[Dr. Kien Vuu] (0:00 - 0:21)
You have a lot of tabs or applications running in the background. All of a sudden your device starts to get sluggish. There's nothing wrong with the system, there's just something going on in the background that's taking up that energy.

That's what happens in the human body when we don't have that capacity. Other people might say they have brain fog, their joints hurt, body's not looking the same. These are all symptoms of poor biological or cellular capacity.

[Angela Foster] (0:21 - 0:30)
Energy, body composition, and recovery can start to feel really difficult in midlife. What's happening at the cellular and metabolic level?

[Dr. Kien Vuu] (0:30 - 0:42)
Life's demands go up requiring more energy and capacity, but also your hormones are going in the opposite direction. A change in that oestrogen is going to affect all systems. It will change basically how your body responds.

[Angela Foster] (0:42 - 0:48)
If someone wants more energy today, what are the biggest levers that they can pull to protect them?

[Dr. Kien Vuu] (0:48 - 1:07)
How do we move our life? Sleep, movement, nutrition, our mental state, how we view the world. Those are the biggest levers, the choices that we make in those areas create energetic signals that speaks to our DNA, telling them how to behave.

There is basically frontier science demonstrating that this energy of living actually turns on the genes of performance and longevity.

[Angela Foster] (1:08 - 1:33)
Dr. Qian Vu, you are a physician, human performance and longevity expert and author of Thrive State. So good to have you here today. When someone is in their 30s, in their 40s or 50s, so they're going through midlife and they feel like, I just don't have the energy that I used to have.

What's actually changing biologically and can that declining energy that people so often feel tell us something about their future health?

[Dr. Kien Vuu] (1:33 - 5:52)
Absolutely. I can speak about this because I've lived it. In my mid 30s, I was actually a hustling interventional radiologist, chief of interventional radiology at my hospital, working long hours, taking long call shifts and completely burnt out.

My energy dropped and then I developed chronic disease. I was about 40, 50 pounds heavier than I am now. I had type 2 diabetes.

I had high blood pressure and was on several prescription medications. And I just felt like I was so drained and fatigued. Now, energy or our felt sense of energy is actually the experience of biologic and cellular capacity.

And this is what I mean about this. Our mitochondria actually converts oxygen and the food we eat into ATP and that's cellular fuel. And that drives every process in the body, including moving, thinking, creating, regenerating, recovering, and healing.

And if we don't have access to that energy, our system shuts down. Now imagine, for example, a computer or a smartphone, right? Well, what happens to that device when there's a lot of background apps that are constantly syncing, when you have a lot of tabs or applications running in the background, constantly merging, constantly syncing, protecting, all of a sudden your device starts to get sluggish.

Now, there's nothing wrong with the system. There's just something going on in the background that's taking up that energy. And that's what happens in the human body when we don't have that capacity.

What happened with me is, I think, something that, when I listen to your story, it's very, very similar. I was a boat refugee coming from Vietnam. And I spent eight months on a boat.

When I came to America, I was put into schools and I didn't look the same as everybody else. I had holes in my hand-me-down clothes. And so when I grew up, I felt like I wasn't good enough.

I wasn't American enough. I wasn't white enough. And then that whole not enoughness was actually driving, that identity was driving the decisions I was making.

And if you live life in that mode, for me, it was constantly seeking external validation, approval, that I have to do something on the outside so that I could feel worthy. So all of that, living in hyper-vigilance actually is very metabolically expensive. Your entire body and nervous system is using up energy to protect, and then it leaves less energy, less capacity to heal.

And so when someone tells me they're low in energy, that's one of the symptoms. Other people might say they have brain fog, or their joints hurt, or their body's not looking the same. These are all symptoms of poor biological or cellular capacity.

And so those early signs, if not addressed, if you're running your life on that programme, will eventually lead to poor performance, and eventually chronic symptoms and chronic disease. And I lived it. And what I love when I listen to some of your other podcasts is you really talk about the foundations.

Now, I talk about the foundations in my book, Thrive State, the five pillars of life that really are the truest levers for human performance, longevity, and resilience. And that's one, physical, which is sleep, movement, and nutrition. Next is mental, our beliefs, our values, what we're focused on, and our attention.

Emotional, which is stress, emotional regulation, recovery. Social, are we connected to a tribe and have a sense of belonging? And then finally, spiritual, our sense of being able to truly be ourselves, live life fully, contribute with purpose.

Those are the five levers. But because I was living life so unconsciously in that space of I'm not worthy, I'm not enough, I was constantly being pulled in lots of different directions, got stressed, and then made very poor decisions on all those areas of life I just talked about. So we could unconsciously drain our energy and our capacity very early by how we live our life, which is why I say how we live our life is our medicine.

And that's why I'm so impressed with you sharing your story, with you going through and being a lawyer, going through your mental health journey, and how the awakening, so to speak, has allowed you to access your performance and your health as well.

[Angela Foster] (5:52 - 7:05)
You know, I love what you've shared there. And just hearing about your story, I think it's one, so inspiring. And secondly, it really identifies something that most people don't think about, right?

So we often, when we think about our health and our cellular energy, and the fact that we don't seem to have as much of it, I think we're naturally drawn to the physical aspect. So we start thinking, I must maybe do some more exercise, or I must eat better, we forget about the other components that are so, so important, right? As you mentioned, the social side, the spiritual side, the emotional side, and these are all feeding into our cellular health and energy.

When we're looking at that, many people will know that at the core of our cellular energy is our mitochondria, these tiny battery packs of our cells. But we also have our insulin sensitivity, which is affecting our ability to use glucose as a fuel. And then we have metabolic flexibility.

So our ability to transition between burning fats and carbohydrates as fuel. How can we see from a kind of objective perspective that our cellular energy is impaired? We know how we feel, but what can we also track to see that actually there's some dysfunction that we can catch early so that it doesn't affect our performance and ultimately our health and lifespan?

[Dr. Kien Vuu] (7:05 - 9:06)
Those are great questions. So let's talk a little bit about the three things that you mentioned. There are actually three parts to the same energy system.

One, we have our mitochondria, which again, turns oxygen and food into cellular energy. And next we have insulin sensitivity, which is our ability to handle nutrients, particularly glucose. And then finally, we have metabolic flexibility, which is our ability to switch between different fuel sources.

There are basically three parts in an entire energy management system. And as you potentially alluded to, lots of these things show up even before we are given a diagnosis. Well before my haemoglobin A1c was in the sevens or my blood pressure went up, I was already starting to feel very tired.

My resilience already was kind of depleting. And one thing you mentioned, I think listening to one of your podcasts, I think you were mentioning that maybe in your teens, you were constantly getting colds and infections. So these are things that we have to start to question long before they show up in lab value.

Now, traditional lab values are looking at fasting glucose and haemoglobin A1c, but that actually shows up very, very late. I think some good markers might be a fasting insulin, but really start asking the questions built around those five foundations I talked about, about where you're functioning and your habits in these different areas of life can give us clues to whether or is actually some of these early signs of resilience. This is getting tired, maybe having some brain fog, not recovering very well, not being able to...

You're starting to develop maybe some visceral fat around your belly. Some of these are additional clues in addition to lab tests, because again, disease rarely begins the day you're given the diagnosis and there's a number on the chart. And so that's why I tend to ask a lot of those questions based on somebody's lifestyle.

And I audit their life in those five areas that I talked about.

[Angela Foster] (9:06 - 9:57)
It's so important what you're saying there. I think people's lived experience and just actually listening to yourself. It's so difficult though, isn't it?

Because for many people, they go and see a doctor and they get told, no, everything looks fine. And then they feel like they don't have the answers. One of the things I was speaking about with someone just this morning, actually, was when you look at wearable data, right?

And because these have algorithms as well, layered over the top of them, we know that heart rate variability, so that interbeat variability is a good measure of nervous system and that it's also very individual. So we don't want to compare against someone else. However, if you start wearing a wearable device during a very high period of stress in your life, and that's what the wearable understands for you, it's then going to start tracking your recovery and strain against that low score.

And so it's like, oh, you're doing well or you're not doing well based around that. That's not necessarily your genetic potential, right?

[Dr. Kien Vuu] (9:57 - 10:35)
No, absolutely not. When you're using wearables in particular, they're great for monitoring trends, but those absolute numbers are so individualised. And so I get people freaked out like, oh my God, my aura ring said that I got poor sleep.

I better not do anything today. I want people to start to maybe understand this, that they can listen to their body. They can listen to how they feel, how they're recovering.

These are all signals. And as we become more attuned to those signals in our body, we can start to trust them and start to understand what our body's trying to tell us from our symptoms or how we feel.

[Angela Foster] (10:35 - 11:02)
Yeah, it's such a good point. And I think we're starting to lose sight of that, which is so important. When we look at women in particular, right?

I think this is true for many men and women in midlife, just don't feel like me anymore. It's such a common thing that I hear. When we're looking at women alongside that energy, body composition, and recovery can start to feel really difficult in midlife.

What's happening at the cellular and metabolic level during this stage?

[Dr. Kien Vuu] (11:03 - 14:53)
This is very near and dear to my heart because my wife is going through a lot of changes and certainly working with a lot of clientele as well. I certainly hear the same type of feeling and sentiments from these women. They're saying, I am doing the same thing, but my body's responding differently.

Or I feel exhausted, but I still can't sleep. I'm not able to bounce back. My body composition is changing.

And I'm more irritable or reactive than I normally am. And what's happening, I think, is twofold. One, your hormones are changing right around that time in your forties.

And then life demand goes up. Now, what actually happens in the cellular or metabolic levels? Well, there's a lot of hormone changes happening around perimenopause or around this time.

The main one being a rapid decline or fluctuations in oestrogen. And oestrogen is super important because it works on our mitochondria, our mitochondrial health, affecting mitochondrial efficiency, our glucose metabolism, our muscle mass, bone mass, and then in general metabolism altogether. So a change in that oestrogen is going to affect all those systems, which will change basically how your body responds.

But at the same time, and I think this is the part that is, I think, overlooked. For a woman at this age, there's a lot of changes that are happening. Career demands, probably you're moving up in your career and you're probably more senior and you might be having more demands on that space.

Your children are getting older and they're pulling you in multiple different directions. And I know for my wife, she's trying to figure everything out for the kids and then she's trying to care for me too. And then this is probably the first time our parents start needing our help.

And so the demand is there. And so at the same time, what's happening is life's demands go up, requiring more energy and capacity, but also your hormones are going in the opposite direction. And it's, I think, very important to understand all of that.

And I think one of the empowering things is to have women like yourself be able to step in and start talking about some of those changes. And I think the body is very resilient and starts listening to those signals. And so for women, I would probably say, focus on those foundations.

Where in the foundations can I work on? Mental, physical, emotional, social, spiritual. And then once you've got the foundation set, then we start talking about some targeted tools.

It might be hormone replacement therapy. It might be taking on some supplementation or some additional biohacks or the new frontiers in science. I think the last thing also, and it's probably more important if you've got support system in your life, is to use the support, because that demand is real.

And I think for a partner, I mean, I think initially when some of these changes were happening, I didn't understand what was going on. I started to take her changes very personally. The more I started to understand this in a personal level, certainly I was treating a lot of different clients in this space.

But when it happens in your own house, you become more cognisant of things. And I think if you're a support person for a woman going through these changes, just allowing to take things off their plate, doing more, and certainly for women, understanding that it's okay to ask for help. One of the things I think in modern day society that we've sort of left out is we didn't used to take all this burden alone.

We used to live in tribes, in communities, and we didn't have to raise a nuclear family alone with just two people. And so how do we start to build more of those support networks, I think are very, very important.

[Angela Foster] (14:54 - 15:45)
I love that Dr. Vu. I think it's such an important point, because as you say, we're operating almost sort of in these silos really, right? And we're relying, if we have time, on connection with friends and things, because we don't necessarily have the family around us.

But then we're also more, as you say, is being asked of us. We may have ageing parents and extra responsibilities. It's interesting, because I talk about the fact as well, being a woman in midlife myself, is that when we look at energy going down, we know that we do need to stress the system, right?

With something like mitochondria, you need to provide physical stress in order for adaptation to take place. But what we're getting actually is a lot of psychological and mental stress, which is putting pressure on our nervous system, increased demands at a time that physical activity levels can be declining, not because we want to through any intentional or a lack of discipline on our part, but because our children are growing. And I found myself more as a taxi driver, do you know what I mean?

[Speaker 3] (15:46 - 15:57)
Naturally become more sedentary. So you're like, oh my goodness, it's the perfect storm of things that are going on. And I'm having to be so intentional now about my health.

Yeah, it's an interesting life.

[Dr. Kien Vuu] (15:58 - 16:30)
You are the hardest working people in the room. I just have to give so much respect for women, not only for the resilience of childbirth, the more I'm starting to... I'm blessed with a wife, an older daughter who's 12, who's my bonus daughter, a five-year-old daughter.

So I'm blessed with having a lot of women, but now truly understanding what it's like in different phases and having more of an appreciation for my mom, for everything that she's done. So thank you for being you and for playing such a important role in our lives.

[Angela Foster] (16:31 - 16:51)
Thank you for everything you're doing and sharing to help women. And I love the fact that it has had that impact on you with your mom. If someone wants more energy today, so they're listening to this, they want more energy, but they also want to protect their future.

They want to be strong, sharp, and metabolically healthy at 80. What are the biggest levers that they can pull to protect that?

[Dr. Kien Vuu] (16:52 - 19:48)
Yeah, I think I talked about this earlier when we started talking about foundations of health and performance, but I think this is a great opportunity to speak of one of my favourite topics, which is epigenetics, which is really the crux of my book Thrive State that you see behind me. There's a famous Danish twin study, and it basically takes these twins and they monitor them over time. And what they've discovered is this, is their lifespan was only about 25% genetically inherited, which means that the rest of the lifespan, the majority of it was actually not based on that, lifestyle factors and things happening outside of the body.

Now, that was a very famous study, but there have been additional studies since then that demonstrates the same thing, that our genetic phenotype, meaning how our cells are, how they behave, their longevity, their performance, their resilience is actually not determined by the DNA that resides in it. The DNA is just a blueprint. So what decides the building?

What decides what the DNA creates, whether it creates health or disease, whether it creates performance or sluggishness is dependent on how the DNA is being expressed. And that DNA is being expressed by the constant signals above the DNA, epi above the genes. So how we live our life, particularly in those five areas I talked about, I'll repeat them again, physical, which is our sleep movement and nutrition, our mental state, how we view the world, where we place our attention, our ability to recover and emotionally regulate, our sense of community, our sense of being able to be ourselves, which is spiritual, to understand that we are worthy already, that we don't have to earn it to do that work and to serve and to live life fully. Those are the biggest levers, how you act in those areas, the choices that you make in those areas, create energetic signals that speaks to our DNA, telling them how to behave.

Now, if we are in the unconscious mode of traumas that haven't been addressed yet, not feeling good enough, not feeling worthy, constantly in stress and survival mode, we're giving our DNA the signal that there's a sabre tooth tiger that's running. So whether you're in busy workhorse mode or trying to extinguish fires in the home, things like that, you're giving yourselves the signals of danger. And that generally turns on inflammatory genes and it decreases your immune system and it leaves less energy, less capacity for growth, for healing and performance.

And that ultimately leads someone to have chronic symptoms and chronic disease. And so what I say to anybody is focus on that foundation. That is the foundation of health, longevity and performance.

[Angela Foster] (19:48 - 21:43)
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[Dr. Kien Vuu] (22:11 - 26:32)
which I call the science of longevity, but the art of living is focussing on the foundation, which I think is very important. But let's talk a little bit about, you know, where supplements do play a role in this or what, you know, biohacks do. Now, longevity is kind of like this emerging field and there's a lot of science going into the space.

And just like anything we're exploring, whether it's, you know, scientists or astronauts exploring space or the early explorers that were exploring the world, think of longevity as this island, right? There are places that are very well mapped out that the explorers have been on where there's a lot of human evidence. There is evidence on dosing and tracking, everything's set, that's mapped.

Then you have some emerging technologies, things that haven't been explored that much yet, but it's very, very promising. There is some initial human evidence there. And then there are things that are more on the frontier space, which is there's some biology there, but maybe the early human studies aren't quite there yet.

Now, every breakthrough that we've ever created started off in the frontier. This is where clinical trials are. This is where something in the bench actually becomes a treatment later on.

So the early explorers have actually, that's what has actually moved science forward. And I want to let listeners know that's kind of how science works. For example, let's take creatine, for example.

Creatine is a molecule that was discovered 200 years ago. And then in the 1990s, bodybuilders started using it for muscles and whatnot. And they've been using it for a couple of decades now, and probably have gotten the benefits of using it for a couple of decades.

But it's only recently that it went from frontier science in the 1990s, where people didn't know what was going on, for more science, more exploration. So it became an emerging technology, and then finally a well-mapped technology. Now we know that creatine is something that is important for exercise performance, lean muscle mass, and now developing a lot of cognitive benefits as well.

But it took some time for it to go from frontier all the way up to being something that's well-mapped. And my role as a physician in this space, I love the frontier. I want to push the bounds of what's possible, but I also want to do it in a scientifically informed way.

And my role as a physician isn't to tell somebody, hey, let's just use all the map products and stay out of the frontier. It's not that, it's letting people know where we stand in the space, being scientifically informed as we explore areas we don't know, and then also have the responsibility to change what we know in the map as the evidence starts showing up. So I think that's super important to know, because there's a lot of stuff in the longevity space now.

And when we talk about supplements in general, I think it's really important to know the supplement industry is not a regulated industry. And there's a lot of brands that are out there. And so if you're looking for something to supplement your health with, certainly you want a reputable brand.

You want them to have good manufacturing practises. You want them to test against heavy metals and contaminants. And you also want third-party testing on the stuff that they're in.

This is why I'm super excited to be a brand partner and advisor to Solaray. They're actually a company that has developed a longevity line called Unlimit. Now, when I start thinking about taking supplements or doing a biohack or doing anything in the longevity space, they might not have the science yet.

I like to leave with four questions. Number one, is there biology? Do we know that there is a biological mechanism for the outcomes that this said intervention is supposed to have?

Next is, is it bioavailable? Whatever it is, whether it be a supplement, a pill, a peptide, or red light therapy, is it getting to the target that we want it to get to? Number three, is it safe?

What do we know about the dosing? What are the dangers if I'm wrong doing the thing? And then the last thing I ask is, is this adding to a foundation that I've set or am I trying to replace or put a bandaid on it?

That's how I approach supplements altogether.

[Angela Foster] (26:32 - 27:29)
It's really interesting because I think so many people, so many of us are taking supplements. Often, people will have a supplement cabinet or draw, but they're not quite sure why everything's in there over time. They've accumulated and not sure why they're taking them.

I like as you to think of it as having the foundations in place and then you supplement where you might need support on top. Or if you're looking at enhancing your energy, your cellular health, and you want to be at the frontier of that, is then using that process that you've identified there to think about, is this something that could benefit me? And I like to think of the body in terms of systems.

When we're looking at different systems within the body, because I think this would be a really great education for our viewers and listeners on this, if we look at oxidative stress, for example, why is glutathione so important for cellular health and oxidative stress as we get older? And is there a case for supplementing with glutathione?

[Dr. Kien Vuu] (27:29 - 30:08)
That's a great question. Well, first of all, what is an antioxidant? Glutathione is one of the body's major antioxidant systems.

Now, what happens in the body when we run all these cellular processes is we actually have some waste or some exhaust. In fact, creating ATP creates some exhaust. All these cellular processes have these reactive molecules, oxygen species, nitrogen species, free radicals.

And normally what happens is the body actually has enough antioxidant defence system to balance those things out, and we're okay. Well, what happens if we stress out the body with toxins or the way we live our life and poor sleep, that increases these reactive molecules in our body, and that creates a state of oxidative stress. That's dangerous because when you have two of these reactive molecules happening or occurring in your body, you damage your cell membranes, you damage proteins, you damage your DNA, that eventually kind of erodes the system that will ultimately lead to chronic symptoms, chronic disease down the road.

What happens with the antioxidant defence systems? Well, over time as we age, we just have more oxidative stress from exposures and living life. And at the same time, our internal defence mechanisms, such as glutathione, tends to be less robust.

And so it would potentially make some sense to supplement with it. Now, the problem with glutathione is the following. There've been many glutathione products out there that if you just give glutathione on its own, it tends to break down in the gut.

It's a tripeptide, and it'll actually break down into its components even before it reaches the cell. There actually have been some human studies studying liposomal glutathione. And what is liposomal glutathione?

Well, a liposome is basically lipid particles, much like in the cell membrane, used to encapsulate a molecule. And there's been some human studies demonstrating that taking a liposomal glutathione actually increases glutathione stores and actually leads to decreases in oxidative stress in the body. And so Solabrae makes a liposomal glutathione.

I like to actually use it for myself if I'm doing a lot of travelling, speaking, just something like that. I like to take it on top of that. Some people I know kind of take it during the time that they're feeling like they're getting sick, but that could be something that, again, work on the foundations, ask yourself what you're trying to target when you're taking something like this, and see if that would be helpful.

[Angela Foster] (30:08 - 30:10)
When you're under that extra load, right?

[Dr. Kien Vuu] (30:10 - 30:11)
We go through seasons where that happens.

[Angela Foster] (30:12 - 30:27)
What about when we're looking at NAD? There's a lot of talk about NAD. What do we know about it in terms of its ability to enhance energy production within the body, but also its application for longevity?

What does the science tell us?

[Dr. Kien Vuu] (30:28 - 31:45)
Yeah, well, the science is the following. I mean, I would probably say in terms of molecules for longevity performance, it's in the emerging and frontier. We have good science.

Now, what is NAD? NAD is actually a molecule and exists in two forms. We have NADH, which is the reduced form, and that is used in the mitochondria to help create ATP.

Then we have NAD or NAD+, which is actually the oxidised form. Now, that actually is used as a substrate for enzymes in the body, particularly sirtuins. Sirtuins are these longevity proteins that we have.

Then they also work with other enzymes like PARPs and things of that nature, but their major role is cellular signalling, handling DNA repair. It's involved in the stress response. A lot of cellular processes that are important for function, and if you disturb them, tend to lead to accelerated ageing.

The biology of NAD is legit. It's real. It's mapped.

There's a lot of biology that's there. What we don't quite know yet is what happens if we start manipulating those levels of NAD, what exactly is happening, whether or not people are actually getting the energy and the longevity. There's a lot of research still going in that space, but it's very, very exciting.

[Angela Foster] (31:45 - 32:09)
When we look at that space then, you mentioned a few of these here, because I think this is where it can feel confusing for somebody who wants to explore that. We have NAD+, we have NADH, and we have NMN. These things are often in different supplement forms.

For someone who's looking at this, what should they be thinking about and how do they know which supplement to go for? What's the most bioavailable? What's going to give them the best benefit?

[Dr. Kien Vuu] (32:09 - 33:44)
There are basically three pathways and three entry points into this NAD system. First, let's talk about NADH. I would probably say from a science standpoint, there has been the least amount of human trials here, but they have studied people that are chronically fatigued and found that in some cases, NADH has actually led to improvement in energy.

Again, very small trials. Remember, NADH works with the electron transport chain in the mitochondria to help create cellular energy. Then on the flip side, then we've got NAD+.

Now, what we do know is NAD+, is a charged molecule. It's very difficult for it to get transported in the body. Much like glutathione, people who are working with NAD+, there have been liposomal versions of NAD+, which in human trials have demonstrated an increase in blood levels of NAD+.

That's pretty exciting. What is NMN? NMN is nicotinamide mononucleoside.

That is actually an ingredient, necessarily, to build NAD+. It's probably the most studied and probably the most evidence that taking NMN orally actually leads to increases in blood levels of NAD+. That's what we know about all of them.

Then when people ask me, oh, well, which one should I take? Again, I don't give general statements across the board. It really is, are you working on the foundations and what is your life like and what are you trying to target?

The cool thing is, Solarae actually creates and has all three of these products.

[Angela Foster] (33:45 - 33:51)
It's an exciting area. If someone's taking these, can they expect to feel a benefit? Could they be tracking it that way?

[Dr. Kien Vuu] (33:51 - 34:11)
I think it's very early to say. I think we have some people taking NAD+, and they're like, well, I do feel energy in that sense. It's still very subjective.

We're wanting to get some more objective points. I would probably say the studies right now are still in progress as we begin to know its efficacy long-term.

[Angela Foster] (34:11 - 34:18)
Do people need to think about methylation, for example, having enough methyl donors when they're taking these? Is that something they need to be concerned about?

[Dr. Kien Vuu] (34:18 - 35:01)
Yeah. I think as you mentioned that as well, I mean, certainly noticing and checking homocysteine levels, I think, while you're taking them and seeing if it affects things in that way. I would always like to say, work with your functional or your longevity doc to see where all these things go into play.

You don't need a doctor's prescription to buy these supplements, but they actually have an effect on the body. You want to know how everything's working together. Are they interacting with how you're living life?

Are they interacting with the medications that you're on? I think it's very important to discuss these things, particularly if you're not a biohacker well-versed in the space to be adding these supplements in conjunction with a consultation with a doctor.

[Angela Foster] (35:01 - 35:23)
Another really interesting area is autophagy or cellular cleanup. Spermidine is getting a lot of attention because of its relationship with autophagy. What is spermidine doing in the body?

Why might levels matter as we age? How convincing is the evidence that supplementation with spermidine influences healthy ageing?

[Dr. Kien Vuu] (35:24 - 38:34)
That's a great question. We talk about spermidine and its relation to something called autophagy. Let's talk about what autophagy is.

Autophagy is cellular housekeeping. Imagine you're living in your house and you're just doing everyday living. You're going to start accumulating some trash just by living in your house.

What autophagy is is actually taking out the trash and maybe using parts of those pieces that you could recycle to something else. Now, in a process where you have very low autophagy, what happens is you've just got trash buildup in your entire house. Imagine yourself trying to walk through the house when you've got a lot of trash or trying to just do things around when you've got a lot of trash.

It gets to be very inefficient. In fact, if you start accumulating too much of it, some scientists think that potentially that leads to a state of senescence or zombie cells. I think autophagy is a very important concept as it pertains to longevity because autophagy will clear damaged proteins, organelle, and dysfunctional mitochondria.

Now, what is spermidine? Well, spermidine is actually something that our body creates. It's endogenous, but it could be found in lots of different food sources like root germ, like soy products, like aged cheese.

What we found is there is actually roles in spermidine for cell growth, for DNA repair, and also for autophagy. There's been a lot of studies that have been out there. Some earlier studies was actually looking at low-dose spermidine for cognitive performance.

They didn't find that low-dose spermidine had that much effect there. Since then, there has been scientists that actually up the dose to a higher dose, 3.3 milligrammes per day. That initial pilot study demonstrated that people who were taking that 3.3 milligrammes a day daily actually have changes in autophagy-related biomarkers. That's super exciting. This is where I'd like to say it's super exciting to see the frontier of science. Initial studies demonstrating at this dose, nothing happened.

Oh, let's change the study. What if we change the dose? This is what exploring the frontier really is.

It's asking those questions, looking at different experiments, and designing the next set of experiments based on our previous data. I would probably say the biology is getting super exciting. Some of these pilot studies are showing that things are very promising.

Then Solarae, they also have a spermidine product that is created with the same dose that that pilot study showed, the 3.3 milligrammes per day. One of the things I'm super excited about is this company's been around for over 50 years. They even have their own accredited laboratory.

Every batch of anything gets tested against for microorganism, heavy metals, and things of that nature. Again, because the supplement world is so unregulated, it's good to know really great brands that has a good track record of manufacturing processes, purity, quality, and that everything else is still research-based as well.

[Angela Foster] (38:35 - 39:57)
What I'm hearing, just to recap for people, is we're really looking at different areas. We can't give individual advice, but somebody might want to think about if that area is under significant load. You mentioned, for example, first of all, we were talking about oxidative stress.

Similarly, when we're looking at NAD and the precursors involved, really, we're looking at the cellular energy systems and supporting mitochondria. When we talk about spermidine, this is in relation to autophagy. It's that cellular cleanup that's taking place in the body when we do things like fasting, particularly when we're sleeping, for example, and spermidine supporting that autophagy.

What we can't say is that these then definitely lead to extension in lifespan, but that's what is so exciting about this science, is it's continuing to be studied. Something you touched on there that's interesting briefly was you talked about zombie cells, which are fascinating because these are cells that are senescent cells, as you say. They're causing havoc because instead of those cells being recycled through autophagy or the cell being dispensed with because it's old, senescent cells, my understanding is that they're hanging around and they're causing inflammation.

There are these other compounds that are now being studied in relation to senescent cells, things like facetin. Can you tell us more about senescent cells and how some of these formulas might work?

[Dr. Kien Vuu] (39:57 - 41:59)
I would probably say this is probably the most frontier of the science that's there, but it's actually a very active area of exciting research, which is around senescent cells. Now, what are senescent cells? Senescent cells are cells that they've stopped dividing and they've lost their normal function.

If it's a muscle cell that's supposed to be contracting, it's lost the ability to do so. They can't divide yet, but the body hasn't cleared them out. There's just like, oh, I'm not doing anything.

They're like zombies, so to speak. What it's also doing is they start to secrete these inflammatory signals that affect the cells around it and the tissues around it, so it can actually worsen the cellular health of nearby cells and cellular performance in general. Now, what we do know is compounds like facetin, which is a flavonoid.

You find it in persimmons, in grapes, in apples, but it's particularly concentrated in strawberries. Now, what we do have now is preclinical studies that suggest that facetin actually has some senolytic activity. Now, this is preclinical, so that's pre in the body and in more laboratory studies.

It's not yet proven to actually clear a healthy human of some senescent cells, so the science is still there, or the science still has to get there. One of the problems with studying senescence is you're looking at different type of cells all over the body, like a heart cell, a lung cell, a liver cell, and they're all different when they turn into zombies, so trying to find the right biomarkers to see, oh, what exactly? Are there more specific biomarkers that can look for senescence?

We're still trying to figure that out. One of the problems is we're discovering when we're talking about senescence, it's finding the right biomarkers to measure. I think we're still early in the clinical science, but this is a super, super exciting field, and my eyes are on the pulse in that field right now.

[Angela Foster] (41:59 - 42:01)
This is something known as senolytics, right?

[Dr. Kien Vuu] (42:02 - 42:03)
Yes, senolytics.

[Angela Foster] (42:03 - 42:57)
Targets senescent cells, but the science is still developing in this area. My question for you then is, for someone listening to this who has started to notice drop-offs in energy, they have a lot of load coming at them. They're very, very busy.

There's a lot of demands placed on them. Where is the best place? I know that the foundations are the most important, right?

Supplements have to always be supplemental too. If you're not sleeping well, you're not exercising, you're not eating well, you're not seeing friends, you haven't got that social connection, you haven't come into connection with your sense of spirituality and oneness inside, then that is definitely the best place to start, but assuming that we're doing those things and we want to support ourselves as a woman in midlife, what's the best place to start in terms of thinking about some of these supplements?

[Dr. Kien Vuu] (42:58 - 46:47)
Yeah. I think, one, you raise a very important point. Sometimes I'll have somebody come in, and I get this all the time, whether it be emails or texts, and there'll be 20, 30 things that they're taking, peptides, senolytics, and all these different supplements.

Then later on in the conversation, like, oh, I'm barely sleeping, every day feels like an emergency to me, and I haven't lifted anything heavy in a long time. Like you were saying, let's start with the foundation because I like to say this, that we earn our biohacks. You can't just take a supplement and expect for it to work.

Supplements, particularly when they're in the emerging or frontier field, they only work under a foundation that is working. They amplify what you create in the foundation. If your foundation is leaky because you're not working on those things, the supplements that you take might just come into your body and be wasted, or you might be creating a state from how you're living life that the supplements are just touching that and not giving you the amplification process that you're talking about.

After you've worked on some of that, then it's a personal conversation for women going through this process. I think it's starting to have their labs looked at for the first time and actually have somebody who can sit down with them for an hour to understand what exactly is going on in your life. When I approach somebody, everybody's going to comment a little bit differently in terms of their mental, emotional states, what they're going through on a daily basis, and their labs look different.

This is very personalised and individualised. I know some women, they're like, I don't want to take anything exogenous. I just want to work on things.

I'm against hormone replacement therapy. Then there's some people that are open to something like that. As a physician, talking to somebody like that, I want to look, where are the easy wins when I'm looking at the labs, when I'm looking at their lifestyle?

What's going to give them the most bang for their buck? What little tiny shift can I make to improve their resilience? It might just be giving them a couple points throughout the day to say, hey, can we work on regulating our nervous system?

Pause and recognise this breath. Every time you get triggered, maybe ask yourself, what's happening in my body? Where is it happening in my body?

Is it an old belief of I'm not worthy? I got to handle everything. I'm not safe.

I need to control everything. Can I look at that? Whew.

Is that real? Is it true? Can I let it go?

How do I want to show up instead? Sometimes just being a little bit more conscious about how you approach life is the big shift. If you can get somebody that big shift early, they'll feel an energetic shift.

Here's the thing, all the energetic cues that I talked about, mental, physical, emotional, social, spiritual, they're all energetically connected. If you're able to switch one thing and allow them to shift the way they feel, creating a new change in those other areas of life become a lot easier. For me, it's really looking at where a person is and what's going to be the easy win for them, because getting an extra 30 minutes of sleep might be a lot easier for one person than it is another person.

Somewhere in the laboratories, I could say, oh, wow, this could be very easily fixed by adding a supplement here. Okay, let's give them that win. I think it's very generalised in terms of where I go next with the patient, but it's always focussing on what in the foundation is going to get fixed first and what are the easy wins that I can tack on on top of that.

I'm really looking at their goals together that we start adding so many of these targeted tools and supplementation. Generally, for me, is adding some basic supplementation and then various targeted supplementation moving forward, but again, supplements being the supplement and not the main thing.

[Angela Foster] (46:47 - 46:53)
Yeah, I think it's so important and not losing the supplement, not using the supplement to compensate for the fact that you didn't do the behaviour.

[Speaker 3] (46:53 - 47:06)
You can't eat right up until bedtime and then decide you're going to take spermidine because it's going to do the autophagy for you instead of sleeping or like, now I haven't slept, so I'm going to go and really high dose my creatine for some extra brain energetics.

[Angela Foster] (47:06 - 47:35)
Yeah, it's not, as you say, it's about getting the foundations first and then layering in what's needed on top. We will link to some of these compounds that you and I have been talking about because I do think they're really exciting areas that are developing, so I'll put a link in the description if people want to go and check those out. Is there anything else that I haven't shared?

Maybe you can, I guess, share for us how you combine a family and your busy job as a physician and everything you're doing and maintain that high energy.

[Dr. Kien Vuu] (47:36 - 48:50)
Such a great question and I do a lot of the personal work. There are days or multiple times a day I'm asking myself, am I truly living right now or am I reacting, responding to the stresses of life? I want people to have a long life and if you want to explore and live to 120, go do it, be there, but if there's one idea I want people to get from the conversation is this, that longevity isn't something you take.

Longevity is something you live. We have this breath and because we have this breath, we have the agency to choose how we sleep, how we move, how we treat our body, how we want to build this up. Whether we're truly being ourselves versus running around a mask like I did when I was very unconscious and are we contributing to other people?

Are we loving on other people? That's truly living and there's basically frontier science demonstrating that this energy of living actually turns on the genes of performance and longevity. That's what I want people to walk away with that recognise that there are so many exciting things out there, lots of new molecules to try, but at the end of the day, it is going to be you that is your best medicine.

[Angela Foster] (48:50 - 49:05)
Amazing. Thank you so much. Thanks for coming on and for everything you've shared.

You are a great resource for staying up to date with the science as it's coming through. We will put all the links in the description in the show notes so people can go and check that out and everything else that we've talked about today. Thanks so much for coming on the show.

[Dr. Kien Vuu] (49:05 - 49:07)
Angela Foster, thank you for having me.

[Angela Foster] (49:07 - 49:24)
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Dr. Kien Vuu and I talk about cellular energy, estrogen, NAD+ and spermidine in midlife, and how to build more energy today while staying strong and sharp at 80.

Physician and Thrive State author Dr. Kien Vuu breaks down the three parts of one energy system behind midlife fatigue: mitochondria, insulin sensitivity and metabolic flexibility. He explains why falling estrogen hits mitochondrial efficiency, glucose metabolism, muscle and bone at the same moment life demand peaks, why fasting glucose and HbA1c move late, and how he sorts longevity compounds into mapped, emerging and frontier science before deciding whether glutathione, NAD or spermidine earn a place on top of the foundations.

WHAT YOU'LL LEARN

- Why the felt sense of low energy shows up long before fasting glucose or HbA1c move

- What falling estrogen does to mitochondrial efficiency, glucose metabolism and muscle mass at the exact moment life demand peaks

- How to sort any longevity compound into mapped, emerging or frontier science before you spend a penny

- The four questions Dr. Vuu asks before adding a supplement, and why he says you have to earn it first