Mitochondria, Menopause Energy, and NAD: Why You Feel Flat and How to Fix It | Siobhan Mitchell

If you're doing all the right things, training, eating while, sleeping while, but still feel like your energy and focus aren't where they should be or you simply want to level up your energy, today's episode is going to help you fix that. One of the biggest shifts from me, especially through perimenopause, has been supporting my cellular energy. Alongside high quality nutrition, sleep and exercise, one of the key ways I do this is by supporting my mitochondria with NAD precursors. NAD is like your phone's battery capacity. You can be doing all the right things, charging it, closing apps, optimizing everything, but if the battery only holds half the power, you'll still run out of energy faster. In real life, that looks like you're doing all the right things, eating high quality nutrient dense food, exercising regularly, sleeping well and managing your stress, but still feeling off. That's exactly what can happen in midlife. NAD levels naturally decline as we age and by around 40, most people have roughly half the NAD they had in their 20s. Even if you are doing all those things, eating well and exercising, your cells have less capacity to produce energy, repair themselves and stay resilient under stress. That's why supporting NAD has made such a noticeable difference to my energy focus and mental clarity, and exactly why I wanted to invite today's guest on to explain this properly. Dr. Shivorn Mitchell is the chief scientific officer at MITOQ with a PhD in neuroscience postdoctoral research in brain aging and senior research roles across global companies where she's led large scale studies on cognition, mood, performance and metabolic health. In this episode, we go deep into the science that most people never fully understand, but directly affects how you age and perform. By the end of this conversation, you'll understand what's really driving low energy and faster biological aging at a cellular level. You'll also learn how mitochondrial health and declining NAD affect focus, fatigue and recovery in midlife, and you'll get clarity on which interventions actually move the needle and which are just noise in the longevity space. We cover quite a bit of science here, so we're always trying to pry this practically, but if you want the studies, summaries and resources that we reference, you'll find everything over on my website at angelapostopperformance.com. I've also added links in the show notes, including the NAD supplement I personally use, which is NAD plus by MITOQ and a discount code using code Angela. This episode is really about working with your biology, rather than pushing harder against it. So let's dive in. Shabon, we hear so much at the moment around mitochondrial health, inflammation. These terms that kind of get banded around, and I think that my audience listening will be familiar with these mitochondria being the battery packs of ourselves. I think we're all aware that they impact our energy, but I'd love to dive deeper with you because it's such an area that's so important for longevity, and I know that you're an expert in this field. Can you explain to us really what our mitochondria are and how they are affecting our energy and cellular aging? Yeah, for sure, and that's a pretty big question and stuff, but let me just get going, I might take a while. So mitochondria, yes, they are the powerhouse of ourselves. They make up to 95% of the energy of ourselves, so they're very, very important for all cellular function. And so what they're doing is they're making ATP through all the foods that we eat. So carbohydrates, protein, that, and it's great that they make this energy and they do it all the time. I can give you all the sorts of stats about how much ATP you make every day, literally kilos and kilos of it. But I think what's really important to realize is that there's a trade-off in making all this energy. And so the fact that we have this incredible powerhouse in ourselves is also meaning that we make a lot of oxidative stress to create that ATP. And the way that happens is that we all know that we need to breathe oxygen to live. And so this oxygen is so important because we're using it to make that ATP. So every time you're making an ATP molecule, you're using some oxygen. And oxygen is highly reactive when you start to use it, when you break it apart. So when I say oxidative stress, I'm talking about the fact that oxygen causes oxidative stress when you break it apart because then becomes something called a free radical. And this free radical basically is like looking for electrons. It's on this hunt for electrons because it doesn't feel complete. And when it looks for electrons, it looks for the closest thing. And so that's usually the mitochondria membrane, the mitochondria proteins. And also it's DNA because mitochondria also have DNA. And so when you have that damage going on where it's grabbing electrons from your membranes, from your DNA, your protein, this can cause dysfunction over time. And so oxidative stress that's continually happening in the mitochondria can cause a lot of damage that can lead to aging. And the great thing is, like this sounds really scary, the mitochondria over billions of years have developed a lot of ways to deal with that oxidative stress. So a lot of enzymes that they use, that they're making themselves to keep that down. But the same thing as you ate these enzymes, these antioxidant enzymes, things like COQ-10, you probably heard that. It's all start to get depleted because the mitochondria are just still having so much damage. And they're not able to kind of renew themselves very well. So it's this constant battle inside ourselves to make all that energy that we need. But even when we're making more energy, when we're having high stress, high intensity, anything, we're making more oxidative stress at the same time. And this could be more damaging if you're not doing a good job with your oxidative stress systems and having the right antioxidants. So that's one thing that we should all be aware of with mitochondria. It's a little bit a deal of the devil. And so when I hear people say that when they're stressed out and they're having that energy to completion, I'm like, yeah, because stress causes your mitochondria to rub up. And at the same time, you're making more oxidative stress and causing more damage. And so over time, that can be much more of a depletion of how your mitochondria can function. So yeah, that's, that's the whole thing. I could now just go on to another thing that mitochondria do that is also really important in the way that we age, but I wouldn't just take a breather and see if there's anything else you want to follow up on. Yeah, thank you for that. Before we go on to the other things that mitochondria do, I guess if we could clear up sometimes, because I think these are also people hearing more and more about these. So we have mitochondria, these powerhouses of our cells. And then what you are describing now, I believe, is we need to renew our mitochondria, right? And recycle parts of them just like we have people who have heard of autophagy because people are familiar with fasting. My understanding is that we have mitochondria in terms of our mitochondria. And then we also have mitochondrial biogenesis, which is the creation of new mitochondria. So would it be fair to say that as we age, we get less good at, like less good wise, let's get at three things, right, effective use of our mitochondria in the way that we did when we were young, effective recycling of those mitochondria and renewal, and then less creation of new mitochondria, would it be fair to say all those three things start to take place with aging? Yeah, that's exactly what happened. So perfect, like you're just adding on to the story that it's true that mitochondria, because of the damage that is incurring in them, it's good to recycle them from time to time, and that's part of the process of all your cells all the time, but as you age, they don't get recycled as much. And so you just have these dysfunctional mitochondria just sitting there. And for instance, you've probably heard of senescent cells, zombie cells, so these cells are just that they're doing nothing and actually cause information. They're being caused by mitochondrial dysfunction. So when mitochondrial dysfunction turned over, so that term mitophagy is not happening. This leads to more chance of senescence, these cells just sitting there and becoming zombies and doing nothing. And these are in all cells, right, even I learned like even in skin cells and then they deplete collagen and things like that. So we don't want more of those. You talked there about oxidative stress, and when we are under stress, there is more oxidative stress. So one area, I think you mentioned there was us just being under stress, right? And we are modern life is very stressful, both in terms of I guess mental stress, but also toxins and things that we're exposed to. But then also high intensity training, for example, can we distinguish in any way between those types of stress? My understanding is that with high intensity training, for example, this can actually help with the creation of new mitochondria, is stress, different types of stress, are there differences in the way it's impacting on mitochondria? Yeah, yeah, exactly. This is a really important point is that there's stress, things like as you say toxins, mental stress. And there's, I would say, this is a very interesting term, hermetic stress. And hermetic or hermesis is basically this term that means when you kind of push a system to adapt and make it stressed a little bit. And then it's able to deal with bigger stresses in the event of like a bigger stress, right? So that's hermesis. And that's basically what's happening when you exercise. So you're stressing out your muscle cells, you're telling them, okay, we need a lot of ATP, we need a lot of oxygen, and they get a little bit stressed. But then this causes them to adapt and exercise you adapt by making more mitochondria that myocondrial biogenesis, you make more ability to take that oxygen and turn to ATP, so that's sort of machinery of it. And this is good over time because the more mitochondria you have, the better able you'll be able to deal with things like mental stress and deal with, you know, other kinds of inflammation and aging and all the rest. So exercise is great for you in terms of telling your body, okay, we need more ATP, we need more oxygen to deal with this intensive exercise. But what is not good over time is when you just have a stress that's not controlled, you don't have a recovery time. So exercise, of course, has a nice recovery time where you get everything back to normal and all the rest. A lot of these toxins don't give you that chance to go back to normal, a lot of the mental stress we have, don't give you that chance to go back to normal. And that's what it becomes a real problem. Yeah, yeah, exactly, especially in how we're living today. When we look at exercise, I, from the research I've seen, we can kind of almost bucket exercise into two areas where when we go, as you were mentioning earlier, high intensity exercise, that helps us create new mitochondria. My understanding is that if your body thinks you out, run, out around the tiger, then it's going to upgrade itself in case it happens again. And then when you're going at low intensity, kind of classically zone two, you're improving the way those mitochondria behave, the way they act and support your energy. I'd love you to like share, you know, if that's right, and more on that really. Yeah, that, that is really how it works. So what's interesting is when we talk about intensity, we know that people who professionally are athletes have twice as much mitochondria in their muscle cells than other people. And the fact that they have that extra mitochondria helps with their metabolism. So they're now able to take it in glucose much better than normal people. And that helps protect them against diabetes, for instance. So if you're not exercising a lot and you're not having that ability, you're free muscles to use that glucose really quickly, through making more glucose transporous, for instance, and having these mitochondria that can use all that glucose, you are much more likely to start showing pre-diabetes and then have also each in acceleration. So there's also some benefits of exercise in various ways, these adaptations. I could go on in a lamp, but that's just one example. Yeah, great example. And it like, as you say, makes you more resilient. So hopefully we can give people permission who feel a bit too busy to add in, you know, more exercise. Because actually, as you mentioned there, it's making you better able to deal with stress. So you actually show up better at work, take more on potentially mentally, right, because you have better mitochondria and have better attention, better focus, better energy. When we look at, before, and I know you're going to talk about another role that mitochondria have, when we look at oxidative stress, so this is just, as you said, it's kind of the deal with the devil, right, we've got to, we've got to breathe out oxygen, otherwise we're not going to stay alive, but then as soon as we use oxygen, we create oxidative stress, what can we do to support that in terms of like reducing oxidative stress in the body? Yeah. And then this is a tricky one because the oxidative stress that happens in the mitochondria, there's not a lot you can get inside the mitochondria. So it's a very privileged area because it's so important to the cell, it doesn't allow a lot of things in, it's got lots of special transporers that allow certain things in, but it has this double membrane and it just only lets a few things in. So in terms of the antioxidants that you know can get into mitochondria, there aren't that many. You can use something like your vitamin C or vitamin E, but they tend to go elsewhere in the cell, not really that much in the mitochondria all the time. CoQ10, I know people are very excited by CoQ10, but CoQ10 is very large and there's no transport system inside the mitochondria. So even though people always hear about, oh, CoQ10 is really good for mitochondria. When it's made inside the mitochondria, naturally, but when you're taking an oral CoQ10 supplement, it's not like going inside the mitochondria. So that's a real issue. So one thing I would recommend is, you have the, the foam you pick. Does that make a difference in the mitochondria? Yeah. CoQ10 is really about its oxidation status, so it's still kind of the same molecule, this very bulky molecule. That's very hydrophobic, so it doesn't like being in water. So it's just not even getting absorbed into your gut very well, and it's probably getting through cells or sort of mitochondria that well, it needs its transport system. So the, the other thing that I like to tell people is that there are antioxidants out there that have been designed for getting into the mitochondria, and that's mitochondrial mesolate, also known as mitochondria. So that can get inside your mitochondria and address a lot of the oxidative stress. There's a lot of other things that, you know, on top of something like mitochondria that just makes sure that you're not going to have that much oxidative stress in the first place. So good diet, lots of exercise, you know, keeping that stress level down. That sort of thing, like very basic stuff, but the other area that is really good for keeping down oxidative stress is keeping your NAD levels up as well. So I think people have heard a lot about NAD, but I can just go into a little bit about how NAD, because it's got such an important role in the mitochondria, and I can kind of go into all sort of functions in the mitochondria, but one of its functions is to help with your redox daily mitochondria, and when I say reox, it sounds like a terrible word, but it just leaves me how much oxygen is in your mitochondria and how much oxidative stress is in your mitochondria. So it helps regulate that, so we have less oxidative stress in your mitochondria. And one way that does that is through activation of searchuins, searchuins are these big family of molecules that basically do that kind of adaptation to stress that I told you about that or mesis. So searchuins are basically turning on a lot of cascade of genes that help our cells deal with oxidative stress and also to, I would say, very complex pathways, but the end result is they turn on a lot of longevity pathways as well. So allow the pathways that searchuins turn on are them able to keep our cells doing for longer, have more of that, you know, mitochondrial biogenesis in mitophagy. And this is where I think it's really fascinating because people have heard about searchuins a lot, but what is really interesting about searchuins is that they're one of the first longevity pathways that we have ever learned about. So the way we learn that you can actually extend your lifespan is through calorie restrictions. So the mice, they saw that a few strict calories up to 40%. You can have a mouse live like 25% longer, 30% longer, and they're like, this is great, but no one's going to do calorie restriction, we know that. What's the pathway that's getting turned on in calorie restriction? And they found out that the pathway getting turned on was through searchuins. Searchuins were basically telling cells to be better at clearing away oxidative stress, have the cells being ready for more stress coming through and also use energy very efficiently. And so they're really a master switch of longevity. You can't out train low energy, it starts deeper than that. I'm often asked how I juggle running my business, raising three kids, and still training the way I do. And honestly, it comes down to one thing, protecting my energy. That's why I'm intentional about how I support my body at a cellular level. And one of the ways I do that is with mitopia, longevity gummies. They're the first clinically proven uralithine gummies designed to support your mitochondria, the powerhouses inside your cells that drive energy, strength, and healthy aging. What I love is how simple they are. I don't really enjoy taking lots of capsules, but timeline gummies are easy to take and they taste delicious, which is probably why my husband keeps nabbing them. They're also free of sugar and artificial sweeteners. I think of this as charging your internal batteries every day, helping your body produce energy more efficiently so you can feel clearer, stronger, and more resilient. Yvegan, non-GMO, NSF certified, and the number one doctor recommended uralithine supplement. If you want to feel stronger rather than just trying harder this year, this is a smart place to begin. And that's why I've partnered with Timeline Long Term, get 35% of a one month subscription of mitopia gummies at Timeline.com/Angela35, that's Timeline.com/Angela35 while the offer lasts. When you talk about that, the thing that brings to mind is that's a better route, right? Then caloric restriction, because when you start to have caloric restriction, your energy is going to go down, so you're probably less likely to exercise anyway, but it can have profound implications for muscle health, for bone health. Then we start affecting other areas that are really fundamental for longevity through like really extreme caloric restriction. Before we come back, because I do want to talk about constituents and NAD, I think everyone wants to really dive into that, you mentioned there was another role that you wanted to touch on of the mitochondria. Did we go over that? Yeah, yeah. Let's go into that, because I think this is maybe not what people have heard of their high school biology class, but super interesting, in fact, it's the big interesting field of mitochondria right now, so this is big. It's the fundamental goal of mitochondria in your immune system, and also being the master's switch of your cells and how you deal with inflammation and immune responses. This is very exciting right now, because I think we're all very worried about immunity and inflammation. Everyone's aware that inflammation is a huge cause of aging. But as new is in the last few years, understanding that mitochondria might be the reason why we have a lot of this uncontrolled inflammation over time, and just to make sure everyone understands what inflammation is, inflammation is basically when you turn on a whole bunch of immune cells that are supposed to clear away infections like viruses, bacteria, that kind of thing. But if they're getting turned on a lot of time, they end up causing more damage to cells, because they're causing a lot of chaos in their cells through these things called cytokines, which I can go into. But the main thing is that we're now seeing that mitochondria might be the reason why you have inflammation just getting turned on all the time and staying on all the time. So for instance, with COVID, they showed that with COVID, an infection, basically when the virus enters the cell, it makes the mitochondria release a lot of its DNA. So I mentioned that mitochondria has its own DNA. And the reason why mitochondria has its own DNA is it used to be a separate organism billions of years ago that got swallowed up by a larger cell. And this larger cell was like, oh, this thing makes a ton of energy, how useful, we're going to keep this. And so then it got incorporated into this larger cell, and then which is used as a powerhouse. But it still has this DNA that's kind of concerned foreign. And so whenever you have foreign DNA coming into a cell, that's kind of a sign that something's infecting you, right? Because that's what viruses do. They come into your cell and they try to insert their own DNA or their RNA into your system and you have to attack that. So what's happening is mitochondria are being kind of used as a canary in the coal mine, kind of a master switch of like something is wrong, something is wrong with the cell. And so when it releases that DNA, or even when mitochondria release a lot of oxidative stress, so they usually try to keep all that oxidative stress within itself. But if a lot oxidative stress gets out into the cell, it basically causes this immune response. And this immune response, I could give you all the names of it of how it works and everything. But what is interesting is that then can lead to something called a cytokine storm. I don't know if you've ever heard that term before. You used a lot around COVID. Yeah. Basically, that's that's mitochondrial orientated a lot of the time. And this cytokine storm is basically causing the cell to often die or become damaged. And then that cytokine storm gets released into the bloodstream and causes more damage elsewhere. So I think it's really interesting for people to be aware of that we want more energy and we should take care of our mitochondria for more energy. But we also want to keep your mitochondria just really happy, really in a good balance because this can help prevent that constant inflammation, that immune response that we don't want, that doesn't have anything to do with an infection. It's just kind of there and it's causing a lot of damage to our cells. And this is especially bad in the brain. So the brain has a lot of this kind of information that's just occurring, like a lot of immune cells in the brain are just getting turned on. And there's more and more sort of demonstration that this immune activation in the brain might be leading to all summers, for instance, in a lot of neurological diseases. So if you target your mitochondria, if you take care of your mitochondria, this is the big secret to helping keep your brain healthy as well too. And in fact, there's a lot of evidence right now that if you can target your mitochondria to do something like white OQ or co-Q10 or other kinds of NAD, activating mechanisms. So increasing NAD in the brain, you can get rid of a lot of all summers pathology. So it's a really exciting field. Do you know, it's really, really interesting because sort of observationally what I've noticed is, so when we look at kind of from a fitness perspective, one of the sort of fitness tests that I do with my clients is to look at how many watts of power they can produce at a low intensity. So when they're doing, it's fully aerobic exercise. So they're at 75% of max heart rate. And we would look to see, can they produce at least two watts of energy per kilogram of body weight. And in people who are having a lot of inflammation or they have immune problems, they're struggling with their energy, they just can't get their heart rate has to go up in order for them to produce that power. And so one of the things we work on alongside all the other things is actually, how can we get them better at lower intensities of producing this power and work on the mitochondria and then also mitochondria renewal. And so it's very interesting what you were saying because observationally that's what I've noticed is people who seem to be under pressure from an immune perspective also have problems with producing this power. Yeah. And this is why a lot of people with autoimmune disorders have so much fatigue. So that's literally just their mitochondria just having a super amount of dysfunction. And it's just, yeah, you're not making as much energy, but you're also creating this vicious cycle of more than immune activation, which then is to more mitochondrial dysfunction, which leads to more immune sort of dysfunction. So it's, yeah, it's, it's really a little bit scared when you think about it. So it's, I always tell people when you really have to clamp down an inflammation as soon as you can through your mitochondria, but then also through a lot of other things that you can do to at least address the cytokine levels. And that's a lot of polyphenols. So I always tell people like, you have to tell a lot of polyphenols. So all those, those berries and green tea and spices. And I know everywhere right now is like really to carnivore diet and I got to get more protein and I'm like, no, no, you need more polyphenols. Like, don't forget notes. They're so important. So important. Yeah. And what you were saying there around the mitochondria now, might your mitochondria maybe affecting brain health, so making it more likely that you suffer with Alzheimer's. What was the mechanism there? Oh, yeah. So the mechanism is basically that the brain is the most energy intensive place in the body, right? And continually needing all its neurons to have this endless supply of ATP to do all the functions that we do, even at resting state, even when you're sleeping. And so I have a PhD in neuroscience, I've studied this all my life. Like my life has been dedicated to trying to understand how do we prevent brain aging and things like dementia. And I used to think it was, oh, it's amyloid. This is like what everyone talks about, like amyloid plaques, tau pathology. But over the last few decades, it seems clear that there's more probably an inflammation and mitochondrial origin that leads to problems with the way that, yeah, obviously the brain makes energy. And so if the brain's not making energy, this can lead to that inflammation. It can lead to more amyloid, for instance. So people think of amyloid is like, oh, that's the main problem. But what's causing the amyloid to get overproduced? The amyloid is getting overproduced as a immune response. So that immune response can be triggered by mitochondria and it also can be dampened down if you get your mitochondria back to a more functional state. So and this is, this is something where I can really get into in terms of woman because what I really want women to know about, especially with the menopause transition is that when you're going through the menopause transition, estrogen is really important for the brain and really important for your mitochondria. It's protective for your mitochondria and when we lose estrogen in the brain, your brain mitochondria start to have a lot more issues making the right UTP, having more inflammation and that kind of thing. And you know, even things like these menopause symptoms like night sweats can be an indication that your brain is having dysfunction, that your brain through these night sweats is now needing more energy than it did before suddenly and it doesn't know where to get that energy. So it starts to use the white matter of your brain. The white matter of your brain are basically these kind of like fatty little sheaths around all our neurons that make our neurons work faster. So it kind of helps the signal, it's like a telephone pole kind of thing. It's sort of helping the signal go faster than normally does. When you kick away those those fatty sheaths that the white matter, your brain becomes slower. And neurons are not as fast as they used to be so that it can beat to things like brain fog. And then over time it can lead to actual cognitive decline. So it's especially important for women to take care of their mitochondria and also, you know, find ways to do something especially around the menopause time. So that's that's my big message. And to think about estrogen, right, it's also important. Yeah, definitely. And I love talking about phytoestrogens too, but maybe for another time phytoestrogens can also be really good for mitochondrial function as well. So along with polyphenols. Yeah. Right. Interesting. And creatine also really good, right, for creatine is the, for literally that, yeah, that way of helping your brain maintain its, its energy. So getting that ATP recycled in a super quick way. Yeah. Yeah. And when you're talking then, so when we talk about hormetic stress, just briefly, you're talking about a stress that we place on the body that basically makes us more resilient. So this would be things like exercise stress, sauna, cold exposure, I think wild plants, right, things like that, or hormetic stress. The constituents, just so we can come back to that, because I think this is also really important. So the constituents are kind of our longevity genes, would you say, how do these operate? Some of them I know, for example, I can't remember which one it is, whether it's one or three, but one of them affects our metabolic rate, right, and how lean we say, I think as well, has an impact to a degree on that. Yeah. But all these. Sorry? There are many rules, but yeah, go on. New rules. Yeah. So when we're thinking about constituents, can you just explain how these are affecting our longevity and the best way to support them? Yeah. So they're supporting our longevity through these pathways that I think some people have heard of before. So for instance, I know if people have heard of NRF 2, NRF 2 is this longevity pathway that basically prepares yourselves for more stuff, more damage to happen in the future by, as I said, helping use energy more efficiently and also turning on genes that can kind of clear up stuff, you know, like have that autophagy, mitophagy. And also these other pathways that help rebuild the cell. And then there's other things that search ruins do that are even more around what you just talked about, you know, helping people lose weight or use energy more efficiently. And that's through AMPK. So I don't know if you've heard AMPK. Yeah. Yeah. So these are all different things that it can do, but they can get really complex. So search ruin three, for instance, search three is one that's in the mitochondria. And this one is really important for the mitochondria to have resilience, especially in the mitochondria. Other ones, search one, for instance, is more about helping with DNA repair. So turning on genes that help with DNA repair. So they do all sorts of different stuff, and it's, I would say, really interesting to look at all the different kinds of molecules. And like I have to say, also supplements that can turn on these genes. So probably the one that everyone knows about is a reservoir, a 12 or 12, where you got it. Turning on some of these search ruins, like sort of one, but then there's also a lot of other things that can turn these things on as well to like PQQ, like my go Q, which I also mentioned. So yeah, I think just finding these different kind of pathways, also working together. It's really important. So I try to tell people use a lot of different kind of search ruin activating situations. And that includes NAD as well. So NAD precursors. Yeah. So NAD is something that is becoming more and more popular that people have heard of, right? And it's definitely becoming a bit of a buzz around it, I think, because when we think of NAD, now we think of energy. And from my understanding is this halves about every 20 years, right? So I think we're not as good at supporting our NAD levels. So now we've also got another mechanism, right, that can be lowering our energy, causing some of that brain fog and things like that. Can you explain what NAD is? Yeah. Yeah. So I will try to use maybe some analogies, because I think that always helps with this kind of thing. So NAD is kind of like the, I would say, fuel oil or kind of like precursors that help you make the ATP. So there's something that the mitochondria make as they break down things like carbohydrates and thoughts. And so it's basically really important for the mitochondria to make a lot of these NAD, because these NAD have a very important role of carrying what's called protons, and protons are basically what's used to make the ATP. So you want to have a good collection of these protons being carried by these NAD molecules that at some point kind of get collected at this one part of mitochondria machinery, the ATP synthase. And basically what's happening is all these protons are getting kind of released from the mitochondria, and this causes ATP to be made. It's sort of like this electrical force that NAD is basically delivering to the mitochondria. So it's basically kind of delivering sort of a battery to the mitochondria. And so then if you don't have NAD, if you don't have a good supply of NAD, you can't make this ATP, or you're not going to make as much ATP. So that's a real problem, but that's just one role of NAD. NAD is also used for a lot of other things that the body needs to kind of turn on for things like dealing with cell stress. And so I mentioned searchuins. NAD is really important for turning on such searchuins in all those longevity pathways. It's also used as an immune response. So kind of fast enough, there's another pathway that's called the CD38 pathway. And CD38 is basically this receptor that tells cells that you need to turn on a whole bunch of immune response machinery. And it needs NAD, it basically breaks NAD in half to do that. The problem with CD38 is this is another thing that tends to go up when you age. And so it's located especially on fat. So for instance, people who are overweight tend to have more of this CD38 in their fat cells, and just more of it just in general, because they have more fat cells at a post-issue. And this CD38 then basically requires more and more NAD. So if you're overweight, or you have a lot of inflammation, or mental stress, things like that, then you're using a lot of this CD38, and then you're using a lot of your NAD. So one of the hypothesis of what is NAD go down as you age is that you're having more CD38 expression, and this causes more NAD to get used up. So yeah, that's a sort of interesting hypothesis right now that people are exploring. But then it becomes also really interesting to understand like, how do we prevent that? How do we turn off the CD38 gene? And they show now through a lot of MAPS knockouts, what I don't have CD38 that these mice are healthier, they have a longer lifespan, they don't get as many diseases. And also if you apply a CD38 inhibitor that you can overall kind of improve function in these mice, they're probably now, I would say, getting more data in humans. But that's sort of initial promising data. What's interesting is just to kind of round that out is that you can actually have a CD38 inhibition through also some other kinds of molecules. I think one of the best ones that people have talked about before is Apigenin. Have you heard of Apigenin? Yes. Yeah. That's things in pastures. Also helps with sleep. Apigenin, right? Sorry. Apigenin, I understand, can also help with sleep. Yeah, I can actually, it's, I would say it's like a multi-functional kind of molecule. That's the sort of different pathway, or I mean, it could be a little bit related. I would have to go check, but definitely it's a CD38 inhibitor. So it's really fascinating for people to look at how Apigenin can help. There are other ones that are also coming out that are really fascinating. So PQQ is another one that seems to be helpful for decreasing CD38. So a lot of these different kinds of molecules are now being looked at, you know, especially from supplement levels, because it'll probably take, you know, 10 years for a CD38 inhibitor to come on the market, but a lot of these supplements do seem to be very helpful. For years, I did everything right. I trained consistently, ate well, prioritized sleep, and yet I kept seeing the same pattern in midlife women and in myself at times too, fatigue that didn't match lifestyle, brain fog, poor recovery, wired, but tired. One of the biggest missing pieces for me was minerals, not just magnesium or sodium, but deep cellular mineral depletion driven by stress, training, and hormonal shifts in midlife. That's why I use B minerals. I take electrolyzen the morning and around training sessions, and micro boost daily to support detox and recovery. I notice the difference in my energy, my focus, my sleep data, and how quickly I bounce back. If you're training regularly, navigating perimenopausal or want to support longevity from the inside out, I've partnered with B minerals. They're the mineral system I personally use, and you can try them at beamminorals.com/angela using code "angela" for 20% off. That's beamminorals.com/angela and code "angela" for 20% off, and I'll also add a link in the description. And with CD38, you're saying it gets more activated in the cases of obesity or inflammation, obviously inflammation tied to obesity, so actually staying lean and healthy is really important, lowering inflammation, but then in order to stay lean and healthy, you need to look after your mitochondria, which obviously a lot is contained in your muscle as well. So it's a circular thing, we come back to it. With NAD, we have precursors that we can take, and then we also have the recycling. We can create more, and it has a new NAD that we can also recycle some of it. So there's two things going on, I think, support NAD, and I think that's an important thing to look for. I'm going to come into the other areas that you've spoken about that are also important when we're looking at supplements, but my understanding is that when we're looking at supplement to support NAD within the body, we need to look at precursors to help us create more, and then also other compounds that are actually going to help us recycle what we have. Yeah, yeah. And so what are the main ways that recycle NAD is through a salvage pathway that takes up Nyson, so I think everyone's heard of Nyson, it's a B vitamin, B3 that should be something that we take more of in our diet, but I know a lot of the time we don't. This is converted into NAD through this enzyme called NAPT. And NAMPT is basically, yeah, kind of restarting up our NAD supplies in a very quick way, because if you make NAD from scratch all the way from chip to fan, it can take a long time for cells to kind of build up supplies. So this is really, I think, the most fundamental and useful way that we can, yeah, build up our NAD supplies really quickly. So what's really important to think about when you take an NAD precursor is that a lobby's NAD precursors, whether it's NR, whether it's NMM, they will end up getting converted into nicotine and need. This is like really clear. I think for a while people are like, oh, we're not sure, but NR, NMM, they basically are converted to nicotine and need, which is a derivative of Nyson in your gut, and then also in your liver. And then through that pathway, what's their nicotine and need? They get converted into NAD through NAMPT. And so what you need to do is you need to make sure that there's a lot of NAPT that can then convert it into that useful form, which is NAD. So, yeah, you want to have things that activate NAMPT. Things like PQQ has been shown to help with NAPT expression. And just so people are aware, NAMPT is also something that gets a lot more expressed when you exercise. So that's another cheap way of getting NNPT to come alive in your system. So yeah, this is where I definitely, people don't understand though what they take that precursor. If they're not having the delivery systems to make that NAD, then it's probably not going to go where you think it's going to do. If you don't have enough NNPT expression, then all that NR, you're taking all that NNM, just gets converted into methyl-tikinicotinimide and then just gets flush out your system becomes kind of useless. So that's a really fundamental thing. The other fundamental thing to know about when you're taking a NAD precursor is that it's very helpful that mitochondria is we just discuss, but you also need to make sure your mitochondria are functioning in other ways. So, mitochondria, they're healthy. They don't have as much oxygen as stress and have all their machinery intact. And so then that's where it becomes important to have these kind of other activators of mitochondria health. Other ways you can activate surgeons like the respiratorol that I mentioned, and PQQ itself is a really great antioxidant, so that's really important for helping with oxidative stress in the mitochondria. Yeah, I should mention PQQ is a mitochondrial antioxidant that has good entry into the mitochondria, so it can be very helpful for decreasing oxidative stress and also increasing that AMPT expression that then allows more use of your NAD. So it's really about like a whole system of how to make sure your NAD is working best for your mitochondria. So you get more energy, you get more of those benefits that people are looking for. So just so I can make sure that I'm clear and everyone is quite a lot of science in. So I want to try and like summarize it in my sort of layman terms. So we can make an NAD, but we also can do it more quickly through NAMPT, which we need to activate. We can activate that ourselves physically through exercise. Is that all type of exercise or is it particularly aerobic exercise or resistance training or any exercise? It's I think exercise where it's pretty intense, like it's not going to go crazy if you just take a walk. And I think you've heard of that too. Like mitochondria are not going to get that much done for a walk. You have to make it so that you're actually breathing hard, you're feeling that lack of oxygen, which then tell the mitochondria like something that is happening. We need to get ready. We need to turn on gene expression systems like the NAD, like the Hormetic system. So you want to get that out of breath feeling and that's the signal to the mitochondria. You need to do something to make you ready. Be more resilient. And yeah, that's why workouts then become easier and easier is that your mitochondria now become more resilient and they can handle more use and energy. Yeah, got you. Okay. So that comes back to the Hormetic stress. So then we need to create this NAMPT, otherwise we can't use. So if we're just taking NAMN or NAR, actually, as you were saying, a lot of it is going to get flushed out. So exercise can help, but then so can PQQ you mentioned. And then we also have the statuans, which are supporting our, they're like longevity mechanism within the world to support healthy cellular health and healthy mitochondria. How are they coming in just so we can, if you could summarize the whole picture, that would be really helpful. Yeah. And I know it gets really complicated. But yeah, like so, as I said, there are special surgeons, especially for the mitochondria, where they need to get turned on. So things like searching for you to have a lot of that mitochondrial turnover that able ability to have this stress response that helps the mitochondria, you know, have that hormisus for exercise, things like that. So like a really fundamental pathway to make sure your mitochondria still healthy is through the search, search your own crews. And PQQ we know as well actually gets into the mitochondria, whereas coQ10 does not seem to. Yeah, not that, not that much. Yeah. Not that much. You're like five percent to get into the mitochondria. Yeah. A little bit less. Yeah. Okay. Really slow. Okay, amazing. And then we have Apigenin, which is a CD38 inhibitor, so that's going to help calm this inflammation, but then also take care of our health and having good mitochondria and not having too much inflammation and not obesity is also going to in turn help deactivate that pathway as much as possible. MitoQ has the special ingredient. So it's supporting mitochondria on multiple levels. I've certainly noticed big differences in my energy since starting it. And I know that it's not just me, right? There's really good science behind how this works. Can you explain what's in that and how it's supporting our energy? Yeah. So I think you're referring to one of our products called NAD booster. NAD booster. Yeah. Yeah. And this is one of our newest products. So I am very passionate about mitochondrial health. As I said, I have dedicated decades of my life to figuring out how we can we can make our mitochondria work better for longer. And so MitoQ had a lot of products focusing on this mitochondrial muscle, this special targeted antioxidant. But what I also felt was really important is that we target NAD and we find ways to replenish NAD. So we basically worked on this, this, yeah, supplement that could have the NAD precursors, but we know that's not the whole job that, you know, having those NAD precursors, the NR, the nicotine of need, they might just get flushed away. They might not get used unless you have that ability to convert it into the NAD, the proper form for the mitochondrial function. And that is through, yeah, making more NAD PT, which is that salvage pathway sensei sort that that enzyme. And so we also added PQQ to have more of expression because we know even though you should exercise a lot and get your NAD PT to go up that way, not everyone has time to do it all the time. So we want to make sure that that was an activation that was in the product. And then we also included risk-varriage wall, which is very well known, search-u-n activator. And search-u-nce are very important for overall myocontrial function, is I just explained. And then we also want to make sure that there's less information overall in the body. So helping tamp down that CB38. So yeah, the risk-varriage wall, the PQQ with this antioxidic capability, could also just tamp down to information and oxidative stress as well too. So your overall NAD levels can stay as high as possible through multiple different mechanisms. Got you. And so then it's actually getting into the cell. Yeah. Yeah. So this is, yeah, that's the other thing is getting into the cell. I think people aren't really aware like this is what I find really frustrating when people say like, oh, I did an NAD IV, it was amazing, I felt amazing. I'm like that NAD is not really getting into your cell. It's just in your blood. Yeah, it's not going to get into your cell unless it's in that precursor form. So the precursors could be very effective, but you just need to make sure you take that precursor that you have a way of converting into NAD once it gets inside the cell. So super important to think of that. I honestly feel like a lot of those IV kind of NAD infusions, like they're just causing a super strong immune response that make people feel like something's happening. It's almost like a placebo fact, but it's not really doing anything because most of the NAD that is infuses, then just getting flushed away. Well, and it has to be delivered very slowly, right? Because it like causes rapid popitations. I mean, I mean, I mean, people have bad reactions to it because they're literally having a bad immune response to it. Yeah. So yeah. And as you say, it's going into the blood, which is not really where it's needed, it's in the cell, which are the precursors that's needed. But then if you're just taking something like NMN, you might end up just flushing it away because you haven't got the other ingredients that you need to help with the NAPT, which is why you formulated it in a very specific way to do that. When thinking about taking it, is it energising on the day, is it, or is it more of a build up? So like, should you take this in the morning? Yeah, I would say it's energising over time, and I would take it in the morning. So in fact, that's when our body is making the most NAD is in the mornings. That's when all these salvage pathways, things like that are turned on the most. So if you want to get that best kind of conversion to NAD, like definitely take it in the morning, I had some people say that they feel better, you know, in a few days of taking something like an NAD booster. I happen to notice more of an effect. Actually, I think after like a month or so, like my workouts get easier. Yeah, so NAD is especially useful for recovery from workouts, from high intensity workouts. People don't realise that when you do a high intensity workout, you're actually causing d-day damage and a lot of inflammation. And so you want to be able to deal with that as quickly as possible. And so d-day damage can be stopped or can be kind of repaired through PARP, which is another NAD kind of activating system. So you need a lot of good NAD levels when you're exercising to make sure that your PARP systems activated, you get that d-day repair after a workout. So then you get the recovery to go and do more exercise. So that's another thing, because I feel so frustrated and I hear people say like, oh, I did a good workout, banana exhaust, I don't really want to do anything for the rest of the week, or I feel like my next workout felt terrible and then they get demotivated. So I want every workout to feel great. So I really recommend taking something like an NAD booster to make sure that every workout feels great. And that's what I've noticed as well. Yeah, that I've noticed that. And also just you're, as you say, your recovery time between workouts, but also your recovery time between intense efforts. So between experience, for example, is improved. Exactly, is what I've seen. Yeah. So it's great for exercises, great for strength, it's great for power. Is there then a best time of day to take these NAD precursors? Should they be taken in a fed state? Should they be taken pre-exercise? What's the best time? Yeah, I would say still in the morning is the best time, because I'd even heard that people who take it in the evening feel a little bit like they're they're not able to sleep as well. So I would say, yeah, in the morning, when you have all your kind of NAD expression for synthesis and all the rest, kind of it's most active. Is there any irritation on the stomach if you take it first, it is a best taken with food? I think it doesn't really make a difference. I tend to say to people, if you are noticing any kind of like gut issues, like then take it with food and then they'll go away, in terms of bioavailability, it doesn't really matter if you have food. I do always tell people to take water, like a decent amount of water with it, just to kind of help its absorption and make sure that it's getting to everywhere it should go. Yeah, okay, amazing. Super interesting. And as you say, this is really important for women in particular, right, going through parimenopause, just there's multiple mechanisms here because so often I think the most common thing we recently did a survey of over a thousand women and the most common thing coming out of it was my energy just feels really low. I feel off. I'm putting in the effort but I'm not getting the same results and I'm not recovering from exercise and I've definitely found these NAD boosters to make a massive, massive difference. Yeah, Enix the time of sense, like literally estrogen is helping regulate your search winds as well. And so, yeah, once you lose that estrogen, your search winds are kind of a little bit dampened down and yeah, you just need that NAD to help activate that all and get your ATP up. Yeah. Thank you, Shivon. This has been so interesting. Where can people go to find out more? Is it over? I think we have a special discount code as well for them to try the NAD plus. It's over at mitoq.com is it? And I think post-minoq.com. Yeah, mitoq.com. You can see all the prints of the the sort of mitochondrial supplements and mitochondrial kinds of activity and advice that we think people should be aware of because we fearfully strongly that people need to get educated a lot more than mitochondria. So I'm always happy to spread the word, but yeah, mitoq.com has got all of our research. We actually help sponsor and fund a lot of research as well to unmitocondrial health and NAD boosters and things like magnesium and fish oil, like all the good stuff for your mitochondria all there. I think that's what's been so useful for me because it's like you can literally go and explore the science and everything that we've been talking about and a bit more detail there over at mitoq.com. And then we'll link with them if you want to try it with a special discount code with my name with Angela in the in the show notes below this episode. It's been super interesting speaking to you. I think I'd love to have you back and we can talk about phytoeistrogens and the brain and things like that run out of time today. Is there anything around mitochondria that I didn't ask you that you want to share? Yeah, I think we covered a lot of that mitochondria. I just want people to be aware that like even though I think mitochondria seems like a really crazy subject, it's not that hard. It's mitochondrial health through a lot of exercise, a lot of just paying attention to your overall energy levels and finding the things that work for you to kind of keep your mitochondria feeling good. And yeah, then the rest is simple. Healthy ishing should not be hard. That is why I think. I love that. Yeah, it shouldn't be hard. Amazing. Thank you so much to Vaughan. I really, really appreciate your time and sharing all this research. Okay, it's so cute. I hope today's episode inspired you on your journey to vibrant health and high performance. Make sure you check out the show notes for a summary of all the important links to everything we talked about. And if you enjoyed this episode, hit the follow button and share it with a friend on social media or leave a review over on Apple Podcasts. Remember, achieving high performance health is about getting 1% better each day. So think about one thing you learned from today's episode and start implementing it today. Share with me what you've learned on social media over at Angela S. Foster. I love hearing from you and connecting with you. Have a beautiful day and always remember you are worthy of your dreams. Now for the legal stuff. This podcast is for informational purposes only and does not constitute medical, nutritional or other professional advice. Always consult with a qualified health care provider before making any changes to your health routine. Some of the links I share may be sponsor or affiliate links, meaning I may receive a small commission if you make a purchase at no extra cost to you. That said, I only have a link to products that have undergone rigorous testing and that I personally use and love. 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