BONUS Why NAD Matters for Women’s Health & Hormones with Dr. Andrew Salzman

This podcast is the first episode in a series featuring companies I am eager to explore and share with my community.

Today, I am thrilled to welcome Dr. Andrew Salzman, a Harvard-trained medical doctor, pioneering scientist, and esteemed inventor. Dr. Salzman is the Chief Medical Officer at Wonderfeel, where he applies over three decades of medical innovation. His research into DNA repair with NAD-activated enzymes led the way for a groundbreaking treatment for BRCA-related breast and ovarian cancers, which he licensed to Genentech. Dr. Salzman was among the first researchers to publish papers on the gut microbiome and leaky gut syndrome in the 1980s, and he has published over 170 peer-reviewed papers and holds more than 50 patents.

In our conversation today, we dive into what NAD is, its significance, why it matters, and how it impacts fertility, menopause, and sexual health. Dr. Salzman walks us through the symptoms of NAD deficiency and explains how an enzyme called CD38 can emerge when NAD levels are low, triggering inflammation and oxidative stress. We explore the difference between pharmaceutical agents and nutraceuticals, examining why oral NMN is preferable and how sleep and alcohol can influence NAD levels. We cover the risk factors for breast, ovarian, and uterine cancers, looking at what we can do to reduce them, and we also talk about Wonderfeel and how their supplements and botanicals enhance wellness for women. 

This is an invaluable discussion with Dr. Salzman, so you will likely want to listen to it more than once.

IN THIS EPISODE YOU WILL LEARN:

• How our NAD levels change as we get older

• The role of NAD in energy production 

• How oxidative stress and inflammation affect NAD levels in the ovaries

• Why NAD is essential for sexual health

• Lifestyle choices that could affect NAD levels

• How inflammation can increase CD 38 levels and deplete NAD

• Why oral administration of NMN or NR is the most practical and effective method for maintaining NAD levels

• How alcohol affects NAD levels and increases the risk of cancer

• How, with Dr. Salzman's input, Wonderfeel developed a product combining NMN with botanicals to enhance NAD levels

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“With inadequate levels of NAD, we have a fall in ATP production, we feel weaker, we lack strength and endurance, and we can’t think as clearly.”

-Dr. Andrew Salzman

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Connect with Cynthia Thurlow  

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• Submit your questions to support@cynthiathurlow.com

Connect with Dr. Andrew Salzman

• On the Wonderfeel website

Transcript:

Cynthia Thurlow: [00:00:01] Welcome to Everyday Wellness podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.

[00:00:30] Today, is the first in a series of carefully curated podcast episodes that are driven by specific companies that I'm interested in learning more about and sharing with my community. 

[00:00:43] Today, I'm thrilled to welcome Professor Andrew Salzman, a Harvard-trained medical doctor, pioneering scientist and renowned inventor. He's the Chief Medical Officer at Wonderfeel. And Dr. Salzman brings over 30 years of medical innovation. His research on DNA repair using NAD-activated enzymes led him to the groundbreaking treatment of BRCA-related breast and ovarian cancers which he licensed to Genentech. He was also the first to publish about the gut microbiome and leaky gut issues in the 1980s and amazingly has published over 170 peer-reviewed papers and has over 50 patents. 

[00:01:20] Today, we spoke about why NAD is so important, its primary roles and how it shows up in terms of symptoms, specific ways that NAD impacts not only fertility but menopause and sexual health, if NAD is too low in the body, how a very specific enzyme called CD38 can show up and drive inflammation and oxidative stress, differences between pharmaceutical agents versus nutraceuticals, why oral NMN is superior to other routes of administration? What is optimal dosing? the impact of sleep on NAD as well as alcohol and lastly, risks for breast, ovarian and uterine cancer in women and how we can help lessen our risks. And finally, we talk about Wonderfeel, specifically this supplement and botanicals that work to potentiate the benefits that we can experience as women.

[00:02:21] I know you will find this to be a truly invaluable conversation, likely one you will listen to more than once. Well, Dr. Salzman, such a pleasure and an honor to connect with you. Welcome to the podcast. 

Dr. Andrew Salzman: [00:02:36] Thank you. Very happy to be here. 

Cynthia Thurlow: [00:02:40] Yeah. We haven't actually explored the concept of NAD on the podcast and as I was mentioning to you before we actually officially started recording, I think a great deal of that has to do with I was clearly waiting for the right expert and I think that bringing you on and having your ability and your knack to communicate information, scientific information and making it accessible is certainly very important. What is it about NAD that is so important for women to understand? And how does do NAD levels actually change as we get older, especially as women?

Dr. Andrew Salzman: [00:03:13] Well, NAD is one of the key molecules in our body which really serve so many different functions. We can think of it as really the orchestral conductor who's there with so many different players and so many things happening, but somehow, it's in the middle of all of it. And when we have good levels of NAD, we're healthy in so many different ways, which we'll talk about today. And when, unfortunately, NAD levels are not so good, a lot of disease can occur. Some of the disease we call aging, some of those diseases we give specific names to. But fundamentally, when you're dealing with a molecule that is the centerpiece of health, any kind of derangement, any fall in that molecule is going to be a problem. 

[00:03:56] And unfortunately, the levels of NAD are not stable. They fall as we get older. When we're young, 10, 15, 20, we have great levels of NAD. We're full of energy. We can run forever. There's nothing we can't do. But some time, maybe in the mid-20s, we start to see a fall. And it's progressive and it's inexorable, it just keeps going down and down and down. So that by the time we're in our 50s, we've lost more than half of our NAD levels and that's significant. When we go on beyond that, we're talking about folks in their 60s and 70s, 80s, even older, they're really precipitous falls in NAD. And that leads to really very significant major health problems. And we'll talk about those today.

[00:04:38] So, it is not a molecule that we can ignore. It is probably the most, for me in my career, it is the centerpiece of all that I've studied. It connects in everything, every way. 

Cynthia Thurlow: [00:04:48] And I think for listeners to fully appreciate and understand NAD at a very significant molecular level, it's involved in ATP production and energy production. And as that is falling, I think for so many of us, we assume, “Oh, we're X age, and it's just normal to be tired.” And a lot of that is tied up in this decline in NAD, which impacts our mitochondria, which impacts our energy levels, but it also impacts our ability to repair.

[00:05:16] And so I know that you speak about this DNA repair piece that is so significant, and we could probably talk about 15 or 20 things that NAD is involved in, but I think this makes it very tangible to understand that at a very basic level, those fluctuating and declining levels of NAD really lead to a decrease in the ability to generate ATP, which is this energy molecule inside of cells. And how that leads to many of the sequelae that we see, you know, symptoms that are inflammatory in nature, people that are dealing with chronic pain, noticing things that change with our skin, acceleration of aging in women, aging is really our ovaries, so ovarian senescence, and helping all of us understand and put those pieces together.

[00:06:00] So when you're thinking about how NAD declines in NAD present in terms of symptoms beyond pain, inflammation, energy, are there other kind of telltale signs that you will see when you're explaining this to women at this stage of life? The perimenopause to menopause journey group in particular. 

Dr. Andrew Salzman: [00:06:18] Right. Well, let me take you through a journey, if you will, in which I try to focus on women. Although obviously men are-- They also have many issues with NAD. But I'd like to focus today's discussion really on women. And let's walk through what are the real major components that a woman would care about at various times of her life. So, you've already started by talking about energy. And of course, everybody wants to do things. They want to walk. They want to go do sports. They need to have activity. And the role of NAD in the production of energy is absolutely essential. It produces ATP, which is the driver. That's what moves our muscles, that makes us think, it allows us to function, to digest. Everything is based on that common currency, which is ATP. So, we have to have that.

[00:07:03] And when we have inadequate levels of NAD, we will see a fall in ATP production. So, we will feel weaker. We won't have the same strength, the same endurance. We can't think as clearly and as sharply or we can't digest as well. So, all of the functions that are associated with energy in our bodies start to diminish, to decay, to degrade over time as we see a progressive fall in NAD. This is for true for men and for women. 

[00:07:33] But I'd like now to turn our attention really more towards women. And let's begin with fertility. So, we're talking here about women who are of childbearing age, which of course, from an evolutionary perspective, was teenage years. And then today in our modern society, we see people even in their late 40s, who are able to have children. So, what is the role of NAD in fertility? Well, the key organ, of course, in fertility is the ovary. That's where we begin. And the ovary is actually quite a complicated organ. It's not so simple. It has lots of different parts and different cells, but it all comes together for one purpose, and that is to nurture over decades these eggs that women were born with. And then at the right moment, to allow them to release, to hatch, if you will, to come out of the ovary and then to be available to form a baby.

[00:08:24] So, what is that function, and how does NAD fit into that? Well, the first part is that the eggs have to be preserved. And we're talking about women having these at birth, so we're talking about decades. So, here's a precious cell. You can't get more precious, actually, than an egg. It has all the genetic information for the next generation. So, this is the most precious part of a woman, for sure. And the genetic fidelity of that information, making sure that every single part of that DNA is in exquisitely good shape is essential, because that's the transmission to the baby, that's the next generation. So, there are mechanisms within the ovary, surveillance mechanisms all the time looking for any evidence at any minute that there could be damage to any of the DNA in the ovary. 

[00:09:10] If there are, if there isn't-- If that's identified, then there is immediately a series of steps that get to work to identify it, to isolate it, to fix it, and to repair it, to make sure that egg, at the right moment, if it's ever becoming the next generation, will be in perfect condition. Okay, and NAD is exquisitely involved in making sure that that happens. And it happens because of an enzyme within the cell called PARP, and that is the second most abundant protein in our nucleus. And it's looking all the time, any evidence, anything that may have happened to our DNA, and immediately gloms onto it grabs it, and then NAD is next to it, and it grabs NAD as well, and it uses that NAD to make the repair. 

So, if we don't have NAD there during all this time, these decades, that these eggs are being nourished and waiting, then we're going to have a genetic defect in the baby. So, it's absolutely essential. That's the first part, to make sure you have a healthy babies, make sure your eggs are in great condition. 

[00:10:13] Now, after that oocyte, after that egg is there for decades, at some point, there's a trigger where it's going to become a follicle. And every cycle in a woman, before her period, many of these eggs, maybe five to ten, suddenly emerge and become ready. Not all of them will be released. If that were the case, then we would have litters rather than one baby. We'd have, like a dog, you'd have eight to ten babies. That's what happens in animal where you have multiple eggs released. In the human is typically one, could be two, can have twins, could be three, rarely, but all--

[00:10:48] There are about 10 to 15 of these eggs that are getting ready. It's time to go. And so, they have to develop, that's energy requiring. That requires a lot of energy pouring in to make that follicle, to put the fluid in there, to get everything ready, to blast off, if you will. And that is entirely dependent on NAD. And then once they're ready to go, they have to leave. They can't stay in the ovary, they have to egg, there has to be egress, they have to hatch, if you will. That whole process of taking off the cover and allowing the egg to leave the ovary again, that requires energy and that's dependent on NAD. 

[00:11:22] Now how do we know this? Well, people have looked at ovaries in animals and what they've seen is that as we get older, the NAD levels in the ovaries start to fall. And they fall in a very specific place, which is right around where the egg is. And we now know why they're falling. We actually have discovered the mechanisms in the ovary of why the NAD levels go down as we get older. Why does a 20-year-old woman have a high level of NAD around her egg, but a 45-year-old woman has only half, well what's the reason for that? What's the cause? And we know now, first of all there is oxidant stress all the time from inflammation. And as we get older, there's more inflammation. We can talk about why later, but trust me, there is. 

[00:12:06] And as you get more and more inflammation, it's in your ovary as well. Your ovary is not separate from the rest of your body. And so, when there's inflammation, little by little, you get that happening within the ovary and you get oxidants that are produced and those can actually start to cause a problem. And as a consequence of that, you get activation of PARP in response to oxidants and it uses NAD. And so, the NAD levels can go down. So, we do see NAD levels from that a little bit. 

[00:12:36] But the major cause now, and this is only in the last three or four years that we know this, is that there is another enzyme. This is so important to your listeners. I want them to really hear about this because you won't have heard about it before, but believe me, this is the major cause of aging. I'm not exaggerating this. There's an enzyme called CD38 and I really want to talk about this today because it's bad news bears. I mean, this CD38, we need it, a little bit of it to fight infection and it's involved in our immune system a little bit. But the problem is that as we get older, there's more of it and more and more and more, progressively more and more and it builds up. And this enzyme has one of its singular duties to chop NAD in half. Literally, it's like scissors, just cuts it, its usage is gone, it cuts it in half.

[00:13:29] And so, if there's NAD in your ovary, which there has to be if you want to have ovulation, once these scissors comes in there and cuts, well, it's going to make less NAD. And that is why we've now got absolute proof from animal studies, complete ironclad proof, that the CD38 in the ovary is what is causing the diminution, the progressive fall in NAD within the ovary. We know that now because we can take animals that do not have CD38 and their NAD levels in the ovary are maintained. 

[00:14:01] Now what are the consequences of this? Well, amazingly, the animals that get older have trouble getting pregnant. They still have the normal size litter, but it's rare, few and far between. So just like a woman, it's more difficult to get pregnant as she gets into her 40s or late 40s, so it's true in the animals, but if they don't have CD38, if that enzyme is not present in that animal, they will continue right ahead and they will ovulate just like younger animals and they will have babies just like younger animals. It's as if they didn't age, the ovary was able to maintain itself. 

[00:14:40] Now, I mentioned that there’s also the oxidants. Eventually when you get out to the animal age, that's equivalent to a 90-year-old, the ovary is not working. Okay, so even in the absence of CD38, eventually the oxidants catch up, so I don't expect that women in their 90s are going to be having babies. But certainly, if you can preserve your NAD levels, you're at a much better chance of keeping your ovary functioning. 

[00:15:08] Now that in fact, there are some anecdotal reports of women who went into menopause and then got NAD supplements and then started having periods again. They started to have ovarian function. So, what is menopause? Menopause is defined as the first step is the cessation of periods, the ovaries no longer making and releasing eggs. I mean, there are a lot of consequences of menopause, but that is the first part and that is dependent on ovarian failure. The follicle isn't being made properly and it doesn't let it out, doesn't let the egg out. And we can block that by making sure that NAD levels are preserved. This is so important and it's a revolutionary concept. It changes how we think of menopause. We used to think of menopause as just it happens. I mean, why? We don't know, it just happens and it's an event and live with it. Maybe we can give some medicines, maybe we can give some hormones or something, but it is fixed. Stop thinking about it as something you can manage or do something about it. It is an event, but that's not the case. It's actually the result of things that happen over time, and so we can do something about that.

[00:16:17] Now at some point you don't want to have-- At some point you need to have menopause because these eggs, as I said, are there when you're born. When a baby girl is born, she has those gametes, they're there. So eventually they're going to accumulate genetic injury. And we wouldn't want an 85-year-old woman to use those eggs because they would have genetic damage in them. It's not safe. So, menopause is a natural event at some point enough is enough and you can't take the risk of having a genetic injury there and having an offspring. But for the woman who wants to, if we can somehow preserve or lengthen that period of time, very, very helpful. So, this is why I talk about fertility. 

[00:16:58] Now, the data in those studies, they've shown that the follicles, they're more follicles that are getting ready, they release better, they're healthier, the quality of the genes in them is better. All of these things lined up beautifully and all of them were associated with knocking that CD38 level down or by giving a supplement to give NAD and we'll talk about how to do that. So that's the whole issue of fertility. 

[00:17:24] Then the next issue for women that I see is the issue of female sexual dysfunction, which unfortunately has gotten a lot less notice than male sexual dysfunction. And there are many reasons for that, socially, sociologically, but it is a fact. And we now know over belatedly, we know how female sexual dysfunction occurs. What are the mechanisms? Why it happens? And amazingly, it is all tied up in this same story of NAD. So, I wanted to spend a second talking about that because it really so central and we can, I think, start to do something about it, so let's talk about that. 

[00:18:01] What is female sexual dysfunction? Well, it actually encompasses a variety of things. First of all, there's arousal. And we now know that there is a gas called nitric oxide in the hypothalamus which triggers arousal. This gas, nitric oxide, we'll talk to you about in a second, because nitric oxide is formed from NAD, so when NAD levels fall, it will become more difficult to achieve arousal. Once that arousal occurs, there is nerve stimulation, and it triggers specific changes in the clitoris. Let me talk about that. The clitoris is an organ that has-- It is richly endowed with a lot of blood vessels. And these blood vessels are normally constricted, so there's not much blood flow there. But when an arousal signal hits the clitoris, those blood vessels are made to relax. And when they relax, they open up, they dilate, blood flows in, and the clitoris becomes erect. This is very important for a number of reasons.

[00:19:04] First of all, the clitoris, most people think of it as at the top of the vulva, but in fact, that's not the case. It extends behind and it goes down the back wall of the vagina in two places, and it extends the length of the vagina to four to five inches when it becomes erect. Well, that whole extension of the vagina is completely dependent on clitoral engorgement, and that is dependent on these blood vessels relaxing. What causes them to relax? It's the same gas I talked about. It's nitric oxide. 

[00:19:33] Now, for nitric oxide to form in the blood vessels of the clitoris, it has to be made. Where does it come from? How do we get nitric oxide? It's made in the blood vessels, and it is made specifically by a special enzyme in the blood vessel called nitric oxide synthase. Synthase, means to make. So, it's making nitric oxide. And how does that happen? How does the nitric oxide synthase do it? It does it as an enzyme. It converts one thing to another, but it can't do it by itself. When nitric oxide synthase tries to do that, it needs something else to hold on to. And that thing happens to be NADPH, which is a form of NAD. So, if you do not have good NAD levels, you cannot make nitric oxide. I want to really be clear about that. If you do not have good NAD levels in your sexual organ, you will not make good levels of nitric oxide, you will not have clitoral erection, and you will not have an elongation of the vagina.

[00:20:37] Okay, there are other things as well. The blood vessels not only are present, richly endowed inside the clitoris, but also in the walls of the vagina. So, my group was the first to show in 2003 how important this was. We did studies in female rats and we found out that the blood flow in the vaginal wall was not really very good in older rats. But when we gave nitric oxide exogenously, we were able to get a tripling of blood flow. And when we did that, there's so much blood pouring through the wall of the vagina that the plasma, which is part of the blood seeped out of those blood vessels and into the lumen of the vagina and that is vaginal lubrication during sex. So that is completely dependent on these blood vessels relaxing and that's dependent on NAD. 

[00:21:31] We know that also if we take-- There was a clinical study where they took men and women who had high blood pressure. What's high blood pressure? It means your blood vessels don't dilate. They're constricted. And they gave them an NAD source to swallow every day. And their blood vessels opened up, their blood pressure returned to normal. These are people with standing blood pressure. So, we know that blood vessels respond to NAD by dilating because of this effect on nitric oxide. So, during sexual arousal, the elongation of the vagina, the production of fluid of lubrication, the stimulation of the clitoris, all of that depends ultimately on NAD. So, if you're a woman who has low NAD, you have a problem there. 

[00:22:18] And we see in older women something called female sexual dysfunction, where either they have a trouble getting aroused, which is also nitric oxide dependent, or they do get aroused, but they have a difficulty with these things and they have pain on sex, which is called dyspareunia, and that is a consequence of that. 

[00:22:35] Now, men have a comparable situation, it's actually the same situation, and they need nitric oxide for erection, but they have a drug that they can take called Viagra, which protects the effects once nitric oxide has done its thing and produce cyclic G in the cell, it protects it from being broken down. Women, when they take Viagra, have an even more amazing result than men. This has been shown in a clinical study. But for reasons I cannot fathom, the FDA hasn't approved that. Yeah, I don't understand that. But this Viagra is a very powerful way of maintaining this response. If you don't have NAD though, you'll never make the nitric oxide and the Viagra won't work. Viagra does not work in all men. And the reason for that is some men are so deficient in NAD they don't make any nitric oxide, so, the Viagra is useless. So, what we need is to get NAD levels up in women and of course in men and so that they can have normal sexual function as they get older. These levels will drop unless you do something about them.

[00:23:37] A 60-year-old woman does not have the NAD of a 20-year-old, not close, so her sexual function will be impaired. And we know that's [audio cut] unless we do something to overcome that, so that's what I meant by female sexual dysfunction. Obviously, very important. 

Cynthia Thurlow: [00:23:50] Absolutely. And what's interesting to me is that, you know, when I started as a nurse practitioner, it was at the heyday, the beginning of when Viagra was brought to market and I worked in cardiology. And you can imagine we couldn't keep Viagra samples in the office. And we used to joke and say that most of the male cardiologists were taking it home to try it out. But the thought process that there's been so much focus on female sexual dysfunction being a byproduct of loss of sex hormones. And I know that estrogen and nitric oxide are, there's an interplay there that's quite significant. Not realizing all this time that NAD is driving a great deal of that makes so much sense. 

[00:24:29] And I would imagine we're looking at fertility and looking at-- There's even premature ovarian insufficiency or we used to call premature ovarian failure, it now has a new name. But there's so many little things going off in my brain making me realize there's a lot that we are not putting together as clinicians about this aging trajectory. Curious, in terms of the things that are driving down NAD levels in our modern-day lifestyle. Are there things that you as a researcher look at to say these are really bad lifestyle choices that are going to accelerate that loss of NAD and probably exacerbate these types of symptoms and conditions and concerns that many of us express as we are getting older? 

Dr. Andrew Salzman: [00:25:13] Yeah. Well, let's look at why NAD levels are where they are and why they go down. So, in order to keep your NAD level at A good level, you need to be able to absorb it, you need to swallow the precursor for it. It has to go to the right place, and then it has to stay there and not get broken down. So, let's walk through that for a second. So, if you swallow NAD just as it is, none of it will get into you. It's a charged molecule. It just doesn't cross the gut, that's it. You can't take an NAD pill and somehow get NAD into your body because it's not absorbed. 

Cynthia Thurlow: [00:25:48] This is very important because there are a lot of people out there convincing individuals like this is one point I'm so glad that you're making early on so important, sorry, I didn't mean to interrupt. I just want to make sure everyone's very focused on what you just said. 

Dr. Andrew Salzman: [00:25:59] Right. So NAD, I mean, it sounds sensible in the first-- When you think about it, you're low in NAD, take it. 

Cynthia Thurlow: [00:26:05] Right. 

Dr. Andrew Salzman: [00:26:06] But unfortunately, it's not absorbed. So, what's happened is there's been research in this area, and there are two molecules that are actually related. You can call them kissing cousins. They're very related to NAD. They are NAD, really, but they have one little extra thing attached to them. And one of these is called NMN, where you have an extra phosphate stuck on, and the other is NR, nicotinamide riboside. Okay, so NR and NMN are very related. So, people said, “Well, gosh, Hmm. maybe we should give these a try.” So, they gave them orally in a pill or a capsule. And lo and behold, they said, “Wow. I mean, my gosh, the NAD levels in our tissues are going up.” So, somehow, they're absorbed, so there's been a lot of research in this. 

[00:26:52] And now we know that when you take NMN or NR. When you take it orally, you swallow, it will actually get into your blood and it will go around and it'll get to the tissues and it goes into the cells. And only once it's inside the cells, it gets clipped by little scissors. There's a little enzyme in there, its clipped, and you have your NAD. And this has been shown in animals and it's been shown in humans. And there is no question about this, that you can supplement yourself. You can take NMN or NR and it will get into you and it will raise your NAD levels. And that is why the company that I've been providing scientific advice for, Wonderfeel, that's why they have a capsule which has NMN in it. 

[00:27:36] There are also companies with NR and that's also been shown to work too. So, NMN and NR are wonderful things, but just taking it is not enough. And I'll give you an example why? Let's say you have a bathtub and you turn on the spigot and you start to fill it up with water. Of course, the water will go up. The level will go up. If you then open the drain, you will also have water going out. But how high will the level of water get in your bathtub? Well, it kind of depends. It depends on how fast the water's going in and how fast the water is going out through the drain. If you have a gigantic drain, you're hardly going to get-- You could pour all the water you want in the world, it won't go up. And if you don't have much going in, it's not going to help either. So there has to be a balance, there has to be a balance.

[00:28:23] So, when we have to get enough NAD coming into us to provide a reasonable level in that bathtub, you know, to get the NAD level up where we want. But at the same time, we can't have a huge drain. And this is what CD38 is. It is like a drain. It's chopping it up. So, if you have high CD38 levels, you can take all the NMN in the world, but the bathtub will have a low level of water. You've got to have a way to slow down CD38 and increase your supplements. 

[00:28:58] Now, let's talk about CD38. What can we do in our lifestyle and how is that related to CD38? Is there anything we can do at all? What is the trigger for CD38? What makes it go up as we get older? Why is it something that just as we get year after year, why is it going up? Well, now we know, it goes up because of inflammation. It is an inflammatory response. I'll go one further. Aging is an inflammatory disease. Think about that. So, if you had no inflammation, you really wouldn't get older. How do we get inflammation? Why do we have inflammation as we're getting older? What's the reason for that? Well, it turns out that the major driver of inflammation as we age is actually ourselves. There is in our gut trillions upon trillions of bugs, of bacteria. They live there in our colon. It's full of it. 

[00:29:50] Fortunately, we have a very sealed gut. It's got a gasket around it. These bugs don't get into us. They would kill us if they did. It's called sepsis, but they stay inside. But as you get older, this gasket starts to loosen and loosen and loosen. And little tiny parts of these bugs, we call them endotoxins, they can actually sliver, sneak by. They get through the wall and they go into our blood and they go around and around they stimulate inflammation, subtle, we're not sick in bed, but it's there. And you start to see a rise in CD38. As that CD38 level goes up, the NAD goes down. And then we have problems with our blood pressure and we have problems with other inflammatory problems. We have sexual dysfunction. We don't have energy. We're couch potatoes because we can't run 10 miles like a 12-year-old just goes out and runs, you can't do that. 

[00:30:48] So, this progressive inflammation from the loss of integrity of the barrier in the gut is what happens as we get older. So perhaps through probiotics or other things, I don't know. There are a lot of people who are thinking about this. This used to be actually my area of interest. I was the first to really study how this opened up back in 1988. I published all the first papers on what regulates that gasket. Not thinking about aging, at the time. I was 30, I was not thinking about anything getting old, but this is what happens. So, we have to understand better how to control that gut and prevent that inflammation in the CD38. That's probably the best thing we can do. 

[00:31:28] I also recommend supplements of NMN or NR so that you can do your best to get and both together. And we designed in our supplement not just NMN, but we put in there two botanical agents that block CD38. So, we're trying to do both things. Have a small drain on the bathtub and turn the spigot on full blast. Now that was the idea. We use drugs that are not drugs, but they're actually botanicals. So, this is resveratrol, which is from grapes, and hydroxytyrosol which is from olives. And they have an ambition, they block to a certain extent mildly, the CD38. And that was our idea that you should do both at the same time. And I think it was a unique approach and it makes sense. 

[00:32:08] I know the pharmaceutical industry is out there working very hard to make CD38 inhibitors, which makes a lot of sense and I wish them luck. These will be wonderful anti-aging drugs whenever they eventually get out into the market. They haven't gotten there yet, but there's a lot of hope and excitement about that. So that's something that you know on the pharmaceutical side. Right now, we don't have those. 

Cynthia Thurlow: [00:32:29] I think something that for listeners, they may not be aware of when we're talking about bringing a drug to market versus bringing a supplement to market that's well researched and there's a lot of thought behind each and every ingredient. It takes a long time to bring a drug to market. There's a lot of research. There's several phases of trials. Because you've been on both sides, can you at least speak to that, to give the context of how challenging it is to bring new drugs to market versus creating a nutraceutical that allows you kind of speed up the process and you're still doing it with tremendous integrity and research and a lot of thought behind it. But I think most people don't realize how long it takes a drug to come to market and how exhausting the process can be. 

Dr. Andrew Salzman: [00:33:10] Well, you're speaking to the right guy. Because I started off, my dream was first to take care of patients. I mean, I went into pediatrics and then in pediatric infectious disease, and pediatric intensive care. And I became the founding director of pediatric intensive care at Children's in Cincinnati. I built the biggest ICU in the country for kids. And I thought, this is a great way to help kids. You're there at the bedside, you're working all night, you're helping really sick kids. But after five years there in Cincinnati, and after 15 years of doing this, I came to the conclusion that really the best way to help kids who are really sick is to come up with a drug because then you could help thousands of people that you'd never see. 

[00:33:53] So I abruptly, in the middle of my research career, I left. I just went into my chairman and I said, “I'm leaving.” He said, “Why? What's got into you?” I said, “I want to make a drug to help kids, and I need to do that in a company, so I had access to the capital.” So, I left and I started that in 1999. And I worked as hard as I could and I had some successes. We developed the first PARP inhibitor for cancer back in 2005, and I sold that to Genentech and I developed drugs for rare metabolic diseases in kids and things like that. But it is a very long process, very long. 

[00:34:27] I'll give you one example. In 2009, I co-invented a drug for homocystinuria, which is a terrible metabolic disease in kids. It worked in animals beautifully. We're so excited. It's 2025 right now and that drug is just about to get approved. Now it works, but that was 16 years and over several hundred million dollars. And it worked. I knew in 2009 it already worked in animals. I knew it would work in people. So, you think about that. You have an idea, a drug that you think can help people. You show that it works in a gold standard animal model and 10 or 15 years later, you're still battling that why? Because you have safety studies and complex manufacturing and toxicology studies and then clinical studies and phase 1, phase 2, phase 2B, phase 3, on and on and on. And it's become almost impossible to get it. And some drugs succeed, but you're talking big business, big companies like Pfizer and Merck. It's huge daunting task. 

[00:35:29] On the other side, if you can exploit nature, take advantage of botanicals, what God gave us, you know, the-- I mean, most of the drugs, by the way, that were in use until the last, let's say, hundred years all came from plants. I mean, they're amazing [crosstalk] Digitalis and all of these things. So, if you can find a botanical like we have done for resveratrol and hydroxytyrosol that inhibits and target an enzyme that we wish to block. Well, it's in the food supply, it's safe, you can just start using that. Now, maybe it's not as good as a pharmaceutical, that could be. Maybe the pharmaceutical has a little bit better properties, it's more potent, it's more selective, could be, but how long do you want to wait? And if you have something that works, help people. I'm not begrudging pharma. I am a pharmaceutical person, so I'm not begrudging the field. I love the field. It can do a lot of good for people, but it's not the only way. We have to be open to the other approach, which is the nutritional supplements. 

Cynthia Thurlow: [00:36:27] Well, and I think you bring up so many good points and I think especially with your background and wanting to make an impact and wanting to help people, you're still able to do that and draw upon an incredible trajectory of your medical and research career. Now, one thing I want to make sure that we touch on before we talk about Wonderfeel, routes of administration for NAD, because I would-- There is not a day on social media that I am not asked, “Can I take oral NAD? Can I do IV NAD? Can I do subcu NAD? Can I do IM, which is intramuscular NAD?”

Dr. Andrew Salzman: [00:37:02] Right. 

Cynthia Thurlow: [00:37:03] Let's talk about how the routes can be ineffective at best from those perspectives. Just kind of a high-level perspective, largely because NAD can't penetrate the cell, it can't get intracellularly where it actually needs to work. 

Dr. Andrew Salzman: [00:37:17] That's right. That's exactly right. And there's a lot of research, I must say, on this subject, even recently, the last few weeks, that-- So, I don't have the last word. I don't think anybody does. But the little that we know now is that as I said, NAD by itself as the molecule cannot be taken orally and get into the body. Okay, so that's out. So, these other precursors, if you will, NMN and NR, how are they given? Well, the original way people did that was orally. They put them into capsules or into tablets or something like that, and people swallowed them. They would find their way across the gut, through the mucosa and into the bloodstream. And it was proven that in humans that you can raise NAD levels in the body by doing this. So there's no doubt about that, that is a way to do it. 

[00:38:05] Then people thought, well, maybe there are better ways. Better absorption, better uptake, more consistent perhaps. And so, there's some folks who've talked about giving it IV. Now, what does it mean to give a drug IV? For those who don't know, IV means you need an angiocatheter, you need like a catheter in your vein. This is not something you can do at home generally. I mean, it's not the place for that. Means you have to come into a facility, a healthcare facility, and someone has to stick a needle into probably your arm. It's pretty painful. It's not the end of the world, but it's not something that people like to do and they certainly don't like to do it often. Okay, it's not something you would do every day. Nobody would do that unless they-- For some special reason they had to, but basically no one would do that. 

[00:38:49] So those people who are giving NAD by an IV route, well, that's going to be a very odd way to do it. It's clumsy, it's unwieldy, it's not practical. And what happens to the NAD anyway, when it goes in, does it get into the blood? Yes, it will get into the blood. Does it get into the cells? No. What recent paper just came out and showed that lo and behold, when you give IV NAD, it actually gets into the liver, changed and excreted into the bowel and then is taken up again as NMN and NR further along in the colon. So, this whole concept of giving it IV, it just doesn't pan out and it's unwieldy and it's kind of a crazy idea actually. It's just not practical.

[00:39:39] We have millions of people who need, in my opinion, to boost their levels of NAD. We have to have a way that's practical for everybody. Not people are going to the clinic and getting an IV, it doesn't make sense. subcu, I suppose, yes, of course you could give NAD subcu, but it would face the same issue. When you give something subcu, you're just kind of getting closer to the blood. It's better than oral, yes, but it's not in the blood. And eventually it will get into the blood and it'll circulate around and it's no different than giving it IV. I guess the only advantage is that maybe you can give it at home a little more easily, yes, that's a fair point. But still, why bother if you have the ability to give something orally? This is easy. It's a capsule, it's a pill, two seconds. So, there's really no reason. 

[00:40:26] The only time in pharmaceutics that we don't give things orally. What are the reasons? Number one, we have a life-threatening urgent disease and we can't take a chance. Intensive care unit. That's not relevant here. Number two, there is no possible way to give it orally, forget it. You have to give it, this isn't the case. And you know, there's some other esoteric reasons, but there's no logical reason to give something IV if you can give it a chronic disease orally. Okay, so that's my take on take the capsule, take the pill of NMN or NR if you want to get the NAD levels up. 

Cynthia Thurlow: [00:41:00] Well, and I think this is significant because I think that there are, I have to believe, well-meaning people, whether they're running IV centers, infusion centers, or people that are creating supplements, but they're kind of presuming people don't understand that taking oral NAD is not going to be effective. You have to really take these kind of precursors. And looking at NR versus NMN, based on all of my reading, NMN is preferred because it actually has a little transporter to get intracellularly and that takes one extra step out. In terms of dosing because inevitably people will ask, well, how much NMN or how much of this product should we be looking for? What dosing should we be looking for? What does it show in the research that helps replenish NAD levels in the blood or intracellular really, what is the most therapeutic range of milligrams to be taking?

Dr. Andrew Salzman: [00:41:54] Well, fortunately that's been looked at so we can answer with data. Folks have tried 250 mg, doesn't do very much. They've tried 500 mg, not the best. They've tried around 1,000 mg, it's great. And when they've done one study where they gave much more, first of all it was safe, which is always good to hear. You've got to safety margin, but it didn't do a lot more. So, the proper dose is around 900 mg, 1,000 mg. We happen at Wonderfeel to have chosen 900 mg. 

Cynthia Thurlow: [00:42:26] And is there an optimal time of day to take it? Is it something you want to take earlier in the day versus evening in case it's stimulatory? I mean, that's always the place I come from because most middle-aged women most struggle with some degree of either falling or staying asleep, so we try to keep sleep time very precious. Presumably better to take it in the morning. 

Dr. Andrew Salzman: [00:42:47] Well, it is because you want to-- Most of the energy in your activities, in your daily life is-- in your daily life not in your nightly life. So, you should be taking in the morning. What we recommend is people take it at the same time they brush their teeth just so they remember. In the morning, brush your teeth take, because that gets you at a high level, your peak effects, your peak levels are occurring when you're most active during the day. 

Cynthia Thurlow: [00:43:09] And is it something that you take long term? I'm presuming, yes. Are there benefits from taking a couple days off a month? I know there are some products in my kind of milieu that we'd hold for one day out of the week. Are there any benefits from taking a break or is this something that we're taking consistently? 

Dr. Andrew Salzman: [00:43:28] In my judgment, it should be taken consistently. The reason that you would interrupt medication from daily use would be if there's tolerance building up or if there's a risk of overdosing and you want to have a washout. That's not really relevant here. People don't get tolerant to NAD supplementation. And as I said, the rise of CD38 is inexorable. It's going to happen. NAD falls as a function of age. It's no going back. So, if you're going to take it to have these effects, you need to take it every day. 

Cynthia Thurlow: [00:43:57] Yeah. And so, understand there's this inverse relationship as NAD is falling, CD38 is going up. And what we're trying to do is kind of adjust those so that it's the reverse is what we're kind of focused in on.

Dr. Andrew Salzman: [00:44:10] Yes. 

Cynthia Thurlow: [00:44:11] In talking about lifestyle, because on the podcast we talk a lot about exercise and sleep and things like this. How is NAD impacted by, let's say sleep as an example. I know that in listening to you on other podcasts, there was a lot of discussion about how important NAD is for clearing things like adenosine, which is important for sleep.

Dr. Andrew Salzman: [00:44:32] Well, the whole process of sleep is triggered by the brain basically becoming exhausted at the end of the day. The brain is actually the most metabolically active organ in our body. The blood flow 25%, 1/4 of all our blood flow goes to our brain. So, it's extremely active organ. It desperately needs ATP to function 24 hours a day. It desperately needs that, but it doesn't keep up. So, what one sees is that by the time you get to 10 o’clock, 11 o’clock, or 12 o'clock midnight, you have accumulated waste products. These are breakdown products of ATP, most importantly adenosine. And that causes a profound desire to go to sleep. It's almost, you can't fight it, you will go to sleep. Okay, maybe you can fight it a little bit, but it will make you go to sleep. 

[00:45:22] And so the brain during the night has to clear out that adenosine. And how does it do that? It doesn't throw it away, actually, it salvages, it recycles it, and it takes adenosine and it adds phosphates to it. And eventually you have ATP, which is adenosine triphosphate, that process during the night of rebuilding ATP stores. Where does it get the energy from? It gets it from NAD. So, the NAD goes in there, takes adenosine, and it turns it into AMP, ADP and ultimately ATP. So, during the night, your NAD is critical. So having a good night's sleep means allowing yourself to clear this adenosine reservoir and rebuild yourself. And that's why NAD throughout the day is very important. 

Cynthia Thurlow: [00:46:09] And what I found really interesting, something I'd actually forgotten, is there's a specific drug that actually blocks this clearance. And it's something many of us drink without realizing and its caffeinated beverages. How many of us wake up in the morning and we're really dependent on kind of caffeine to get us through our day. We don't realize that's interrupting this very delicate process by which our body is unwinding and replenishing. 

Dr. Andrew Salzman: [00:46:33] That's right. All the caffeine is really doing is just blocking the adenosine from binding to these receptors which say “Go to sleep.”

[laughter]

Dr. Andrew Salzman: [00:46:44] Okay, so you feel great. I mean great. You feel you're awake, but you should be sleeping. You need time. And talking about lifestyle, obviously, having a proper amount of sleep is critical in brain function, allowing NAD the time to restore the brain. And people who think they can get by with three or four hours of sleep and a lot of coffee are going to have terrible health over time. They're not helping themselves in any way and they're not giving-- Even if you have normal levels of NAD, you have to have-- It takes time for the brain to-- It takes six, seven, eight hours at least. What does it mean to have a good night's sleep? It means to fully recover and recycle the adenosine. 

Cynthia Thurlow: [00:47:23] And what are your thoughts on alcohol use? I think that probably both during the peak of our training and subsequent years, we were maybe not in a pediatric population, but we would say to patients, “Have a glass of red wine a night.” And what we're starting to learn is that alcohol is considered to be this toxin that may have a little to low therapeutic benefit. How does alcohol impact NAD as well as PARP, which we kind of touched on earlier? 

Dr. Andrew Salzman: [00:47:50] Well, alcohol is going to form oxidant stress. I mean, alcohol is so many disruptive things about it, we could talk for days about it. It causes membrane damage, it causes specific injury to certain enzymes, but it also triggers a lot of oxidant stress on the cell. It's not the only form of oxidant stress, but it is a major one, particularly if you have high levels. We are not designed. We haven't evolved as an organism to handle much alcohol. We can detoxify a little bit. We can handle very small amounts. So, one need not be a complete teetotaler and never touch alcohol. But anything in more than a very moderate or measured amount is going to overwhelm our natural systems to protect ourselves from oxidant stress. And when that happens, you will get part back, you'll get damage to the DNA. I mean, that's a sad fact, but drinking alcohol does damage your genome. I mean, it is causing oxidant stress. 

[00:48:45] We published all of this, the role of oxidants, in 1994 through 1997. I published dozens of papers showing that oxidants can actually directly damage your DNA. And when they do that, what they do is they nick the DNA, the DNA is two strands that are wound up together, two strands of your genetics. And if you cut one of them, that's a nick. You haven't cut the whole strand with the scissors, but you cut one of them, it's loose, you have loose ends. This is a recipe for a mutation when the cell divides again. So, the body has this PARP enzyme there to go in and immediately recognize this and then to repair it and that uses tons of NAD to do that, but it's essential. 

[00:49:28] Well, alcohol is causing oxidant stress, it's causing damage to the DNA. So, is it okay to have a little? Probably a little is okay because we can handle that. But anybody who is taking excessive alcohol, which means more than what I just said, you're setting yourself up for all kinds of problems with aging, with disease. And worst, of course, is if the cells divide. If they divide when you have this damage, there will be a mutation much of the time, one or two mutations doesn't really mean too much usually, but over time, if you accumulate mutations, at some point you will actually have a cell that starts to divide on its own. That's called a malignancy. That's what cancer is. Cancer results when you have not one mutation usually, but you've accumulated five, ten, and the cell can no longer function. And at that point we have a full-blown malignancy, which I did want to talk about, because in women, of course, breast and ovarian and uterine cancer is something we should talk about. And you notice that these diseases rarely occur, if ever, in young women. We don't see this in 10-year-olds. 

[00:50:34] 10-year-old girls don't typically get breast cancer or ovarian cancer. I never heard of it even. It could happen, but it's extremely rare, even in the 20s, unusual. As we get to 30s and then 40s, suddenly it becomes something that's more prevalent. Well, the reason for that is time. And you get the accumulation and accumulation and accumulation of mutations. How can we avoid that? What can women do to avoid that? Well, the way that you repair these insults, we call them insults, when there's an oxidant hit on the DNA, we need the PARP and we need the NAD to repair that. So, if you are deficient in NAD, you will not repair properly. And it's just a question of time. You'll get malignancy or have a high probability. So, I urge people to think about that and recognize, especially for females, I mean, these are three organs that are highly at risk. These are not quiescent organs. This is not like a muscle. I mean, think about it the ovary is constantly doing things. It's making new follicle and then it's regressing and forming the corpus luteum, and it's growing again. 

[00:51:43] The uterus, every month, the lining disappears and a new lining is made. The breast, people breastfeed and you have all the growth of the breast. These are highly active organs that are dividing. This is a prime area where you can get into trouble and get cancer because they're dividing anyway. They're very active. So very important for women to take care of themselves and have good NAD levels so that they can keep their organs intact without genetic damage. 

Cynthia Thurlow: [00:52:11] That's such an important point. And, these are highly dynamic organ systems. I'd love to kind of end the conversation, really, speaking to the product that you have helped develop, which the more I understand about the ingredients and how they all work synergistically, it's really exciting. They're designed to be able to not only be able to use NMN, but have these botanicals on board that are going to limit the issues surrounding CD38 and do it in a way that it's highly tolerable. I've been taking this for the last several months. I'm happy to report there's been a lot going on in my personal life, and I feel like I've been able to show up with a lot of energy, mental clarity, etc., so let's talk about Wonderfeel, because I'm really excited to have this conversation and be able to share this with the community. 

Dr. Andrew Salzman: [00:52:58] Well, I think the nice thing about the group at Wonderfeel is that they listen very carefully. And I've always believed, when I was at Harvard and they were teaching me about-- At the medical school, they said, “If you want to find out what's wrong with the patient, listen to them.” 

Cynthia Thurlow: [00:53:11] Yes. 

Dr. Andrew Salzman: [00:53:12] Very few doctors, by the way, do that today. They sit there in front of a computer. But really the best way to learn about your patient is to listen to them. Because most of the time they'll tell you what's wrong if you listen carefully. So, the same thing is with Wonderfeel, what we do there is we-- What we do is we listen to the customers. And when we do that, well, these are people who most of them are in their 20s or 30s. Also, we have women in their 40s, obviously, and then we have a bunch of people who are elderly, in their 70s or 80s. And I listen to all of them, and we've heard, for example, people say--

[00:53:47] I'll give you an example. There was a woman who unfortunately had vascular dementia. She was in her 70s. Her husband loved her very much, and they used to do crossword puzzles all the time. And she could hardly-- Well, she couldn't finish any of them. And he started her on Wonderfeel. He heard about it and after about a month, she was doing three to four crossword puzzles a day. So, for him, that was a success. 

[00:54:08] Another example would be arthritis and inflammation. We haven't talked about it much. We haven't really focused much on the effects of NAD and inflammation. We could talk about that. But suffice it to say, it's been very effective in reducing inflammatory diseases. And we've seen that mainly in arthritis. So, we have a lot of people with either rheumatoid or osteoarthritis, very uncomfortable, people who--

[00:54:27] One of the women I know was in her 50s and was a tennis player. And she was amateur tennis player out there having fun, and she couldn't do that at all. She was not bedridden at all, but she couldn't go out and have fun. And she started the product, and after about a month, she wrote back to us and said, she's back on the court. That's a good example. Certainly, in sexual health, both males and females have written to us extensively, and all of them have commented, “Better orgasm. Just better sexual--" That has been ubiquitous. We've heard that from many, many people. Energy level, some people, kind of couch potatoes. And, we had one guy who's a runner and he's back. He wasn't for a while. And so, I think this-- We hear consistent reports. We take a registry. Everybody who writes in, we carefully record it. We're publishing a paper now which shows the registry. And so, I'm hearing good things. We haven't had any negatives. 

[00:55:19] The one area that we haven't talked about that I find a lot of in elderly women is the issue of beauty. We've had people starting in their mid 50s, and they talk to us about three things. First, their skin seems to be more hydrated and tighter. As you get older, your skin sags and that's because the elastin starts to get broken down by MMPs, by matrix metalloproteinases. And also, the hyaluronic acid levels fall. It's not as hydrated. You can tell a 90-year-old skin immediately from a 10-year-olds. You instantly, you can see that. It's not as full of water, it's not as elastic, it sags. So, we now know that NAD can block those things. And we've seen repeatedly people say “My skin looks better, younger.” 

[00:56:03] The other thing is the spots, because in the skin as you get older, there is a tendency to produce melanin. It's a pigment, it's a dark pigment, of course. And you get these age spots, they're light brown to dark, you get it on the face in different places, people have seen that these go away, they revert and they don't come back. So, this is very important to a lot of women, I would say in their late 60s to 70s have written to us about those spots. We've also had women in their 60s write to us about their hair. The hair is part of the skin. Most people don't know that, but it is part of your skin. It's a skin appendage, comes out of your skin. There's a follicle there that the hair grows from. That follicle is rapidly dividing. Think about the ovary here, rapidly dividing, subject to oxidant injury, accumulation of DNA damage over the years and eventually what happens? Two things. The hair gets thin, the hair gets white. It's lost its ability to take in pigment. It's lost its ability to make a real lustrous thick strand. And you can immediately tell the hair of an 80-year-old from a 12-year-old. There's nothing like-- no comparison. That's all because of the loss of function. Just like in the ovary, it's the loss of function over time of the hair follicle. So, we've seen a lot of people talk about that and that's gratifying to see that.

[00:57:24] So, with all these good anecdotal feedback we're getting, I feel gratified that we're doing something for people. That's why we're out there at Wonderfeel. It's a nice group of caring people, energetic. It's pioneering where we are trying something a little bit different. I think the synergy was something that-- No one else had really put that into play. We spend a lot of resources on research. I will say I think this differentiates us from many other companies that are selling things on the market. I mean, we pour-- Really, actually every cent we've got, we poured back into research. So, I'm doing research right now with Eurofins and a number of other organizations, basic research, fundamental research, to really understand the mechanisms of how we can improve the product to make better effects on NAD, and we're going to continue to do that. That is absolute commitment. We've discovered a bunch of new approaches with which we're patenting now. Eventually, maybe we'll even go to the other side of the river and make a pharmaceutical. I don't know. I hope not, but it could happen. But we are discovering, we're intent on bringing research to the forefront because we want to make a difference. 

Cynthia Thurlow: [00:58:31] Well, I think it's really exciting and I'd love to just touch on the botanical piece with Wonderfeel before we end the conversation today, just to better explain it. These are things that are naturally derived, but they're also, they potentiate, improve the ability for the NMM to function and optimize in our bodies.

Dr. Andrew Salzman: [00:58:49] Yes, that's right. So, we have four ingredients, four major ingredients in the capsule. The first one, of course, is the NMN, which is at 900 mg, so that's the key part of it. And then we have resveratrol, resveratrol is an organic molecule, it's a small molecule that's present in grapes. And it was found to be good antioxidant, not the best in the world, but a good antioxidant. And in addition, it was found to inhibit CD38. So, it had that dual functionality, so we've added that as well for the reasons I mentioned about CD38. Then I've become very interested. I'm living in Israel right now. We're very close to Greece. We have a Mediterranean diet. And there's voluminous literature on the effects of Mediterranean diet on a number of aspects of health. 

[00:59:40] Well, in Greece, it's very close. And right here in Israel, because we have olive trees actually in our front yard. Olives are very big. They're used in all kinds of dishes and especially in Greece. And there are many different types of olive trees, as I'd learned that too. It's not just an olive tree. And there are certain cultivars that are very rich in certain flavones and in other polyphenols. And this hydroxytyrosol is a very interesting part of that story. And so, there's been a lot of research, originally in Greece, but now in other places, which shows it has wonderful antioxidant properties, but also anti CD38. So, we gravitated to that right away, and we combined that. 

[01:00:20] And then the last element of our concoction is ergothioneine, which is an amino acid. It's actually found in nature. It's a natural amino acid. We don't have it in our bodies, but we ingest it. And it has remarkable properties on aging, actually, it's been shown and on oxidant injury, on preventing DNA damage. So, it's a very important and natural amino acid. I'm not saying that everything in nature is safe. Don't get me wrong, there are poisons out there too. But nature does provide this vast reservoir of possibilities. And when we take foods and these are all present pretty much in certain foods, we have a track record of safety. We don't want to harm anybody. First, do no harm. So, by taking natural ingredients, we short circuit one of the problems with pharmaceuticals. A lot of pharmaceuticals are magnificently, wonderfully effective. And then you find out belatedly that there's also some side effect of toxicity. And that's because people, these are new molecules. No one's ever tried them. That's the purpose of the clinical trials. But when you're using a natural ingredient, let's say from an olive, where billions of people have taken olive oil, you're not going to find something that's toxic. It just is not going to be the case. So, you start with a leg up right away when you begin from the botanical perspective.

Cynthia Thurlow: [01:01:40] Well, this has been such an amazing conversation. Thank you for your time today. Please let listeners know how to connect with you outside of this podcast. We'll connect to all of your relevant research and to Wonderfeel as well. 

Dr. Andrew Salzman: [01:01:53] Well, we have a website called getwonderfeel.com. And when you write in, first of all, as I said, we listen. We're really interested in your comments. I mean, truly more than you think. We really, we write them down, we will get back to you sometimes. We feel that you're our partner in a way because we're embarking on something where you have the information and we care about you. So, it's a joint endeavor and we'd love to hear from you. 

Cynthia Thurlow: [01:02:19] Thank you so much. 

Dr. Andrew Salzman: [01:02:21] Okay, thank you. Pleasure. Take care. 

Cynthia Thurlow: [01:02:24] If you love this podcast episode, please leave a rating and review, subscribe, and tell a friend.

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