Molecular Science of Longevity: Can You ACTUALLY Live Past 120 Years? | Andrew Salzman

What is nad?

NAD is a small molecule. It's the centerpiece of biology, and it really does three things in our body. Gives us our energy, protects us against oxidants, and it saves us from cancer. We used to think about diseases as being sort of these isolated instances of bad luck. Oh, I got diabetes. Oh, my goodness, I got cancer. But that's the 1950 ways to look. Today we have to see these really as an integrated whole. Why do we get sicker as we get older? The aging process is a core fundamental derangement that then spawns injury in all these different organs. If you happen to have an injury in your knee, suddenly you have arthritis, but it's really not arthritis. What it is fundamentally is aging.

I look at it like this. If I age, it's my fault.

A lot of people think that aging starts when you're 60 and 70, but actually aging doesn't start when you're 65.

Given what we know with AI, with new research, all the work you've done in your life, how long do you think humans could live if we just pull out all the stops? You're listening to the Human Upgrade with Dave Asprey. This is going to be a really fun episode recorded live in the studios here in Austin, Texas, because I like talking with really, really smart people who've done a lot of big things in the world. There's so much we can learn. The episode today is about longevity. It's about NAD, and it's with a guy who's only written like 170 scientific publications, 50 patents, and the guy who created the first PARP1 inhibitor, which is really, really useful in preventing cancer. He's also the chief medical officer for Wonderfeel, which is a new NAD focused company making some supplements that are, I would say, the next generation of what's happening in the world of nad. If you're new to the show and you don't know what NAD is, we're going to go into that. This is a compound I wrote about in my longevity book, and it's a compound that you've heard from maybe David Sinclair on the show talking about it. And it's something that's very fascinating because if you can control your NAD levels, you can control one of the many pathways of aging that you need to control if you want to live to at least 180 like me. So let's bring one of the luminaries in the field onto the show to go deep on it. None other than Dr. Andy Salzman. Andy, welcome to the show.

Thank you very much.

You're an interesting guy. So you were a practicing physician, Harvard kind of guy, and then you suddenly one day decided, I'm going to wake up and go do research and make drugs instead of being a doctor. Why?

I love taking care of patients and being at the bedside and helping people, helping children, talking to the families. I went into intensive care because I deeply cared about critically ill kids. But, you know, after, after about 10 years at the bedside, I realized that I wasn't able to do enough. I could work all night, I could take care of kids. But ultimately the real advance is when you develop a new drug or a new intervention that can save not one kid at the bedside, but thousands. Thousands that you haven't even met. And so I committed myself to research to do that.

Does it have to be drugs? I mean, could it just be.

No, no. Any kind of intervention, but something different, Something outside of the normal pattern of medical behavior that we are accustomed to in the hospital.

So something that scales better than, let's send everyone to the hospital, let's give them something that can work even if they don't have to go to the hospital.

That's right.

You're working with a supplement company, but you did a $600 million deal on a cancer drug you invented, that you sold to Genentech. So why the cutover from pharmaceuticals to nutritionals?

Well, I work in both areas.

Okay.

Okay, so I don't have a preference. Well, I will say I do have a preference, actually. I think that non pharmaceutical approach today has become faster, it's richer in terms of the possibilities. You can exploit the pharmaceutical world for all of the good it can do. It's just very tedious and slow. And I want to get a lot done. I'm ambitious. I have a lot of things I have to do.

We're going to go deep on NAD in a minute. Sure. You have some interesting perspectives on this. If you wanted to create a new pharmaceutical, and I know you invent them on napkins in your sleep, probably. So you have this idea, how much money would it take on average to get a pharmaceutical to market in the.

U.S. oh, at a minimum, you're talking 75 to $100 million.

10 years. If you came up with a new Nutraceutical, how much money would it take to get that to market?

250,000 to $500,000 in six months.

Okay. Why such a difference?

Regulation. And look, the concept of the FDA was good at the beginning. In the 1930s, they cared about people. They didn't want Anyone to get hurt. They wanted a certain type of procedure and protocol to follow. Every kind of new development for the sake of the good, do no harm. But it metastasized. It became so extraordinarily complex and involved that it just takes a lot of different things to do, and it adds up, costing money and time. No way around that.

Did you just say the FDA metastasized? I'm afraid so. I've never heard that before, and I can't disagree. Yeah, And I've been involved in longevity medicine for 25 years on the nonprofit side. And just with what I do. And I've seen so many companies just leave the United States in order to get things done. And it doesn't feel like it's serving Americans or even the world when we have this kind of resistance. And I can see why you'd say, well, if I can solve a problem with a half a million dollar investment or $100 million investment, it's almost like they're punishing pharmaceuticals.

At some point, perfection becomes the enemy of the good. And it's a brilliant thing to have an absolutely bulletproof drug that's been through all of these myriad tests. Love to have it, but it takes too long. And if we rely entirely upon that process for the discovery of the next generation of drugs, we're going to be waiting a long time. I don't have the time.

There you go.

And a lot of other people don't have the time. The people who need help, who want interventions, who want improvements, they're not going to wait 10 or 20 years. We need to do it now. We have the knowledge. Let's apply it.

One of the things that drives me nuts in the world of longevity is you'll see some of these people saying, well, we have no evidence that you can extend human life, therefore you can't. And there never will be evidence because they would have to die. Meanwhile, we do have aging clocks, and we have the ability to measure all sorts of aspects of aging. So we could say, well, let's do what's most likely to be beneficial and let's see what happens. And I'm on that path. What do you think about the ability to measure someone's age and to predict whether we can extend their lives?

Well, aging is really two things. Aging is measured in years, which can be, as you said, a very long process. And we have to wait for people to succumb in order to know whether we've made a difference in mortality. But aging is also reflected in the quality of our health. And our organ function, and we can use that as a proxy for longevity.

That's where I am. And I'm saying, if I can make my organs younger, I can make my mitochondria work better. And we can measure all these things. At a minimum, I'm going to have a really good time when I'm 80. And if I die on 86 on average or something, I still win. And the odds are very high that it'll be longer than that. I know our current best is 120 or so years. Given what we know with AI, with new research, all the work you've done in your life, how long do you think humans could live if we just pull out all the stops?

We have to ask ourselves whether the ultimate longevity of the species is determined in some type of inexorable and unchangeable way, or whether it's the accumulation of damage over time that ultimately forces us to succumb. If we look at more broadly at the ecology, we see animals that live two weeks and we see animals that live 400 years, like the lake shark. What we're learning by these experiments of nature is to better understand what are the underlying principles that guide their ultimate demise. We know, for example, in the leg shark, which is such an interesting animal, 400 years old, this animal has massive duplications of DNA repair enzymes. So they have a tremendous investment on making sure they don't accumulate mutations. It takes so much energy to do that that the darn creature can hardly move. He doesn't have much energy left for anything else, but he sure lives a long time. So there's a trade off from an evolutionary perspective where every species has evolved either to have a wonderful quick life with tons of energy, like the mosquito or the housefly, or a very long and somewhat slow life like the tortoise, or a giant tree that doesn't do very much, or in the case of the lake shark. So if we understand what are the fundamental determinants of a long life, then we can start to make interventions to specifically interdict these. And what we've learned from these experiments is that the lake shark and other animals like that have invested massively in protection of their genes, because ultimately it is the accumulation of mistakes, of mutations that will ultimately lead to dysfunction, aging in the broad sense, and death.

The logo for my company, Upgrade Labs, AI Exercise Longevity company, is the axolotl, which is an animal that can regenerate limbs or even its entire spinal cord over and over and over. I'm like, okay, it can be done how do I install that in myself?

There's the poss. Look, everything's based on knowledge. Knowledge is power. As we start to understand really what are the fundament drivers of longevity and of death, that will give us the information from a scientific perspective to go out and make the right intervention. So I don't think 120 years is the ultimate barrier. It is right now because we really haven't made those changes we need to. But science is moving very quickly. So I would predict that in five to 10 years we're going to start to see changes. It's going to be 130, 140. At some point maybe we'll be like the lake shark. I don't think so far. Who would want to live 400 years? But I think we will make, we will crack that barrier.

I certainly think we can, and I'm totally willing to be wrong to just have a great life in the meantime. I've seen in my 20s, when my health was failing, I remember my, my friend Mike, who's on the board of the anti aging nonprofit. He would call me at 11:30 at night. He had more energy than I did and just, I watched people reverse their age when they were in pretty advanced. I'm like, I wish I had that much energy. And so I've seen it. They're outliers. But if one person can do it, then we gotta study them and figure out what caused that. And your relentless curiosity in your career, I think is, is pretty interesting because you've done a lot of different areas of work and you arrived at NAD as something to.

Oh, I've been focused on nad since 1985.

Oh, wow.

Okay.

So you're an early, early adopter.

Oh, yes. By 1994, my career was focused on. Nadia was focused on NAD. When I became involved in the PARP work, I recognized that NAD was the centerpiece of biology as far as I was concerned in the icu.

Because NAD powers parp.

Oh, it. Well, NAD has many important functions, but for parp, it is absolutely the critical cofactor parp. Without nad, it doesn't work.

Okay, let's explain what NAD is and what PARP is. So first, what is NAD and why do we care about?

Well, NAD is a small molecule that, like I said, it's the centerpiece of biology. And it really does three things in our body. First of all, NAD is absolutely essential for energy. NAD controls the production of ATP, which is the currency we use in order to think, to move our muscles, to have our digestion work, to Metabolize. So NAD is absolutely essential for the energy in your body. You have low nad, you have low energy. Okay, so that's the first thing. Second thing. NAD is absolutely essential for the production of an antioxidant defense. We are bombarded continuously by the environment, by cosmic rays, by oxidants. We make. We are in a bath in a world of oxidants. We must have an efficient and effective antioxidant defense. NAD produces or is converted to nadph, and NADPH is the driver that protects us. It produces glutathione, it produces all of the antioxidant functionalities. So we need NAD to survive in an oxygen rich environment. That's the second thing. Third, NAD is used by parp. PARP is the second most abundant protein in our nucleus. It enshrouds all of our DNA, all our genetic material. Every minute we are undergoing changes in the DNA because of the environment, because of oxidants and cosmic rays. And there are breaks, they're little. You know, DNA is a double strand. It's a helix, though. That helix is susceptible to nicks or breaks in one of the strands. And they're happening about 70 times a minute. So over the day, every day, we are having an assault on our genetic material. If we do not immediately recognize that and correct it on the spot, those breaks persist. And when the cells divide, if there is a break, you will have a mutation. Well, when you're 10 years old, maybe you won't have many. By the time you're 30, you're going to have a bunch. By the time you're 50 or 60, if it's not corrected, you will have loads and loads of mutations. And that spells malignancy. If you remove any of the DNA repair enzymes, you are going to get cancer. And the best example, of course, are BRCA deficiencies. So PARP is the enzyme in the nucleus that identifies the problem, the nicked DNA. It gloms onto it, it then twists and becomes active, and then NAD flows into it and it uses the NAD to repair. So low DNA. No DNA repair mutations, ultimately malignancy. So those are the three things that NAD does. It gives us our energy, it protects us against oxidants, and it saves us from cancer.

And the protection from oxidants is going to provide cardiovascular protection, right?

Oh, my goodness, yes. If you look at the vascular system, the oxidants that bathe our blood vessels over time, those lead to endothelial dysfunction, leads to hypertension, calcification, all of the problems we have with plaque buildup. So yes, it is a critical part of the vascular system. And then, of course, of the cardiovascular of the heart. The oxidant injury to the heart impairs the muscle function. So as we get older, we have a heart that beats less strongly and blood vessels that are more rigid, they don't provide the kind of blood flow and nutrition we need to sustain us. So the role of NAD in cardiovascular health cannot be underestimated.

It's funny, in the world of longevity I talk about, there's these four killers. If you want to live a long time, don't die first. So that would be don't get cancer, which we're talking about with NAD and parp, and then don't get cardiovascular disease, which is actually more deadly than cancer. And then what's behind both of those is don't get diabetes and then don't get Alzheimer's. And I look at diabetes as kind of the first of the four, because if you get that, your risk of the other three big things that'll kill you goes up.

We were the first to show that in diabetes. We published in Nature that in diabetes you get a fall in nad.

There you go.

Right. And that leads to all the complications of diabetes on the blood vessels, on insulin sensitivity. This is all bound up, up with having a healthy level of nad. It's got. You've got to maintain NAD to maintain your health.

Longtime listeners have heard me talk about niacinamide, which is the very oldest way of raising nad. And then the first research came out about NR about 18 years ago or something. I started taking it then. And then NMN came out. And so I've been on these things for a long time. I've done the IVs and talked about what that looked like. What is the benefit of taking nad and what is the. Or NAD precursors and what is the downside of taking nad?

In order to boost nad, there are only two things you have to keep in mind. One is you have to have enough there. You gotta have a supply. And secondly, you need to prevent its consumption or its depletion. So let's look at each one of those.

Okay.

You were taking supplements, NR initially, then nmn. Why did you do that? Because NAD itself cannot be swallowed and expect to cross the gut into the blood and get into our cells nad. I mentioned how important it is, but it's important inside the cells. That's where it works. So if it's outside the cells, it's not going to do anything, even with.

An intravenous infusion, Even with an intravenous.

Infusion, it'll be in your blood, but that doesn't mean it's in your cells. And when it works, it's got to be inside the cell. That's where it does those three things I mentioned. So how do we get it into the body? How do we get it through the gut? How do we get it from the blood into the cells? We use nature's own way to do it. Nature has designed a thought about this. So in our bodies, we have precursors, NMN and nr. And they're there for a reason, because there are specific shuttles that exist in the cell membrane that move these from the outside to the inside. Remember, NAD is a very precious molecule. God made it with charges on it. It's a polar charged molecule. It will not leave the cell and it will not get into the cell. It can't cross a fatty lipid membrane because it's charged. So in order to get stuff into the cell, there was a jacket created around it, if you will. That's what NR and NMN are. They're a jacket on nad. And that jacket is recognized by a shuttle, which whisks it in to the cell and. And there the jacket comes off and NAD is alive and well and ready to go inside the cell. So the supplement industry recognizes this, and that's why NR and NMN dominate that industry. You have to supply those in some manner to get enough nad. That's the first goal. The second goal is you gotta keep it there, right? Doesn't do you any good to boost the stuff and get it all in there and then only find out that there are depleting mechanisms that scarf it away, that steal it away.

I think this is a problem that I ran into. But actually, first I have to ask. There's pretty good evidence that alcoholics who get 10 to 20 NAD infusions have a much lower risk of starting to drink again. And if it can't enter the cells at all intravenously, why are we seeing clinical results?

Because NAD in the blood can be converted by enzymes in the blood and in the tissues to nmn.

So when I get an NAD iv, my body's converting it back to nmn.

Yes.

I did not know that.

Okay, yes, yes.

So you can save a lot of money by just taking the right supplements without having to do the IVs.

Not many people want to walk around with an IV.

Plus, it's pretty uncomfortable nad IVs. I finally got to where I could do a gram in about 45 minutes, but it's like something sitting on your chest and you're turning red. It's a methylation thing.

Yeah.

So we can just stop doing that.

Yes. I would recommend good oral supplements that make sense, that provide the precursors, these jacketed forms of nad.

How much time I've spent with needles in my arm that I didn't need to. With the knowledge that we now have that we didn't used to. Yes, okay, that's fascinating. So let's say that I've taken some NR or some nmn. What's going to steal it?

Well, there is, there are a lot of interesting theories on this, but now we know a lot more than we did five years ago. It turns out that there is a major enzyme in our body which has the specific role of clipping NAD or NMN and cutting it in half and destroying it. And that is called CD38. May have heard of this. CD38 is an enzyme that's present in most of our tissues. When we're young, we have just enough that we need, but as we age there's more and more and more. So by the time we're 50 or 60 or 70, we've got way too much of this. This enzyme is positioned in different places in the cell. There are actually three different. But the one we care about is on the cell membrane itself. It sticks out into the blood and as NMN whisks by, it says, haha, there you are, I got you. And it cuts it in half.

Why would this exist in our cells?

Because it needs to do that in order to fight infection. It is something involved in the inflammatory response. So a little bit of this great thing. There are three enzymes that use NAD or nmn. One of them is parp, I already mentioned, to affect DNA repair. The second one is the sirtuins. Changes a lot of the physiology we need. And the third one is CD38 which uses it to fight infection. A little bit of something is a good thing. It's natural, we need it. Unfortunately, as we get older, we get more and more inflammation, probably from leaky gut. And CD38 responds to that by being more and more expressed. And as we get way too much of it, by the time we're 50 and 60, it is out there and it is destroying the NAD. So you can take all the supplements you want, you can load yourself up with NMN, NR, but this enzyme's out there when you're 50 and 60 and it's chewing it up. So the right approach is give the supplements. Yes, great idea. But concomitantly with that. At the same time, slow down CD38.

Okay.

And this is the key combination approach, which we think is the next generation approach.

So if you were taking extra NMN and Extra NR, your CD38 activity is going to go up and up.

CD38 is going up because of your age.

Well, does it go up even more when you have NMN and nr? No, I thought it consumed.

It does, but it's an enzyme. It's not used up. When it catalyzes the degradation of nad, it is, it is an enzyme. It's being regenerated. You don't lose it.

Okay?

Yeah, it's just there and it's doing its thing, which is eating up your nad.

So if you wanted to live a very long time, you probably should brush your teeth really well. Because if you have a lot of oral bacteria, which drives your whole microbiome and also escapes directly into the bloodstream, you're pissing off your immune system. You're living in a house with toxic mold, like I did as a kid, which causes strobe throat to grow as well. You're pissing off your immune system. So the more chronic infections you have, even low grade, the more you're going to have an aggressive immune response and the more likely. I'm just, I'm kind of making this up as I go along, but I'm.

Well, all of the things you've said are absolutely true, but there's an even bigger gorilla in the room here.

What is it?

The real cause of the major cause of progressive inflammation as you age is the ability of your intestine to seal itself and not permit the egress of endotoxin, other bacterial constituents from inside the gut to the blood. We know that the major protein in the gut, which is the seal, the gasket, is Z01 and Z01. Unfortunately, as we get older, its levels go down, the gut gets leakier and leaker. Look, if you take a 25 year old person, they have trillions of bacteria inside them. None of them get into their blood. You take a 60 year old, there's lots of garbage coming in. And that garbage stimulates our immune system. And it says, whoa, time for inflammation. We have infection. And that infection, if you took a 70 year old person, they're inflamed. Aging is an inflammatory event and that inflammation turns on the expression of CD38. That's where it's coming from. So the microbiome and our ability to protect our gut is key. Proper diet. There are various things we can do about the microbiome. I'm sure you've talked about that in other shows. This is central to maintaining longevity because that starts the whole process. Our gut is the driver, ultimately the initiator.

In my longevity book, I referenced a couple papers that showed taking activated charcoal, which just binds to endotoxins in the gut, is associated with about a 15% lifespan increase just from reducing some of those. And when you look at things like germ free mice where they have no microbiome because they live in little bubbles, they live a long time, they're ripped, they can eat whatever they want.

This is where I began my career really in 1988. I was in the intensive care unit and there was a brilliant young professor that I teamed up with named Mitchell Fink. And we had the idea at that time that the barrier of the gut might change during disease. No one had thought about that. And I discovered that endotoxin can actually open up the gut. And we published these papers from 88 to 92 showing that it was malleable, that the gut not sealed, the barrier is not fixed, it can respond. And we found a lot of. We found that hypoxia will do that. We found that acidosis would do that. Certain cytokines and all of that work show that it's dynamic, that they're opening.

And closing the junction.

Yes.

How would you go about sealing as best as possible the gut so that nothing leaks out of it over the course of decades?

That's going to require, I think, understanding of diet and the role of the microbiome.

Okay.

Right. That's not an area that I'm in anymore. But there's tremendously good research looking at that, and that's very important. That is a major factor in longevity. That should be emphasized. There needs to be more research in that area.

Okay. I've been for almost the last eight years now advising viome, which has a really good data set now where they're starting to figure that out. I know that because I was on antibiotics for 15 years every month, because I had chronic sinusitis and strep throat, because I lived in a house with toxic mold, that I probably don't have an advantage there. In fact, the fact I'm not obese right now is kind of shocking given all the crap that I went through. And so I feel like I'm coming from behind in my longevity journey here. For an average person, maybe they're a little obese, but they haven't had that big of a problem. Is there a pharmaceutical intervention or is taking these NAD things like you're making with wonder feel, where do you start?

Well, it's actually interesting now you're talking about a positive feedback loop. It turns out that, and this is also work that I did in 1992, the energy of the cell in the gut is directly responsible for how well the gut seals itself. We published the first paper on this where we related NAD and ATP levels inside the gut cells to their ability to maintain the integrity and not let MOLEC slip through. So you can imagine if that gets out of hand, out of whack, and then you start to leak and you get inflammation. CD38 expression goes up, NAD goes down. The gut now doesn't have enough NAD to maintain itself and it gets progressively leaker. It's a snowball effect. So the key thing is keep the NAD at a healthy level, have a good, healthy gut, do whatever interventions science is telling us to do, keep our gut good and healthy. And then to further augment that, take NAD supplements or actually NAN or nr and find a way, which I'll talk about a little later, to stop the activity of CD38, depleting this precious NAD that we have.

So even if you have immune activation as you age, you can stop the CD38 so that you can slow it down. You can stop it? Yeah, absolutely.

There are two approaches. There's the pharmaceutical approach. I wish them well. It'll be another 10 or 15 years. I'll be a little bit old at that time to enjoy the benefits. But I do wish them well because CD38 is a target that the pharmaceutical industry should go after while I'm waiting. We have botanical approaches, natural approaches, which we include actually in our wonderfill product, which slow down the activity of CD38. So that combination I mentioned is so critical. Give a boost with a supplement, but stop the depletion.

You mentioned ATP and I think a lot of listeners know what ATP is. Just in case we have some new listeners, talk about ATP for a minute and what it does in the gut.

ATP is the ultimate means. It is a currency. Think of it as a cryptocurrency. It's a currency in every cell that is there. And it is the final common molecule that provides energy to various processes, whether they're metabolic processes, hormonal processes, movement of muscle, activity of neurons in our brain thinking ultimately ATP provides the electron reducing equivalent, is providing the power to do things to make the body work. NAD creates the ATP. So if you don't have nad, you don't get ATP and why did I care about this? As an intensive care specialist, we're not worried about longevity in the long term in the icu, we're worried about whether you live the next hour or two. Okay. When someone comes in with a heart attack, for example, they have an acute interruption of blood flow and oxygen to their heart. Okay. What happens when you have no oxygen coming into your heart? You don't have enough NAD? PARP is activated within about 5 seconds. NAD is massively consumed and there's no ATP made. And because there's no ATP made, that heart muscle, which is at risk in the first few minutes, sadly, it goes on to die, to infarct. So if you maintain nad, you maintain ATP during the heart attack, you won't get the infarct and you won't die. So we made every effort, we designed drugs, and this is what I licensed to Genentech. By blocking PARP activation, it didn't consume the NAD during the heart attack. ATP levels were maintained and the heart did not get an infarct.

Wow.

Same with stroke. Stroke's the same way. A lot of these and I could go on and on and on, but PARP is very important in these acute events for aging. Though this is not done over minutes, this is a problem over decades. So the principles are the same, but it's not as dramatic.

So PARP is helpful because it repairs your genes. But if there's a. A traumatic event or an overactivation, it stops being useful for gene repair. And it causes all kinds of damage by stopping ATP.

So we showed this. If you take an animal or a person and you interrupt blood flow to their coronary arteries, their heart is deprived of the oxygen it needs. Within about one to one and a half minutes, you get a massive influx of oxidants in that cell that attacks the DNA. Attack. Your genes cause huge numbers of DNA single strand breaks, millions in the cell of the heart. Those activate PARP like crazy. Suddenly, PARP consumes NAD within about two to three minutes. If you measure the NAD levels in the heart after two to three minutes after heart attack, zero, undetectable. And of course, you wait one more minute, no ATP, you wait another five minutes. Dead cell. So, yes, PARP overactivation in the acute setting is a killer.

Would it make sense to block PARP before you play a football game because you know you're going to get hit in the head?

That is something I never heard anybody suggest. It's a wild idea, but it's an interesting concept. We did prophylax animals many after head we did traumatic brain injury studies with parp, and, yes, you can preserve brain function, reduce neuronal injury. I'm not suggesting anyone do this, but. Okay, okay, I'm with you.

If you're an MMA fighter or a professional football player, I have protocols for what to do before.

No doubt. No, it would help there.

Yes.

Yes. We have done dozens of studies in traumatic brain injury. We've done them in sheep, we've done them in mice and rats, and we have shown conclusively that you can ameliorate and prevent the sequelae of a concussive or a worse event. Yes, it is protective in that sense. Not making a recommendation, but it works.

No one that I'm aware of is using PARP drugs like the one you invented for this, and there may be side effects I don't even know about. But what I do know, having had a titanium knee to the head at high speed and gotten a brain injury, I'm fortunate that I know what to do for that. I have a neuroscience clinic, so I was able to repair my brain. And as soon as we knew what happened, I started with the antioxidants and all. But the incidence of brain injury, even in kids or in highly functioning adults, you get in a car accident, you get whiplash, and it ruins marriages.

It.

It messes with people.

It's a major killer in the. And not just killer, but it leads to very sad situations where people have chronic brain injury that just doesn't get better.

I know. Six weeks after I took that knee to the head, I sent Tim Ferriss an angry email about something he didn't even do. Like, I was out of my mind. I was swearing all the time. And, like, what is going on? And some of this has to do with the fact that my brain, which actually, at the time especially didn't even have enough blood flow regularly, according to Amen clinics. And then I ran out of ATP for the parts where I scrambled my eggs. And so it took me a little while to recover. And the good news is we have neuroplasticity. You can recover.

Yes.

But I look at people who are at risk of these things and saying, all right, I know having ketones present reduces oxidative damage. There's all sorts of different strategies that are all mitochondrial enhancing. And when you peel all that stuff away, ultimately it seems like NAD is the most important of all of those.

It's the centerpiece, it's the major player.

Wow. All right, so what about liposomal nad? I've seen some formulations of that. Does that work?

Well, there's liposomal NMN that's been looked at because people want to optimize the amount of NR or NMN that's coming in. And I'm all for that, but it needs to be done in a way that's effective. So far, we haven't seen studies that really prove to me that liposomal NMN is better than just regular nmn. It might be, but I haven't seen the studies. I will say that liposomes are not easy to work with, having spent quite a bit of time with those. They leak. They leak over time. So there's stability issues even on the shelf. So it's a difficult modality to work with. More power to them that they should do great research and maybe that will improve it in the long run. But I haven't seen that yet.

Got it. And I realize I'm using big words, if you're listening. Well, lipa, whatever. A liposome is a little. Call it a bubble of fat that you can use to put a pharmaceutical or a nutraceutical inside it. So it'll absorb through the gut lining or absorb into cells. So the very first liposomal glutathione on the market, I hope to bring that to market years and years ago. And then I had a dry liposomal bulletproof. And like you said, they're very hard to work with. My friends at Quicksilver make some cool stuff. There's even, like liposomal testosterone formulations and things now. So it's a cool delivery system. That's very finicky.

Finicky. That's the right word. Yeah. Difficult, unstable.

And what you have with the stuff you're doing at Wonderfeel is you're. You're doing NMN plus you're blocking CD38.

At the same time. Right. We have two natural products and their ingredients, if you will, in our solution. One of them is resveratrol, which of course is from red grapes. And that has been. And it's in wine. Red wine. And that has been shown to block CD38. Very interesting. And the other is from olive oil, hydroxytyrosol. Okay. In the Mediterranean diet there. And that is also a blocker of CD38. So that's why we took those two and we added those to NMN so that we would increase the supply, but we would block the depletion simultaneously.

And you are the only person who's ever talked about hydroxytyrosol on the show. And I looked at a lot of the research around olive Oil. And there's plenty of evidence that says 30 grams of olive oil a day is good for you. Above that, it's a bit of a. It's a bit challenging. If you take a lot of oleic acid, the primary fat in there, it increases something called D5D and D6D, which means that your body way more easily oxidizes all the other Omega 6s. So olive oil. Good. Excessive olive oil drives oxidation.

Well, we don't provide olive oil. We just purify the hydroxy tyrosine.

Exactly right. So hydroxy tyrosol is the most likely beneficial compound in olive oil. So when I put together one of my. I think it was my fat, my omega 3 formula back when I was at bulletproof. And guys, I don't have anything to do with bulletproof. I don't. I don't believe they're following my formulas. I don't even track it. So, no. No commentary there I can offer you. But the thing I formulated years ago, I put hydroxy tyrosol on it. And my formulators are like, what is this? And I said, oh, there's a supplier. We got to do this because I wanted the benefits of drinking a gallon of olive oil. I just don't want to drink the olive oil because I don't think it's good for you at high doses.

Right. Hydroxytyrosol, of course, is an antioxidant, has lots of different functions. One of them is the CD38 blockade. But the antioxidant effect is also important. And to that end, by the way, we've added another ingredient in our wonderfeel, which is ergothionine. So this is a natural amino acid. It's very, very powerful as an antioxidant. And the reason we did that was that we didn't want to have a lot of DNA damage. DNA damage activates parp. PARP consumes nad. So by giving that heavy hit with ergothioneine, we have a lot of antioxidant power in there now that reduces the amount of DNA damage and reduces the need for PARP to fix something which would consume nad. So all of this was focused on keeping NAD levels high, using antioxidants in conjunction with. With boosting the nad. Very important. And that's why it was necessary to include ergothioneine.

Ergothioneine is another one of these longevity molecules that most people haven't even heard of. And I look at this as foundational as glutathione. And when I started the whole Biohacking movement. Glutathione was the rock star, and it still is. You need this for your liver, for your brain, inside all your cells. And orgathioneine is as potent via different mechanisms? Yes, it is. I mean, most people don't know.

I should also add that glutathione, just to make a full circle here. Where does that come from? Glutathione is produced by a glutathione reductase. And the energy to make glutathione comes from NADPH through. And where's nadph? What is that? That's from nad. So NAD is acted on by NAD kinase. It makes nadph, which then creates glutathione, which is amine, a major, major important antioxidant. If you take animals that can't make glutathione, they die. They do not do well. Okay. And any kind of limited injury, even a minor, trivial injury, becomes a major problem. So glutathione is one of the most important natural antioxidants that we have, and that's all dependent on having NAD there to make it. Without nad, you cannot make glutathione.

Wow.

Be very clear about that. Yeah. So NAD has a very important antioxidant functionality in that way.

One of the concerns that I've had, and this goes back to when I started in longevity, it was actually the late 90s, where I'm in my 20s and I'm learning from people in their 80s, and we were taking a lot of antioxidants, sort of like oxidation's the devil. And problem is, we have this ox redox reaction that makes ATP. How do we know that when we take wonderfeel and now we're getting ergothioneine and we're getting resveratrol and we're getting all the other animals?