exertion, yeah, the level of perceived exertion. And in nearly all of those cases, their level of perceived exertion for the same bout of exercise was lower. So I mean, that's clearly something that would, in my opinion, improve athletic performance. Yeah, you can push yourself harder. Yeah, you can do it again. But those are also correlated with changes in say lactate levels. Those levels are also lower. Which, you know, the reason you make lactate in the first place is because there's a mismatch between how fast you need ATP and how quickly your mitochondria can make ATP. So if you need ATP fast enough or faster than what your mitochondria can provide, you have to go through glycolysis and you start producing lactate.

1:06:50Gary Brecka:You've got to use carbon dioxide instead of using oxygen, right? Yeah. Well, it's not just carbon dioxide. Carbon dioxide is only produced during the TCA cycle, the citric acid cycle. Glycolysis doesn't use oxygen or anything. It just breaks down your glucose molecule. And in order to continue driving glucose, the end part of glycolysis is this molecule called pyruvate. and then pyruvate normally enters into the citric acid cycle and then gets converted to acetyl-CoA and then citrate. You do the whole citric acid cycle. Then you make NADH molecules. Then you go through the electron transport chain, complex one, two, there's three, complex three, right?

1:07:26This whole process takes quite a bit. Makes a lot of ATP. One glucose molecule can make 30 or 32 ATP molecules. You even use oxidative phosphorylation. But glycolysis only makes like two net ATP, but it's a lot faster. I won't give numbers, but it's a lot faster. So if you can't oxidize pyruvate fast enough, then you convert pyruvate to lactate. And that's important because lactate production allows glycolysis to continue going. So lactate production actually delays fatigue. It allows you to continue exercising. It prevents or delays acidosis, for example, because the whole purpose of lactate production is you're actually regenerating a molecule

1:08:11Gary Brecka:that you're familiar with, NAD+. NAD +, drives glycolysis. And if you convert all your NAD +, to NADH, you can't do glycolysis anymore. So by converting pyruvate to lactate, you convert NADH to NAD +, and then NAD +, can drive from glycylaldehyde 3-phosphate and can cause that oxidation to 2 ,3-bisphosphoglycerate. So you get NAD +, being produced. So in these studies where lactate levels are lower, there's a couple potential things that are going on. Number one, maybe because this exercise intensity, you need X amount of ATP. And so maybe what's happening is the hydrogen helps your mitochondria function better.

1:08:54So you can provide the amount of ATP you need via oxidative phosphorylation through your mitochondria as opposed to anaerobic glycolysis.

1:09:04Gary Brecka:So in other words, it's just, again, to pull us out of the weeds, it's allowing you to exercise at the same intensity for a longer period of time. Yeah, exactly. Either because of improving. Because that's anecdotally what I noticed. That's right. And my son and every athlete that I put it on. I mean, I bathe them in hydrogen water. I have them consume hydrogen-rich water. And I have hundreds of clients that by bathing and consuming it have both reduced their pain, improved their recovery, and increase the duration that they can exercise at a high level of intensity. And this has been in a number of UFC fighters and a number of professional athletes that most people watching this podcast would know that perform at a very high level and now they would swear by it.

1:09:48Gary Brecka:Yeah, that's amazing. And the research is still ongoing with that. And I think we'll start to see some of the differences in the mechanism because when you drink hydrogen water, actually a lot of the hydrogen gas is excelled out of your lungs. So a lot of that doesn't actually reach the muscles, yet we still see these direct benefits versus say inhalation of hydrogen gas, that's going to have some different effects as well. But they both have very, you know, obviously benefits that we see when you look at the clinical studies. So let's go through some, again, I want to pull this out of the weeds.

1:10:19Gary Brecka:So now you know the mechanism. I want to pull this out of the weeds. But, you know, I want to talk about women's hormones and women's health, PCOS and hydrogen-rich water, we touched on athletic performance. There was also a really interesting article published in the Journal of Experimental Gerontology. And in this article, I think it was a six-month study, they broke these gerontology patients into two categories. One drank hydrogen-rich water, one did not. they used tattoo markers for methylation. They measured sit-stand ratios. They also measured different cognitive scoring, short-term recall, learned memory.

1:11:10Gary Brecka:There were a number of different measurements for cognitive function. And it seemed to universally improve the hydrogen-rich water side significantly across all of these markers. That was another one that really piqued my interest in hydrogen water because, you know, a lot of studies are in young athletes, you know, like 22-year-old soccer players, you know, 25-year-old, you know, competitive swimmers. But here you have a population that's deconditioned. You know, they're not out there sprinting. and part of their protocol wasn't to change their exercise regimen, yet they had exercise benefits.

1:11:56Gary Brecka:I'm calling it sit-stand ratio. There's another term for it. And that was another study that really drew my interest to hydrogen-rich water because that was the only intervention that they made for that six-month period of time. Yeah, and I'm familiar with that study. It wasn't one of the ones that I participated in, but I know the authors, the researchers. and yeah, it was a very powerful study because to your point, this was number one, it was a longer study. They're using the hydrogen producing tablets and so you get a pretty high dose of hydrogen which is important because sometimes some of these studies, they use hydrogen water but the concentration, it may have found more effective benefits if it was a higher dose.

1:12:39This is one of the potential trends. We found this in metabolic syndrome study, for example, maybe we can talk about later. but that study showed some of these potential benefits that you already mentioned and it was like six months it was a pretty good duration and that makes sense when we think about the mechanisms hydrogen is not a super powerful molecule and that's what makes it largely safe as well and so it's going to go in and it has these effects in the mitochondria and in the cell and it's this long term benefits that we start to see so that's why going longer like for six months you might still see more of these benefits.

1:13:15And also, this is why it gets me excited because, yes, I'm very interested on the mechanisms of biochemistry just because I like to see how things work. Clearly, you are. But we want to know that those clinical endpoints. And here we're showing that it's being translated, right? It's translatable between the cell culture to animal studies and then finally to the human studies, right? And I know you mentioned with the women, with that PMS and PCOS as well. You know, more research needs to be done on this. I was involved, I helped author one of those studies, but it was more of a subjective type thing that we looked at.

1:13:56And it does show favorable effects. So I wouldn't say, you know, hygiene is like a hormone or necessarily mimics those things. But again, by helping to improve the terrain, the cellular terrain, and how the inflammatory process and oxidative stress, you can start to help maybe regulate things that are really outside of homeostasis. So really think about hydrogen as a homeostatic adaptogenic regulator. Yeah, yeah.

1:14:22Gary Brecka:You also are in the 24-week metabolic syndrome. Yeah, that was the one. This I find fascinating because the vast majority of Americans with chronic disease have metabolic syndrome. and the vast majority of my deconditioned clients have metabolic syndrome. 41 % of children have metabolic syndrome. That's very sad. 52 % of adults. I mean, we've become the sickest, fattest, most disease-ridden nation in the world despite the fact that we spend$5 trillion a year on health care largely because of metabolic syndrome. And metabolic syndrome is a combination of things, hypertension, high triglycerides, poor insulin sensitivity or insulin resistance, obesity.

1:15:08Gary Brecka:And that was another one that was very fascinating to me. Can you talk about what happened to those patients, what changed and what, if anything, surprised you? And what does this mean to hundreds of millions of Americans that are suffering from metabolic syndrome? Yeah, this was a six-month study. It was conducted in India with some of my colleagues there and it was a pretty big undertaking. We used the hydro-producing tablets in the study because we could provide a high consistent dose of hydrogen. Which by the way is why I'm not a proponent of the hydrogen bottles any longer. I used to be a big proponent of the hydrogen bottles.

1:15:42Gary Brecka:I'm not a believer in those anymore. I noticed that the proton exchange membranes would break down over time. The seals would break down over time. A lot of these would, if you didn't clean it regularly, you would get almost like mold in the bottom. And then because there were so many Chinese fakes on the market, I had clients that actually had these things explode on them. And to get a relatively low dose of hydrogen versus getting like 12 parts per million to 13 parts per million from an elemental magnesium tablet, I mean, it's apples and oranges, even cost-wise. And I hadn't seen any studies using hydrogen bottles.

1:16:23Gary Brecka:I'd seen them with hydrogen inolation, hydrogen tablets. Maybe there were some with hydrogen water bottles that I'm unaware of. But I haven't. Yeah, I mean, the bottles can work, but there are a number of caveats. I think you mentioned all of those, right? There's some bottles that are okay, but then the longevity of those. The nice thing about the tablets, just for research purposes, is it's a lot easier to give a client a bottle of tablets and teach them exactly how to use it, and we know they're getting at least a minimum. Same dose, yeah. Even if it's not exactly the same, we know they're at least getting a certain amount of hydrogen in order for it to be clinically relevant.

1:16:58A minimum threshold, okay.

1:16:59Gary Brecka:Yeah, hitting that threshold. Yeah, so can you talk a little bit about the metabolic syndrome paper? Yeah, so this paper, it was actually both surprising but also expected because there were a number of other studies already on the metabolic syndrome area, but we were using a higher concentration of hydrogen and a longer duration. And what we found was we found improvements in cytoglycerides and cholesterol levels in the ratio, for example. we found decreases in some of the inflammatory markers and oxidative stress maybe something that was surprising was the BMI was lower specifically because of weight loss those seemed to be more fat loss in the hydrogen water group you just converted half my audience really?

1:17:51Gary Brecka:better fat loss? it wasn't a primary end point but it's something that was observed And this has actually been shown in a number of studies where there seems to just be some modest weight loss, specifically from fat mass and potentially an increase in lean body mass. And it's interesting. You'll probably like this. This is really interesting. But there was an animal study. It was published in Journal of Obesity, I believe. It was a nature publishing group also, or it used to be. But in this study, they used a leptin deficient mice. So leptin deficient, leptin is a hormone that makes you feel full.

1:18:29And so if you don't feel full, you want to keep on eating. And so these mice would overeat and they're fed a high fat diet.

1:18:34Gary Brecka:But they would blunt leptin so they wouldn't have a satiation response. Exactly. So just keep on eating. Well, those given the hydrogen water, they like were so much thinner than the other rodents were. I mean, there's pictures in the article. You can just visibly tell the difference. In fact, the drinking of hydrogen-rich water in this case was equivalent to like a 20 % caloric restriction. Wow. And mechanistically, they found that hydrogen increased FGF21 or fibroblast growth factor 21, which increases energy expenditure, which is again something that happens in the mitochondria. So it's metabolism, improves metabolism.

1:19:12Gary Brecka:And wasn't there recently a paper, you might have been involved in it, comparing it to GLP-1s? Oh yeah, there was a study on that. I wasn't involved with that paper, but that was interesting because hygienists seem to have some benefits in terms of basically helping restore some of the losses that can happen with obesity or whatever. So you can have basically the right levels that you would otherwise, you're supposed to have. And maybe that's helping to regulate somebody's weight or their satiety or just their perception, their desire. there's a lot of, hydrogen is very multifactorial because of what it's doing to the brain, what it's doing to the gut and what that in turn is going to do to the brain.

1:19:54And then if that's going to change, you're going to have your dietary habits will change. That's further going to change your gut microbiome. And then you might feel like exercising, you have more energy because you're improving the mitochondria. And now if you start to exercise and we see that some of these studies of people where they're taking hydrogen and water, like I write down the journal, I feel like exercising more, I walked more, which is kind of a confound, but it's also that's very interesting that people are wanting to just move more and do things more. And that's very important for overall health.

1:20:23Gary Brecka:Well, you know, there's also a link between the reduction of fiber in our diets over time and the reduction of this production of hydrogen gas. Oh, that's a very interesting correlation. And yes, basically, if you have a healthy diet, if you have a healthy microbiome healthy microbiome if you have all these that are healthy and good you naturally produce a lot of hydrogen gas. Actually you can produce up to over 10 even 13 liters of hydrogen gas a day just by having a microbiome with a lot of fiber. Now a lot of that hydrogen gas is not is going to be consumed by other bacteria it's going to be lost in flatulence So you don't actually get a lot of...

1:21:12Lost in flatulence. I love the scientific term. And it's explosive. Just bust an ass.

1:21:18Gary Brecka:Yeah. And it's explosive. Because it's above 4%. Yeah. But, you know, it is interesting when you look at some of these studies, Parkinson's, Alzheimer's, a lot of neurological conditions, they tend to have lower hydrogen gas in their air, in their exhaled air. Their breath hydrogen gas is lower. And when you look at my collaborators at Nego University, they looked at approximately those patients and the bacteria in their fecal matter actually had less hydrogen-producing bacteria than those who don't have those diseases. So again, a very strong correlation. Again, correlation does not equal causation, of course.

1:21:58But these are important correlations that you would expect that would exist if there were a causative factor going on, right? Same thing with the Japanese centenarians, right? Those who become centenarians, they have higher excelled hydrogen gas levels than younger people who don't end up living as long, basically.

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1:23:32Gary Brecka:Now let's get back to the Ultimate Human podcast. So for somebody that's new to hydrogen water, what is their entry point? What's the entry point to start consuming hydrogen water if they've never consumed it before? Well, I guess it's pretty simple. One hydrogen tablet a day, start it in the morning, take it with food, take it without food, take it before exercise. how would you tell somebody who's compelled maybe after listening to this podcast to say I want to add this to my routine that's kind of my first thought first, what does the research say? what is your situation and circumstance? because hydrogen is not proven that's kind of anti-science also we don't prove anything in science we try to prove things our fault and if we can't prove their faults that it increases the probability that they're probably true.

1:24:26But we never really know if it's true. And so I guess first, I'm just saying, I don't want to misrepresent the emerging studies. There's like, yeah, 200 human studies, but they're kind of all over the place, from universities all over the world, not like just a focused look at this specific primary endpoint so we can make this specific claim or whatever, right? So there needs to be more research to really categorically say, yes, if you do hydrogen, you will have this benefit, this is what it is. Instead, I think that people should have an informed consent. They should understand, hey, there's an emerging area.

1:24:58The safety is very high. The research looks promising, especially animal research, but the number of clinical studies look good. And if you have the funds, the discretionary means to try, then by all means, you can try it. I believe the safety is high enough that you can do that, right? And so if that's you and you do want to try, then I guess if you're going to try the hydrogen tablets, for example, then yeah you actually only need one in fact most of the research just one tablet will provide you more hydrogen than the majority of all the clinical publications because most of them did not use hydrogen tablets but that's starting to change because the hydrogen tablets have been now used in clinical research a lot because they're convenient and you provide a very high dose and now there's looking at some of these studies that potentially dose dependent effect and if you also look at the translational effects.

1:25:51So animals, they drink a lot more water compared to us. I mean, like we'd have to be drinking like over a gallon of water a day, you know, and to drink the equivalent to what an animal would, a rodent. So they're getting a lot more hydrogen. And so maybe one of the reasons that they are more responsive to the benefits of hydrogen is they're also getting a higher dose. There's a lot of other metabolic factors as well, but there's some trending in some cases when the higher doses is beneficial, which is why a lot of researchers are choosing to use hydrogen tablets. And there are some studies that show that a high concentration is not more effective than a low concentration in that specific area.

1:26:31But there are other studies showing that a higher concentration is more effective in those specific areas. But there are no studies for hydrogen water. There are no studies where a higher concentration is less effective than a lower concentration. Now, that's not true for inhalation of hydrogen gas.

1:26:48Gary Brecka:So if you're going to do it, yeah, that's 2 % to 4%. So if you're going to do it, taking a tablet that's 12 parts per million, and when would you consume it? First thing in the morning? Yeah, first I would just consume it daily. We just think about what's the easiest thing, just consume it daily. And then if you want to be, okay, figure out some regimen, we don't have enough research to really say this is going to be the most effective. For example, you can take it fasted. there's IEDs if you take it faster well then maybe you don't have any noise in your blood or whatever and then hydrogen gas can directly cause the signaling and you can get those benefits take it before you exercise but you could also argue I take it before I exercise every time yes and that makes total sense is that when you take it?

1:27:34in general I feel like I do hydrogen water before I exercise and I do inhalation of hydrogen gas after post exercise but you can do, there's arguments both ways and we just need more clinical research to see if there's really any difference. So you're just saying, just take it. Just take it because it's not like caffeine. If you want the benefits of caffeine to help you exercise, you actually just take it before you exercise, right? That's not true with hydrogen. Hydrogen is going to provide a benefit that kind of stacks on top of itself over time. And because we start to change gene expression, we start to change the function of the mitochondria.

1:28:10So we start seeing changes over time and they become more and more. Consistency is the most important. And now if you're really thinking about something important to you, then yeah, take the hydrogen before you exercise. But for that matter, take the hydrogen after you exercise also. So you can safely take a number of these, say, tablets. There's no safety concern when it comes to hydrogen gas itself, just pure hydrogen. There's really no safety concern. They've been using hydrogen gas to prevent, say, decompression sickness since the 1940s at orders of magnitude higher than what you would ever talk about therapeutically.

1:28:44dissolving a gas in water and then drinking it. So there's not a concern there. You just start running up against how much magnesium can one tolerate, for example. So you can probably take it.

1:28:54Gary Brecka:Because there is a trace amount of elemental magnesium that remains after it ever passes. Yeah. Right. It's not a therapeutic dose of magnesium either, but it's. Well, not necessarily because most people, see most people are only getting around 300, 400 milligrams of magnesium. Most people are deficient in magnesium. So simply by taking one to two tablets a day, you're literally no longer being deficient. And that can literally move the needle, just not being deficient in magnesium. And I would suggest that the research indicates, at least my interpretation, that taking closer to around 700 milligrams of magnesium is probably better for you.

1:29:28So taking several tablets a day, yes, you get the benefits of hydrogen, but I'm just saying you also are getting some of that magnesium as well. And that can help move that needle a little bit more. because magnesium we know has a lot of benefits to it.

1:29:45Gary Brecka:Now, what is like really exciting you about the research in the hydrogen? Because as I've poked around the research, I've seen it in concussive injuries, comparing it to the standard protocol for concussive recovery and being magnitudes better than the standard protocol. I've seen it used to soak limbs immediately after injury compared to the RICE protocol, RICE, rest ice, compress, and elevate. There seems to be significant indications in cognitive studies, the Journal of Experimental Gerontology. There seems to be significant impact for delayed onset muscle soreness and maybe bunting the lactate threshold for athletic performance.

1:30:32Gary Brecka:um you know i i i certainly think that making it a part of your daily routine definitely not going to have any negative side effects and there's this whole host of selective antioxidant benefits that you're not getting from your regular you know um ingestion of antioxidants um i will say that again anecdotally i have seen the greatest uh impacts from people that are bathing in it um in terms of like immediate benefits like my you know sage my wife has an l5 s1 fusion and so when her back acts up it travels right up her spine and she literally just cannot sleep it locks up when i rub her back it's like as hard as a it's hard as a rock um but if she gets in a 25-minute hydrogen bath right before bed, she'll sleep seven hours.

1:31:28Gary Brecka:And I put Navy SEALs in there, I put Sean Ryan in there. He called me the next day and was like, dude, this is the first time I got eight hours sleep in 15 years. The first time I woke up in no pain in 15 years. And it, you know, maybe lasted 48 hours. I put arthritic patients in these tubs, bathed them in hydrogen 25, 35 minutes. No one's ever gotten out of there and said, I feel the same or feel worse, almost without exception related to inflammatory conditions, knees, hips, shoulders, rotator cuff, low back. There seems to be an immediate benefit for people and pain, inflammation, like range of motion.

1:32:08Gary Brecka:And I have seen this so many times and so consistently that I'm absolutely convinced. And so what are your thoughts on that? Well, that's exciting. I mean, it's interesting because - That's exciting. Super exciting. Well, it's interesting though, because what you're talking about is your experience. Yes. And I want to be cautious to say exactly that. Yeah. And these, I guess we could term it anecdotal evidence, which is not something we just throw away, but it's anecdotal, but it's still a form of evidence. By the way, eczema and psoriasis too. Yeah. In front of my eyes, I've seen it. And there are actually some case studies on those areas also, right?

1:32:48So there can be some mechanistic sense to some of these things. But bathing doesn't have as much research as say drinking hydrogen water or inhalation. So I have to be a little bit more cautious on what I can say, what we see clinically. Mechanistically, I could see how some of these examples make sense. You get in the water and immediately hydrogen gas, the smallest molecule, it can penetrate the skin and it can actually get into those areas. Almost like it's not there, right?

1:33:19Gary Brecka:I mean, it's transdermal. Yeah, it goes to transdermal. I mean, it's still, we're going to go into some of the Brownian diffusion aspects. No, please don't. I'm just kidding. But it can get to those areas. And, you know, we can see effects. Like in our research, we found that hydrogen influenced the mitochondria within as little as two minutes, right? So we can see effects immediately. And when you drink hydrogen water, you're influencing the microbiome and you see excelled hydrogen gas within just a couple of minutes also. So hydrogen gas is going to the body. But again, the concentration is probably not very high, if at all, in say, your knee or something after you drink hydrogen water.

1:34:01So the benefits to the knee come through other mechanisms, other second messengers, other things that are happening versus if you were to bathe directly there or if you were to inhale hydrogen gas. Now that hydrogen gas is getting fared into the blood and getting into those joints specifically. So those are different mechanisms and they can be supported by mechanisms actually. I mean, I've seen it so consistently. Yeah, which is why I think you can't necessarily, what's better, bathing or drinking or inhalation? Right. You know, really, if you can, you should do all of them. Right. I would say most of the research is on hydrogen water and inhalation.

1:34:39Right. And bathing is starting to emerge. And that's becoming maybe more popular. but mechanistically we understand how hydrogen gas works on the mitochondria level. It's effects on calcium signaling, for example. So some of these can start to make sense.

1:34:57Gary Brecka:Probably is why some of the exercise benefits. So let's talk about inhalation because hydrogen is amazingly effective at very low doses. I mean concentrations, 2 % to 4%. Yes, and we don't want to get confused because the concentrations in water is very different than inhalation. Right. Because we want to reach at a certain micromolar level, several micromolars in the bloodstream. When you drink hydrogen water, you only have, you know, let's say you're going to drink this, you're going to get around three to four milligrams of hydrogen gas dissolved in the water. You drink that, it's going to be diluted by your body.

1:35:37Right. By the time it gets into those areas in your portal vein and your liver, you're going to be around 5 to 30 micromolar concentration. When you inhale hydrogen gas, based on Henry's Law, between 1 to 4%, you also get around 5 to 30 micromolar concentration. And that's what we see in the research in the animal studies. So that Nature Medicine publication, again, that was 2 % hydrogen gas. Now, this is one of the most powerful and interesting areas of research I'm going to get to some research going on in Japan right now with hydrogen gas. That Nature Medicine publication was 2 % hydrogen gas.

1:36:20Then they looked at stroke, so an actual clinical study. That was an animal study of stroke. They used actual hemo studies 10 years later in 2017. They did a safety study and a comparison to see how effective hydrogen gas was. Again, about 2 % hydrogen gas. And in this study, they found that inhalation of hydrogen gas compared to standard treatment, a standard drug, hydrogen gas was more effective at improving the National Institutes of Radiance scores of the stroke and a number of other parameters to go back and look at the study. But it was essentially more effective in all those parameters.

1:36:56So again, this ischemic reperfusion injury, free radicals, oxidative damage, inflammation.

1:37:01Gary Brecka:And lungs are an excellent delivery mechanism directly into the blood too. Exactly, yeah. And that's important clarification too because hydrogen gas, unlike oxygen, does not bind onto the hemoglobin. It doesn't get carried through a specific protein. It just dissolves into the serum of the blood. And then as it's dissolved at that 5 to 20 micromolar concentration, it reaches the target organs, has its effect. When you stop inhalation or stop administration, then it goes back to baseline within an hour. So when you drink hydrogen water, all the hydrogen gas is gone after an hour. The benefits remain for like 24 hours or potentially longer if you were constantly doing hydrogen water.

1:37:39So same with inhalation. It's gone after an hour or so, but those benefits remain. So they also looked at in animal studies in post-cardiac arrest syndrome in animal studies, and they found that the 24 hours survival. In 24 hours in the control group, about 43 % survived. When you do the normal therapy, which is targeted temperature management, so basically cool the body down like a therapeutic hypothermia then you have 77 % survived.

1:38:09Gary Brecka:Wow. That's why that's a normal treatment. When you did hydrogen gas 92 % survival. Wow. When you combine the two 100 % survival at 24 hours. You're kidding. That's huge. Why isn't everybody talking about that? Well it was an animal study. It was an animal study. Okay but this was enough. That was enough to get the Japanese government to approve hydrogen as a class 2B medicine for the study of hydrogen in post-cardiac arrest syndrome patients in hospitals. When do you think that study will be? That's already been done. I'm going to tell you the results. Okay, good. See, that's exciting. We waited the whole podcast for this.

1:38:46Gary Brecka:We should talk about this minute one. Messing around with the free radical, you know, stage four of that, you know, electron transport. This is the meat. Yeah, but understanding those mechanisms helps us understand these observations, right? So the Japanese approved this so they could do a study. And it's not approval like now they're going to use it in the hospitals or whatever. It's just they can actually do a study because you have to make sure this is safe. You're talking about people who are coming in comatose, who are already on the verge of death, and then you're going to do some other radical therapy.

1:39:18You've got to get approval for that.

1:39:20Gary Brecka:Right. All right. So they gave this approval. There's a major study undertaking 15 different hospitals that were involved, but then COVID happened. Oh my gosh. So unfortunately the study got truncated. And so it wasn't - And they all died because they were vaccinated. Well, but they didn't go as long as they wanted to. But we do have some of those results. Wow. And basically the couple of the endpoints, so they use 2 % hydrogen gas, all right? Again, this was not with a nasal cannula, we're like, you know, so many milliliters of flow rate. This was like with a face mask, a tank of exact, precise concentration of hydrogen.

1:39:58Because remember, 2 % seem to be more effective than 4%. So you really need to control everything. And you can't have it be flammable. It has to be below 4 % or else you can't do the study. Okay, so in the study though, they looked at a couple of things, but I was going to give you two main results. The 90-day survival, because typically after post-cardiac arrest syndrome, you know, yeah, you're able to resuscitate the person, but then the survival is not very high because it has so much damage, they end up dying several days, weeks later. They looked at the 90-day survival. And in the hydrogen, no, in the control group, the control group, I think there were about 77 patients.

1:40:39It was going to be like 380 or something patients, but it got truncated. But there was like, in this study, there was a 61 % survival in the standard treatment group. and in the hydrogen group, it was an 85 % survival.

1:40:56Gary Brecka:Wow. So if you had 100 subjects, 61 % survived with Santa treatment, 85 % lived. It's like, what, 24, you know? Right. I mean, that's a pretty significant. Significant, yeah. This is people's lives. This is an actual study. Yeah. So these people are alive because of hydrogen gas. Wow. And then the primary endpoint was improvements in neurological scores that they were looking at. And in the standard treatment, it was a 39 % improved neurological scores. And in the hygiene treatment, it went up to 56%. So still a pretty big difference. Now, because the sample size is a little bit smaller, this statistically did not reach statistical significance, but still 39 % improvement versus 56 % improvement was a pretty big...

1:41:50That's a massive improvement. Especially when you consider that the survival increase from 61 % to 85 % was more. So more people who are maybe on the verge who would have died anyways, they also survived. And yet you still saw an increase in the neurological improvements. Wow. So this really has got a lot of people's attention. And so there's a lot more research that's being going on in this area. And then these are comatose patients. I mean, they're inhaling hydrogen gas, right?

1:42:23Gary Brecka:Wow. Now, more research, of course, is going on in this area, but it's trending because I believe that, you know, there's a lot of corruption and problems with like the FDA and like all this kind of stuff and everything. But that corruption is everywhere. It's not just with these organizations, right? But I do believe, and maybe I'm just too optimistic, but I believe that if we had true, good, concrete evidence with clear primary endpoints, then hygiene therapy could be a standard care. But in order to get that approval, we have to have that evidence. And how do we have that evidence unless we do the clinical studies?

1:43:05Why are the clinical studies going to happen unless we educate people about it? And that's really what I'm here today for. I want to educate people about what's going on, allow people to have their informed consent. We can raise the awareness about this. This is going to allow for more research to happen. And if hygiene really can radically revolutionize healthcare, wouldn't you want to know? Wouldn't you want to use it? Again, something so safe, so simple, that's affordable to anybody. And that's precisely why we're working on this education. And that's ultimately why, as you know, I helped to invent that Inhal H2 unit.

1:43:44The entire purpose is not because we know this is going to cure every disease known to man. It's because we want to do clinical research. I care about you working on educating everyone about it. Well, we want to do clinical research. And now we can do that without tanks of this gas and everything. Explosive. And we can monitor the concentration, make sure it's therapeutic. and so that's the whole idea behind inhaleH2 is initially it was for clinical research and then with Alex, people actually want the unit. There are people right now today who would want to use this. 100%.

1:44:18Gary Brecka:Everyone listening to this podcast probably wants to. Yeah, because you get hydrogen water, which we see those benefits and we have inhalation. So it's a really nice combination but I believe people should understand the limitations and the preliminary evidence. That's how you overcome skepticism because being skeptic is so important. That's how you prevent falling victim to a scam. Being skeptic means that you are open-minded, not so open that your brain falls out. I think that's Oberg's dictum or something. But that means specifically that you do not reject the information without first evaluating the evidence.

1:44:56And you don't accept the information without first evaluating the evidence. You do both. yeah right and so i want people to know what the evidence is and we're not uh claiming that it's going to cure the disease we have all this evidence that's proven to do this that's the antithesis of science no we're just saying hey this is what's shown in the animal studies the emerging clinical studies if it makes sense to you if you have the desire and the monetary means well then you can give it a try and now you have options available yeah you know when i was doing my research um and doing a phd i was i remember seeing some of the results and you were like to Damn, I wish I had one of these.

1:45:31No, I totally didn't. I want to get into this study. We had to take a medical grade hydrogen gas with exact percentage. And I'm thinking, why not?

1:45:42Gary Brecka:Yeah. I inhaled that stuff, you know, and I want this. The same thing with making hydrogen water. I would make hydrogen water in the laboratory. And so I read these papers. I look at the research and I'm like, we know this is safe. Maybe it can help me. And so I want to try it. And so I would use it. So now they're like these tablets or this NLH2 machine. People can use it and they can get clinically relevant doses that we use in the clinical studies if you want to do that, right? But I would not say that evidence is so compelling that you should do hydrogen therapy instead of, say, go to the gym.

1:46:19Like if you have the choice to go to the gym or just drink hydrogen water, dude, come on. Go to the gym, right? But if you're not able to exercise at all, for whatever reason, you're so busy, and you have the discretionary funds, why not try hydrogen water, which acts as an exercise memetic according to some of these animal and early studies, right? Or do both.

1:46:43Gary Brecka:I don't have a single client that I don't recommend taking hydrogen water. And that's why I'm so glad that you're here to sort of return, you know, the noise to the balance of, you know, what are the claims that, you know, we could make based on the research today. And then where does the research look like it's heading? And I think the nicest thing is that the research indicates that it's extraordinarily safe and offers a plethora of benefits, even though there's additional research. It doesn't impair performance. Yeah. It doesn't make things worse. The emerging evidence in animal studies is very promising.

1:47:21The emerging evidence in clinical studies is very promising. It makes mechanistic sense. But of course, I would not say that hygiene therapy is more important or there's more evidence than getting your sleep right or exercising or maybe sauna. Sleep, whole food, diet, and exercise. Those are the foundations. But if you can do both of them, if you can do all of them, and you have the discretionary means to do so, I believe that people should have should be able to make their own choice to do that and luckily there are good products on the market now where people can make that informed choice right I agree

1:47:55Gary Brecka:Tyler this has been amazing dude you know I know it was very granular for a lot of folks for my super nerds which is probably half of my audience they're going to love this for the Andrew Hubermans out there that really want to know the mechanism they're going to really enjoy this I've been a huge proponent of your research. I've been a huge proponent of hydrogen water. My family drinks it. My parents drink it. After that experimental gerontology clinical study, I put both of my parents on it. They've been on it the entire time since I read that study. I think that was published in 2018, November 2018.

1:48:34Gary Brecka:But I'm really deeply appreciative of this because even though we went very granular on the science, I think people understand now why this is such a unique molecule. Maybe they understand what the difference is between an antioxidant and a selective antioxidant, which makes hydrogen so unique. It's almost like this miracle molecule with how it reacts in the body. So if my audience wants to find you, where can they find out more about you? Are you on Instagram? Yeah, you can find me on Tyler W. LeBaron on all channels. so Tyler W. LeBaron I'll link your research to in the show notes I'll link your hydrogen inhalation machine in the show notes but I always wind down all my podcasts by asking my guests the same question so you probably know that this question is coming oh no I'm worried everybody gets the same question there's no right or wrong answer to it but before you do I want to end with this hydrogen think of it as a redox adaptogen that benefits the mitochondria I want to change the narrative that hydrogen is not just this antioxidant.

1:49:44There's a buttload of antioxidants out there. Think of it as a redox adaptogen that benefits the mitochondria. Yeah, that's a great way to frame it.

1:49:53Gary Brecka:So what does it mean to you to be an ultimate human? That's a great question. I think a lot of that comes from within something divine aspect about that. To be the ultimate human means you are reaching your full potential. It has nothing to do with being better than anybody. It's just, are you making changes? Are you being better today than you were yesterday? And that is an all aspects of your life. How do you treat your neighbors? How do you, are you making the world a better place? Are you improving this gift that we have of our body? Are we, you know, we say if knowledge is our power, then learning is our superpower.

1:50:45Are we learning? Are we doing these things? I think to be the ultimate human, we have a balanced life where we're trying to become the ultimate to reach that potential and all those things. And it's not necessarily that we reach our potential, but we're striving for that. We're just making these small changes, just like hydrogen, a small molecule, but it's constantly there, just slowly getting better and better and better. It's not trying to brag or anything. It's just always there. And that's really kind of what we should do. I think I'm going to sum it up. It's just being incrementally better in all the aspects that we can on a daily basis.

1:51:24Gary Brecka:Man, phenomenal. We're going to head over into my VIP group now. the VIPs are the only ones I tell who's coming on the podcast before they come on the podcast. And so I let them know you were coming. They were super excited. There's a whole host of questions for you. If you guys are interested in becoming an Ultimate Human VIP, just go over to theultimatehuman.com forward slash VIP. Would love to see you in there. Private podcasts, one-on-ones with me, Ask Gary Anything. There is a 10-month course on becoming the ultimate human version of yourself. It's entirely free. It's all inside of the VIP community.

1:51:56Gary Brecka:So I hope you enjoyed this podcast we're going to have Tyler back again for sure um as you continue your journey on hydrogen I want to keep people um up to date on your research and and the emerging research and some of the new findings would love to see if this study in Japan ever gets completed that one is completed yeah I mean oh the one before COVID yeah no it's done yeah published in e-clinical medicine so we will link that one yeah and until next time guys that's just science