10 ways to boost your mitochondria
In this episode of the MitoPod, Scientific Affairs Manager Georgia Truman sits down with MitoQ Chief Science Officer and neuroscientist Dr. Siobhan Mitchell to explore the science behind mitochondrial health and what you can actually do to improve it. From exercise zones and red-light therapy to cold water immersion, sauna and key supplements like N-acetylcysteine and Mitoquinol, they break down the evidence-based strategies that support your mitochondria at every level. They also dive into the fascinating role of estrogen in metabolic health, why a little mitochondrial stress is actually a good thing, and what makes MitoQ uniquely targeted as a mitochondrial antioxidant.
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Georgia (00:16) Thanks for tuning into the MitoPod. My name is Georgia Truman, and I'm the Scientific Affairs Manager for the MCRP, which is the Mitochondrial Collaborative Research Program. Today I'm joined by Dr. Mitchell, who is our in-house neuroscientist and the CSO of MitoQ. So thank you so much, Siobhan, for joining us today. We're going to be talking about some evidence-based ways that you can improve mitochondrial function.
Now Siobhan, you have a PhD in neuroscience and you've published papers from Alzheimer's, Metabolic Function, Even Behaviour and Weight Loss. So my question to you is, why do you care about mitochondria?
Siobhan (00:57) my gosh, how could you not care about mitochondria? I'll just really be brief. I'll just say that everything in my research for the last 20 years has indicated that mitochondria fundamentally seem to be causing a lot of diseases of aging, and we just need to think about them every day, how to support them. So I could just post millions of reasons, but I'll just say that
For sure, especially your brain, you need to preserve your mitochondria and help make sure they're running well.
Georgia (01:28) Mm-hmm. Mm-hmm. If it's something that I've learned from working through the MCRP, like we have so many different researches and it's such a a broad category of what people are interested in mitochondrial function or mitochondrial dysfunction for. So I think it's applicable for like all areas of health and disease and longevity.
so I'm gonna start off with something which I thought was gonna be quite simple when I first started looking into it, which is exercise.
So I'll start with a question for you, Siobhan. I know that you are fit and healthy, but what kind of exercise do you enjoy? And when you're thinking of your exercise routine, are mitochondria like ever in your mind, or is it a completely different goal that you have?
Siobhan (02:12) Yeah, so I'll start off by just saying I usually run. So I like to go for a run at least 40 minutes or so. And sometimes I bike too, but running is my main thing I do. And I think about my mitochondria all the time while I run. And just to give you a sense of what I think, one is that I know I have to sprint a little bit to kind of get my mitochondria revved up and.
I force myself to do that even though I don't like it. I do force myself. And then the other thing I always think is like sometimes I have that feeling of like, you know, I'd rather stop after 20 minutes, but I know it's the volume of exercise that you do that help your mitochondria. You need to do at least 40 minutes or so to start with that really good beta oxidation kind of, you know, fat burning. That's so important.
Georgia (02:39) Heh.
Siobhan (03:00) to get our mitochondria once again metabolically adaptive. So we can go into that more. I'm sure you've got lots to say on that. So go ahead, yeah.
Georgia (03:06) Yeah. Yeah, for sure,
for sure. so I I'm similar. when I exercise, I do running. So I've set myself a goal at the end of the year that I want to do another half marathon, but take it very, very seriously. So that is gonna be a lot of zone two training, but then you know my
My cardio fitness isn't great, so I do need to push myself as well. And that is something that I have found through reading some of Dr. David Bishop's work. There was a really good review article that came out last year. It was Dr. David Bishop, so he's from the University of Victoria in Australia, and also Martin Picard, which we are very familiar with. And they were looking at what types of exercise.
do you need to do to actually elicit a change in mitochondrial function? So mitochondria obviously so important for exercise because they generate our ATP, our muscle has a very high density of mitochondria. ⁓ but mitochondria are also responding to exercise, like you say, with beta oxidation ⁓ improvements if you really push yourself.
so in terms of a routine and the different parts of the mitochondria that we might want to be improving, Dr. David Bishop sort of mentions three main categories of adaptation for mitochondria. So the first being increasing mitochondrial mass, which is not increasing like the size of every individual mitochondria, but more so how many mitochondria are actually in the tissue, the density of mitochondria.
So do you have any idea how dense your muscle is in mitochondria? If you had to give a percentage for yourself?
Siobhan (04:44) Ooh, density. I don't know that one. I would guess numbers of mitochondria, but not density. Ooh.
Georgia (04:46) I know, it's a bit of a strange one. So
typically an untrained individual, and I would put myself in this category, I'm an office worker who's mostly sedentary, a little bit of exercise and running here and there, you're looking at like two to three percent of your muscle mass would be mitochondria. But if you go through training, especially if you are an athlete, you can push that up to like eight to ten percent.
So mass is one thing that you can improve, and the next thing would be changing your mitochondrial morphology. So that's more about the shape of the mitochondria. specifically looking at the cristae density. So that is your inner mitochondrial membrane all folded up nice and tightly. the denser that it is, the more surface area that you have for ATP production. and then
improving mitochondrial function in terms of their capacity for making energy is the third adaptation that we can have. So for mitochondrial mass specifically, like you were saying, consistency is key and the volume of exercise is like the big part. So you want to be having higher volumes over longer periods of time. So yes, running slowly a lot of zone two cardio
Aiming for about four sessions per week if you can at a moderate to light intensity. So if you are doing weight training, I don't know if you do any resistance training at all.
Siobhan (06:10) I do push-ups every night, but that's all I can make myself do.
Georgia (06:15) That's still resistance training.
There's some calisthenics in there.
Siobhan (06:18) Yeah, it's amateur hour though, so yeah.
Georgia (06:21) Yeah,
yeah. But the idea is that if you're gonna be doing resistance training, ⁓ you could lower the weight. So calisthenics would be a great example of this, and then high repetitions. So that's to help with increasing mitochondrial mass. Although Dr. David Bishop does mention that you do have to push yourself over a certain threshold to really see these adaptations in mitochondria. So that's where you're sort of talking about like every once in a while you are gonna have to pick up the pace and do some sprint training.
in there.
Siobhan (06:51) Yeah, even though it's painful, the pain is worth it.
Georgia (06:51) Unfortunately. It is painful, I'm sorry.
For me, like getting into zone two is just like walking up a hill. Like a steep hill, but still just walking up a hill.
Siobhan (07:03) so then do you do resistance training as well? Because this is where I feel like everyone's getting on this bandwagon and I am now starting to feel like I should join the gym and do it.
Georgia (07:12) Yeah, I know that I need to be doing resistance training even just for like metabolic health. But as I get older, like I'm going into my 30s now and I really need to make sure that I'm, you know, building up my muscle reservoirs, especially for going into perimenopause, which is gonna happen sooner than I would like to think.
Siobhan (07:30) Wow!
Way to psych yourself out. Yeah.
Georgia (07:33) I know. No,
you've gotta you've gotta think about the future.
Siobhan (07:36) True, true. I was thinking about perimenopause when I turned 30 as well.
Georgia (07:41) I think 30 is just like this age for women. Okay, so the other thing, the other thing that we can improve in terms of mitochondria is morphology, so Christae density. initially it was actually thought that this wasn't something that you could change, but there's been some recent research to show that for
Siobhan (07:43) It's the moment.
That's the dream.
Georgia (07:58) Endurance trained athletes, so marathon runners, ultra-marathon runners, their density can be about 25% higher than untrained individuals, and for resistance training, so weightlifting, about 16% higher. So you can move the needle a little bit. for example, hummingbirds, so they have to beat their wings extremely fast. So the mitochondria that are in their wing muscles, their density is about twice.
that of a normal human, which is kinda cool. Yeah.
Siobhan (08:28) that's cool
actually. That's their secret.
Georgia (08:30) Yeah, it's all in the mitochondria. but again, for these dramatic changes, high intensity, unfortunately. So I don't know if you're a fan of like hip workouts, but those would be great in this instance.
Siobhan (08:41) Yeah,
I am not, but I will make myself do it for my mitochondria. That is the number one. Yep.
Georgia (08:45) Exactly.
in terms of actually increasing energy capacity per mitochondria, again, you've got to bump things up. So it is higher intensity, especially for cardiovascular fitness. So we're not too sure what kind of resistance training is going to be good for improving ATP production, but we definitely know that high intensity aerobic exercise can improve protein synthesis in the mitochondria and your respiratory capacity.
But again, you know, like if we're increasing mitochondrial mass, if we have more mitochondria, like you do have increased capacity for ATP synthesis, but not necessarily like at the mitochondrial level, like each mitochondria.
Siobhan (09:27) So just to sum it up, it sounds like you're saying that we need to do it all. We need to do that zone too. And we need to do the high intensity and we need to do the resistance trading. Is this what I'm getting?
Georgia (09:39) Yeah, pretty much. So if you wanted to break it up into like a split, you might have three or four sessions of zone two cardio. So from about forty-five to ninety minutes if you can manage it, like the longer that you do it, that's gonna really increase your exercise volume, which is important.
Get maybe one or two high intensity sessions per week, that's really gonna be good for those morphological changes and increasing your energy capacity and then resistance training. Even if it's not for mitochondrial purposes, you just need to make sure that you're looking after your muscles, especially as you age. It's all to do with metabolic health and insulin sensitivity. So I would not recommend any type of training regime that didn't have resistance training in there as well.
when we're talking about things that you can do at home, so red light exposure and red light therapy has been trending a lot. Especially these like domestic devices that you can take home, whether it is like those panels that you could sit in front of.
Siobhan (10:35) Yeah, those are all over TikTok.
Georgia (10:37) So I kind of wanted to go into what are the mechanisms of red light today? Has it got anything to do with mitochondria? And is there actually any evidence for metabolic health?
Or for skin health. And it turns out, yes, this is something that is mitochondrially mediated. So red light therapy, the technical term for this is photobiomodulation. So using light to have a change in our physiology. And it is interacting with the mitochondria. There's a specific protein in the mitochondria called cytochrome C oxidase. This is otherwise known as complex 4 of the electron transport chain, and it is really important for generating ATP.
So it sits right before ATP synthase, so it's like the second to last step of generating ⁓ energy for our cells. So what's interesting about cytochrome C oxidase is that it contains chromophores which absorb light energy. And it can essentially convert this into chemical energy and sort of upregulate enzymatic activity, which in theory then goes on to improve ATP production in the mitochondria.
So the thing about red light is that you've got to make sure that you're getting the right wavelengths so that you actually get this activation of those chromophores and can penetrate the skin. So we mentioned TikTok. I think there's probably quite a few devices on there that might miss the mark in terms of the specific wavelengths that they are reaching, the intensity of the light when it is actually getting to your skin. So you've got to be
Quite careful with the types of devices that you're buying. ⁓ and you're right, some of them do look a little bit scary. Like sort of like this, like, I don't know, alien technology, bathing in red light. But there has been some clinical evidence to show that whole body red light ⁓ therapy can help with metabolism, and then also there's more
targeted devices to the face can improve skin as well. So, in terms of red light, there is a technical definition for what red light is. So, we're wanting to be sitting between 620 and 700 nanometers. And then there's also near infrared light, so we're shifting up to about 700 to 1400 nanometers.
Red light is good for skin, so maybe some of these facial masks that are sitting like quite close to the skin. But if you're wanting to penetrate into deeper tissues, so through the dermis, through the fatty layer, and into muscle, that's when you're going to be looking more at near infrared. And I think that's why a lot of these like new dry saunas have the near infrared lights attached to them because it's sort of more around like muscle recovery.
And as well as a little bit of metabolic health in there as well.
Siobhan (13:18) That makes sense. So there
actually is data supporting near-infrared to help muscles through mitochondria, or is that not as well known?
Georgia (13:27) ⁓ mitochondria are definitely able to absorb near infrared light. I think through the mitochondria, specifically in muscles for muscle recovery. Like if it is just shorter wavelengths of red light, they're not going to be able to penetrate as deep. Yeah. But for red light, there is some metabolic evidence as well. So there was one study looking at 670 nanometers, so that's in that visible red light spectrum. And just
Siobhan (13:44) Got it.
Georgia (13:54) 15 minutes applied to the upper back in a very small, sort of like two credit cards put together, very small surface area on the upper back, about 45 minutes before eating. And what happened was that when the researchers then went to take bloods from these patients two hours later, there was a decrease in a blood sugar spike.
So there was some kind of metabolic mechanism happening there where it was ⁓ protecting against a blood sugar spike after red light exposure. They think that it's probably to do with increasing mitochondrial efficiency to be able to better handle blood glucose to turn that into ATP. A similar sort of thing looking at red light therapy, kind of going in from
red into near infrared so this is like 630 to 940 nanometers and this is a whole body exposure. This study was done on obese women and it was just a 12 minute session looking at resting energy expenditure. So sort of like your basal metabolic rate. And just 12 minutes under that light they had a 9.3% increase in energy expenditure at rest.
Which was kinda cool. So they're kinda looking at ⁓ red light as potentially like a non invasive therapy for metabolic health, potentially even weight loss, but I think it's in very early days still.
Siobhan (15:09) Mmm.
I'm almost ready to get one of these now that you mentioned those studies. I will say that. But go on, do you have anything else about the skin kind of benefits? Are those really true as well?
Georgia (15:24) Ha ha
Yeah, so there have been some clinical studies on skin health, and I think a lot of what people are using these devices for are like fine lines and wrinkles. and these devices do definitely sit a lot closer to the skin than a panel that you might sit half a meter away from. and when they look at the molecular, like the mechanism of what is happening,
There is a decrease in MMP1 proteins, and this is an enzyme or a protonase that degrades collagen. So it's all about protecting the collagen that we have, preventing it from degrading. And when they looked at ⁓ ex vivo samples, so some skin samples taken from humans and then do some little experiments in a petri dish in the lab.
They could see that there was an increase in genes associated with collagen synthesis as well as hyaluronic acid, which is really important for like water retention in the skin, skin hydration. So I do think that there is some genuine science here for red light therapy. if you're gonna do it as like a holistic health mechanism, if it's gonna be put into a sauna or it is something that you, you know, maybe do like
Don't want to go too airy fairy, but maybe some like meditation or grounding work in front of your your red light in the morning. I think there are a lot of people that do incorporate that into their routine and it may very well have some metabolic benefits.
Siobhan (16:55) Yeah, I think everyone can spare at least 15 minutes and if it can have all those benefits of metabolism and skin health, definitely seems like you might want to invest in that.
Georgia (17:05) Yeah, I mean if you're just gonna be sitting there anyway, you might as well be looking after your mitochondria while you do it. but just in terms of what to look out for if you are gonna be purchasing one of these devices, so I mentioned the wavelengths. So if you want to incorporate red and near infrared, you wanna look at something that's like six hundred and sixty nanometers and an eight hundred and fifty nanometer wavelength.
And then there's another thing to look out for, which is a radiance. This is measured in milliwatts per centimeter squared. It is just a measurement of like how much light is being admitted by these devices. So about a 50 to a hundred milliwatts is what you're going to be looking for. 10 to 20 minutes a day, do it maybe three to five times a week and just making sure that you're doing it consistently. If you want to be
extra sure that you're getting the right thing, go for brands that have some clinical backing behind them.
Siobhan (17:56) Good advice. Okay, so we just talked a lot about heat from red light and that kind of thing. What other types of environmental interventions can we do to help with our mitochondria?
Georgia (18:09) So we mentioned heat and now we're gonna go completely opposite and go to cold water immersion, which is another trend, but also is grounded in some science that is specific to mitochondrial health. So cold water immersion can be anything from a very cold shower or jumping into a deep ice bath, which I know a lot of people, especially athletes, do for muscle recovery.
Do you ever do cold water immersion at home?
Siobhan (18:37) I mean, I go
swimming in cold water, but not in something with ice chunks. I always thought of that as some like sort of masculine ego kind of thing. So no, I don't do that. But is there really anything worthwhile in exposing yourself to really cold things?
Georgia (18:56) Well, I kind of think it depends on who you are. So you might have kind of hit the nail on the head with the the bro comment. for men, taking the water immersion down to a colder temperature, so between sort of like five and ten degrees, can definitely be beneficial, especially for muscle recovery. But there is some evidence to say that women maybe don't really need to take it.
quite so cold. So Dr. Stacey Sims sort of mentions that even like twelve to fifteen degrees, which in New Zealand is sort of like a winter day, and is probably the temperature that you'd be hitting if you were gonna go and have a cold beach swim for about ten or fifteen minutes, is probably gonna be enough to elicit this cold shock response for you. So I don't think that you need to jump into a ⁓ a tub of ice if that's too intense.
Siobhan (19:41) Hmm.
Georgia (19:48) What I'm hearing from you, Siobhan, is that you like to do these things, but you like to do do them moderately and not be too uncomfortable.
Siobhan (19:56) Yeah, I don't want it to ruin my day. Let's just say that like, oh my God, that is going to be something I will not enjoy. yeah. So do you like cold water swimming and cold immersion? Do you see any benefit for yourself?
Georgia (19:59) Okay.
Yeah, I don't think you need to to look after your mitochondria.
I love it, but the benefit that I love is just like that immediate kind of like wake up response that you get from being in cold water. It's something that I do spontaneously, like with friends, and maybe that is my like a little bit of my bro ego coming out of like you're not gonna do it, but I'm gonna do it. ⁓ it's not something that I have done consistently as something to improve metabolic health.
or mitochondrial health. but I can go over at least some of the mechanisms really quickly before we move on. So there is an action through mitochondria for cold water exposure. So we're gonna have a ramp up of energy production. You get a trigger of mitochondrial biogenesis as well. So this is through PGC one alpha which we're probably gonna mention multiple times through this podcast to be honest. So this is
Upregulating the creation of new mitochondria. And it also activates brown adipose tissue or brown fat is what it is most commonly referred to. And I think that you might have some ⁓ sections in here on brown fat as well as we go through the podcast.
Siobhan (21:21) I do, love brown fat. I will admit it, it's so full of interesting mitochondria, but we'll get into that soon.
Georgia (21:28) So when you jump into cold water it activates your sympathetic signaling, it sends off a lot of adrenaline and this has a cascading effect on some pathways like AMPK, so this is your energy sensing pathway, as well as MAP kinase, which is involved in the cellular stress response. Both of these pathways come in to PGC1 alpha to create more mitochondria. So it is sort of this central signalling mechanism.
So making more mitochondria, improving the oxidative capacity of the mitochondria, and up rate up regulating those energy production pathways. So brown fat, actually, would you like to explain what brown fat is, since you love brown fat so much?
Siobhan (22:13) I do, love brown fat so much. So
it is basically fat that is much more metabolically active and fat cells, there are usually different variants. There's white fat cells or adipose cells that are just full of fat and they don't really do that much metabolically. Their mitochondria are kind of like slowly doing stuff, but they're not expending a lot of energy.
Then there's brown fat cells and they actually look brown if you look at them in the microscope. And that's because they're so full of mitochondria because they're very metabolically active. What they're doing is they're taking fat from the body and they're basically burning it to make warmth for your body. And the way they do this is that normally your mitochondria in all cells are making ATP.
and then your ATP is used for all sorts of cellular functions. But in brown fat cells, mitochondria basically don't make ATP that efficiently. They're terrible at making ATP because they have this special protein called the uncoupling protein that's being expressed in the mitochondria. And this uncoupling protein, to kind of put it briefly, basically makes it so that the mitochondria become very inefficient at making ATP.
And so instead of making ATP, they're just generating heat for you. So when people think about like, brown fat, that's so great for metabolism. The reason why is it's basically expending a lot more energy for you than other fat cells. So that is the beauty. And I spent a lot of time trying to figure out how do I build up my brown fat cells? I want more of them, more and more. So maybe, Georgia, you can tell me, how can I get those?
Georgia (23:56) So, ⁓ yes, cold shock exposure is one way that you're gonna start to build more brown fat because as you say, brown fat ⁓ is all about thermogenesis, so creating more heat. The body essentially is saying, I'm really cold. I need to create more heat, I need to upregulate my mitochondria to make more energy and to also make more heat ⁓ through these brown fat cells.
Siobhan (24:00) Yes!
Georgia (24:22) Which is pretty cool.
Siobhan (24:22) And in fact, what's interesting is these studies have showed that for whatever reason, some people are really good at generating a lot of brown fat when they're exposed to cold.
And then some just literally don't make that much more brown fat. And it's a little bit of a mystery of why some people just seem to be resilient against making brown fat. And the way that they usually make more brown fat is it's just around your chest area. So whenever they're trying to do these kind of scans of where metabolically most active, usually you're showing a huge amount of heat being generated.
right around your chest, kind of like close to your throat. So yeah, it's kind of cool.
Georgia (25:02) So
through my investigations,
I realize that women tend to have more brown fat than men, and they rely more on brown fat thermogenesis than muscle shivering, which is another response that you get when you go into extremely cold water or you have cold shock. Do you know like what why women have more brown fat? Is this something to do with estrogen having an increase in like metabolically active fat tissue just because women have more adipose tissue in general?
Siobhan (25:33) Yeah, so women actually do have a lot more metabolic adaptation in their mitochondria. So that is the secret. So for instance, they can also make beige fat, which is, yeah, beige fat is great because it's really taking white fat cells and beiging them so they become more metabolically active and generate more heat for you.
Georgia (25:43) Have not heard of beige fat.
Siobhan (25:54) So yeah, women do have that trick much better than men. Beige fat is still not completely well understood, but it's definitely clear that women seem to have like more of a handle on that. yeah, and obviously babies, let's also just point out that babies have tons of brown fat because they're so tiny, that they need a lot of brown fat to keep warm because they just don't generate enough heat from just their whole bodies doing whatever it is they're doing and they're not very insulated.
Yeah.
Georgia (26:22) So I guess that does play into the fact that women actually don't need it as cold as men do. We're just a little bit more sensitive to these temperature changes in general. ⁓ so fourteen to fifteen degrees Celsius if you are a woman. Siobhan I don't know what that is in Fahrenheit. Can you do that conversion off the top of your head?
Siobhan (26:42) Yeah, yeah, yeah, like maybe about 60 degrees water temperature. Yeah, nothing crazy.
Georgia (26:44) Okay, so kind of brisk, but nothing too crazy. ⁓
for about ten to fifteen minutes. if you are a man, you can drop that down to maybe five to ten degrees, eight to ten degrees to get the same effect. So talking about cold as one extreme, I'm gonna throw it back to you because you're gonna start a discussion about soreness and what they can do for mitochondria.
Siobhan (27:07) Yeah,
And just to kind of give everyone an overview of the things that we're talking about so far is helping your mitochondria. All of these are basically causing stress to your mitochondria and then having your mitochondria adapt so that they work better.
And this is called mitohormesis. And this is such a huge topic in aging. This is the thing that seems to be the best working to make sure that your mitochondria can handle anything that comes at you. And that is important because if you think about all the environmental things that we can't control, this is where, yeah, every time you get your mitochondria ready to do a lot of work, like an exercise or exposed to a lot of cold or exposed to a lot of heat,
they're now learning, okay, I can adapt to this too, and I can survive. And that's really what we want our mitochondria to do. So yeah, let's go to heat. And this is a beautiful thing because heat is something that if you control it and you give yourself very small amounts of it, the way you do in a sauna at certain temperatures, your mitochondria learn to respond by heat shock proteins. So heat shock proteins are
whole slew of mitochondria signals that basically tell the rest of your cells you're going into a stress, build in a lot of antioxidant responses, so you know fighting all the oxidative stress that happens when you have now made your mitochondria work harder because they're dealing with I would say an unfamiliar environment like heat. So for instance if you think about heat and what happens to you is that you first want to make sure that
you're trying to regulate your body temperature as much as possible. So all your blood vessels basically start to work extra hard when you go into that sauna. And what they're doing is they're trying to vasodilate where they're close to the surface of your skin. So to get rid of heat as quickly as possible. And so this requires a lot of work for your mitochondria. And this is also making it so that you need those heat shock proteins and you need these adaptive responses. So.
While you're using a lot of ATP, you're all now going to be depleted of ATP. And this is when another mechanism called AMPK is activated. And AMPK is another area that is thought about is like maybe the holy grail of how to stay younger, of how to kind of keep your mitochondria at sort of younger kind of working level. And AMPK basically also sends a huge metabolic cascade to the rest of your body.
saying, okay, let's one, build up more mitochondria. So have more mitobiogenesis. That just means you're making more mitochondria. And we're also going to be better at using glucose and fat. So we're becoming more efficient and we're making less oxidative stress while we're using that mitochondria fuel. So what are the benefits of sauna? So despite what you might think that, you know, when you first go to that heat, you feel like you might have a heart attack.
This is actually something that has been shown to decrease risk of heart attacks. So for instance, they have seen that prolonged use of sauna decreases blood pressure, especially after exercise. can increase your heart rate variability. And just to give everyone kind of that quick primer of heart rate variability, this is...
how much difference you have in terms of the time between each heartbeat. And each kind of heartbeat is basically an interesting kind of way you can look at how well your heart is adapting to the environment. So if you have a lot of adaptability, a lot of difference in the rate of your heartbeats, this means that you're able to once again be more resilient to things. So lots of heart rate variability is good. So yeah, going back to blood pressure,
One study actually showed that you could reduce hypertension by 25%. So I think that's very impressive. And the thing to remember though, is that when you have sauna and you're trying to figure out like, how long do I have to stay in here? So the benefits to your heart will probably only occur if you're spending at least 30 minutes in the sauna. So that seems like a long time. I know a lot of people are like in and out.
five minutes, that's not going to be enough, and that you're doing it regularly, so at least three times a week. And interestingly, in all those countries that use sauna lot, in Finland, et cetera, they have shown that people who are using sauna in a somewhat regular way seem to have longer life. So that's obviously another benefit. Then you're probably wondering, so what's the temperature we need the sauna at? So, hate to say this, in American saunas,
They're usually not warm enough. So they're usually something like less than 70 degrees Celsius. And that's probably, you know, a lot of these gyms and everything trying to make sure that people aren't complaining or saying that there's too much in the sauna. But really you want a temperature between 70 to 77 Celsius for best effects.
another good thing to know is that if you can't exercise, if you've injured yourself, if you've caused too much strain and you need to recover and you can't exercise for whatever amount of time, sauna is a great way to preserve your muscles while you can't exercise. So that's another clinical study that was done.
where they're looking at, well, all right, if you're just sitting there with an injury, if you are using the sauna, you can basically maintain your mitochondria proteins and your rate of respiration. So, yeah, this is enabling you to get back onto your exercise regime faster with, yeah, kind of feeling of more, I would say, resilience.
People have then wondered, What if I bring my exercise bicycle into the sauna? Is that gonna bring any more extra resilience? Hate to tell you guys, this is not going to help you. The thing that probably helps your exercise, yeah, preserve your mitochondria, is the warming of the muscle already that you're getting. If you're going and exercising in the sauna, which is also warming you up,
Georgia (32:53) Okay.
Siobhan (33:05) it's just not an additive benefit. You're not really actually improving anything. So either just exercise alone or go sit in the sauna and relax. That's what I recommend there. And then lastly, I would say the thing to also remember is that uncontrolled heat, that is always bad. So when you hear about all those people dying because they've been in a hot city and they don't have air conditioners, that is something that is really a problem. So
Know that you should never stay in a sauna for more than 30 minutes at a time. Go out, take that cold shower, or just sit around and let your body adapt again.
I really think it is the effect of this adaptive response. So as you heat up your body and you're causing more ATP to be used all of a sudden, that is a little bit mimicking exercise in your muscles. So kind of cool, right? So don't think you can exercise though and just do saunas instead. You still have to do both. But I think the same way that that kind of exercise sort of, you know, I am now going to force you to make more ATP more efficiently.
This is also happening in the sauna.
Georgia (34:08) And I know there's been a little bit of a debate online, I'm not sure if you can answer this for us, about whether infrared sauna or your classic ⁓ hot sauna, so like either through like hot coals or just through irradiated heat is better. Because infrared might be good for muscle, but is there a difference?
Siobhan (34:28) I would say the data at least, the clinical data is stronger for sauna so far. So if I had to choose one or the other, I would do sauna over infrared just because the data is better. And interestingly, there have been a few studies showing that sauna can have other benefits that go beyond your mitochondria. So for instance, in one study they looked at sauna for two days a week, just 15 minutes.
And they saw that not only were they improving heart health in these subjects, they're also improving depression and quality of life scores. So literally just well-being was also being benefited by the sauna.
Georgia (35:08) Okay, so I think we're gonna move on now from some environmental stresses and maybe go into some different supplements that we can potentially take for mitochondrial health.
Siobhan (35:18) supplements, yes. Let's bring it on. Let's bring on one of my favorite supplements I don't always get to talk about because obviously I like to talk about mitochondria supplements, but one that seems to be always a little bit below the radar is N-acetylcysteine. And N-acetylcysteine has had a little bit of an interesting history in America. So it's been historically used for a lot of therapeutic...
benefits that deal with toxicity. So its clinical history was that N-acetylcysteine was used particularly for Tylenol overdose. And this is because N-acetylcysteine is the precursor to glutathione. And glutathione is what I would say the universal antioxidant of the body. Glutathione is so powerful. So if I had to talk about anything that your body makes,
Georgia (35:51) ⁓
Siobhan (36:07) to help get rid of oxidative stress naturally, glutathione is tops. People always say, ⁓ great, now that I know that, let's take glutathione. And I say, no, no, no, no, no, you cannot do that. Glutathione is a peptide. If you try to eat it, it'll just get broken down in your gut and it will not do anything. But what they have shown, this is really quite well known over the last 50 years, is if you take the glutathione components,
So N-acetylcysteine and glycine, you can take the N-acetylcysteine and this is actually a sign in your body because it seems to think that this N-acetylcysteine is a breakdown product of glutathione. It goes, you know what? I think I need to make more glutathione because obviously I'm losing it. So your body makes more glutathione as soon as it starts to see that N-acetylcysteine and then you get more antioxidative capacity.
So this was used in those Tylenol overdoses to protect your liver because the toxin metabolite that you get from Tylenol creates a huge amount of oxidative stress in your liver because your liver is the main place that is getting rid of toxins obviously. So what they would do is they would give you a ton of uterine cysteine, they'd get converted into glutathione and then it would all go to your liver and protect your liver.
Over time, they have definitely shown a lot of interesting therapeutic possibilities. And now in the last few years, they have really started to look at anti-aging, which is where I'm super excited. So historically, N-acetylcystine has been good for kidney disease. It's been good for addiction, interestingly. And people always ask me why. So why would an antioxidant be good for addiction? And I will tell you why.
One thing is that a lot of addictive substances are targeting dopamine, so it's your big reward chemical. Dopamine, in order to metabolize dopamine in your brain, you're creating a huge amount of oxidative stress. So you actually need a lot of antioxidants to deal with all that oxidative stress that dopamine is making, and especially if you're releasing a lot of dopamine, which happens with a lot of drugs.
you need to then protect your brain from all that dopamine metabolism, which is causing a lot of oxidative stress. Anyway, N-acetylcysteine is not only great for alcohol addiction, other kinds of addiction, it's good for anything that's about mood swings. So for bipolar depression, it's very effective. So it's got a lot of uses. Surprisingly, it's not always used as a sort of first line kind of situation for a lot of these therapies because it's
kind of considered a supplement. So it's always a little bit downgraded in terms of, obviously you want to use medications first and then maybe you'll use N-acetylcysteine as an adjunct. But let's go on to anti-aging. So N-acetylcysteine, obviously as an antioxidant, seemed to have a lot of good potential for anti-aging. And it was just a few years ago that I would say the real seminal study of this was done. And the way this was done was that N-acetylcysteine was given
also in combination with glycine, so that other precursor to glutathione, to older adults for 16 weeks. And what they showed was that they looked at all the different things that we know are important for aging. So physical performance, cognition, insulin and glucose use, even things like general wellbeing and inflammation. And so after 16 weeks, they saw amazing benefits of N-acetylcysteine and glycine together.
So not only did it help with cognition and also physical function, they showed that it helped with mitochondrial function. So it made the mitochondria better using fatty acid oxidation, which I, as I said earlier, is kind of sign that your mitochondria are metabolically more adaptive. And it also cleared up a lot of inflammation. And fascinatingly, what they also did at the same time as they were giving this special intervention to these older adults,
they looked at young people and what they saw was that in almost all the different kinds of areas that they're looking at, whether it was like blood pressure or insulin or glucose response, all these older adults taking the N-acetylcysteine start to look a lot like younger people in terms of their overall metabolism and their physical and cognitive function. So I am very excited about this study. I believe these researchers are now doing a much bigger study.
That's what I'm excited about as well.
it's also good for exercise. So it's been shown to be helpful for not only athletes that are
having a lot of oxidative stress because they're doing a lot of that high intensity exercise we talked about earlier. But it can also be used during times, once again, of injury. So when you're not using your muscles as much, N-acetylcysteine seems to be able to help your mitochondria stay resilient and functioning. And then lastly, this is one of my favorite studies of all time with N-acetylcysteine beside that anti-aging one.
is a fascinating study this is pre-clinical, but still very, I would think, relevant to our conversation. They understood that there's a definite antioxidant sort of deficiency in humans while they're doing difficult cognitive tasks. And this has been shown through brain imaging. So Carmen Sandy, a few years ago, took a whole bunch of human subjects.
and made them do these difficult cognitive tasks, saw that the people who did worse in the cognitive tasks were those that were basically showing a deficiency of their antioxidant potential. So she was armed with that information, and then she went to mice and looked at whether giving mice N-acylcysteine could increase motivation to do hard tasks. And what she saw was that they actually could. They would do better because all that N-acylcysteine
is being turned into glutathione and basically improve their ability to stay on task and get the hard work done. So if you're still not interested in N-acetylcysteine for aging or exercise, but you might need help with motivation and productivity, maybe give N-acetylcysteine a try.
Georgia (42:07) So does that mean that N-acetylcysteine can cross the blood brain barrier, or is it just that the glutathione can?
Siobhan (42:14) N-acetylcysteine can cross the blood-brain barrier and I think that's really the that it's being made is it's being converted once it reaches the brain.
But let's talk about some other supplements. We haven't even gotten started, right? So I would just also want to start talking about, I would almost call them a class of supplements that all seem to have this one kind of activity. And this is mild.
mitochondria uncoupling. So you're probably like, what the hell does that mean? That sounds crazy. Let me try to give you another sort of instance of what that means. And this is actually going back to our earlier conversation about brown fat. So mitochondria are usually extremely efficient at making ATP. And they do this by having a membrane that has very strong potential that allows the movement of protons through
I would say almost as like it's like a tunnel called ATP synthase. And so the more protons you have on one side of your membrane and protons, if people want to remember what those are, those are basically just hydrogen ions. These protons are able to make more ATP if there's a higher amount of them on one side of the membrane.
So if you have a high mitochondrial membrane potential, you're going to make a ton of ATP. in some cases, you might be thinking, okay, all the time I would probably just wanna make as much ATP as possible. You would be wrong. Sometimes it's quite good to make not that much ATP.
And obviously there's the instance of brown fat. So brown fat doesn't make that much ATP, it just makes heat instead. But there's also situations in just regular mitochondria in regular cells where if you have a low mitochondrial membrane potential and you're not making that much ATP, e.g. you're having low mitochondrial efficiency, this can be good
But the main thing to remember is that the more ATP you're making, the more oxidative stress you're probably going to create as a byproduct. So if you're making not that much ATP, if you have low mitochondrial membrane potential, you are going to make less oxidative stress. And that can be overall good for your aging. So you might be thinking,
All right, so what causes that? And so what they've been actually showing is that, for instance, there are a few key medications and also supplements that do that really well. And one of the best known is metformin. So metformin, probably everyone knows, is usually used for diabetes. It's very good at helping regulate blood glucose. What's fascinating about metformin is not a lot of people know how it works. And in fact, most scientists are still trying to figure out
How is metformin working? What is it doing in the body that allows it to control glucose that well? Well, one possible mechanism that is being explored right now is the fact that metformin can act on complex I, and complex I is part of this of mitochondria machinery to make ATP. And complex I is like the first step of trying to convert all the sort of energy you're making.
from the glucose and the fat being converted into sort of, you know, these substrates of the mitochondria that basically will end up being made into ATP. So with complex one, it's sort of like that first step that's almost like the main decider of how much you're going to try to make ATP in that mitochondria. So if you prevent the complex one from working that well, you're also going to inhibit a lot of ATP being made as well too.
So if you have something like metformin.
that can act on complex one and inhibit its function, you are then going to make less ATP and you're going to make less oxidative stress.
Georgia (46:29) So the idea
is that you're still expending calories, like you're still metabolizing the glucose, but it's just not getting converted into ATP.
Siobhan (46:37) Yeah, yeah, you're still expanding
the glucose, but you're not getting it converted as well. This is exactly the way to say it. Thank you, Georgia. ⁓ So anyway, so what has been known about metformin is that in a lot of models of life spans, so when they give metformin to mice, to worms, to flies, it seems to keep the flies and the worms alive longer.
Georgia (46:41) Mm-hmm.
Yeah.
Siobhan (47:04) and they believe this is because of this mild mitochondria uncoupling. And what's fascinating is one of the best lifespan extenders that we know of ever, which is calorie restriction, one of the things that it also seems to be doing is increasing uncoupling of the mitochondria. So it does seem to be this kind of longevity pathway of just clearly having some benefits.
And so what has been sort of fascinating about some of these kinds of molecules they do show that people on metformin for a very long amount of time seem to have overall better metabolic health.
Obviously, most of these people have diabetes already, but clearly it seems to be something that is good for health span and people with diabetes.
And interestingly, if you think about, for instance, hibernating animals, one of the things that happens when they're hibernating is they're basically having a seasonal uncoupling. So they're telling their mitochondria, now I'm just going to rest and stay asleep for a few months. And while they're asleep, it really seems like their aging process is also slowed. So, for instance, when they look at animals who hibernate,
compared to other kinds of animals that are similar size that are not hibernating, they see that hibernation seems to always prolong life. So another interesting indication. So then you might be thinking, all right, I'm not going to be able to get hold of metformin very easily, but there are other types of couplers that are more easily obtained. So for instance, berberine is also a well-known complex one inhibitor. So that's also something you can try. A few other things that
Georgia (48:23) Wow.
Siobhan (48:42) have an even more mild effect are fish oil. So, polyunsaturated fatty acids from fish oil like EPA and DHA can activate uncoupling proteins. So, we talked about uncoupling proteins and how they make it so you're less efficient at making ATP and increasing that leak of protons across the membrane. These also have that same sort of effect. once again, jury's still out of whether
EPA and DHA are going to prolong your life, but they definitely seem to have this effect. And then lastly, I will mention MitoQ is a mild uncoupler of mitochondria as well. It does a lot of things, mostly to do with antioxidant kinds of effects, but it can also have a little bit of a complex one inhibition, fairly similar to metformin. And just to go into some other areas that are not supplements that have a mild uncoupling,
Cold exposure is one, so we just talked about that with the brown adipose tissue, and then also exercise. So I'm very excited about the future of melaton couplers, and I hope we can devote a whole episode to that soon. But maybe we should go into something that has more evidence.
Georgia (49:51) Sure, so I am gonna go into something that we know is very safe and is very easy to get a hold of, which is omega-3s, as Siobhan just mentioned. so omega-3 fatty acids, the best way to get them from food would be fatty fish, especially DHA and EPA. You can also get ALA from nuts and seeds. There is a little bit of an issue with ALA.
In that the body can't really rapidly convert this into EPA and DHA, so it's a good idea to take all of them, but if you're gonna be taking a fish oil supplement, most of the time it is going to be a combination of EPA and DHA. In terms of mitochondrial function, EPA and DHA are actually able to embed themselves into the mitochondrial membrane.
And this is really important for membrane fluidity, which is essentially the flexibility of the membrane to be able to allow different structures to come in and out of the mitochondrial membrane and just the cellular membrane in general. As well as with fluidity, EPA especially is really potent antioxidant.
Against oxidative stress in the membrane. So lipid peroxidation of mitochondria is one of the ways that oxidative stress can show up as well as damage to mitochondrial DNA. But lipid peroxidation is particularly insidious. So if you are looking at protecting that mitochondrial membrane, you might want to consider taking some omega-3.
⁓ the ratio of omega-3 that has been studied the most is usually a two to one ratio of EPA to DHA, although there is some good evidence to show that EPA in isolation can be quite beneficial for cellular membranes. But there was a study in 2014 looking at 3 grams of omega-3 at a 2 to 1 ratio, which is 2 grams of EPA, 1 gram of DHA, just over 12 weeks.
Was enough to increase the omega-3 ⁓ quantity of the mitochondria membrane by about three to four hundred percent. So very easy for you to put into your routine a few servings of fatty fish a week or taking a really good fish oil supplement.
You want to make sure that this supplement has a lot of good third-party testing, because they do go rancid quite quickly. So, usually through IFOS certification, you can make sure that you've got a good quality fish oil.
Also, back to PGC1 Alpha, again, that master regulator of mitochondrial biogenesis. EPA and DHA have been shown to increase this transcription factor, as well as search winds, which are really important for repairing DNA damage. They are associated with ⁓ longevity as well as improving mitochondrial.
dynamics and mitochondrial control pathways.
So I'll keep it really brief with Omega 3 unless there was anything that you had to add, especially from like a cognition space. Siobhan I know with your ⁓ neuroscience background, Omega 3 is particularly interesting for you.
Siobhan (53:06) Yeah, I love omega-3s for cognition and I will say I have done research on it and seen the beneficial effects. So omega-3s can improve cognition at any age. So I think that's really important, but for sure, especially when you're aging. And interestingly, there was just a meta-analysis that came out showing that intake of fish oil can also help with aggressive behavior.
a lot of aggression starts with the amygdala. So the amygdala...
Georgia (53:32) Okay.
Siobhan (53:32) being overactive. So it could just literally be that those omega-3s are somehow calming down those neurons in the amygdala. So more to come on that. But yeah, the other area that I think is also great for fish oil is how it can help with mood. So lots of data on how different omega-3s like DHA and EPA can help with depression and anxiety. So I think this might be related to those kinds of mechanisms as well.
Georgia (53:59) So talking about mood and talking about the life stages that we go through as a woman.
I know our next topic that is coming up is all about estrogen.
particularly how estrogen is important for women's health, but mitochondria especially as we go through perimenopause and menopause. So I will let you take it away with why estrogen is important for mitochondria.
Siobhan (54:24) Yeah, Georgia, it's true. I could not let an episode about best ways to boost your mitochondria go without a nice mention of estrogen. And I have been talking a lot about this at podcasts lately, but it's worth a mention again that estrogen is simply really great for mitochondria, especially for women, but obviously for men too. So men are not completely left out. But it's true that women get the benefit of estrogen.
through the whole, I would say, lives up until perimetopause. And then when we lose our estrogen, we are now a bit more vulnerable without that estrogen. So let's just describe why estrogen is so important for mitochondria function. So estrogen is thought of as a reproductive hormone, but it's actually what I would say a master metabolic regulator. So estrogen is very important for how we're using glucose, how we're using fats.
And so a lot of that has to do with how we're using our mitochondria. So there are a lot of estrogen receptors on our mitochondria that then direct mitochondrial function. And in particular, estrogen receptors that are called beta receptors are very important for how much our mitochondria can replicate themselves, so that mitochondrial biogenesis, which I have mentioned, and also how mitochondria are using fuels.
how much they're using glucose and how much they're using fat. And estrogen are especially useful for ensuring that we're going into beta oxidation very easily, so that metabolic flexibility, so the best mitochondria are mitochondria that can switch to using substrates from glucose or substrates from using fat and have that kind of adaptiveness versus being sort of stuck in one mode of only preferring one fuel.
So anyway, yeah, what is the evidence for estrogen and how it can affect mitochondrial health? Well, for sure, in clinical studies, they have shown that loss of estrogen affects mitochondrial function in terms of that oxidative phosphorylation, in terms of how much antioxidant gene expression it can have. And so this obviously is the way that mitochondria protect itself. So once estrogen is cut off, usually an animal by removing its ovaries,
you see that mitochondria suffer by having more oxidative stress, more damage, and then more damage to cells as well too. So when women are young, they have all this estrogen that is keeping our mitochondria healthy by allowing it to grow more, allowing it to defend itself more, and allowing ourselves to use fuel more. And then we go through perimenopause and that all starts to change
but we see that basically now we have much more risk of heart disease, of dementia, of diabetes, And interestingly, when they started to look at, for instance, does estrogen help with lifespan? So in animal studies, they looked at estrogen-like kinds of molecules. In particular, they looked at 17 alpha estrogen in mice, and they saw that
In particular, this estrogen could help increase lifespan in male mice. And so this 17-alpha estrogen is a little less strong than estradiol, which is like, I would say, the main estrogen in women and females. But interestingly enough, it seems to work on more of this estrogen alpha receptor.
So it seems like at least for male lifespan, you want to hit that estrogen alpha receptor for more lifespan. I do find it fascinating that when they do these mice studies and they're not removing the ovaries of the female mice, they're not really looking at a true model of perimenopause like that woman, humans, experience because mice are able to make estrogen all their lives. There's a little bit of a depletion, but not like the way that women
have a cliff of basically estrogen loss when they go through menopause. So yeah, I think if we did have a better model to look at lifespan that had more of that perimenopause transition, I think we would also see that estrogen is helpful for females as well. In another study that was actually looking at humans, this is a UK bio bag study that looked at literally hundreds of thousands of people taking all sorts of different medications
towards the end of their life, they saw that women that were taking estrogen kind of meds, so for instance, estrogen patches, anything that had an estrogen activity, were more associated with having a longer life than women that were not. So I think this is also a really important kind of indication that maybe estrogen is good for our whole life. And I know people will start saying, ⁓ wait, but I have heard that when you have estrogen,
and then you stop making it, if a number of years go by and you start taking it again, this is bad for you. I think the jury's still out on that. We're not very clear because the one study that we have, the Women's Health Initiative, that looked at giving estrogen to women who've gone through menopause after 10 years, it's really difficult to say whether the form of estrogen they're using was the problem or it was the timing of estrogen. So that's not completely well known.
There is an interesting theory out there that's called the healthy cell bias hypothesis of estrogen, especially how it works in the brain. So estrogen can be very protective for healthy cells. And we obviously see that in younger women, but harmful in disease states. So if you're an older woman and you have some sort of underlying disease, estrogen might be more problematic. So for instance, there is some data showing that
If you are having, for instance, lot of amyloid production in your brain, that estrogen might actually make that worse. But if you are giving estrogen all through, for instance, paramenopause and then postmenopause and preventing any kind of amyloid overproduction from occurring, this can be protective. So, yeah, this is still being figured out to early days, but definitely an interesting area. One other thing I want to point out, though, is that
There are other molecules that are not estrogen that we're getting from our diets that can have the same benefits as estrogen. It was. It is definitely not just HRT. We can also get some benefits from phytoestrogens. And these are these molecules that are in plants, especially plants like soy, that look a little like estrogen. They can have the same kind of activity as estrogen, maybe not as powerful, but enough to help.
Georgia (1:00:37) That was my question. Is it just HRT? Is it just HRT or is it other types of estrogen?
Siobhan (1:01:00) improve our mitochondria function enough to improve our metabolic health. So this is, I think, another really interesting active area of research, but some phytoestrogens like genistein, deadecine from soy, and then S-Equal have been shown to be very beneficial in not only preclinical models, but also clinical studies showing women can not only get rid of the sort of menopausal symptoms that are very kind of well known, the hot flashes and the night sweats.
but also just improve their metabolism overall. So yeah, then this is all to do with helping your mitochondria.
I actually want to just go into a different direction now and talk about
And interestingly, magnesium is very important for mitochondrial function. So it's a cofactor for many of the processes that help us make ATP.
So it actually complexes with ATP itself and helps maintain ATP until use. So that's another benefit of magnesium. And there are many, many studies showing that when you have magnesium deficiency, you're going to have more oxidative stress, which can lead to all sorts of diseases of aging. This is especially seen in preclinical models that you can cause more oxidative damage and bring on diabetes in mice. And when you supplement magnesium,
It can help with your blood glucose. It can help with your mitochondrial oxidative stress. And so, yeah, this is where magnesium has thousands of functions. I'm only just kind of limiting myself to a few that I'm going to mention, but definitely it can help with your mitochondria and your metabolism. So the thing is, is that people are like, all right, you know, I'm convinced I'm going to go crazy and take a lot of magnesium. There are some, I would say, just
warnings about magnesium that are good to know. And what I'm going to really point out is that you want to have magnesium intake that is balanced because too much magnesium can also be bad. So for instance, when they looked at a clinical study of magnesium chloride being given two times a day, 300 milligrams in younger athletes, they saw that that magnesium could decrease VO2 max
They also saw that with that magnesium intervention that it decreased the mean power output and sprinting and the actual muscle of these subjects, they saw that mitochondrial respiration was decreased. And so it's kind of fascinating. It's still not quite well known why this is, but this study
has been replicated a few times. There is a belief that maybe magnesium is decreasing cardiac output. So we haven't talked too much about the heart yet, but the heart contains a huge amount of mitochondria. So yeah, you were mentioning how muscles maybe have what, like 3 % mass of mitochondria in each one. In heart muscle cells, it can be up to 30 % the mass is mitochondria.
So they need a lot and it could be that this magnesium overload is actually decreasing how well your heart is going to work. So more to come on that, but it is interesting.
So what was interesting was that that sprinting time was off, you know, that was decreased. But when they looked at a longer kind of race, so a 10 kilometer race, that performance was not affected. So
Georgia (1:04:08) Mm.
Siobhan (1:04:21) Endurance is fine, even with a magnesium overload. Sprinting, that's where it's affected. So maybe it's just mitochondria efficiency. And so, yeah, you're thinking, all right, you know, that that sounds bad. Maybe I'll be very careful about magnesium. But there are also some studies showing that if you do have a deficiency and you're an athlete, it does help to get your magnesium back up to, I would say, a balance level.
And they have shown this in studies that, for instance, athletes who are magnesium deficient are literally performing worse in races and also have worse mitochondria in terms of ATP production. So this is all something to consider. But yeah, I would just make sure that people don't think more is more with magnesium. You want to be careful with it. But it does have, obviously, a lot of benefits for mitochondria at the right level.
Georgia (1:05:12) Is there a certain type of magnesium? Because there are so many different magnesium salts that you can choose.
Siobhan (1:05:17) Oh yeah, this is an interesting topic because I know there's all sorts of belief about like this magnesium is best for this function, like magnesium threonate is best for brain, magnesium glycinate is best for sleep. I don't think that's really well shown yet. I think yeah, maybe there are a few studies that have been done in 3-8 to show some sort of brain benefit, but the problem is that we don't really know if that's the best form for the brain.
or if maybe you get the same results if you use a different form. So that's still not clear. magnesium that's been given in kind of inorganic form, so magnesium oxide, for instance, is less bioavailable, so maybe that's not the best form, but magnesium that is chelated to, for instance, amino acids, like the glycinate or, you with arginine or some other things like threonate.
that does seem to be more bioavailable, so you should definitely go for those. Yeah. Yeah.
Georgia (1:06:14) Speaking about bioavailability and specifically bioavailability to the mitochondria, I guess we can move on to our final our final topic for boosting mitochondrial function, which is of course going to be mitoquinol and mitoquinol mesylate.
So mitoquinol mesylate is a very special kind of mitochondrial antioxidant. It's kinda similar to ubiquinol, except it's also completely different to ubiquinol. It's similar at least in its structure. So it retains that ubiquinol moiety, which is the antioxidant portion.
It has a shortened tail compared to CoQ10. CoQ10 is very famously a large liphilic molecule. And then at the other end of mitoquinol, we have a triphenyl phosphonium cation. So it makes mitoquinol positively charged. And if you know anything about mitochondria, you know that they are negatively charged. So what happens is when you take mitoquinol mesylate orally, it can actually get through your cellular membrane and get into that.
inner mitochondrial membrane just from the electrostatic differences, just the opposites attract of positive and negative. So there's been quite a few clinical studies on mitoquinol mesylate, just over 30 human clinical trials,
And MCRP has about 15 still in the pipeline, and these range from healthy individuals to cardiovascular disease, mental health conditions, as well as cancer. So this is all about supporting mitochondrial function as a foundation, and we know that you know mitochondrial dysfunction is a hallmark of aging. it is indicated in a lot of different diseases just because of
mitochondria being absolutely systemic and energy production being so important to every area of the body. But in terms of what mitochondol mesylate does, we know that it's a mitochondrial antioxidant. We know that when it gets into the inner membrane it is able to mop up a lot of those reactive oxygen species.
especially things like hydrogen peroxide. One, it's doing that innately because it is an antioxidant, but we also know that it is a slight mitochondrial stressor to some degree. And this is sort of what we have been talking about throughout the entirety of this episode is a little bit of stress for the mitochondria is actually quite beneficial. Sort of like what doesn't kill you makes you stronger.
So MitoQ can trigger the NRF2 pathway that goes on to upregulate things like glutathione peroxidase.
Catalase and superoxide dismutase. These are these really powerful and important internal enzymes that the body produces to get rid of oxidative stress. So these have been shown in a clinical setting to be upregulated, and the flow-on effects of that is, like I say, rescuing against oxidative stress. So reductions in
not just ⁓ nuclear DNA damage but also ⁓ mitochondrial DNA damage, about a 35% reduction. and that is in response to very high intensity exercise. So exercise obviously is very energy expensive. You create a lot of free radicals.
but sometimes this can be quite damaging.
Obviously
you need reactive oxygen species as a big part of your exercise response. But MitoQ seems to be so specific to the mitochondria that it's not actually blunting any of these key adaptations, kind of the way that a more broad antioxidant might be.
Siobhan (1:09:43) Exactly.
Yeah, and it seems like it's because it's just targeting the mitochondria. And so the kind of adaptive response for exercise is obviously getting some oxidative stress out into the cell and having an effect in the cell. But no MitoQ is out in the cell. It's just in the mitochondria. So if you have something like vitamin C, which can be everywhere in the cell and you take too much of it, it is now blunting that oxidative stress response.
in the cell that makes exercise beneficial.
Georgia (1:10:19) And there has been some clinical studies as well looking at a 20 milligram dose of MitoQ over six weeks. And we have seen a reduction in oxidized LDL cholesterol, which is particularly insidious for endothelial function. ⁓
This is the type of cholesterol along with triglycerides that can go on to cause arthrosclerosis and a whole host of vascular issues. So cardiovascular health has been one of the, I guess you could say, main focuses of clinical research on Mido Q. I was just over in Philadelphia for the North American Artery Conference, where I was fortunate to meet so many members of the MCRP, and we actually had
Had
a symposium specifically dedicated to mitoquinol mesylate. So we had Dr. Vienna Brunt who was showing her research that she has been doing on polycystic kidney disease and how MidoQ might help to sort of alleviate some of those morphological changes that happen with that disease, as well as improving vascular function. Dr. Matt Rossman was there, he has been doing some great research on older but healthy individuals and seeing how.
How MidoQ can help vascular function, as well as in combination with exercise. And we had Dr. Zachary Clayton as well. So he has been doing some research on using Mido Q as an adjunct therapy to chemotherapy to help to reduce some of the damaging effects of the reactive oxygen species that are produced when you give doxo chemotherapy to individuals. So we have a
great research community. There's a whole lot that is going on at the moment. We would love for anyone who is listening, if you are a researcher, please reach out to us through the MCRP. It's something we can provide you complimentary mitoquinol mesylate in a powder form.
Or also in capsule form we can give you those matching placebos as well, ⁓ all for free, just in the name of good science and understanding how mitochondria are being affected. I don't know if you had anything to add, Javon.
Siobhan (1:12:27) Yeah, that's beautiful. I think you explained everything so well, Georgia.
I think the great thing about you hosting this podcast is getting the word out about MCRP, getting people excited about
how can they improve their mitochondria health.
Awesome. Okay, well thank you, Georgia.
Georgia (1:12:44) Well thank you, Siobhan, for coming and chatting to me. ⁓ it's been a great conversation.
