Welcome to Pushing The Limits, the show that helps you reach your full potential with your host, Lisa Tamati, brought to you by lisatamati.com. 

Lisa Tamati: Lisa Tamati your host here at Pushing The Limits. Super excited that you're here with me again today. Thanks for tuning in. I do love and appreciate your loyalty. And I would love to hear from you. If you've got something to say about the podcast, you’ve got some comments and questions about some of the topics that we have raised, please do reach out to us. We love hearing from our listeners. And if you can give us a rating and review if you're enjoying the content, that really really helps the show. 

We've also got our Patron VIP premium membership now open. If you love our show, if you love what we do, what we stand for our values, our principles, the work that we put into this podcast, which we've been doing now for five and a half years, without any money or any—just for the love of it and for the passion of it. If you want to help support us and keep us going and want to get a whole lot of premium membership benefits, then head over to patron.lisatamati.com. I would love you to join our VIP tribe. That's patron.lisatamati.com. For the price of about a coffee a day or a little bit more, you can be involved. There's two tiers in there, with different levels of premium member benefits. And we would love you to join us there. So if you can please do. 

Now today's superstar is Dr Elizabeth Yurth. And if you follow the podcast, you might have remember that name because she was on just a few weeks ago. And she is now one of my favorite teachers. I have been learning from her at the Bone Longevity Institute of Human Optimization Academy. And she is a brilliant teacher, and a brilliant orthopaedic surgeon and longevity expert. And she offers the world's most advanced research-based health care. And it's all customised to you. And the information that we're going to share with you today—today's topic if you like, is all around mitochondrial health. Now we do deviate a little bit because as we do in these conversations, we go off on a few tangents. But it is really all about understanding what your mitochondria are, why you need to know about it, how to keep them healthy, because these little bacteria if you like, and these little powerhouses of our cells are absolutely crucial to health and longevity. 

And Dr Yurth says that the mitochondria, she thinks, are at the very basis of all diseases. So when these little guys go awry, that's when diseases come into play. And everything from cancer, chronic fatigue, to all of the diseases right across the spectrum can be affected by mitochondrial health. So we do a bit of a deep dive into that today. So I hope you enjoy this session with Dr Elizabeth Yurth. She's a lady who walks the talk. She's an incredibly amazing person, athlete, orthopaedic surgeon. She loves this. She breathes it the way she loves, as you know, in complete alignment with what she also teaches, so make sure you check out all her links in the show notes. Right. 

Now before we go over to the show. Just want to also let you know about our NMN, our supplements. They’re longevity and anti-ageing supplement. We are into longevity. We are into health span. We are into increasing our lifespan and healthspan. So if you want to get into having—to boosting your NAD levels in your body, we've recently done a couple of episodes with Dr Elena Seranova on this topic, then head over to nmnbio.nz. And grab your NMN supplements over there to get your longevity regime underway. 

And in today's podcast, we talk a little bit about this. We talk also about spermidine, which we've also mentioned in other podcasts. There are some amazing compounds out there that are going to help us stay healthier and longer. And there's a lot of techniques and things that we can actually engage in. We don't have to be passive bystanders to our ageing, we can do things about it, we can slow it down, and even reverse it in some places. So I hope you enjoy this episode. So do check out my Longevity Supplement over at nmnbio.nz. And enjoy today's show with Dr Elizabeth Yurth. 

Lisa: Well, hi everyone and welcome back to Pushing The Limits. Super excited to have another wonderful guest that we've actually had on before and back by popular demand. That was a very, very popular episode. So I have Dr Elizabeth Yurth with me. Hi, Dr Yurth, how are you doing?

Dr Elizabeth Yurth: Lisa, thank you for having me again. I love being with you. 

Lisa: Oh, it's just that, our last episode was just so full of information that I've had it on repeat going, for me, because there's so much in there and so many people have written and have been asking questions. So I want to get started by saying if after this interview, you want to talk to Dr Yurth and one of her team at the Border Longevity Institute, you can do that even when you're in New Zealand or Australia, you can do teleconsults. And yeah, so if you are facing some difficult health problem, and you really want some help, make sure you do that. And we'll have all the links in the show notes and so on. And before we get underway, there is a Bold Longevity of—what is it called, optimisation? 

Dr Yurth: Human Optimization Academy, right? Yeah, from the Border Longevity site, or just go to bliacademy.com and sign up. But you guys have definitely signed up for that we actually are trying to really put together tons—and all the information you guys need to try. And you'll have one place where you can go get all of these things that we talked about, and all the things that Lisa talks about, and really be able to learn about them. Because as we know, doctors don't really learn this stuff very well. So you guys have to do it yourself. And so we're trying to give you a place to do. It's coming from a very experienced...

Lisa: Yeah, and if you want on the latest, so make sure bli.academy.com. And I'll put that in the show notes too guys, so you can find it. 

Now today's subject is mitochondria, one of Dr Yurth’s favorite subjects. Okay, for starters, what is a mitochondria?

Dr Yurth: What's really so cool about mitochondria, right, is they're actually they were actually their own little bacteria. So they invaded us back when we were threatened to kind of moving from an anaerobic to an aerobic environment. So when we went from sort of anaerobic organisms to actually living in air, we couldn't do it. And so these little bacteria got into the cells, and they formed a symbiotic relationship, so that we could survive outside of water and air. And so they were responsible for us being able to move out of the ocean and into an air or an aerobic environment. Well, they're actually their own little organism. Right? I mean, that that is weird, right? That we have this essential part of our cell. Now our essential part of survival is actually its own organism. 

And it was a one celled organism, it gone to formed a symbiotic relationship, it allowed the bacteria to survive living inside ourselves. And if we allowed ourselves to survive, so amazing. And that's why they're so unique is that they actually contain a whole genome that is separate from your nuclear genome, right? So they have a mitochondrial genome that's completely different. And it's only inherited from your mother. So that mitochondrial genome is not inherited from your father at all. It's probably one of the reasons your mother's health at the time, because even though the mitochondria has its own genome, that genome is impacted by things you do. So if I have a baby, and I'm super unhealthy, I've altered that mitochondrial genome. And then I've transferred that mitochondrial genome only from me—the dad was great and doing everything right—to my children. So that's one of the...

Lisa: So that’s the epigenetic…. Because I'm just about to go through IVF, as I said before, very interesting for me. So even though I'm going to have an egg donor...

Dr Yurth: You wanna make sure she’s healthy, right? 

Lisa: Yeah, she's just—she is, and we've got her on everything. Her DNA is coming into the egg, but actually, my mitochondria will be a part of this baby, if we have one.

Dr Yurth: So you will alter—so basically, she's, you're going to be, the baby will have her mitochondrial DNA. But because you will be growing this baby, you will be altering that mitochondrial DNA by epigenetic influences that you're doing, right. So now you're going to be changing some of that DNA structure, or the genome of that mitochondria by things you're doing. The mitochondria, so even though it's coming in, and again, you want her to come in with this great mitochondrial DNA in the first place. Right? So we want this good genome in the first place, which is why you do want her to be healthy and fit and all those things. And younger.

But then you know all about the epigenetics, and so you're going to be potentially altering some of that, too. So that's one of the really amazing things. Now, what we used to think is, all the mitochondria did was do oxidative phosphorylation, and make energy, make ATP. And that's what they did. They were our energy powerhouse. That's all we ever learned, right? High school was like, ‘Oh, the powerhouse of the cell’. 

So we now know, they do a whole lot more than that. So they're not just responsible for aerobic metabolism, and making ATP. So they're not just energy production. And in fact, there's the communication back and forth between the nucleus of ourselves and these mitochondrial DNA that's imperative to health. Well, I'm gonna make the case that actually every single disease, from cancer, to cardiovascular disease, everything related to ageing, osteoporosis, everything comes down to mitochondrial dysfunction.

Lisa: Wow. So this is pretty–

Dr Yurth: It's imperative and, and you're gonna start reading more about this, is that the key to fixing our health is going to be fixing the mitochondria. And we've already figured out like, you know, you I know you're big into NAD that, improving NAD and I know you have a product that does that. And that is— that's critical, right? To mitochondrial health. We know that's critical to mitochondrial health. But there's more to that story. And the big thing is that is that piece of communication, that mitochondria sends messages out to the nucleus, and the nucleus sends messages back to the mitochondria.

Lisa: Okay, so what are these messages that they’re sending backwards and forwards? And why does this have to do with the function of the mitochondria itself?

Dr Yurth: Well, there's, as the body goes through the oxidative phosphorylation pathway, that Krebs cycle, that cycle that makes energy, right. And we know that we create these free radicals. And that's been one of the big theories of ageing is this free radical theory of ageing, that mitochondria produce all these free radicals, as free radicals overwhelm the body, they damage cells, and we get damaged tore into our DNA? Hmm.

Lisa: So we all thought that antioxidants would be the answer, recommended…

Dr Yurth: Right. We just take a bunch of antioxidants into the mix, and you're going to be great, because now, all those free radicals, you're not going to have any damage. The problem is that we know that there's been this—the mitochondria has a very, has a way to handle this oxidative stress. So there's a few things that happen. Obviously, stress is really critical to the mitochondria’s health. So as it creates these free radicals, and and it's rust by things, it actually produces what are called mitochondrial peptides. So it has its own genome, right, that's now been activated by this stress. And it creates these—its own peptides that no other structure in your body can produce. So it's producing these little chains of amino acids. 

And there's quite a few being developed now or that or that we were learning about, but the sort of the three main ones that we kind of have a pretty good knowledge about right now are something called MOTS-c. There's another one called humanin, and another one called SS-31. And those are what—the SS-31s, and a group of them are called small humanin-like peptides or SHLPs. Those peptides, so once the mitochondria is stressed, it encodes this DNA to say, ‘Oh, you need to go out there and tell the nucleus to do some good stuff’. 

So these mitochondrial peptides now go outside of the mitochondria, and they tell the nucleus to to heal things and get stronger and do better. And then that sends messages back to the mitochondria. So that stress, that oxidative stress actually, it's just like, you know, what doesn't kill you makes you stronger.

Lisa: And actually it’s a fact on this.

Dr Yurth: It’s really a fact that mitochondria health, that these medical peptides are imperative to health. In fact, humanin which were first developed actually was looking like a cure for Alzheimer's. And it may be really—well, it may be actually very, very baffling here, but very, very helpful in dementias and a lot of other diseases. We know that higher levels of humanin, people who live to be a hundred and above have much higher levels of humanin, so we know that these mitochondrial peptides, the higher they are, the healthier you are. No mitochondrial stress. If I just impound my body with antioxidants all the time, then I'm actually probably doing some damage. So cancer, right, so where—now again there, I can also overwhelm, right? 

There's also another response, the mitochondria have, it's called the UPR, unfolded protein response. So as the mitochondria are stressed, and these damaged proteins that are produced when we're under stress, right, we get damaged or proteins, that's where we're kind of linking that to Parkinson's and Alzheimer's and some of the plaques that form...

Lisa: The tau proteins and things. 

Dr Yurth: Yeah, yep. When the mitochondria is stressed, it actually sends messages out to the nucleus to activate what's called the UPR, the unfolded protein response. A little protein response actually takes these bad proteins and it strings them back out and makes them normal. Or it says, ‘These guys are so damaged. Let's just get rid of that mitochondria and initiate basically autophagy or mitophagy, eliminates the bad mitochondria that are too damaged. There's too many damaged proteins. We've overwhelmed the unfolded protein response’. Now it initiates this response to kill off the bad mitochondria. 

See, if I'm just now taking a ton of antioxidants. Maybe I've blocked this response to get rid of all these bad proteins. Right. And I'm actually inducing more of these bad, abnormal proteins that are going to cause damage. 

Lisa: I've talked on a couple of episodes with Dr Elena Seranova about—who is a molecular biologist on autophagy. And I think we talked about it too last time. So that's getting rid of the damaged proteins in the cells or in the mitochondria itself, getting rid of it. And we talked about fasting last time and how critical fasting is for autophagy in getting rid of these bad proteins and clearing things out. 

So if we—so you're saying we can overwhelm this protein, and what do you call unfolding... 

Dr Yurth: Unfolded protein response, UPR. 

Lisa: Yeah, we can overwhelm it with too many antioxidants and actually stop it...

Dr Yurth: Stop the UPR from being activated. So now we don't actually kill it, we don't actually—either fix the damaged protein or get rid of the cells that are too damaged.

Lisa: Wow, okay. And so in this is this two-way communication between the mitochondria and the DNA, this is the nucleus of the cell. This is all within the—if we picture a big, nice fat round cell, and inside, you've got thousands of mitochondria per cell. And you've got the actual nucleus, which has that nice double helix, you see in the graph– 

Dr Yurth: Where all the DNA is.

Lisa: –where the DNA, your code for life is– 

Dr Yurth: Right. 

Lisa: And these are talking backwards and forwards to each other to keep the health of the cell good. And then when we do autophagy, or mitophagy, we're getting rid of the damaged parts of the proteins that have been damaged through—is this through, so the damage that occurs in the cells is happening because of DNA breaks? And what are toxins and things like that, right? 

Dr Yurth: Exactly, these reactive oxygen species that you know, they're starting to damage the DNA too much inside the mitochondria and creating abnormal proteins. Right? So now we've created these dysfunctional proteins that are going to do damage, so the body tries to get rid of them. And it's not, I'm not gonna say there's no place for antioxidants, right? But what you have to be careful of, is sort of cycling through phases where you're off of your antioxidants, and maybe inducing more autophagy, right. So we now want a little more oxidative stress to induce this healing response to give the cell some stress, and then maybe going on antioxidants for a little while to make sure that we don't ever have too many.

Lisa: Yeah, if you've gotten a lot of antioxidants, or sorry, or oxidative stress, because maybe you're exercising a heck of a lot or you've had an infection, or you've got something other high stress... 

Dr Yurth: You eat like crap, or you're fat or… Then you might need extra antioxidants. And just to support the baseline of your functional health. But even those people, right, need them off and on, they should not be constantly. They should do phases, right? They should cycle it. I'm just a big advocate with diet, with exercise with everything, everything's done so quickly. Because we want to go through phases all the time, where we're getting rid of bad stuff, and then regrowing and getting rid of bad stuff and regrowing. Right?

It’s just like cleaning your house. You got to get rid of all the crap, but then you're gonna…

Lisa: Bring the new groceries.

Dr Yurth: Yeah, right. It's get cluttered again. And then you got to go clean it all out again, and things get cluttered again. Yeah, I mean, that's the world's clutter wouldn't happen, but it does, right. Even the most pristine non hoarder person, there's still clutter that happens, and you still have to do your spring clean outs.

And that's—so I like to think about the body in the same way, you know, going into the spring clean outs where you go through a big autophagy phase where you're fasting, we're using hydro spermidine, where you're using things that will help to really clear out all the bad cells, all these damage, mitochondria that are producing too many reactive oxygen species, right? And then going through growth phases, where where I'm now maybe I'm inducing a little bit more toxic stress, I'm exercising harder, I'm lifting more weights, I'm running more, right, I'm inducing more oxidative stress. Maybe I'm eating more calories during that time. Now there's more oxidative stress cells a little bit stressed that actually initiate some growth and some healing. Right. And then I can do the same thing over and over again.

But there's really interesting new research leads when you kind of look at ‘Okay, well, how does this all make sense’? So it's probably going to come down more to this. This is what's called the MPTP or mitochondrial permeability transition pore. And what they've now found is that that's probably where we need to focus is this little pore is letting stuff in back and forth through the mitochondria. So the right amount of things get through. So we know this little pore opens and closes. As we're in worse health, or older, it stays open longer, allowing more bad things to go In and out. So it's designed to open periodically, closed periodically. So for brief periods. 

So what a lot of focus now is on anti-ageing. And mitochondrial health is focusing a little bit on this mitochondrial transition pore. In fact, there's a really cool study just came out where they're actually taking out these mitochondria and actually changing the pore structure for treating cancer. So they can actually make the pores in these cancer cells more permeable, so they can get drugs with a little nanobot that's poking holes in the mitochondria. 

But on our home base, is what we really would rather do is keep these little mitochondrial transition pores closed most of the time, let them open periodically. So there's some interesting things that do that, melatonin does that? Oh, so higher dose melatonin seems to work primarily on this pore to actually regulate keeping it closed more often. So it’s spermidine, that's one way spermidine induces cellular or mitochondrial biogenesis is by restoring this pore structure.

Lisa: And we're big into augmenting spermidine. I've just got my first shipment, I'm working on getting that down here guys. 

Dr Yurth: Spermidine is kind of amazing. Because it really is so good for mitophagy, getting rid of bad mitochondria, but also mitochondrial biogenesis probably because it does focus a little bit more on this pore. Making more mitochondria, right. Right, make more mitochondria, we need more mitochondria. 

The other thing interesting, I don't know how many of—how you or your listeners have looked at things like minocycline, right? Antibiotic, we always think antibiotics are bad, right? Yeah. Well, interestingly, minocycline and doxycycline. And minocycline is a little bit better, probably actually has a very nice anti-ageing effect, used periodically, to actually close off these pores, and let the cell kind of develop and grow more than mitochondria grow more. So minocycline has a really distinct effect on the mitochondrial transition pore as well, for this permeability pore. So there are a few simple things that you can use, and I like. 

Lisa: And it doesn't want your good microbes and stuff when you take them.

Dr Yurth: You know, definitely antibiotics have the downside of changing the gut microbiome. And we know that there's downsides to that, which is why you're not going to stem minocycline all the time. But like anything, it appears to have some very significant benefits in our cell health. So by doing that, maybe twice a year, doing like a 10-day course of minocycline, you can actually restore cell health. Now, after that, do you have to really work on gut health? Probably depends on how bad your gut is. So if my gut is super healthy, it's probably gonna regenerate, divide, right? Otherwise, it would, I have a lot and I know you're really interested in some gut microbiome stuff. Because you're gonna be a really—you're gonna see a really big connection coming up here soon between the gut microbiome and mitochondria even. But we know the gut microbiome is most affected by butyrate. 

So using tributyrate, which is sort of pre-butyrate that can turn to be right in your intestine. So if I had somebody on an antibiotic, do I throw—I'm just gonna throw probiotics into the mix? Well, no, because the probiotics aren't gonna survive. So what you have to do is first throw butyrate into the mix. Remember what the good bacteria in our gut do that we eat fiber? The anaerobic bacteria. Turn that fiber into butyrate. Butyrate has all these far reaching effects. Number one, it's imperative for the colonocytes, the colon cells to be healthy, that's what they—that's what they use for energy is butyrate. So they're different from your other cells, they use butyrate for energy. So when they use butyrate, for energy, I have these nice healthy colonocytes, they create a nice anaerobic environment where my anaerobes can thrive. And they can make more butyrate. And you have this nice cycle.

But butyrate has some really interesting effects. There was a great study for your distance runners using butyrate to increase performance. Because higher levels of gut butyrate also seemed to help the cell, the mitochondria, and actually produce you actually, were able to use the butyrate for fatty acid oxidation and actually improve aerobic metabolism by having higher levels of butyrate. 

Lisa: Was it like yeah, the athletes with keto. Yeah, because butyrate is like, isn't butter got butyrate in it? Or am I? Butyrate, butter. 

Dr Yurth: Oh, butter. So butter does have butyrate in it, yes. So you can even increase butyrate by eating a whole lot of butter. You'd be—so your medium chain triglycerides, the short chain fatty acids do have butyric acid in them. The problem with when you eat butyric acid, when you eat butyrate, it doesn't really reach this lower intestine very well. Okay, and so even though it has some benefits, probably some other places, you really have to get the gut bacteria. And so the only way to really get butyrate to the lower intestine is either to take a pre-butyrate form, which is I like tributyrin, one has research behind it, or to use it rectally. So that's the other thing you can do is use it rectally. 

Lisa: Okay, then that gets direct into the colon and then can get the right to the cells there. 

Dr Yurth: Yeah, and this actually has a genetic—do you remember your PGC alpha gene? So when you get hired to get butyrate, you actually upregulate PGC alpha. And that's one of the things that improves aerobic endurance in your long distance athletes. You can actually—they did a study with butyrate on improving endurance in sort of your distance runners, your higher level endurance athletes, and besides, it's significant improvements. Also in race horses. Same thing. 

So butyrate does affect mitochondria in other places, including skeletal muscle, and around that. So there is this big connection that we're just learning about between the gut microbiome and mitochondria. So if I'm going to put somebody into minocycline. I'm going to also make sure I have them on tributyrate so I'm keeping that nice anaerobic metabolism going. I'm making sure I'm getting butyrate to myself. Now I've repaired the mitochondria. I've given it another source to work better. And I'm going to have overall better endurance, better health, better aerobic metabolism. Better Vo2max.

Lisa: Yeah, wow, that's just crazy. So butyrate—but if we just taking butyric acid or in through butter or that type of thing. Brother just arrived in the background. It’s all good. Podcast life. At least the cat’s not running from down as well. 

So butyric acid, when I take it in the form of say medium chain triglycerides or butter and stuff, it's not going to help my colonocytes and my colon, but I still get through to the mitochondria and help.

Dr Yurth: Yeah. I mean, there's significant benefits to it, but you really want to replenish the butyrate in the lower intestine, where you really need that for overall health. You really have to either do it rectally, or take it as a pro butyrate or a pre-butyrate form or tributyrin–

Lisa: Tributyrin. I'll put that in the links. 

Dr Yurth: You know what is interesting, my patients who have the worst, now are the sickest, like I take care tributyrate. I have no problems with it. I'm fine. I feel good and most people. But if you're sick or not well or have a bad gut and you take it, you'll feel pretty miserable. Because you actually can't turn it into butyrate very well and it actually causes a lot of GI distress. So some of those really sick people the only way to replenish butyrate first is to do a rectal suppository. So you can get rectal suppositories of butyrate right. You do like a high dose, like two grams of a rectal suppository, butyrate, replenish the butyrate then you throw like a spore probiotic or probiotic and now I've created this nice anaerobic environment I've replaced the good bacteria. Now actually they do fine as a maintenance with the tributyrate now that I've restored the gut health.

For people who are not well, and I'll tell you, if any of you patients or your people, you talk to your clients, you talk to them use him take tributyrin, and they get they're like, ‘Oh, I'm nauseous, I can't take it’, or ‘Gives me diarrhea’, but it's because they have a bad gut and you've got to work, you know, right? Yeah. So tells you, right, that you need to replenish the butyrate. And again, the only way to do is rectally.

Lisa: Can you buy that as a consumer without a doctor who's until….

Dr Yurth: But there is a company and I don't know that, here in the US that's called MitoZen. That does make a pro-butyrate, it's a suppository. It's a two-week course, you have a high dose butyrate and it's actually pretty cool as a spore biotic mixed in. So I use that product a lot. It's on the pricey side like all this stuff. But I really find like a two week course of it. People do pretty well. All you do is two weeks of it, and then you can get them into the oral much less expensive form. The rectal butyrate smells bad. One of my patients, like ‘All my dogs are following me everywhere’. Other people—when you're doing I don't think other people can smell it on you but you can kinda smell it when you do it. It’s kind of like urine. Some people don't like the smell of, I don't mind the smell of that, but some people say they don't like the smell of that either.

Lisa: Okay, men and tributyrate, so if he’s not really sick, so if they’re really sick. So if you've got something like Crohn's disease, or IBS, or something–

Dr Yurth: Those people you wanna do the rectal, and they do amazing. I will tell you, they do amazing. There's a big stage just coming out with Crohn's being a mitochondrial disorder, too. It's got mitochondrial disorder, but IBS, your SIBO patients, you put them on the rectal butyrate, two weeks so that they do absolutely amazing. Honestly, it's incredible how well they do in a lot of illnesses. I mean, it's been our go to for a whole lot of different disorders. And it's amazing how well it works. As you're learning the gut is everything. And now we're learning it may even be imperative to the mitochondria.

Lisa: So how does it connect with mitochondria? So that piece here I've sort of like, haven't quite got in my head. How does—like you said, mitochondria are the basis of health, because they are the ones that are producing the energy for the cell, talking to the nucleus, they're causing this cascade of different events in the cell. They're actually producing ATP, which is our energy. So if you look at things like say, as you get older, your EGFR goes down, your function of your kidneys, in other words, starts to deteriorate. And this is, as an ultra endurance athlete, we smash the crap out of my kidneys with rhabdomyolysis a hundred times. I've had real battles getting my EGFR back up and managed it to quite a good degree, but it's still a problem. And as we get older, we sort of lose about 1% a year they say, of kidney function. 

So then it’s just another example of it's actually the mitochondria that in this case, and the kidney cells that are not able to do their energy production to do what the kidney cells should be doing. So how can we reverse that train and get our kidneys working in this case, or our brain or in another case, or heart cells? All of these areas are affected by the mitochondrial function. And how does that link connect to the gut situation?

Dr Yurth: So it connects to the butyrate because what butyrate does, at the mitochondrial level, is increases PGC-1 alpha and AMPK. And so you're, you're inducing on a genetic basis, a better oxidative capacity, right? So you're restoring the oxidative capacity to the cell, the mitochondria healthier. And so it's really working—the butyrate and searching fatty acids are really working on a genetic level, probably primarily at PGC-1alpha, I think we'll probably find more and more because this is very new. But it looks like that PGC-1 alpha is where it's happening is a very distinct effect on mitochondria. And then the AMPK through the ACC pathway. 

So basically, I think, if you think about it, probably from your training and everything, think about it as an epigenetic influence changing genetic output, right. So that's probably where the short term fatty acids are working in terms of mitochondrial health, I think there's going to be more to that story. You're right, kidney disease brain to these, everything comes down to we have to have mitochondrial health. So exactly what you said, first, have a healthy gut, let's replace the butyrate. Because we know that that's important for those pathways, then, what we have to do is go through phases where we really induce mitophagy. That's where you're fasting and your spermidine comes in, right. So we've got to basically induce, get rid of all the bad mitochondria. So that's gonna induce mitophagy right. So get rid of all the bad stuff. 

And then we want to do more of a build up phase. So what I'll do is all patients go through different courses, 6-12 weeks of really kind of more real time food restrictions, and using spermidine at a higher dose, and I'll get them sort of clean slate right. Now I want to regrow and that's where I want to actually regrow in. So I'm gonna have them now, get a little bit less out of eat a little bit more a little less calorie deficit, I want to create a little bit of oxidative stress because now I'm going to induce those humanin-like peptides, those mitochondrial peptides, my MOTS-c, SS-31, the small humanin-like peptides, humanin itself. So we know that those are so imperative for ageing, and that when those peptides are released, they induce your nucleus to have a healthier genome. So now I'm going to have everything else be healthier, because it's going to send messages back to the mitochondria, mitochondria is going to be healthy, but then that's gonna get overwhelmed after a while. So then we go back into our, you know. 

So when you think of things that way, always that sort of breakdown-cleanup, breakdown-cleanup, kind of an easier way to live right? Don't get bored. Always live in this super restricted capacity.

Lisa: Especially with calorie restriction and things.

Dr Yurth: Yeah, like caloric restriction and right eating very low calories. Yeah. 

Lisa: It makes you miserable too. 

Dr Yurth: That’s right. And so when you can tell—when you tell people listen, I want you to do this for 12 weeks, and then we're gonna let you kind of, you know, have a little me, I'm not gonna tell them go eat cake, but we're gonna be able to, you know, do a little bit more and go through growth phases. And people feel better, and they look better and they have more muscle mass, if you're always in that AMPK state right, that break down, but not really break down state but that more longevity stat, more catabolic state more, yeah. Which is good for longevity, right? But when you look at those people, they always look so healthy. I'll look at someone's people. And you're like, I mean, sometimes they don't have much muscle mass, their hair is thinner. So we do want to go through these phases where we allow the body to kind of grow a little bit, right, especially if you want some muscle, we know that muscle is imperative to health. 

And then I think we're sort of in the long term now they've got the mitochondria in this good homeostatic balance state where I've gotten it, but how do I keep that reactive oxygen species as low as possible? That's going to be where you look at them. That mitochondrial transitional pore, where, how do I keep that balance? And I think that's where maybe a lower dose spermidine every day, like one or two tablets every day of spermidine but I love melatonin for that purpose. 

Lisa: I wanted to come back to melatonin. So I understood like melatonin—I was a little bit hesitant to take melatonin because it can change or can fix your circadian rhythms and so on. But after listening to you a couple of times talking about melatonin, why is it not a problem then? Do we take it at nighttime? And what sort of dosages do we need to take? 

Dr Yurth: It’s interesting. I mean, we will dose—so for my osteoarthritis patients who have, for instance, high levels, most patients who have diffuse arthritis, or degenerative discs have very high levels of a cytokine called interleukin 1 beta. Interleukin 1 beta is very damaging in mitochondria, that's probably one of the reasons you get cell death and, and your chondrocytes all die off. So one of the things we know blocks interleukin 1 beta is higher dose melatonin. We also know that that's very anti-cancer, right? Probably for the same reason it's creating this balance, this homeostatic reaction in the mitochondria. So I actually like, in those patients, high dose melatonin, a high dose melatonin sounds interesting. Unlike the lower dose melatonin, it sometimes actually has more of a stimulating effect. But it actually does help restore your own circadian balance at a higher dose. 

I have a lot of people who take it in the morning, because if they take it at night, they actually are stimulated by it. If you take in the morning, they're sleepy at bedtime, and they sleep through the night. While I'm working with your own. Your super charismatic nucleus and tinea, we're kind of brain level, a kind of balance you back out.

Lisa: So what sort of level is like, I'm at the moment, just me personally, anecdotally, I'm taking a five milligram dose of melatonin at night time to optimise my sleep. And is that a low dose? Is that or is that a high? Yeah, what is the high dose?

Dr Yurth: So high dose is like 20 milligrams. We use the high doses in our people who have osteoarthritis primarily, cancer, we use high dose melatonin, especially your breast cancer patients will use high dose melatonin. So we'll use that, you know, as a trigger adjunct. Not always, you really have to kind of work with people, there's people who do great take in at night. One of my sons does great, it's 20 milligrams of melatonin at night. Sleeps through the night and wake up early in the morning. Me, I actually take it in the morning. If I take it at night, I'm wide awake all night. But if I take in the morning, I have a really nice, good sleep with good deep sleep on my Oura ring. I get a good  hour and a half of deep sleep. So it seems very different in different people and how it's interacted. And I'm sure that has to do a lot with kind of genetic, what are your clock genes? So I think that that probably has a little bit of a genetic influence. And I do have people who just don't follow—can only tolerate very low dose. You know, but we're finding more and more reasons to be very cautious with oh, you don't really want to take more than three to five milligrams of melatonin. Yeah, really finding that the higher doses seem to have a very advantageous effect on...

Lisa: Without putting your body clock out. You're super right.

Dr Yurth: Actually, potentially really benefiting your body clock, your circadian rhythm, which is critically important. And right now, that's one of the sort of easy things we can do that we know is going to be working. And as I said, I think what—it's going to come down to when we look at this mitochondria, it's not going to be trying to figure out what is my perfect dose of antioxidants. It's gonna be figuring out how do I get that mitochondria with the pores, letting the good stuff in, letting the bad stuff out? 

Yeah, in the right sequence because we know that, for instance, cancer cells that port stays open all the time. There's this very imbalance in this other mitochondria are really getting all this stuff all the time. So we know that a huge factor to health is trying to restore this normal port. I think that we're—there's a drug that's coming out. I can't remember the name of it. Yeah, I can't remember the name of it, but that will probably be actually really, if we can get it will be actually really interesting. It's actually coming out for the treatment of ALS. But that looks like it might be really helpful for that pore. 

Lisa: They’re shutting the mitochondrial pore. 

Dr Yurth: Yeah, I mean, if that will be something we can get. I don't know. But we'll find more things. Like I said, I think minocycline is a really nice thing to go to, like twice a year, I'll use a 10-day minocycline course, really benign. 

Lisa: Minocycline. How do you spell it?

Dr Yurth: So, minocycline, M-I-N-O-C-Y-C-L-I-N-E. Cheap antibiotics. I mean, it's like a $10 antibiotic. Right. And that has, but it has really—and it's been looked at in the anti-ageing field for a while, but we kind of weren't so clear of its effect on the mitochondria. Well, now we actually have found it's actually working on this pore, to actually balance out and keep the pore closed more, which is what you really want. When we're young, the pore is not open as much as it does when we’re old, there's less bad stuff coming through the mitochondria.

Lisa: So itis getting porous, isn't it? So basically, the membrane is getting porous. 

Dr Yurth: Exactly, that's probably where—like some of the mitochondria peptides like SS-31, which was the cardia lipid membrane, which helps them that endoplasmic reticulum inside the mitochondria to be healthy. So that's why peptides like that are so beneficial.

Lisa: Yeah, yeah. And there's lots of, you know, we can't get these fancy peptides, unfortunately, that easily. The caveolae pan is an enzyme that is a very important enzyme for us. It's a stabilising enzyme, isn't it? So, we want more of this and this is what one of these peptides is right. And so hopefully, there's going to be more research around that and more drugs even coming out around that.

Dr Yurth: Yeah, and remember that one of the ways we induce some of these mitochondrial peptides is exercise. Right? MOTS-c is a little bit of stress for our body, right and so it reduces the mitochondria to produce some of these mitochondrial peptides. MOTS-c which is kind of considered exercise in a bottle because you can actually give at least mice you can give them MOTS-c— basically this mitochondrial peptide and it acts just like exercise.

Lisa: Exercise hermetic.

Dr Yurth: Yeah. So it's very cool. Of course, it's very expensive and... But way cheaper to go exercise, but it's a nice thing to offer people who can't exercise for some reason. Like, you'll have an injury or elderly people who are just so sarcopenic and trying to get them to do anything until you build a little bit of muscle is almost impossible. So things like that are going to be really nice in that realm as peptides like MOTS-c. 

There's a whole company here that is actually just working on these mitochondrial peptides as drugs for treating things like this. Right now, we know that one of the best ways to produce MOTS-c is to exercise, stimulates your mitochondria to be a little stressed. Mitochondria produces more MOTS-c. MOTS-c helps with glucose metabolism, it helps with fat loss, it helps with turning white fat into brown fat helps. It helps with kind of overall aero metabolism.

Lisa: Just briefly on that. What is white fat versus brown adipose tissue, you know, brown fat? And why is brown metabolically active? 

Dr Yurth: Yeah, so you know, white fats what—that fat we get as we get older and you know, it's really doing nothing beneficial. Brown fat is what little kids have, right? Brown fats—we look at babies or you look at little kids and they have that little chubbiness. Well, that's usually brown fat. Why? You know, maybe boys made fun because I'm always cold and so I'm way overdressed. My kids, but little kids don't get nearly as cool. We don't have to like them quite so bundled up as we do, because they're really covered with brown fat, which is metabolically active, that's what it was designed for. And when you're born you have this brown fat, you can stay warm. I mean, really, we were meant for survival, right? These babies who are born, they need something to keep them you know. Also there when you were caveman and you were just laying there in the cave, you survived. 

So brown fat is metabolically active, it's helping for warmth and heat production. It's actually burning calories. White fat is what we get as we get older and we just eat too much and we sit around too much. And all it does is coat our organs and do nothing beneficial. So brown fat actually you can convert white adipose to brown adipose, so you can turn it into metabolically active tissue. Then you're actually going to be able to burn more calories and you'll be way more metabolically active. You actually want brown fat. You can convert white fat to brown fat. You know, and that's probably does come down to—that's one of the things that when you looked at butyrate it was one of the places that butyrate actually worked was actually helping to convert more brown fat and white fat. So there was a big problem putting people on butyrate can really help with fat loss using butyrate and if you're overweight people who are all have metabolic their guts are horrible. Yeah, uterine those patients can really help with fat loss. 

Lisa: I just had Dr Austin Perlmutter on you know, probably… And he was talking about the white fat cells, the visceral fat cells having not a consciousness but they have an ulterior motive to keep themselves alive. So they seem that all these—make you hungrier, send out inflammatory compounds and so on to make sure that they stay alive. They end up killing the host in the end. But like a cancer cell, they although they have their own agenda independent of what was actually healthy for your body. So they don't want you to do fasting. They don't want you to do any of these things, because they're not going to get knocked
off. 

Dr Yurth: Yeah, I mean, fat is metabolically active too. Remember it converts—fat cells have—they convert testosterone to estrogen. So men who are fatter will start converting all their testosterone into estrogen. So it's one of the places that that we have, you know, aromatase is inside fat cells. White men tend to have bigger breasts, and you know, is that fat cells actually are converting very mostly into this bad estrogen. So even your testosterone, you put them on testosterone, a lot of them just convert it to estrogen.

Lisa: Wow. So that's independent of your innate genetic pathway for your hormones. 

Dr Yurth: Fat cells have aromatase. Fat cells have aromatase.

Lisa: Oh, wow, that's—I didn't realise that. I mean, I thought your genetic pathway was your genetic pathway. And you'll be converting your testosterone to estrogen is more if you have that genetic predisposition.
 
Dr Yurth: It's certainly genetic there. But yes, that fat guys have breasts, right? You look at breasts because they're very estrogenic. And so if you try and get—if you take some of your overweight males, and you put them on testosterone without using things to block estrogen or getting rid of fat first, then you just keep making more estrogen, making more fat. They’re making it worse, right?

Lisa: So okay, so it's not just to do with your genetic pathway, but also to do with how much fat you have. And the more fat tissue the more estrogenised you’ll be. That's in the new—okay. So that's why. Because you see, a lot of young people nowadays are thinking over probably growing up with less quality food than what we grew up with in our generation, seem to be more estrogenised and have more of these issues, and the actual body shape, the phenotype, the way it secretes, is this more estrogenised than past generations?

Dr Yurth: We're seeing a lot of twenty-year olds who come in, who have high estrogen levels, low testosterone levels. I think drugs have to do with that, too. I mean, here in Colorado, we have legal marijuana, which is unfortunately not very good for testosterone. 

Lisa: Oh, wow. I didn’t know that either. Marijuana is not good for testosterone. 

Dr Yurth: It's not good for testosterone levels at all. And then our food, right, bisphosphonates all these things that are so we're seeing this you know, these really young guys with testosterone levels that that you're a god awful.

Lisa: And then estrogen levels higher than the...

Dr Yurth: Estrogen levels that are high, right? 

Lisa: Yeah, I just did my estrogen levels and my—I know mine are low because I'm going through menopause and so on. And I was looking at my husband's and I was thinking, ‘Oh, it was about…’

Dr Yurth: You do start good to see that right. You start to see that these men—these older man look like woman, it switches. Yeah. You know, and they start taking on more female build, right? They get the bigger breasts and bigger bellies and they start getting this more female build to them. 

Lisa: I mean, I've had lots of things so that it's not it's you, going the other way and there's testosterone is good and bad. Yeah, that is what you see in older and older men is that tendency to go and eat. It's really really hard to get testosterone replacement therapy or hormone replacement therapy for men or—for woman a little bit easier. They've seen you know, the doctor seems... I am willing to give it to woman but well, this integrated medical fraternity for bioidentical hormone replacement? And, you know, it's so easy...

Dr Yurth: It kind of kills me because I get this—we're putting together this course called what to fix for us to kind of help people. In this journey of getting healthy, what do I do? Because I'm overwhelmed. And as I was putting together, I was like, ‘Okay, well, you start with exercise’. And that's it. No, actually, you kind of have to start with hormones. Because if I take somebody who has no testosterone, and no hormones, they have no progesterone, so they can't sleep, they have no testosterone, this is both men and women. So you know that their joints hurt, because there's progesterone receptors on joints, they've no testosterone. So trying to get them to go into the gym, and is impossible. 

So for me to say, follow a good diet, do exercise without replacing hormones. It's really kind of not right, right. I mean, as I was putting together a talk, I said, you know, actually, the first thing I do is get these people hormone stabilised, because then I'm going to go to motivate another, their testosterone levels are good, they feel more motivated, they're going to build muscle, they're going to lose fat, they're going to feel like they can actually exercise, you know, they’re making progress, they can sleep. And that starts young.

And so to listen to, you know, your story of people not being able to get access to these things, and just, you know, it is almost criminal in my mind. To just say, you know, well just eat better and go exercise. Well, you can’t get it like that, right. You can't, right. You can't get out of bed much less go to the gym.

Lisa: And I know you'd like in my life, you know, when I was doing ultra marathon running and doing absolutely ridiculous amounts of training, I got fatter, because my hormones were going out of whack and my adrenals were totally, yeah, and fluid retention, and so on. And so, it's so counterintuitive, and now I train, it’s still hard, but it's short. And I'm not knocking the crap out of my hormones, and I'm on hormone replacement therapy. And, and I can get leaner on a 10th of what I was doing. So it's not all about exercise. In that case, I should have been skinny before and I shouldn't be so now.

Dr Yurth: Yeah, it's not, you know, I mean, obviously, exercise is critical, but not—you don't have to be doing extreme exercise. What I’m really trying to get across is just sensible stuff. We just did a thing about just taking a walk after dinner, right? The metabolic control of taking a walk after... Nobody does it. But it makes a huge difference in fat storage. And so there's some simple things you can do. You know, we always talked about all these big, you know, cool things and that are amazing. Yeah, peptides and hyperbaric and all that cool stuff. But there's some really simple things that cost nothing.

Lisa: So let's talk about that briefly. Because the blood sugar levels we're talking about in this case. So regulating your blood sugar is absolutely crucial. And nobody like—when I talk to the average person around me and clients and so on, that I'm working with, none of them have even ever taken their blood sugar once. Or maybe the doctors done at once every year and they don't understand the—and this is what I take constant glucose monitors. I mean, I want to get one, one year.

Dr Yurth: Pricey. But they're cool.

Lisa: Exactly. Yeah. Again, it's always a matter of where to put my results first. Constant glucose monitors give you that feedback of where your blood sugars are, what's causing them to go up and it's not just food by the way, it can be your emotions and your stress levels and so on and get like—I've been taking—I you know, prick my finger 10 times a day just to see where I'm at and to keep an eye on it. 

Funny story, I thought I was getting, I was becoming diabetic, right? Because I was getting up in the morning and my blood sugar levels were very high. And I was like, ‘What the hell you know, I'm really slim’. What's going on? And I've been through a very stressful time and I thought maybe that's it. I've been doing in the morning cold showers and then Wim Hof sort of breathing. I was getting my blood sugar levels high, which is fine for the…

Dr Yurth: ...short periods. Fine, right. And again, those of those little stresses mean is that what about the mitochondria? Right? That's one of the things that causes mitochondrial biogenesis is that cold shower for the same reason. That little bit of stress, like I said, what doesn't kill you makes you stronger. And that's what that cold shower, the cryo does or you know, just taking that two minute cold shower. It creates that little shock response to mitochondria like ‘Shit!’, and they start producing more mitochondrial peptides which creates more mitochondrial biogenesis. So, you are right and just like the blood glucose going up, these little temporary stressors are good for us. It's the big long stressors that aren't.

Lisa: Yeah, and so regulating our blood sugar is really porting and understanding what does that and I just found out that doing that tumor breathing in the morning and stuff does. And that's fine. It's a great old story. So that's for a specific reason. And for my cortisol levels to go up in the morning isn't a bad thing, because that helps… etcetera, etc. But I did panic thinking that I was hitting towards diabetes. ‘I don’t want to see peptide tiers? Because I must have type one because I can't even type two’. And it's just a funny story. 

But when you're measuring these things, you can actually see what things are doing. Yeah, like you might eat a banana thinking a banana is a healthy food, but it seems your blood sugars right through the roof. And when you know that you're going to avoid bananas. You know?

Dr Yurth: I mean, I think they're going to be sort of a critical piece to understand because, you know, it is hard to figure that out. I mean, there are things that like, in certain people, you can't figure out why their blood sugar is out of control. It could be very specific activity or something like that. That's doing it. So I do love the CGM. I wish they weren't so expensive. I wish there was some access to them. You know, it was not so pricey, because, you know, again, that's like $400 a month for the CGM. 

Lisa: You can't afford it, and so many people.... And we could be like, this is like, for me from a regulatory perspective wouldn't that be great if we did this prevention stuff. And then we wouldn't have so many people with diabetes, because diabetes is the entranceway to cardiovascular problems, and urine, and all the rest of it. This is why blood sugar levels are really, really important. 

So one of the things that Dr Yurth did recently was to challenge everybody listening out there on Instagram, when you've had your evening meal, or your big, big meal at lunch is big, to go for a 20 minute walk after, a 10 minute walk even. And that will actually slow the release, so you won't get that big sugar spike. And so I've started instigating that as well.

Dr Yurth: It’s so easy, right? And it's really nice and peaceful. My family took everything to drag them out. But you know, it was like, because of COVID, my kids are done at home. And you know, and but we don't talk, we don't see each other. And actually these little walks at night, were such a nice thing. I say that I got them to do for the week, and then we're done. 

Lisa: But there are a couple of other things that we can do to lower our blood sugar levels. What do you think about things like Vanadyl and cinnamon and chromium and these sorts of things that can actually lower blood sugar levels as well, just to help you…. 

Dr Yurth: They can work really—honestly I used them a ton. I tell people just to use you liberally you can use it until, you know. I think chromium works on some people really well. And some people not so well, there's probably a bit of a genetic basis, or just if you're depleted it kind of basis to that. So that can be really helpful for glucose maintenance too. I do think people forget about cinnamon, put some on your coffee, put some on your oatmeal, but you know, you know it. 

And then I just did a little Instagram thing yesterday, because there's a very interesting study that came out from American Diabetes Association of eating your protein before your carbs. So if you've got a plate with broccoli, and a little piece of bread, and some grilled chicken, what they did was they took people and they had them for one week, eat the protein first, actually at the car person, their salad and their bread first and then the protein. And then they measured blood glucose and insulin levels at 30-60-120 minutes. The next week, they did the opposite. They ate the chicken first. So the protein first and then the carb, the impact was 40% difference in blood glucose and insulin levels at 120 minutes. And the people went just by eating the protein…

Lisa: That makes sense, right? Proteins a little harder to break down. 

Dr Yurth: So you start the digestive process and you know, yeah. Very simple, right? So if you're going to eat some carbs, if you're eating and remember carbs, even your vegetables, that you're gonna have lot less glucose impact and insulin impacts simply by eating the protein first and then in the carb. Or if you want to have something—I mean, what do we do right here in the US, at least we eat our salad first and then you know, hey, then we're eating the breadbasket. And then we eat our chicken last. Switching that around, so even if you're gonna have your little bread, your little ciabatta roll or something, you eat that after you finished your protein, and eat that last there was much less glucose in that.

Lisa: Wow. And then this is also true for fat and sugars. And I mean, not that we're advocating but if you having Coca Cola or some terrible drink my bed versus—which you shouldn't, I'm not saying that but—versus having an ice cream. Because the fat is in the ice cream, it will slow the response to the sugar compared...

Dr Yurth: Exactly, right. You’re actually, right. You're better off eating something like fatty sugar loaf than you are just eating a Coke. Which is why Coke is so bad for you. It's just so bad. Yeah, those are just easy things, right? 

Lisa: Oh, yeah. I'm never—I'd sort of—what about enzymes like a lot of people are dealing with not having enough betaine, hydrochloric acid. Not enough digestive enzymes from the pancreas. And some of this is genetic. And some of this is age related, not breaking the proteins down and so on. Is there a rule of thumb without having tests and testing for all your pancreatic enzymes and so on.

Dr Yurth: There's some evidence that—maybe like the gut, a lot of things start with dysfunction and bile acids. In fact, one of my friends who's a physician, or medical practitioner, that takes care of a lot of very sick ALS patients, really has a belief that things really begin with the dysfunction of the bile level, you know, the bile acid level, and that we really do need to focus on that more. And I love betaine, you know, and I will—in any of my patients who are sick, or who have kind of more neuromuscular weakness, things like that, or I'm building muscle, I will always focus a little bit on, even if you're not testing digestive enzymes, I'll focus on actually having them use a digestive enzyme. So using just the sort of mass proteases and lipases and using that with their meals, because I do think there's a piece of that we are way overlooking in a lot of people. And that may be the start up of a whole lot of diseases. Is that that level?

Lisa: Yeah, yeah. That makes sense to me. Because when you look at the protein levels, a lot of people or you know, working with a lot of athletes, of course, you're stressing yourself—a lot of repair and so on, having enough protein in the body…

Dr Yurth: Having