Spermidine: The Autophagy Activator with Dr Melissa Cano
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Welcome back to the Health Longevity Secrets show with your host, Dr. Robert Lufkin. His book titled Lies I Taught in Medical School is a New York Times bestseller. See the show notes for a link to download a free chapter. And now please enjoy this week's episode as we look at how to activate autophagy with spermidine with Dr. Melissa Karno.

As we near the end of the school year, I'd like to give a special shout out to Mr. George Gaskins, seventh grade history class at Harvard Wesley School, who are fans of this program.

Now for this week's show, have you ever wondered what keeps your cells functioning properly? The answer might be a molecule with a funny name but has serious implications for longevity. Spermidine, found in every living cell on Earth, is essential for triggering autophagy, which is your body's internal cleaning system that recycles damaged cellular components.

In this episode, biochemist Dr. Melissa Cano takes us deep into the fascinating world of cellular metabolism, explaining how this small but mighty molecule could be the key to healthier aging.

Our spermidine levels naturally decline as we age, precisely when we need its protective effects most. This decline happens through three pathways: diminished internal production, changes in our gut microbiome, and the resulting potentially decreased absorption from food, creating a perfect storm for cellular aging.

What makes this conversation particularly compelling is the growing body of evidence supporting spermidine's role in longevity. Epidemiological studies show that people with higher dietary spermidine intake live 5 to 10 years longer on average. And this is correlation, not causation, but certainly interesting.

In lab studies, supplementation extends lifespan in multiple organisms by 5 to 20%. A groundbreaking 2024 study in nature cell biology that we're going to talk about revealed that spermidine mediates many of fasting's benefits, suggesting this molecule could be a natural caloric restriction mimetic without the side effects of the hunger.

So whether you're already familiar with longevity compounds like rapamycin or metformin, or just beginning your healthy aging journey, this episode offers practical insights for everyone.

Ready to support your body's natural cleaning and rejuvenation processes? Learn how this remarkable molecule works at the cellular level and discover if spermidine supplementation might be just the missing piece in your longevity strategy. Now, this episode is sponsored by Spermidine Life, whose products are mentioned in the program.

This episode is brought to you by El Nutra, maker of the Prolonged Fasting Mimicking Diet. If you'd like to try it, use the link in the show notes for 20% off. What's the best imaging test to assess health and longevity? I used to think it was the CT coronary artery calcium score. Well, I don't anymore because now with the same x-ray exposure and time as a calcium score, I can get a complete metabolic heart scan.

This includes not only the CT calcium score, but also calculated arterial age, liver fat quantification, and CT bone mineral density. These key metabolic and cardiovascular markers can detect the actual disease that blood or genetic testing only show the risk for.

This scan is available anywhere in the U.S. without a doctor's prescription. See the attached link and use the code LufkinCT for $100 off. Join the health longevity medical imaging revolution today. And now, please enjoy this week's episode.

Hey, Melissa, welcome to the program. Hi, thanks for having me, Rob. It's so great to have you here on your second podcast ever. This is going to be fun. As we were saying, we'll have a level of honesty and not jaded. It will come out as it will come out. There's no rehearsing here. I'm

I'm so excited about talking about today's topic, spermidine, which we haven't covered on this podcast yet, and yet it's so important, and I can't wait to dive into that. But before we do, I just want to invite you to tell us a little bit about your background and how you came to be so interested in this space. Right.

Right. So, okay, so let's, how far can I go back? So I'm a scientist by trade. So I've been working as a biochemist and microbiologist all my life. So most of my career, I've been behind a bench doing gene editing in microbes to try to make them produce sustainable compounds for either pharmaceutical or like biofuel industry.

And so I come from a very basic science foundation. So I've always been interested in cellular metabolism in general. And, but again, I've always worked with microbes and plants and algae. My actual specialty was photosynthesis in algae and plants. And, yeah,

And yeah, I've been doing it for most of my career. I loved it. But I guess I've always also been interested in longevity in general, like more of a personal interest. So that was always my reading on the side. And, you know, as a scientist, you're always constantly reading. And so, yeah.

I wanted to dedicate more time to it, and I got an opportunity to work with the team at Longevity Labs. They needed someone that was interested in explaining how cellular metabolism works, how spermidine works specifically, and so I made the jump, and now I get to bathe in topics that are

always been interested in and I finally get a chance to dive into the scientific literature, help coordinate clinical trials with our products. So it's like a new phase in my career that I'm enjoying a lot because I'm learning a lot. So I get to also go back to the basic and explain to other people as well. So it's a great exercise that I've been enjoying.

I love the longevity space. One thing I've noticed, I mean, you're not very, you're not, you're not old, but I noticed that as the older people get, the more they're interested in longevity. I'm getting close to...

my 40s so next year I'll be 40 so you know longevity is coming starting to creep on the back of my of my head here so like I'll get I get into some more and more of course like everybody I mean healthy aging starts very early and especially mid-30s you're already starting to notice the effect of aging you know like again it's just the beginning but it's starting so

Especially as a woman, I feel like there's a little bit of reckoning, like, okay, this is happening. Oh, yeah. So let's start with what exactly is spermidine? It has a funny name. So where does it come from and why should we care? Absolutely. Spermidine, it's a very small molecule, like very small. It's thiamine.

found in every living organism, every cell has spermidine and it's absolutely essential for cellular function. It's essential for a lot of processes, but mainly cell proliferation and the cell cycle.

And so because it's found in every organism on the planet, it's found in all the food that you can ingest and you absolutely need to intake spermidine every day in your diet. So you have spermidine in all the cells of your body and you need to have a certain amount every day to maintain a process that is called autophagy. So autophagy is

is your cell cleaning system, like the spring cleaning inside a cell. A cell can do, I'm going to simplify a little bit, but can do one of two things. Either it has enough nutrients and energy to divide and proliferate, right? That's what life and cells need to do to maintain themselves.

Or they don't have enough and they're going to start relying on what they already have internally and recycle the components before they get too damaged to start impairing cellular function. And that is the process of autophagy. It's the cell inside itself that is going to encapsulate all the damaged components, all proteins, all the organelles like the

mitochondria, but also damaged lipids, oxidized lipids that are going to be encapsulated internally inside the cell, digested to reuse the elements to be remade in you. So spermidine is a small molecule that is absolutely essential to cellular function and that triggers a process that is called autophagy, which is your cell cleaning, internal cleaning system that is absolutely necessary to maintain the cell functioning properly.

So it's, as you say, it's a small molecule and it's not manufactured within the cell. So we need external sources of it, correct? Is that right? Yes and no. So there's actually three ways your internal level spermidines are maintained.

One third of your daily needs come from your diet. Like I said, it's found in every organism. So in all the foods you ingest, some foods, and we can get into it later, have more spermidine than other. But one third of your need come from food. Another third come from your gut microbiome. So your bacteria in your gut are able to produce quite a bit of spermidine, uh,

And this passes the gut barrier into your bloodstream to all the cells of your body. Now, the last third of your daily spermidine need is actually produced by your own cells from other precursors that derive from arginine. But your cells are also able to produce a little bit of spermidine.

And so this basically those three ways of getting or producing spermidine represent about the daily needs you rely on every day. So you can make it. You have to ingest a little bit of it, though, because otherwise you're not going to have enough.

So that's why we start also thinking about supplementation, especially as you get older, because the production, the internal production in your cell is not as efficient. There's some rate limiting steps in the synthesis of spermidine that kind of like

get damaged, not as efficient as you get old. And also you get microbiome, as you probably know, when you age starts changing as well, the good bacteria are not present as much to produce enough spermidine. So you become even more reliant on the dietary intake as you get older. And that's why we start

relying on the healthier foods that have a lot of spermidine. And I can give you a couple of examples, but for example, legumes, nuts, cruciferous, uh, have a lot of, uh, spermidine compared to the other food, but you can also find quite a bit in aged cheese, for example, and obviously the highest source of spermidine, which is not a food that people intake, uh,

a lot, it would be Ouija. And that's what we made our supplement from, is from Ouija, which is the highest source of natural spermidine that we can find in the natural world.

Okay. Well, and let me, let me back up a little bit, back up to autophagy. Our, our audience, we will be familiar with the concept of autophagy and the notion of switching between growth mode and autophagy. And we, we, we talk a lot about mTOR and rapamycin on this podcast. Some people say too much too often, but sorry, we may talk about it again.

No, we can't talk about it enough. I think it's a fascinating topic. And one of the challenges with autophagy that seems to me is everyone, everyone,

knows that autophagy is valuable and it's advantageous to go on fasting. We turn on autophagy, we change our diet, we turn mTOR down, we turn on autophagy, other lifestyle things. How do we measure autophagy? If we want to measure glucose, we could do a hemoglobin A1c or a fasting glucose. But autophagy, what are the surrogates or how do we know we're even in autophagy?

Right. Right. So there is no direct marker of autophagy. You can measure indirect levels of autophagy of recycling just by by looking at the recycling of the components. And you can also see the expression of some factors that are essential for the autophagy process. So it's not like you can actually see it.

like directly and there's one unique factor to measure autophagy because it involves a bunch of factors that

the same way mTOR is related to autophagy, like when you inhibit mTOR, it actually triggers autophagy. The same way when you activate AMPK, it's going to activate autophagy. So at the end of the day, all those pathways, they converge towards the same process, which is this formation of this structure of the autophagosome, which involve a bunch of different components. Some you

that we know very well, like there, I mean, I don't know if I want to go into detail, but there's a lot of factors called ATG with a bunch of number from one to 16 that participate to basically making the structure of the autophagism. So you can measure that. You can measure the levels. Now, there is no...

little sensor that we can clip on the shoulder just yet to measure this. Again, it's a very hard process that is hard to get to because it's intracellular. So it's easily done on a bench, on model organisms, on humans, it's going to be hard because we're talking about like an internal process inside a cell that is not that easy to track. But we know the components of

what makes the autophagy process happen, the structural components of it, and this can be measured. It's gonna be, I don't think, I don't even see how we could do an easy sensor for people to measure autophagy easily.

And again, there's also complexity. Now, some people say, why don't you just measure spermidine in the bloodstream? Because it's not that straightforward. And there's actually been some papers that have been debating whether supplementation of spermidine actually passes.

into the blood and into the cell. We know that they do because there's a lot of papers, but some have argued that, well, if I give that much supplement to people, I cannot measure the spermidine level

in a correlative way in the bloodstream, the QRS. It's a bit more complex than this because the cells are going to take it pretty easily from the bloodstream. And as soon as you get into the cell, the way spermidine is going to be active in trigemotophagy, it's actually going to be metabolized. It's going to be linked. There's different ways it can act, but one of the main ways it's going to be metabolized

triggering the autophagy is going to be linked chemically to a translation factor called EIF5A that is going to trigger the synthesis of all those components necessary to the formation of the autophagy, which is the structure that allowed the autophagy. So it's not as if you can track the spermidine

in real time all the time because it actually gets modified and it also interconverts in other polyamines including putrescine and spermine so it gets all very complicated to just track it as is as a marker of autophagy also because it gets metabolized basically.

Yeah, and before we leave autophagy, it is such an important concept. It's amazing to think that, you know, the Nobel Prize was just given in autophagy, you know, about 10 years ago to the Japanese researchers. Yeah, 2016. Yeah, absolutely. I mean, it's an essential process that

when it gets impaired, it can lead to a lot of age-related diseases. And it's been linked to cardiovascular diseases, to neurodegenerative diseases as well. So the impairment of the autophagy process, I mean, you can think of it when you try to visualize the inside of a cell, which I always try, and it's like impossible to really grasp how

like how many molecules chemical reaction happen at once but if you don't get rid of all the junk that accumulates in a in an enclosed space you can you can get a sense of how this is going to impair the proper functioning of the cell and this autophagy process gets

impaired as time goes by, as people age, it's not as efficient. And that's when the basic cellular functions start not working as well. So I think it's too much. I mean, I guess I'm still very amazed by the fact that it's not discussed

as much, especially in the longevity space. I mean, I guess people know a little bit more about the longevity space, but in the health space, how important of a process it is and how important it is to support it, to maintain cellular function. And again, like I said, you find it in every cell of your body. So

facilitating or supporting the process of autophagy is going to have so many beneficial effects in so many parts of your body that that's why it's been researched in so many potential diseases including cardiovascular disease diabetes neurodegenerative diseases there is a an insane array of um

field it's been looked into and how it impacts health because it's such a central cellular process. Yeah, really at a basic level for all the chronic diseases that we think of as being metabolically based are potentially improved by autophagy and the effects on that. And one last question on autophagy. Is the effect of spermidine on autophagy

modulated through an effect on mTOR or is that upstream to it or does does spermidine affect mTOR or does it affect autophagy and mTOR also affects autophagy or do we really know we do we do know again like we know what we know there's probably in additional connection that are still a little bit hard to to completely decipher but a hundred percent mTOR AMPK and um and

spermidine through the activation of this translation factor that is going to trigger the synthesis of all the genes necessary for autophagy. They either work in parallel, but are also interconnected. Supplementation of spermidine actually helps inactivate mTOR and activate AMPK, which is what you want, right? You want the cell to think, okay, mTOR is going to tell the cell, I don't have enough nutrients, so inactivate, that's going to trigger autophagy.

When the MPK is the energy sensor of how much ATP you have, so you want to activate it, and this is going to trigger autophagy. Spermidine, at the same level of rapamycin, metformin,

is going to act as a calorie restriction mimetic because it's going to trigger autophagy, but it also indirectly through other factor, other translation factor has also a direct impact on mTOR and AMPK. So they are in parallel, but they're also interconnected.

And I want to emphasize one thing you said before, too, that spermidine production, native spermidine production within the organism, within the human, decreases with aging. So like so many other molecules that we produce, as people get older, there's less available. So you were saying that drives the need for aging.

exogenous sources through meal dietary choices or supplementation, as we'll talk about in a bit. So is it a consistent decrease? So you could almost create a biological age based on their spermidine level, right? I love the way you think. I would love to have enough data to be able to create a biological age. The limitation here is that the level is going to

decrease in different rate depending on the tissue, depending on the sex. So we don't really have enough data just yet and continuous monitoring to come up with this, but that would be my personal opinion.

Like dream is to have a, could we make a biological clock with your internal levels permitted? The thing is also going to be dependent of the health of your gut microbiome and what your intake. So it's going to be hard to have it as a very fixed clock. But

we don't have enough data is where I'm getting at, but that would be amazing. Amazing. Our spermidine age is coming, but not yet. You mentioned how repamycin, metformin, other AMP kinase effectors and metformin inhibitors

in parallel have similar effects to spermidine. If a patient's already taking, when should they take one or the other? Are they synergistic? Are they duplicating the effects? If they're already on rapamycin, will spermidine be a benefit or vice versa? If they're on metformin, will spermidine be a benefit? How should people think about that?

So the only data we would have about synergistic effect would be really spermidine and resveratrol, which resveratrol is a bit different, but like through the sirtuin pathway also has an impact on autophagy as well.

There is no data about rapamycin and spermidine. Now, from my knowledge and the data I've always been reading, I would not recommend someone that is already on rapamycin to go on spermidine. I find it would be maybe redundant and we don't know when too much is too much.

Now my take on thing, and I know we're like very different. I'm not an MD. I'm a PhD scientist. And I'm always a little bit cautious about molecules that are not natural.

And that's also because I don't take a lot of supplements. And I always try to stay on the natural route. My take would be, if you're already taking rapamycin, I would not take spermidine. Now, if you're not taking rapamycin or meformin, I would highly recommend to start with spermidine to trigger more autophagy. First, because it's safe. It's a molecule you already ingest every day. So supplementing is just going to help you take it up.

up a notch to improve the autophagy process. You're not going to have any of the side effects that some people can have when taking rapamycin. I think there is a lot of digestive issues sometimes for some people, not everyone, if it's not well dosed. And also at the level of the dosage of spermidine that we propose, we're in the dietary stage

range basically so there is no overdoing it it's like just ensuring you have the healthiest spermidine level you should be intaking ideally if you were living in the most amazing blue zone in the world with the best food with the highest spermidine level that's what supplementing with a natural spermidine source would do is like ensure you get

the base level for optimum autophagy. So I wouldn't do it on top of an mTOR inactivator or mPK activator if you're already doing it, just because there's no data and I'm not an MD. But I will leave you to recommend to people what they should be doing.

Yeah, I mean, with metformin, the usual side effect is GI on that. As you mentioned, rapamycin, there are much fewer side effects at the longevity dosing, which is once a week, but less than 10% of people get aphthous ulcers or cold sores in their mouth, which are self-limiting and they go away after the beginning. Right.

Yeah, and to your point, as it turns out, both rapamycin and metformin are naturally occurring. In other words, metformin is from the French lilac, rapamycin is from rapanui bacteria in there, but still they're exogenous and we have to- Yeah, it's just your body is not used to intake it every day, so there could be some side effects to it. I would say spermidine would be more on the gentler, more gentle trigger of autophagy and

the natural route because you're already in taking it. Now I have nothing against metformin and rapamycin, which can have great benefits on top of that. But I would say someone that is a little bit scared of going rapamycin metformin route, definitely try out spermidine. That's going to be the, your, your, your best and no problem.

no negative side effects route to triggering autophagy. That would be my take on it. And yeah, it's such a great point you bring up then I wonder. So how about someone who is turning down mTOR and AMP kinase with intermittent fasting? Should they avoid spermidine also? Do you think? No, absolutely not. So that's a great point you're making.

There's a paper that came out August 2024 in Nature Cell Biology that actually shows that spermidine is the mediator of the benefits you get from fasting. In this paper, they show that when human, but also in mouse models,

When you fast, your internal levels for me didn't actually increase. So you saw produce more spermidine, which triggers autophagy, which triggers most of the benefits of fasting in the first place.

Now, if you fast and the spermidine levels are not maintained high enough, so in this paper, they decrease the spermidine level. They basically modify the cells so the spermidine level doesn't increase. And so the benefits of fasting do not happen then. So when you fast, if you supplement with spermidine, you actually ensure that you get the benefits from fasting first.

by activating autophagy. So definitely if you fast, I would recommend that it's a good thing to, on top of that, supplement with spermidine. Again, at dietary levels, I wouldn't overdo it because like anything, if you start getting a hundred times the amount you should be taking, nobody knows exactly what can happen. But like, if you just take it up a notch with a natural supplement, you can actually get even more benefits from fasting. So yeah, that's a great point you're making.

Yeah, and I love those papers. There's another one. I think it's a different one, but they took human volunteers and fasted them for 36 hours, water fast, and then took their blood levels and they found elevated levels of spermidine, oleoethanolamide, and a couple other compounds. And then when they gave the compounds to the people independent of fasting, they

they had observable benefits that they achieved with fasting, like decreased appetite, decreased hemoglobin A1C, better glucose metabolism and all. And presumably, spermidine is moderating that effect as well. So if we're talking about possibly having too much autophagy with rapamycin, metformin, spermidine, fasting, you roll it all into one,

What is the problem with too much autophagy? And if we can't measure autophagy, how do we know what's too much or what would be some of the things to watch out for with that?

So I'm going to be honest with this. I've never come across a study that looked into what too much autophagy can do, especially at the organismal level. I think before getting too much autophagy by supplementing too much with spermidine, I'm just going to say on spermidine first,

You could have a problem of excessive oxidative stress. There's been a couple of papers that have shown that a crazy dose of it, of supplementing in mice, led to some oxidative stress. We're not sure exactly what is the definite molecule mechanism, why it would trigger this, especially because spermidine at

dietary level is actually an antioxidant. It can scavenge reactive oxygen species, but also just by triggering the process of autophagy, reduce oxidative stress. So I would say that we don't really know what too much autophagy would look like. Because we don't know, or at least I don't know exactly, I would not recommend to stack up too much autophagy in juicers on top of each other. There is

definitely a case where autophagy might be a problem, but I don't even know if it's too much autophagy, but someone that has a very advanced cancer. So you probably know cancer cell, they can rely on the process of autophagy to maintain themselves and evade the immune system, but locally. So I guess in that specific case,

I would be maybe cautious, but apart from that, if you were to supplement with natural spermidine sources in the range of dietary intake, there is no too much autophagy. Now, also because I'm not aware of it, like maybe, do you know like what too much autophagy would look like? Like, do we know anything about mTOR and rapamycin making, doing too much of it? No, I haven't heard, heard,

I don't know. I'm not familiar with what too much autophagy would look like. But what you describe as a bifolar dose response, in other words, at a low dose, you get one effect, and at a higher dose, you get a completely opposite effect. It reminds me of what happens with the mTOR inhibitor rapamycin, which at low dose, basically a weekly dose, which is what longevity enthusiasts do, six milligrams a week or so,

you get immune enhancement in humans. Their immune system gets better. But if you take that same dose or you take a daily dose of rapamycin, it's one of the most powerful immunosuppressants. So it's FDA approved for organ transplants and renal cell. So it's interesting with that. And obviously it's not specifically autophagy, but it's clearly a...

a different dose response effect that has completely different things going on with that. Absolutely. That's why I would always recommend to stay, say, for example, spermidine, just to go back to it, because those are the numbers I know more.

A daily dietary intake of spermidine can range between 6 to 15 milligrams per day. In diet, right? Yeah, in diet. Depending on what you eat, right? Like say Blue Zone, eat very healthy, you're going to get probably around 15 milligrams. Not great diet, maybe around 6 milligrams, 5-6 milligrams. So

From the data we have and the studies that have been done in humans, again, like specifically in humans, I would not go over daily supplementation of spermidine above 6 mg. Some people, you probably can go safely up to 10 mg supplementing.

I would not go 10 times the amount you should be intaking. Because again, like you said, we don't know just yet what is too much autophagy, what is going to look like. And we do know from preclinical studies in mice that too much spermidine, and we're talking like probably 100 to 200 times the amount they should be intaking in mice, has triggered some oxidative stress. So yeah, definitely the...

Don't do it too much. Do it in the range of maybe two times the dietary intake. That's

That would be the cautious way I would go. Yeah, and there's no evidence or value or variation in doing weekly doses rather than daily doses like rapamycin. Is there any looking at that? Actually, there is no data to compare both, but again, it's very different from rapamycin because you have daily needs of spermidine and you produce it constantly. So

The recommendation is it's a daily supplement. It's consistency every day that is going to make the effect. It's not like a one dose thing that is going to shoot up

the autophagy process to the roof. Maybe it could work at a very high dose, but again, we don't know. We don't have the data. So we treat it as your vitamin D3K2. It's a daily need that you have to tend to, like your daily water and your daily calories. You know, you need to provide it constantly at a reasonable level to your cells to maintain a healthy, efficient autophagy process. Thank you so much.

Yeah, it seems like it's a similar problem with rapamycin. In other words, you have a drug, rapamycin for longevity, let's say, you have a drug that has an outcome that you really can't test for. There are no markers for it. The side effects are rare or infrequent with rapamycin.

what dose do you take? And everyone goes back to Joan Manick's paper that they just came out of a weekly dose of six milligrams or so. And that's what stuck. And it sounds like it's similar with spermidine. In other words, we can't measure autophagy. So we don't know when it's working really. But I guess what you're saying is you work back from the daily dose that we know is required from nutrition and then the fall off would

aging of the gut and you know we're not able to harvest even if we eat enough we don't get enough so kind of projecting from that is that what you're saying? 100% and to your point about going back from the daily dietary intake the origin of why people even started looking into spermidine and its power in combat for

for or like to support longevity is because from epidemiological studies where people correlated high dietary intake of spermidine to a longer lifespan. So I was talking about the blue zone, but in general,

There's several studies from different groups, so it's independent studies that have shown that higher dietary intake of spermidine was correlated to a lower mortality from all cause of mortality and was linked to an extension of lifespan in humans. So epidemiological, I'm not saying supplementation here, from a

five to 10 years of extended lifespan of people that have higher spermatin in their daily food. And so, because this data triggered the very,

first studies into trying spermidine and actually supplementing it. We always recommend to follow those dietary amounts. But again, like in all in modern organisms,

They don't follow exactly the dietary amounts. Also, the food is different from animals, but like in mice, in flies, in worms, supplementing with spermidine in those organisms has definitely improved.

shown an extension of lifespan in all those organisms from 5 to 20%. So it does extend lifespan in model organisms and it's correlated in epidemiological studies in humans to an increased lifespan as well. So

So that's where the amounts come from when we recommend a daily dosage, especially at Longevity Labs, because I don't want to talk about there. There are a lot of people selling supplements at much higher dose, especially synthetic spermidine. I would tell people to stay cautious and not use those amounts because those are not what comes out of the literature and of the data we have. Also,

We have clinical trials that have been done with our product directly at the amount of dietary intake from two to six milligrams that have shown beneficial effects for cognitive function, but also we've seen improved immune response to some vaccines. So this is why we choose those amounts because we have the data and that's

That's what we're driven by. It's the amount we recommend. And talking about animal longevity studies, I always love the interventions testing program that we've talked about on this show a little bit with three mouse populations. They're wild type mice and they famously rapamycin is the one that blew it out of the water. But they've tested all sorts of things. I wonder if spermidine been tested there?

So, okay, so that's a good point. I think it was in the first, before I joined the whole field, I heard that it was in the process of being tested in the ITP. And I don't know if it had been tested originally,

But the dosage was not right, if I remember correctly. And so the very first trials, they didn't get it through the full testing, if I'm not mistaken. So that would be something that I would love to see, like the correct dosage for mice, definitely, to see the benefits for sure for extension of lifespan. Because it's sort of been shown in many different studies in different organisms. So

I would imagine that we could see very positive results if it was done at the proper dosage through the ITP. So yeah, that's definitely something we'd love to see. - Yeah, and Matt Kaeberlein up in Washington has his worm bot project where they do sort of like an ITP intervention testing program, but instead of using mice, they use worms, flat worms, basically C. elegans. And so the whole experiment is compressed

instead of three years, it happens in three weeks and it's all automated with AI, but you know, he, they'll test any, any compound at all with that. Maybe I should reach out and look into it. Yeah, definitely. Yeah. Tell him I said hi. And you mentioned vitamin D. Obviously if I have low levels of vitamin D, we could test for it and

their symptoms or anything. Are there symptoms of low levels of spermidine that we should watch out for? We talked about

Is there any effects that we go, oh, he's obviously low on spermidine. Let's give him spermidine and that gets better. Or is it more a generalized metabolic health thing? I think it would be the latter for sure. It would be hard to pinpoint just at spermidine now, I can tell you.

that because we've had a lot of feedback throughout the years of having people using our supplement, we definitely get a lot of feedback, especially in people that are over 50, that when they start supplementing after one, two months, they get a boost in energy, they sleep better. And the one thing that people notice the most because it's easier to pinpoint and it's a visual effect and it's going to be the nail,

the hair, and sometimes the skin as well. Like stronger nails, they're going to grow a little bit faster as well. Because I mean, those are the cells that are going to divide the fastest. So people notice those effects pretty easily. So

I would never tell someone that has brittle nails and feel tired, oh, definitely just your problem is going to be low spermidine. I think it's always a bit more complex than this. But definitely someone that is not too cautious about their diet is not supplementing with spermidine. I would highly always recommend to give it a try because it's

I doubt someone over 50 that would start supplementing with spermidine would not see a beneficial effect after like one or two months. Most people get a little boost in energy and they feel like a little fog can lift their

Again, it's all dependent on how healthy you are in the first place, right? Yeah. But like people over 50 can definitely see an added benefits from starting to supplement for sure. And so before we get into the supplement in particular, one last thing about food, could you just summarize the foods that have high levels of spermidine in them? Right. So at the top of the food is going to be wheat germ. Again, some people can have it daily, add it to their yogurt or...

What is it? Witcher? What is that? Witcher. Germ from wheat. Oh, wheat germ. Sorry. I blame the accent.

That would be the highest source. Second higher source is going to be fermented soybean like natto, this traditional Japanese dish. Again, not a lot of people are going to eat that, but you're going to find it quite high level in soybeans, in nuts, cruciferous. You're going to find it in aged cheese quite a bit too. Yeah.

Again, in all foods, the healthiest food you can think of, that's where it's hidden. And I'm talking plant-based mainly. There will be some in meat as well, but it's not the most concentrated for sure. So plant-based food with legumes, nuts, crucifers is going to be your best bet to make sure you have enough sperm. And aged cheese, which is always a good thing to add to your list of things to eat.

All good things to eat. But to your point, as we age, even if we eat all those spermidine-rich foods, our gut may not be able to take it up. And we can still, with aging, we get lower and lower levels of spermidine. And we may not be able to overcome it with diet alone, and thus the need for supplementation. So

And also to know exactly how much you're intaking, because just my apologies for like just cutting you here. But one thing I wanted to have is like all those levels of spermidine in these foods, they come from very big average. But what we found is that they vary so much depending on the region where the food is found, the season of the year, because the plants are not going to produce as much. It's also a stress response for the plants. So, uh,

You're not even guaranteed to have this exact amount for any food, depending on where you get it and the time of the year. So you're actually pretty in the dark when knowing how much you intake. So supplementing, it gives you that confidence that you know how much you're getting at least.

Yeah, yeah. And with supplementation, it's kind of the Wild West out there, right? With all the different companies. And your company makes spermidine supplements. So talk about how you differentiate between different supplements that are on the market and what people need to watch out for when they purchase spermidine for supplementation. Definitely the first thing is

I would not advise people to use synthetic spermidine just because the amount is not very well controlled. The way it's done also, it's only spermidine. What we do is we extract from

from with germ, a water-soluble extraction that doesn't use any solvents or other harsh chemicals. And there is actually a spectrum of other polyamines. So just to go back, spermidine is called a polyamine. It's still a small molecule, but it has several amino groups, hence the name. But it actually comes with two other mainly that are always together, which are putrescine and spermin.

And we don't know the effect of just supplementing with spermidine in humans. And we don't think that it would have the same effect as just supplementing with the spectrum of it. Now, other thing to look forward to, we regularly test all the supplements out there in the market. And I can tell you, we rarely found a supplement that has the amount it says it has. So be mindful of that. A lot of the,

The effort that we put in the company is constant analysis screening, whether it's from the wheat germ we use to extract the spermidine, but also the final product. So we ensure the amount of spermidine in the supplement.

And we, just by experience, we see regularly that the amount you think you get is not the amount that's in there. Like it's just almost never happens. And that's unfortunate. And that makes the whole supplement world very scary sometimes because you're... Can you hear me? Yeah, yeah. They just kind of dropped off. Oh, sorry. It's going to come back. Sorry about that. No worries. I think I must have bumped my camera.

No worries. We'll edit it out or maybe we won't. I don't know. We'll leave it in. Yeah. Yeah. Oh, okay. So yeah, just be mindful out there of supplements that are synthetic and, and,

that don't really have a good reputation of being very diligent with the science. I think one of the things that made me very enthusiastic in joining the Longevity Labs team is that this company really is a spin-off of the University of Graz, where Professor Frank Maddow, which is this professor that really has a ton of experience

publication out there linking spermidine to autophagy and to the health benefits in humans that's where it came from so there's a lot of science scientific diligence and and testing behind it that we're really proud of and that we always feel confident to to stand uh uh

nice so i'm at i'm at a i'm at a health food store i'm on amazon wherever i'm looking at a rack a row of all different spermidine manufacturers what can i look for in the label that tells synthetic versus your type of spermidine which is uh extracted from natural ingredients is there are there any labels or or

how do we tell, how do we recognize that? If he doesn't say from with germ or algae, you can also get some spermidine from algae, but it's, it's not as efficient. So most people are going to make it from which term, if you don't see from which term, then you most likely are looking at a synthetic form of it. Um, another thing is, um,

look for organic non GMO sources of wheat germ that can matter. Again, we test for common pesticides and herbicides. We know for a fact there is no glyphosate. Also, the company is in Austria, so we source our wheat germ from Europe.

from Switzerland, Germany and Austria. So we know where it's coming from. Non-GMO, no glyphosate or very little level. It's almost impossible to not see glyphosate anymore in this world. But there is almost none in the wheat germ we use. So be mindful of that too. Make sure it comes from a good source of wheat germ and

that where it's properly regulated for sure and you mentioned that you your company tests uh other competitors projects for products for purity and this sort of thing um obviously it's less valuable because it's a company testing your competitors but still it's better than nothing and uh it's it's useful information is that available on your website no it's not also because um

I mean, it's most internal data for us to stay up to date of what others do and like compare our production

efficiency and to others. So it's kind of us doing our due diligence of our own manufacturing process, but we don't share this data. Actually not currently, but yeah, maybe that's something that could be done in the future for sure. But again, it comes into a gray area where you start becoming

in a negative lens of the brands directly. It's kind of a bit of a yeah, you don't trash other people, certainly. And that can be negative in itself. So basically, with aging,

Everyone is going to face a deficit, nearly everyone as they age. When should people start taking this? What dose should they go at and how do they know what dose to evaluate? How do they know when they've had too much? What are your recommendations on that? Or too little for that matter? Right.

Our very first supplement starts at 1 mg of daily dose. So you're very, again, remember our dietary intake daily is anything between 6 to 12, 15. 15 is a bit ideal diet. So 1 mg is your entry dose daily.

That's a minimum. I would recommend people to start at least two or three milligrams per day and to start anytime after 25. I mean, you start aging pretty early in life and we know that the levels start decreasing from the very first, like late twenties and post.

Not perfectly linearly, and again, it's going to depend on the tissue, but it decreases as soon as the body starts aging. My recommendation still, I think when you're still in your 20s, you should be fine. There's nothing wrong in still supplementing and being proactive. Definitely in your mid-30s, I think it starts becoming a very valuable supplement. Definitely after you're 40, I would recommend anyone to start supplementing to get beneficial effects.

The best thing that people could do would be to go up to six milligram daily. And the only reason I'm saying this is because that's where we do all our clinical trials right now. So we know the health benefits on cognitive function, immune response, blood pressure. All of this is done currently with our product at six milligram.

We manufacture in Europe and we have the European Food Safety Agency NOVA food approval. It's the equivalent of the grass status. In the NOVA food approval, they recommend the maximum dose of supplementing on top of a daily diet at 6 mg.

Technically, we shouldn't tell people to go above 6 mg. Definitely should be safe up until 10 mg, 12 maybe. But I would recommend someone to kickstart their journey in supplementing to start at between 3 and 6 mg daily dose. I think you should start seeing benefits after a month or so.

couple of weeks, some people start seeing effects almost the very first day about sleeping and we're not exactly sure what that would be. It could be related to cortisol levels because spermidine helps decrease cortisol levels. That's not really clear. It could also be from the autophagy process that it's kicked up.

But you will definitely see effect after a month if you supplement consistently. So that's the thing. The trick here is it's not a one time a week shot. You have to take it as a maintenance thing. Like you would shower every day. You should be taking your supplement every day. And I don't know if there's any data on this there. There may not be, but if I started 30, let's say with three milligrams, um,

How do I know if my spermidine bioavailability becomes less and less due to dietary sources over age? When do I change that three milligram? Do I wait till I'm 40, 50, 60, 70? Or we don't know, right? We don't know. And again, I would say three milligram for someone that just want to kickstart. But in reality, because it's safe, because it's in the dietary limit, the best thing you can do is start now.

at the maximum dose allowed by the European Union, at least, would be six milligrams daily. There is no negative side effect known for supplementing with spermidine at this level. So you could definitely start at six milligrams and stay at it all the time. Yeah, and I want to be respectful of your time. One last question that I have to ask about is...

The interesting use of these fasting memetics or these supplements that have the effect on mTOR and everything is that decreased appetite and all sorts of beneficial metabolic effects. And some of these are being used to transition people off GLP-1 agonists, you know, the Ozempic and things. So rather than a lifetime of Ozempic,

They can take Ozempic for a while, get their lifestyle in order, their diet, their strength training, their exercising, and then they taper it off, but they might increase something like spermidine on there. Are you seeing that in your population? You mean of people that would take Ozempic and start... Yeah, are they using spermidine as a kind of a way to wean themselves off the GLP-1 agonist? We don't really have...

that I know of, uh, people that have done both or use spermidine to transition out, but I would highly recommend someone to give it a go to transition out of a Zempik. Uh, spermidine has been shown in many studies to actually support, uh, weight loss, uh, because it promotes, um, thermogenesis. It promotes, um, it limits fat accumulation as well by, uh,

mean of the autophagy process as well. So it can actually be a powerful ally for someone that's already done because Ozempic is pretty strong. I mean, it's really going to stop your appetite here. And I don't think people should be on it forever. So definitely you can do it in parallel. There shouldn't be any contraindication, but definitely it should be a great ally for someone that's trying to get off Ozempic

to maintain the health benefits of autophagy and just weight loss for sure. And it supports metabolism. Yeah, well, this has been great. We're almost out of time. Is there anything we didn't cover that you wanted to talk about? Oh, not sure. No, I think...

I mean, the best thing people can do is just do their own research. Just go online, look at the scientific paper. The amount of evidence is always, I mean, it's amazing to me that I'm still, I feel like I will never be able to go through it all during my lifetime. So just like go look at the data. It's the best thing you can do to find your information. And yeah, just go.

Just look out there for new paper. We have clinical trials that results that will come up shortly that will show beneficial effects also on reducing depression symptoms through the cortisol axis here and the immune response, also vaccines. So just look out for the data is coming up and pouring out every week with spermic research for sure.

And Melissa, tell people how they can reach you and reach your company. We'll put it in the show notes as well, but go ahead. Yeah, thank you. So you can find our products and we have a lot of scientific products.

data available blog. I try to write regular blogs about the newest research in different topics related to spermidine beneficial effects on health. You can find it at spermidinelife.us. You can order there also the supplements. You can also find our products on Amazon, but definitely check us out on spermidinelife.us and spermidinelife on Instagram as well. We have like some, some posts regularly, I think coming up. So yeah,

And to be clear, I want to emphasize, even though the company is out of Switzerland and the EU, this product can be, it's available in the US also. So our US audience can order it as well. See, that's where I'm not a good sales rep. I'm like the scientist of the house. Yes, the company is available.

The company is based in Austria, but we have a little branch here in the U.S. and we're based in Colorado. So we're always available to talk whether about science or just products in general. There's always people in the U.S. to talk about it. So, yeah. Well, this has been a wonderful conversation. You've been a great guest, Alyssa. Now this will be your third podcast, right? No, that's my second. Your second? Oh, my goodness.

Well, you knocked it out of the park. Thank you. It was great talking to you. We'll definitely have you back again. Thanks so much for talking with us and thanks for the work you're doing. Thank you so much for having me. It was a pleasure. If you are enjoying this program, please hit that subscribe button or even better, leave a review. Your support makes it possible for us to create the quality programming that we're continually striving for.

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