Spermidine: The Incredible Anti-Aging Supplement That Inhibits 9 of the 12 Hallmarks of Aging. The Best Way To Supplement Spermidine Using Primeadine with Leslie Kenny. EP 006

Stephen: Leslie, welcome to the Stephen McCain podcast.

Leslie: Thank you so much. It's really an honor to be here.

Stephen: Oh, well, thank you. I mean, we have been, chatting back and forth on Instagram because you were going to Japan and I think we both share, we realized, a real deep adoration for Japan and the culture and the food and all that. And so I was really excited. I'm like, I really just can't wait to talk to her.

Stephen: Not only about your trip, but also about this amazing supplement company that you have built. And I mean, when it comes to Spermidine, that's that's what we're talking about here. And, and maybe you can explain that it's more than that, but I keep finding it seems like. That it just, it, it does so much more than just autophagy.

Stephen: It hits all of these tenets of aging and it's so exciting. And I thought, well, who better to have on the podcast than you? Who's a Harvard graduate? Right? Right. And you're probably like, oh, Don, you know, but I know you're very humble, but I, I would like to start with your origin story as to how you got into this, cuz you have a very interesting story and, I think it would be very, inspiring for the listeners to hear about it if you're comfortable sharing it.

Leslie: Sure, absolutely. Well, for me, it, uh, began when I was diagnosed with multiple autoimmune conditions, um, at the age of 39. And I was also going through I v f treatment at the same time and noticed that my, my hands began to hurt when I was using scissors or. Turning doorknobs, things like this. And I thought, gee, it feels like what I imagine arthritis would be like, but I'm only 39.

Leslie: It's too early, nevertheless, let's have it checked out. And the doctor, I was living in Boulder, Colorado at the time and the doctor's office, I was used to the I V F clinic, Colleen me to say, oh, your blood tests are back, they're fine. And uh, in this case, the doctor, her office called, but she was the one on the other end of the line and said, your results are back, but you need to come in so we can talk about them.

Leslie: And I knew that something serious must be behind that call and sort of brace myself for not great news, but I wasn't expecting terrible news. So she did say that. A hundred percent on your diagnosis of arthritis. What you have is rheumatoid arthritis and here are a box of immunosuppressants that you can inject into yourself to suppress your overactive immune system.

Leslie: And she did then go into explain how uh, an overactive immune system is not a good thing because it's not properly identifying self from non-self. So my body is indiscriminately attacking my joints in this case. And then she said, but you've also got lupus. And I said, okay. And so what's the cure for that?

Leslie: Or what's the treatment for that? And she said, unfortunately, there is no treatment for that. And I proceeded to say, Well, this is, this is, this is actually inconvenient

Stephen: Yeah.

Leslie: I'm doing an I V F round and I, I kind of need a cure or a treatment or a management or something. And really, there's no treatment.

Leslie: Are you sure? There's no treatment? And I'm looking at the certificates, the frame certificates behind her on the wall thinking You are the expert. I'm paying you to solve my problem. I'm outsourcing my problem to you fix it. And she's saying, I'm very sorry, but there isn't anything. So then I go to plan B, which is, is the test wrong?

Leslie: Maybe the test is wrong. Could it be a false positive? And she says, no, no, your cytokines, your TNF alpha. There's just so many of these things. C r P, everything is sky high, not possible. Okay, can I take this test again? Because let's try and just do more, because maybe if we do more, we'll get a different answer.

Leslie: And she said, well, yes you can. Your insurance will cover that. So come back and you can do it later. And I thought, right, I'm going to leave and I'm gonna learn everything I can about whatever this illness is that I've never heard of, and I'm gonna throw the kitchen sink at it and we're gonna take that test again, and we're gonna pass with flying colors because this is an unacceptable answer.

Leslie: It's so inconvenient. I need to have a baby right now. So I, I then began to dig into this and I saw that, in fact, both of these autoimmune conditions, they often occur together and their root cause is inflammation and dysregulation of the immune system. So I thought if I can remove things that are causing inflammation in my body, Maybe that will help.

Leslie: So I went on an anti-inflammatory diet that was Dr. Barry Sears' zone diet at the time, and removed dairy, removed gluten from my, from my diet. And at the same time, I thought philosophically, because I'm half Taiwanese, um, Taiwan is that island with all the missiles pointed at it at the moment, um, from an, from an Eastern philosophical point of view, rather than suppressing something, the attitude would be let's balance it instead.

Leslie: Right. You have no light without dark. No dark without light. Let them coexist together, let them be in balance. And I thought, why? Why suppress the immune system? Why not just bring it back to homeostasis? And with that in mind, I began to look at more research and discovered a treatment called intravenous immunoglobulin or IVIG that was experimental at the time, but seemed to have promise.

Leslie: And I thought, well, she had told me when I said, I really need to get a cure for this because I'm doing my fifth F and I'm using donor eggs, so this has to work. She said, don't bother You have a good five years left. Do not do this. And looking at IVIG and having other immunologists in Britain and in the United States say, oh, it's very risky, I thought, I have no other choice really.

Leslie: Right? Why not? What's, what is the downside? I'll die a little earlier, so why not go for it? And that may have been fool hearty, but it, in my case, it did pay off. And since that time, there have been more and more studies showing that in the case of autoimmunity, IVIG is helpful. Interestingly enough, in some cases of bipolar, it's helpful because the question then is, is bipolar mental health or is it inflammation of the brain?

Leslie: So it seems that intravenous immunoglobulin helps with inflammation and helps with regulating the immune system. So it better identify self from non-self, um, possibly helps it. Regulate itself, uh, in terms of better identifying pathogens as well. So this, uh, this ended up working great for me. And I went back to her, um, to do the test again.

Leslie: And she said when the results came in, she said, well, look at that. Your results are clear. You don't have any of these things. Of course, I was overjoyed, but the penny dropped. Hey, doctors don't know everything. We put them on these pedestals. We outsource our power to them. We expect them to create miracles, when in fact, a lot of the responsibility, the burden needs to be on us as patients too.

Leslie: And we need to really meet our physicians halfway. They don't have all the answers. They have answers that they have been given from textbooks. And they're very good at saying, at diagnosing you have lupus. There is no cure, but they don't know absolutely everything. So I'm living proof that you can reverse some of these things, um, at least in the case of the RA and the lupus.

Leslie: Now what I didn't realize was that I had also had Hashimoto thyroiditis and it had already destroyed too much of my thyroid. So I've lost about seven eighths of it and will, you know, be on thyroid hormone for probably the rest of my life. That's desiccated pig thyroid, but, um, I subsequently went on to, uh, have a biological child.

Leslie: No interventions needed. It just everything went back into, uh, into perfect balance. My hormones went back into perfect balance once I went on the desiccated thyroid. Uh, I, I've never had my joints, my, my hands. I don't have any of the nodules that people associate with arthritis. I don't have any of the aches and pains that you might otherwise have, and I feel quite healthy.

Leslie: People say, I look reasonably healthy for my age. I'll be 58 in June

Stephen: Yeah. You, you look amazing for your age.

Leslie: well, thank you. It's, and I feel amazing. That's some more important thing, is that I feel amazing. I feel vibrant and vital and like I. I'm just interested in waking up every day and learning more things and experiencing life, right?

Leslie: Living a life of joy. And I think that's what we all want. As we, you know, go into our sixties, seventies, and eighties, we're all looking for that. Jude, Viv, right? So, um, once you, once you realize the power that you yourself have with your own body and you, you've actually experienced its innate wisdom to heal and to come back into balance.

Leslie: I mean, there's so much less friction for the body when it is in balance,

Stephen: Mm-hmm.

Leslie: then you can't really look at medicine or health the same way. Now I'm not talking about acute situations where you have a car accident. Obviously you must, you know, you're not gonna be able to heal from that on your own. But for chronic illnesses, things like diabetes or.

Leslie: These autoimmune conditions, these, there are things that we, patients can do. And when I, when I moved to, to Oxford, uh, England, which is where I live now, and was taking my children to their schools, uh, waiting to collect them, at the end of the day, I would strike up conversations with other parents, as you do, and.

Leslie: I couldn't believe the intellectual firepower that surrounded me. And people would tell me about the interesting experiments they were doing. You know, one person was, oh, I've got a, a lithium mimetic called epsilon for bipolar. Or I have, uh, you know, I'm using transcranial, uh, electrical stimulation to beat depression, or I'm using stem cells to regenerate the heart.

Leslie: And I'm thinking, okay, this is, uh, this is amazing. How do I get ahold of this? Or how do I help my friends get ahold of this? And they would always say, no, not interested in, in doing a company. I just want to publish. And, you know, I'm not a business person. And so I'd say, well, why don't I help you? And that was how I got into, um, into Oxford.

Leslie: Science really was. Inadvertently just befriending people and saying, that sounds like a cool idea. Let me help you. I'm not charging you. Let, let's just see what we can do. Let's throw spaghetti on the wall, as it were. And it was through that ecosystem that I then was introduced to, to really extraordinary scientist, uh, professor Katcha Simon and Dr.

Leslie: Gata at the Kennedy Institute for Rheumatology, because they were working in rheumatology, which I naturally as a recovered, uh, or in remission rheumatoid arthritis patient I was interested in. Um, I heard about their work using this awkwardly named molecule spermidine to regulate the immune system and basically rejuvenate the elderly immune system.

Leslie: So that's a quote from a paper that was published in eLife by, uh, by both of them. And that is, you know, I'm not making any claims here. That was just in, uh, in vitro, in a Petri dish with elderly human cells. But it was very exciting. And because spermidine occurs in food, we even manufacture it in our tissues and in our gut biome, but we can eat it in high quantities and things like Japanese fermented soy, nato, Tempe, uh, we can get it in chiaki mushroom.

Leslie: It's in the endo sperm of all seeds. So things like wheat charm, because it's natural, but it has this powerful effect. I thought, well, that's, that's sort of fantastic, isn't it? Because we can all avail ourselves of this. But the folks at the university spin out, um, it was a spinout group that, that has about a billion dollars behind it.

Leslie: They said, unfortunately, you can't patent this and. Yeah, you could come out with a supplement. It's a food, so who cares about a, a food? Right? Because no, no pharmaceutical company will be interested because they can't protect it. Why would they do clinical trials on it when there's no way to defend somebody else coming in and just saying, oh, right.

Leslie: You know, you've done all the clinical trials, you've shown that spermidine works, so we're gonna start making claims with shitake mushrooms or something. And I,

Stephen: Well, I mean, but really it shows there's an opportunity there if something is overlooked, that's very powerful, right? Or has some real promise.

Leslie: that's, that's what, that was my, that was my feeling because I'm looking at it from the point of view of a patient. I want this, in the first instance, I wanted it for, Immune health. But when I looked more deeply into it, I realized that actually spermidine activates autophagy, which is Greek for selfe.

Leslie: It is the cells way of cleaning up all of the damaged mitochondria organelles proteins inside the cell. Uh, it helps with stem cell dysfunction. It helps with shortened telomeres. So I wanted, uh, I wanted sperm edine for these other benefits, uh, once I learned about them and thought it's almost too good to be true.

Leslie: What's the downside of popularizing a food derived supplement that just has concentrated amounts of this ingredient in it? And so that's, You know, it's sometimes it's one of those things where someone say, okay, who's gonna do this? And you hold up your hand and you say, oh sure, I'll do it. Why not? Um, and I did, and I did.

Leslie: I think I've done it with a lot of enthusiasm because selling spermidine, it has a terrible name.

Stephen: Yeah. But,

Leslie: get, pass the name

Stephen: We might as well just real quickly address for anyone that doesn't know, cuz they're probably thinking, is it associated with, sperm and, I think it was found under a microscope a long time ago. Right. And probably from sperm and that's where they noticed that it was first discovered.

Stephen: Right. So they just,

Leslie: Exactly.

Stephen: name.

Stephen: Okay. 

Leslie: did. They did. So, yeah. Uh, so it was discovered in the, um, in the 17th, late 17th century by a Dutch linen merchant named Antony and Lun Hook And why? By a linen merchant because he was fed up with having his linen, his asset being eaten by moths. And so he needed to have developed some kind of a tiny glass, like a microscope or magnifying glass to better see the larvae in.

Leslie: The cloth that he bought so that he didn't lose his investment and that initial magnifying glass ended up becoming a microscope. And under the microscope, he was not only able to see the larvae of the moths, but he was also able to put things like hair, nails, skin, and naturally, as you cast about in your study for other things to put under, you think, well, I'll put, I'll put urine, I'll put semen under the microscope.

Leslie: So put it on a glass, shoved it underneath this microscope, and he could identify, um, the, these crystals that occurred, uh, in semen. That were there after that dried, and he didn't know what it was, but he called that spermine. So spermine is also derived from amino acids, just like sperm aine. And it is part of a class of molecules called polyamide, which just means they come from amino acids and, um, spermidine and spermine and then an equally unpleasantly named poly aiming called putrescine.

Leslie: They actually are part of what's called the poly aiming pathway, which

Leslie: just 

Stephen: Yeah. And the putrescine

Stephen: kind is probably from the smell of it, right?

Leslie: Correct? Absolutely right. Putrid. Yes, absolutely.

Stephen: all about fermentation, right? It's about something as fermenting. Yeah.

Leslie: And you don't, you don't, it, it's funny because actually bananas have, High amounts of putrescine, you don't want so much. Um, and what's great about how it occurs in something like Wheatgerm, all three of them occur naturally in Wheatgerm, but you have high amounts of Spermidine than, um, you know, like say it's a ratio of seven to four to one, um, you have some more sperming and then you have a very tiny amount of risine.

Leslie: But Putrescine is a precursor to both of those other poly, Amy means, and spermine has a superpower too, which is that it, uh, is important in d n a methylation, which helps turn our genes on and off. So we do want that superpower too. Yeah. And, uh, So if you can get it from food, you have all three of these as nature intended, which is fantastic.

Leslie: Um, whereas I know that there are some synthetic products out there. People like, okay, give me the street drug. I just want this synthetic, two-dimensional memetic of this cuz it's really cheap. It costs pennies from China. And I always think, why do we think that we're better chemists than, than plants?

Leslie: They've been here a billion years, right?

Stephen: yeah. Even when you think of like vitamin C, there are these compounds in the skin of the orange, let's say, that help with the bioavailability of all this. So the more plant material in its organic state, you can get the more synergism of activity I think it provides,

Leslie: Yes, absolutely. And some of that is because of when those plant fibers actually go into the gut biome, then you create the gut biome manufacturers metabolites. And some of these metabolites are mimetics of insulin, of serotonin, or they're manufacturing B vitamins, which are very helpful with stress, but also with, you know, with hair or gray hair reversal or, uh, you know, strength of hair.

Leslie: Uh, because B seven is biotin, which of course helps with, uh, you know, with strength of hair and nails. So there are all these magic tricks that the gut biome can do, but we need that whole plant in order to unlock it, because whenever we feed ourselves, we're not just feeding. Us we're feeding a multitude of billions of bacteria, maybe

Stephen: We're actually feeding more of something else than we are feeding ourself in a, in a pure cell to sell comparison. Right.

Leslie: Absolutely right. Absolutely right. And people get very freaked out when you say that The gut biome, the bacteria in the gut biome actually have more d n a than we have. Right. Which is, uh,

Stephen: to imagine,

Leslie: it is, it is.

Stephen: mind boggling.

Leslie: It's mind boggling. And it, what's also mind boggling is that this has been passed down from generation to generation over millennia.

Leslie: It's all from our mothers, right? Because as we pass through the birth canal and the head passes, you know, uh, pushes on the secom, then we are given that first dose, those first colonies of bacteria, and they, you know, that interestingly enough needs to be fed by indigestible fiber and you know, where we get it?

Leslie: Breast milk. So about half of breast milk is made up of fructooligosaccharides, not digestible by the baby, only digestible by the gut biome, by those mitochondria in the gut. Right? And it, yeah, it's, it's absolutely fascinating and it. Does make you wonder if the breast milk that the mother is making is specifically to feed the colonies that she has just bequeathed to the baby?

Stephen: Yeah.

Leslie: Uh, I think there's probably an argument for that cuz there's some great studies out of Spain on how the amount of polyamines and breast milk actually changes depending on the stage of life that the baby is at. So if you have a preterm baby, that baby gets much higher amounts of polyamide, then a baby that is delivered at full term.

Stephen: Hmm.

Leslie: those polyamiines are needed for faster cellular turnover for growth.

Stephen: So interesting. I, I've also heard that if you have a c-section versus a traditional, birth, that, that child doesn't get to pass through all of that and get that, beneficial bacteria, and so they, a lot of times later in life are more prone to certain things because these bacteria are.

Stephen: Protect us, right? And, and we, I don't think we ever get a second chance at getting those particular bacteria to b-infantis or whatever it is, like when you're younger. I think that, once you lose that and that's why you, you know, going on these high dose rounds of antibiotics and just destroying your, microbiome is a lot of times set you up for continuous, issues, ongoingly,

Stephen: and, I'm always a big advocate of try to do it in any other way you possibly can. And that's like the last resort, if you have to go on antibiotics. But I remember when I was coaching a team of athletes and they would get. As soon as they had anything, a little bit of a cold or anything, they would just go get antibiotics from the doctor.

Stephen: Like literally they were throwing them antibiotics constantly. And I'm like, ugh. You know? But, I still think we're so early in the realm of bacteria and truly understanding it because you're dealing with numbers that are so large to try to understand trillions. 

Leslie: Yes. Trillions. It really is trillions.

Stephen: And let, let me ask

Leslie: Very, very true.

Stephen: yeah, let me ask you, this is your product, since it's more of a natural, similar to food, compound,

Stephen: does that help? Yeah. Does that help you with your endogenous production of spermidine versus just trying to exogenously get it?

Leslie: Yes. Because, and that's one of the reasons why we formulated it the way that we, that we have. It's, uh, it's both half of the material in there, so it's about 900 and. 930 milligrams of powder. Half of that is actually the highly concentrated defatted polyamine powder. So the spermine spermidine, spermine, and putracine from wheat germ, but the other half is actually a fructooligosaccharide.

Leslie: And it's made from a particular type of bee. Now it is classed as a maltodextrin, but don't get too excited. It's not as sugar because it actually releases very slowly into the bloodstream. So it becomes a resistant starch. Um, once it takes over 120 minutes to release into the bloodstream, or it is over 70% fiber and that fructooligosaccharide is in there because this is how it is in breast milk, right?

Leslie: And we can use that f o s to selectively feed two strains of bacteria in the gut biome that we know manufacture sperm, aine sperming for you. And that is really important. Why waste the body's own ability to create these amazing and powerful polyA means when? When we're young, we're able to do this. Now, I can't bring tissue production of these polyamide back up.

Leslie: I don't know how we would do that, but the gut biome is such a miraculous bit of machinery that is so ignored and bringing that back online. And you can do this little magic trick with other strains of bacteria too, but you just need to feed it. Prebiotics, not necessarily probiotics, but prebiotics because we often think, oh, I'll just take this probiotic, and they have done studies where people who take probiotics but then are not feeding those colonies the fibers that they need to to survive.

Leslie: You go back and you test these people again a month later, and those colonies are wiped out. If you cease to take the probiotic. Right. So in fact, we need both. We need the colonies and we need food to sustain the colonies. It's kind of like thinking about pilgrims and the early colonies, uh, you know, in the United States and people were just dying of famine.

Leslie: Well, your gut biome, those bacteria will also die of famine if you don't give them fiber.

Stephen: yeah. They are completely, subjected to your circadian rhythm, your eating patterns, what you eat. I mean, you don't wanna piss them off. I mean, really at the end of the day, I mean, even if you're eating like antibiotic, latent meat, probably gonna piss off your bacteria, right?

Stephen: Because

Stephen: that stuff is gonna make it make its way through there. And it's one of those things that I think gut issues are really, out of control right now. And, we talk about autoimmunity. Your story was, so inspiring, I have to tell you. They always say, and I don't know if this is a hundred percent true or not, but from what I've, researched and stuff, that autoimmunity always starts in the gut.

Stephen: And when you think about things like glyphosate, that's in the rainwater, it's all over the place. It doesn't matter if you're eating biodynamic food, there is going to be some glyphosate that has gotten into that food just because it's so omnipresent in the world right now. And that's known to rip, tears in the gut lining.

Stephen: And as soon as you get. Something that's a food passing through that shouldn't or some particle, or some pathogen and it makes its way into the bloodstream. The body's gonna attack it and write an antibody. The antibody is a wanted dead. Or a live sign that says, if you see this, kill it on spot.

Stephen: What the problem is, is some of these foods resemble our own body, right? Like a nut , might resemble your thyroid at a small molecular level and it confuses your immune system, especially when your adaptive immune system, which is the one we're talking about, spirals outta control and is out of balance.

Stephen: And I did wanna say this real quick cuz your story pinged me about a, a real personal story that, you know, my partner went through a autoimmune, condition where super rapid heartbeat hyperthyroidism. They diagnosed her with Graves disease and we found an endocrinologist in Beverly Hills. Sharp guy, but practicing traditional medicine, which I call antiquated medicine for, lack of a better word.

Stephen: It's not derogatory, it's just, it's the old school. And I said, listen, I've just been schooled on peptides. I've taken a course from Dr. Seeds and we've talked about modulating your immune system. I'm gonna do some peptides with her. Do you mind overseeing this? Uh, and just letting me do it cuz you know how to test for the antibodies and the blood better than, you know.

Stephen: I don't know how to do that. I don't know exactly what to look for. He said, sure. Two months we gave her thymosin alpha 1 BPC-157 TB-500. And within two months this thing cleared up. And he was, he was like, uh, uh, uh, I, well, I, I guess you didn't have, I guess you didn't have it, I guess it was just a, a thyroiditis or something.

Stephen: And you know what the, you know what they do for this disease? They ablate.

Leslie: it's radiation. Yeah.

Stephen: yeah. They take it out. And so then you're on thyroid medication for the rest of your life. And, and it just wasn't even an option. And I was so, so fortunate that I had been into this stuff enough to put the pieces together because it was all hands on deck at that point.

Stephen: And, you know, it, it, it, I will. Thank you. I mean, you know, it's, it's, it's one of those things that, um, when you have those experiences, everyone in this industry that I talk to, everyone, everyone that is doing something in this, they all have that story. They all

Leslie: what drives you.

Stephen: Yeah. And so I, I was really inspired by your story and, anyone is ha going through something right now that's listening to this, There is a way you just gotta keep turning over stones and you've gotta just be, keep an open mind and talk to a lot of doctors that are doing i integrative and functional medicine, and they're doing continuing educational, uh, seminars and going to advance things because the, you know, we're able to do things that we couldn't do in the past, you know?

Stephen: But I, I

Leslie: agree. I agree. No, no. It's a wonderful story. And people like, uh, people like Dr. Sandy Kaufman are really pushing the edge on this, uh, you know, with her books and things. She's really helping empower people, uh, learn about this. Of course. Uh, with peptides, the seeds course. That's fantastic. That's, I didn't know you were a seeds practitioner.

Leslie: That's fantastic. And thy 

Stephen: I, I, 

Leslie: Thymosin alpha 1 is, is great.

Stephen: Yeah, I mean, it helps the body say, this is me and this is something else. Right. It really allows them to, to separate the two. And, uh, uh, you know, you just don't get sick. Like, I keep that on hand constantly. More in the fall, in the winter, and or if I'm gonna get on an airplane and go on a trip, I'll just take a, a dose of thymosin alpha 1 and just to kind of button myself up and Fantastic.

Stephen: I actually, I think I'm gonna open the World Peptide Conference this year in Malibu. I think I'm gonna be the motivational speaker to get everyone fired up. So I'm, I'm super excited

Stephen: about that. Yeah. Yeah.

Leslie: Oh, I have to go. That would be, that would be really, that would be extraordinary. That's wonderful. Well, and you know, the, the, the philosophy again is around modulating, not suppressing, like you said, oh, well, let's ablate the thyroid. Let's, you know, let's radiate it. Let's destroy it. Same with, you know, oh, the immune system's out of whack.

Leslie: Let's, let's suppress it. In an acute case, yes, but not for the long term to, you've got to get to the root cause, and you have got to bring the body back to homeostasis.

Stephen: Yeah. And appreciate the fact that the body really is so intelligent and knows how to heal when you get a cut on your finger, you don't have to do anything except keep that thing from getting infected. The body knows that's the innate immune system, right? Like it just knows how to do it. And the body is infinitely intelligent.

Stephen: So it, it's about that homeostasis, we're 30 minutes in it, I wanna start getting to, um, cause I'm really excited about your product. I'm using it. You, I thank you for sending me some and I would like to talk a little. Yeah, I would like to talk a little bit about the, the different, anti-aging mechanisms or l let's say, tenants that spermidine hits on.

Stephen: We've talked about autophagy that's cleaning up the cells and maybe getting rid of some old machinery to build new machinery and things like that. And, taking out the garbage. I always say it's like if you had a party at your house and there was, you know, dishes and, and drinks, empty containers everywhere and plates and, and just stuff was all messed up.

Stephen: You need to spend an hour or two cleaning up your, your house after a party. Well, most of us are just living at a full-time party, eating whatever we want, just activating mTor all day long. Right. We're just going crazy. And it's like something like this can say, no, no, no, no. It's time to, to take out the garbage, so to speak.

Stephen: Right. 

Leslie: and what's interesting is that autophagy and spermidine itself not only activates autophagy, but it activates mitophagy. So this is 

Stephen: Oh wow. 

Leslie: garbage. When it comes to mitochondria, there's something called lypophagy. It does the same thing with lipids. Uh, virophagy does the same thing with viruses.

Leslie: There's also something called ferritinophagy, which helps sometimes people are very high in ferritin and low in iron. Well, you need sperm meine to help unlock the iron that is in the ferritin stores. So it has all of these other auphagy superpowers, which is quite exciting. Um, but at the same time, we know that if we look at.

Leslie: A framework around aging. Since 2013, there has been a paper called The Hallmarks of Aging, which I'm sure you're familiar with, and that posited nine different pathways down which we age. And those were things that I've already alluded to, like stem cell dysfunction, mitochondrial dysfunction, short native telomeres, epigenetic changes, uh, impaired proteostasis, um, impaired intercellular communication.

Leslie: Um, those things all are hit by spermidine so you can inhibit them. There are levers that you can, you can sort of pull on to sort of slow the rate at which you age right now. There are a few others that, um, were in that original paper. Uh, DNA protection and repair, altered nutrient sensing and cell senescence, which, which we.

Leslie: Could not show proof spermidine slowing those down. But what we could do was we could show kacha and gata could show that spermidine actually, um, actually hit on immune senescence. So you talked about the, uh, the immune system earlier. And what we know is that when we're young, the immune cells are sort of trained by the thymus on how to properly function.

Leslie: As we get older, the thymus actually turns to fat and they say that there's a fellow here at Oxford, um, Who is a thymus expert, and he says that the thymus is kind of like the University of Oxford and it continually trains these, uh, these immune cells. But as it turns to fat, the students come in, but they actually don't learn very much and they forget how to behave.

Leslie: And what what has been shown with sperm aine is that you can actually, uh, take, you can get rid of these senescent immune cells and you can actually retrain them, as it were, which is kind of, for me as an autoimmune patient sounds like the holy grail,

Stephen: Yeah.

Leslie: right? Um, so that's very exciting. But technically, Those last three hallmarks of aging DNA n a repair, altered nutrient sensing cell senescence.

Leslie: We don't say that Sarine does those only immune senescence. Now, since the time of publication in 2013, there has been an updated paper for the 10th anniversary of that paper. A new paper came out adding three additional hallmarks of aging and none of these are going to surprise you or your listeners and they certainly didn't surprise me.

Leslie: Gut dysbiosis. Like leaky gut. You already talked about how this is where these autoimmune conditions come from, right? You have these particles of food, proteins, undigested proteins that go into the bloodstream. The body says, oh, right, that's, doesn't say that's a nut protein that says, that looks like foreign, and it resembles the proteins on the thyroid.

Leslie: Let's attack

Stephen: yeah,

Leslie: the, the other additional one that they have identified is inflammation. You're an athlete, you know all about inflammation, right? 

Stephen: yeah. Oh yeah. 

Leslie: so, so that's the, the second new one. And the final new hallmark. Uh, the 12th harm hallmark is impaired autophagy itself. So these new three hallmarks, all three of them are inhibited by sperm edine.

Leslie: Um, put those together with the other six. That it inhibits and you're looking at 75% of the pathways, the known pathways done, which we age can be slowed by this great molecule. Right. And that

Stephen: force multiplier.

Leslie: Yes, it is. And what we know is that there's crosstalk between these hallmarks and that if you actually can influence one, there is spillover effect on the other.

Leslie: And I like to say it's kind of like having that messy party house post party, new Year's party house that you talked about. Now you could clean it up on your own, but if you hired a team of cleaners and window washers and people just to hoover up the floor, How much faster and how much better could you clean that house?

Leslie: And that's kind of what it is. It's like having nine housekeepers come in, clean up a bunch of things and it's suddenly like, yeah, okay, there's still stuff to clean up, but the body is able to do more now. Right?

Stephen: And, and you get it cleaned up faster, right? So less damage is done. That's so

Leslie: Exactly. Exactly, exactly. So, so that's what really excites me about this. Now I can talk about these abstract hallmarks of aging till I'm blue in the face. The ma, vast majority of people are like, yeah, whatever. Am I gonna see this? They don't care.

Stephen: Yeah. Yeah. Well, let,

Stephen: let's let. 

Leslie: about is looking in the mirror and seeing something change.

Leslie: And that also happens with, with this.

Stephen: Yeah, I just spoke at this event, it was amazing. Uh, blue Heron, this big builder here that does these crazy awesome custom homes in Vegas, and it was about longevity and anti-aging. And, and, and I said they had all these different rooms where you could try all these different things, and they were all like really good products.

Stephen: I have pretty much all of them and used them, and I told them, I said, here's the thing, when you weave this stuff into your life, it's not some big thing. I'm not doing this stuff all day long. It's, it's, it's just woven into my life. I said, you start to notice after 10 years go by of doing this, that you are separating and pulling away from the people that you are your friends or that you know, and you start to literally start to see, That, oh my God, I'm aging slower than everyone around me.

Stephen: And, and it's, and you go, oh my God, this stuff works. And unfortunately, some of these things, are happening at, at the cellular level where it's not like, I think you said you're not gonna have fireworks with taking spermidine. You take it and you're like, oh my God, I feel absolutely amazing.

Stephen: But it's one of those things that it's working under the hood, and if you stay with it over some course of time, you will start to go, I think this is really working. And then you'll get to the point where you're like, I know this is working. What I'm doing is unequivocally having an effect on my life.

Stephen: And,

Leslie: Yeah.

Stephen: and so anyone listening, sometimes, you know, when, when you have someone like Leslie here who's a, who went to Harvard, Who is around all these people in Oxford who comes across this supplement that, that hits nine of the 12 hallmarks of aging and the degree, which I can tell. And on your website that you guys have scrutinized the quality of this product and the fact that it isn't synthetic.

Stephen: You're doing it in, its most natural form. At some point, if you care about aging, this is a done for you turnkey solution right now. I mean, here it is. This is what you do. You know, and you just, so l l let's talk about the dosing. So when someone gets this, I know that the serving size is three pills, right?

Stephen: And that equals a milligram. Right? And should you ramp up into that? Should you kind of work your way up into that?

Leslie: Yes, the uh, yes on with both of our spermidine products. And the reason why, let's say I was priming original, which is what you're taking that has a fructooligosaccharide for people who say have been on the carnivore diet, are not used to eating a lot of plant fiber. And unsurprisingly, a lot of Americans are not used to eating a lot of plant fiber.

Leslie: They may think that they do, but. Our diets are so processed that actually we don't get a lot. And uh, so if you take a fructooligosaccharide and you're not used to plant fibers, you might experience a little bit of discomfort in the GI tract, a little bit of bloating. That's because your body is getting used to the fibers again.

Leslie: So we actually recommend that you titrate up to the three capsule, full dose of one milligram, and day one, you take one capsule. And take it with food. And then day two, assuming you have no issues in the GI tract, you go up to two and day three, you go up to three. Now why one milligram? Because that is the amount that is a minimum effective dose that has been shown to improve memory and cognition.

Leslie: So we're really looking for that kind of, um, an impact. And then the European Food Safety Authority has also set an upper limit of six milligrams of food derived supplemental sperm aine. So we didn't wanna go past that higher range of sex. Uh, we do know that clients are taking more and they do get good results.

Leslie: Um, there's a woman in San Francisco who is taking. She's taking, I think five milligrams a day, but she's had really good results with gray hair

Stephen: Oh wow.

Leslie: Um, you have to, you really have to titrate up. If you are gonna do that much, I would never suggest, I would actually strongly recommend people not to do that from the get-go, because you will feel it.

Leslie: It's something that the gut needs to get used to, um, over time. Right? So that's, that's, that's why that particular dose, and we use the same dose with our gluten-free product, which is derived from a very special strain, uh, an unusual strain of chlorella that unusually has no iodine, rare for chlorella.

Leslie: And, uh, we have paired that with two other autophagy, activators, uh, nobility, which comes from an okina lime, and it's from the peel. But that lime is, uh, is, it's kind of like bergamo, but it has much more of this autophagy activating molecule nob than Bergamo does. And then we've got an autumn turmeric in there, which has curcumin.

Leslie: And curcumin has, is also, um, it supports autophagy too. So we have a minimum of the one milligram, but then we added in a couple of autophagy activators just to, you know, see if we could enhance it. And that one has no gluten in it.

Stephen: So that would be good for somebody who's intolerant or has celiac or something like that. Right? That's

Leslie: Yeah. Or Cibo, for instance. Yeah. If you're, if you've got, uh, if you've got leaky gut, active leaky gut, I would say don't, uh, don't do. Primeadine original only because, uh, it could exacerbate things and you want to, you know, you probably want to, um, you know, seal up the gut lining before you do anything else.

Leslie: Now, spermadine itself has the superpower of closing up the tight junctions of the gut. That's actually why, one of the reasons it's so important in breast milk as a, it has this function of closing up the lining of the baby's nascent gut and, uh, as well as activating the immune cells in the gut. So you prevent allergies in those babies later.

Leslie: But, um, in adults, it also will, um, you know, will tighten up those so-called tight junctions. Um, that, yeah.

Stephen: And is there any, should you cycle this at all or is it the kind of thing that it's totally fine in your opinion, to just be on it indefinitely? You know, I mean, I've been on certain things for 12 years consistently that I know work and, um, you know, I have no problem with that.

Stephen: You know? Is this one of those compounds?

Leslie: This is, this is one of those compounds that we, we actually do need. Now, if your body is capable of manufacturing this just through your diet, then fantastic. But you will be, your body has a demand for it, and there will be certain moments in your life where the body will demand more and you should actively increase the amount that you're taking in.

Leslie: And I would say, I would argue, um, when your breastfeeding is one of 'em, um, for instance, Because the woman is giving all of her poly Amys to the baby, right? And this is why some women, because poly Amys are needed also for hair growth. It's why some women, when they're breastfeeding, they end up losing hair.

Leslie: But another time would be if you're fighting off infection. So I talked about vi fige and the ability of, um, sperming to activate Viro fige. So if you think of autophagy as the sequestration, or basically the bagging up of old cellular parts, viji is the bagging up of viruses. And, uh, when you have a virus, uh, could even be, well, it could be, could be any kind of virus.

Leslie: Your body will take the sperming in your body and they will use it to activate viji to fight off the virus. You might find afterwards that you lose hair. Why? Because the body prioritizes and says, okay, we have this limited amount of, uh, sperm aine. We're gonna use it to fight off this infection. Sorry, hair and scalp, but we're not giving you any, we don't care actually if you lose any, because you're not essential to the survival of this organism.

Leslie: And the body is always thinking about the survival of the organism. And it's very interesting with, again, breastfeeding mothers that the body actually prefers to give those poly aimings to the baby

Stephen: Yeah.

Leslie: survival of the next generation.

Stephen: Yeah, I guess you could look at it as, uh, spermidine insurance. So yeah, you might have sometimes in your life where you have enough, but nobody is, I mean, we're all fluctuating. We all have stressful days. One bad night of sleep can really screw up all the resources in your body in terms of like, uh, everything gets shuttled to, you know, you know, certain things, especially with stress.

Stephen: You, your libido and all the non-essential activities go down when you are really stressed out, and so

Leslie: And it can turn you into a pre-diabetic, uh, loss of sleep for, right.

Stephen: Absolutely. A hundred percent. So, you know, maybe a good way of looking at this is that it's spermidine insurance, so that you have the most possible, um, uh, faculties to, to really safeguard against those nine hallmarks of aging.

Leslie: That's, that's how I like to think of it. That's how I like to think of it. And of course, I always tell everyone, don't forget food sources. Try to optimize your food sources of these poly aimings. It is no, uh, wonder that all of the longevity blue zones around the world are getting high amounts of these poly aimings into their diet.

Leslie: So if we look at the Okinawans, and I was just in Okinawa, Japan, they're eating huge amounts of plant fibers. They're the traditional diet. And I'm ta talking about the modern Okinawan diet, which very sadly has been taken over by a and w root beer, Baskin Robbins and 

Stephen: Oh, no, no. 

Leslie: we do have an American airbase there.

Leslie: But, um, so I think it came with the airmen. But, uh, you know, if you, if you, uh, if you look at the traditional diet, something like 66% of the traditional diet is made up of purple sweet potato. Which has a great, it has positive benefits on the gut biome. That's a carb, right? And I know a lot of us are very anti carb, but it's a slow carb, so it's not spiking their blood glucose.

Leslie: And it is feeding the fiber in their sweet potatoes is feeding their gut biome, allowing them to manufacture all of these things so they can live in good health and enjoy long life. Um, pretty much the rest of it is plant fibers. Now if we look at, say the Sardinians are the Nicos, the Quain Peninsula in Costa Rica, um, or the ICARs, they have actually much more in the way of fermented dairy.

Leslie: So goat, small cheeses. For instance, well you have a fermented food, whether it is sauerkraut or kimchi or ma mature cheese, you're going to get sperm aine in there too. And so they're getting this that way. So you could also get it from kafi too. So all of these populations of uh, you know, great long life and health are all getting lots of sperming in their diets.

Leslie: And you can also look at, say, a healthy 90 year old and you can, uh, look at their gut biome and they will still be manufacturing sperming the way that a healthy 50 year old is. 

Stephen: I saw an interesting thing. I don't wanna derail you, but I saw this thing that, really, Pinpointed, something it was something like for, um, 60 to 80, most people have spermidine less than they did when they were 50. But if they're 90 years old, they have as much as they had when they're 50.

Stephen: Meaning that there must be some longevity aspect to this,

Leslie: Yes, correct, correct. So, so unfortunately we go through poor health in that 60 to 80 year old period. And, uh, if I talk to Kacha Gata about this, they'll say, yeah, it's, a lot of it is immune related. But of course there's also cardiovascular component. There's a neurological component. Um, and so that population of 60 to 80 year olds are beginning to lose.

Leslie: Their ability to activate autophagy. They have lost the, the gut's ability and the tissue's ability to manufacture spermidine is no longer there. And therefore, as a population, as a cohort, their overall levels of sperming are lower than those of a 50 year old, but tho, but they die, they die off. The ones who are unhealthy, who have lower levels will die off so that by the time you've got this cohort of healthy 90 year olds, their spermdine levels are high.

Stephen: Yeah,

Leslie: they were always, they were once part of that 60 to 80 year old cohort, but the median of the median sperming levels of that cohort were dragged down by the people who became unhealthy and who weren't able to keep this production up. That's the hypothesis.

Stephen: yeah. And in your research, have you seen any cardioprotective benefits of it? I've seen that it can slow down or stop the progression of atherosclerosis, which is. Pretty amazing. Have you come across

Stephen: any of that at all? 

Leslie: So there are, we know that cardiomyocytes in the heart will preferentially take up sperm aine, and one thing not everybody knows about the heart is that heart cells, we, there isn't cardiovascular plasticity the way that there is neuroplasticity. Um, you know, we're not replacing throughout our life, we do not replace our cardiac cells.

Leslie: Um, at least not very many, um, has not been shown and

Stephen: right? For something like that? Injecting in that area?

Leslie: Yeah. So that, that is something that, that we, we. Don't know. No, bear in mind of course, that for many years we thought there was no neuroplasticity, and now we know that's possible. But, um, with this preference for sperm, aine by the heart, again, the hypothesis is it is to keep it healthy to, to basically rejuvenate the existing cells to get rid of the debris, right?

Leslie: So it's maintenance, it's cell maintenance, and that's what autophagy's doing. So if you have a limited number of cardiac cells and you're not going to be replacing them, you want to take good care of them. So you want that regular maintenance to be done. That's the, you know, that is the, the, again, the, the, the working hypothesis there.

Stephen: Wow. Look, we have shown enough on this, and by all means, I always say go do your own research and verify these things. I think your website is, illustrates a lot of the benefits and you've really done a good job of, well, what if I'm intolerant to this?

Stephen: Or what is it? What about comparing this to liposomal? You know, and we've talked about the food quality of the prebiotics, I mean, look, I think this is a good primer for somebody to be armed with. What they need to take the next step with spermidine, and you've been kind enough to set me up, and give, me an affiliate code.

Stephen: So anyone that's interested in trying this, I'll put a link in the show notes, for everything we talked about, but also a link to where you can buy or Primeadine supplement and get 15% off using the code. Stephen with a pH. 15. So Stephen with a pH 15. And look. I'm sold and I saw you speak years ago at a conference online.

Stephen: I, I just got, I think it might have been Dave Asprey's. And I was really impressed with your presentation and I thought, wow, cuz I had been dabbling a little bit in spermidine and knew about the autophagy, but I didn't know that it had such an overarching effect on so many pathways of keeping us, bulletproof for aging.

Stephen: And, I really appreciate you coming on and

Stephen: sharing this stuff with us. 

Leslie: Uh, well thank you very much. It was exciting to hear you talk about the benefits you had seen. You know, with hair.

Stephen: Yeah. I get a lot of people that come to me and saying, what can I do for hair? What can I do for hair? And hair's a little tricky, right? Because you can have, you know, that's, they're also saying that inflammation is a, is really a, a root cause.

Stephen: There's also the DHT hypothesis. Some people have autoimmune stuff. There's alopecia with de patches that I've seen cured by fixing autoimmunity. But just to have, I've noticed that the thickness and the lustrous of, I guess that's how you say it, uh, of hair, of my hair has been in. Yeah, and I look at your hair and your hair looks amazing, like you have that luster, you know?

Stephen: So I'm like, I'm not surprised. And I'm meeting with someone tomorrow that I'm coaching and one of their interests is I wanna know what to do with my hair. And I'm certainly gonna be bringing up your product and, I had my mom on it too, cuz she called me and said, oh, uh, I need to do something for my hair.

Stephen: Like, I need it. And I was like, well, you should take Spermidine. And so I sent her out a couple bottles of your product. And so,

Stephen: I look forward to, seeing, more what comes down the pipe, in terms of spermidine and, and what it's doing. And I also look forward to seeing what you do because you clearly have, a knack for picking out something your site men?

Leslie: That's really sweet. 

Stephen: Your site mentions that you're potentially offering other products. Is there, are there other things that you're looking at?

Leslie: Yes, there are things in the pipeline, but we need to test them to make sure that they work. And we're really looking hard at these other ingredients from Okinawa, um, because the Okinawas is very interesting. All these men, they have these thick, dark hair and they're in their sixties and these very, very thick eyebrows.

Leslie: And I, I kept looking around thinking, Okay, this is interesting. Is it just genetic or is it what they're eating? And it's not everybody there who has it, because again, the western diet has creeped into modern Oko and life. But those folks who are still, um, you know, living a traditional life, eating a traditional diet, they look amazing.

Leslie: So I met with our turmeric farmer. I met with our chiko Wasa, our Okinawan lime farmer. He's 83 or 86, and he's, uh, these limes, they grow on the sides of volcanic rock like a vineyard. And he's, he's sort of client clambering like a mountain goat, up the sides of these hills. And I'm thinking this is also why they're living longer, right?

Stephen: a very purpose, centered life I dunno if anyone's ever seen that, um, that documentary about that sushi guy, Euro Dreams of Sushi. 

Leslie: Yeah. 

Stephen: Have you ever seen that? 

Leslie: Yes. I saw a snippet 

Stephen: 80. 

Stephen: Yeah. And he is just a machine. I'm like, oh my God.

Stephen: The, the purpose, the Japanese are so amazing at, at really. Committing to perfecting stuff. We didn't get a chance to talk about our, affinity for, the Japanese culture and stuff. But we'll put, we'll have to do that offline sometime because I, I'm, I'm, I'm definitely a little bit, jealous of this, the stuff I saw you posting and I was like, oh my God, I, I'm gonna have to be armed with some of this info when I go to Japan.

Stephen: Cuz that country had the biggest effect on me. It was the first place I went to, as a kid and I was chased in the streets and treated like I was a superstar. Cause I was a little blonde haired, blue eyed kid. And, and it just had this profound effect on me. I know you had a similar experience too.

Stephen: Like, um, we could, that, that could be a whole nother, you know, like hour long podcast, I'm sure about that stuff. But, um,

Leslie: yeah. yeah. No, it's, it's very true. So we are excited about bringing these other molecules that are science backed from Okinawa and, uh, just, uh, so impressed with. So many things that we could bring all for the benefit of health. And it's all food derived, which is great. So looking forward to doing that.

Leslie: And uh, and also, you know, I do a lot of work with something called the Oxford Longevity project.org, and we have free webinars there where we're looking at autophagy in relation to different diseases, whether that's, uh, dementia and Alzheimer's, cardiovascular disease, um, autophagy and fasting, fasting for women.

Leslie: Um, And we'll be going into the autoimmune condition soon. We've got our first event. This is nonprofit. So this is totally separate from Oxford Healthspan. Um, we've got our first event in, uh, Bel College, Oxford on the Saturday, the 8th of July. It's an all day session with, uh, lunch in hall like 

Leslie: Harry Potter and, uh, and we have got a great bunch of speakers, including, we have the 2014 Ironman winner, uh, from Great Britain, so Dr.

Leslie: Tamzin Lewis. And we've got Sir Christopher Ball, who from, uh, for many years until last year, held the Guinness World Record for the highest number of marathons run in the shortest number of days. 

Stephen: Oh 

Leslie: in 

Leslie: 10, 

Stephen: Oh 

Leslie: marathons in 10 days over the age of 70.

Stephen: Oh my gosh. That sounds brutal. I mean

Stephen: that's, I thought, yeah, you know, you know who Dr. David Minkoff is, 

Leslie: Uh, I've heard the 

Leslie: name. Oh, yes, yes,

Leslie: yes, 

Stephen: Yeah, he's done a lot of Ironmans and he's over 70, and I've always been so impressed. He makes great products. He's a big essential aminos, advocate, it sounds like you are just surrounded by really fun stuff.

Stephen: I mean, this is the stuff that gets me so

Stephen: excited, you know, 

Leslie: Yeah, yeah. Me too. Me too. 

Stephen: yeah, I look forward to our paths, overlapping at some point. Because I, I just think that, the quality of humans in this space that are doing it, literally, like I said, from their own personal story of strife and health, and trying to overcome that is just, It's so inspiring, and you are one of those people and you know, you're brilliant.

Stephen: I mean, and I know people probably tell you that, and probably, I know you're humbled, you, you seem very humbled. But I really think that it's, this was an incredible opportunity for not only myself, but for my listeners. And, and look, you, you have a product that can, that can change someone's the trajectory of their life.

Stephen: That is, you know, time is the only thing, is the most precious resource. So if you can, and basically give somebody more time because you can help them live longer and healthier, that's the greatest thing you can do for somebody, right? 

Stephen: I mean, really at the end of the day,

Leslie: I would never make a claim like that. But what I, what I will say is that, uh, autophagy. Is a way to unlock the body's potential and wisdom, and that is really exciting to me. It's such a powerful concept. Our bodies are much more powerful than any of us could imagine, but we need to give them the right tools, the right conditions to flourish.

Leslie: Just like any plant, right? You can't expect a plant to do well without water and sunlight. And this is just, sperming is just one of those things. I would never say it is the only thing, but it is a really, it is an important thing and we should all get more of these poly, these powerful poly aimings into, into our life to help unlock our body's 

Leslie: potential. 

Stephen: Well, I think that is the perfect way to put the cherry on top of this podcast again, uh, Leslie. I really appreciate you coming out. For everyone that's listening, check out the show notes. There'll be a link in the description for all the resources and everything we talked about and that 15% discount on her spermidine product.

Stephen: Leslie, thank you so much and I look forward to talking to you in the future on the podcast and maybe some new product you have. And for everyone else listening, thank you so much for joining us today, and we will see you on the next, episode of the Stephen McCain podcast. Take care, everyone. Stay healthy.