Health Longevity Secrets

Spermidine: The Autophagy Activator with Dr Melissa Cano

• Robert Lufkin MD • Episode 212

Share episode

As we near the end of the school year, I'd like to give a shoutout to Mr George Gaskin's 7th grade history class at Harvard-Westlake School who are fans of this program. 

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

Biochemist Dr. Melissa Cano takes us deep into the fascinating world of cellular metabolism, explaining how this small but mighty molecule could be 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 gut microbiome, and 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 people with higher dietary spermidine intake live 5-10 years longer on average. In lab studies, supplementation extends lifespan in multiple organisms by 5-20%. A groundbreaking 2024 study in Nature Cell Biology even revealed that spermidine mediates many of fasting's benefits—suggesting this molecule could be a natural caloric restriction mimetic without the hunger.

Whether you're already familiar with longevity compounds like rapamycin and 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 the missing piece in your longevity strategy.

This episode is sponsored by SpermidineLife whose products are mentioned in the program.  Use promo code ROB15 for discount. 

https://spermidinelife.us/products/spermidinelife-extra-dietary-supplement?utm_source=Lufkin&utm_medium=podcast

Lies I Taught In Medical School : Free sample chapter- https://www.robertlufkinmd.com/lies/
Complete Metabolic Heart Scan (20% off 'LUFKIN20') https://www.innerscopic.com/
Fasting Mimicking Diet (20% off) https://prolonlife.com/Lufkin
At home blood testing (20% off) https://siphoxhealth.com/lufkin
Mimio Health (15% off 'LUFKIN') https://mimiohealth.sjv.io/c/5810114/2745519/30611

Web: https://robertlufkinmd.com/
X: https://x.com/robertlufkinmd
Youtube: https://www.youtube.com/robertLufkinmd
Instagram: https://www.instagram.com/robertlufkinmd/
LinkedIn: https://www.linkedin.com/in/robertlufkinmd/
TikTok: https://www.tiktok.com/@robertlufkin
Threads: https://www.threads.net/@robertlufkinmd
Facebook: ...

Speaker 1:

Dr Melissa Kano is a biochemist and molecular biologist with a passion for cellular metabolism and biotechnology. Over the past 15 years in academic research and development, she's focused on developing innovative and sustainable bioproducts. Now, as director of science at Longevity Labs, she leads global research collaborations and drives innovation to translate cutting-edge science into practical solutions for health and longevity. Hey Melissa, welcome to the program.

Speaker 2:

Hi, thanks for having me, rob.

Speaker 1:

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.

Speaker 2:

It will come out as it will come out.

Speaker 1:

There is no rehearsing here, 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.

Speaker 2:

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, my actual specialty was photosynthesis in algae and plants and and yeah, I've been doing it for most of my career. I loved it.

Speaker 2:

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 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 I've 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.

Speaker 1:

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.

Speaker 2:

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.

Speaker 1:

So especially as a woman. I feel like there's a little bit of reckoning like, okay, this is happening. Oh yeah, so, so let's, let's start with what. What exactly is spermidine?

Speaker 2:

It has a funny name, so what is?

Speaker 1:

it, where does it come from and why should we care?

Speaker 2:

Absolutely Spermidine. It's a very small molecule, like very small. It's 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.

Speaker 2:

So autophagy 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 cell 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 is the cell inside itself that is going to encapsulate all the damaged components old proteins, old organelles like 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 anew. 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.

Speaker 1:

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?

Speaker 2:

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 lingual organism, organism, so in all the foods you ingest. Some foods and we can get into it later have more spermidines than other. But one third of your need come from food. Another third come from your gut microbiome, so your bacteria and your guts are able to produce quite a bit of spermidine, and so and this pass 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.

Speaker 1:

So you can make it.

Speaker 2:

you have to ingest a little bit of it though, because otherwise you're not going to have enough.

Speaker 2:

So that's why we 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 I mean 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 have a lot of spermidine compared to the other food. 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 a lot, it would be Ouija, and that's what we made a supplement from is from Ouija, which is the highest source of natural spermidine that we can find in the natural world.

Speaker 1:

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

Speaker 2:

Sorry, we may talk about it again.

Speaker 1:

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 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, we change our diet, we turn mTOR down, we turn on autophagy, we. You know other lifestyle things. What are the? How do we measure autophagy? And if we want to measure glucose, we could do a hemoglobin A1c or a fasting glucose. But autophagy, what are the surrogates? Or what are the what? How do we know we're even in autophagy? Right, Right.

Speaker 2:

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 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 involves a bunch of different components, some that that we know very well, like there I mean I'm 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 1 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 um, uh little uh 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 an internal process inside a cell that is not that easy to track, but it's. 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. I don't even see how we could do an easy sensor for people to measure autophagy easily.

Speaker 2:

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 a bit 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. It's a bit more complex than this because the cells are going to take it pretty easily from the bloodstream the QRS.

Speaker 2:

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 triggering autophagy. 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 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 spermidine. So it gets all very complicated to just track it, as is as a marker of autophagy, because it gets uh, metabolized.

Speaker 1:

Basically, yeah, and before we leave, autophagy. It is such a such an important concept. It's amazing to think that. You know, the nobel prize was just given on an autophagy. Uh, you know, about 10 years ago to the japanese research.

Speaker 2:

Yeah, 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. Inside of a cell, which I always try, and it's like impossible to really grasp how many molecules, chemical reactions happen at once. But if you don't get rid of all the junk that accumulates in an enclosed space, 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.

Speaker 2:

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. 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 an insane array of field it's been looked into and how it impacts health, because it's such a central cellular process.

Speaker 1:

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?

Speaker 2:

We do know again, like we know what we know, there's probably in additional connection that are still a little bit to completely decipher, but 100% mTOR, ampk 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 AMPK 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.

Speaker 1:

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 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?

Speaker 2:

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 rates 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 dream is to have a. Could we make a biological clock with your internal levels permitting? 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.

Speaker 1:

So our spermidine age is coming, but not yet. Well, 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?

Speaker 2:

So the only data we would have about synergistic effect would be really spermidine and 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 things and I know we're very different. I'm not an MD. I'm a PhD scientist. I'm not an MD.

Speaker 1:

I'm a PhD scientist.

Speaker 2:

So and I'm always a little bit cautious about molecule that are not natural. So I'm always and that's also because I don't take a lot of supplements so 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 a notch to to improve the autophagy process.

Speaker 2:

You're not going to have any of the side effects that some people can have when taking rapamycin, like 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 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 the base level to to for optimum autophagy. So I wouldn't overdo, I wouldn't do it on top of of of an m m taurine activator or mpk activator, if you're already doing it. Um, just because there's no data and and I'm not an md- but.

Speaker 2:

I will leave you to recommend to people what they should be doing.

Speaker 1:

You're 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.

Speaker 1:

Yeah, I mean with metformin the usual side effect is GI. On that, you know, 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. But yeah, and to your point, as it turns out, you know, 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 yeah, it's just your body.

Speaker 2:

It's not used to intake it every day, so there could be some side effects to it. The the I would say spermidine would be more on the gentler, more gentle, uh, trigger of autophagy and the natural route because you're already intaking it now. I 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 your best and no negative side effects. Route to triggering autophagy that would be my take on it.

Speaker 1:

And yeah, it's such a great point you bring up. Then I wonder so how about someone who is turning down mTOR and up AMP kinase with intermittent fasting? Should they avoid spermidine also? Do you think no, absolutely not.

Speaker 2:

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 of spermidine actually increase. So you self-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.

Speaker 2:

So when you fast, if you supplement with spermidine, you actually ensure that you get the benefits, the benefits from fasting, 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, 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.

Speaker 1:

Yeah, and I love that. 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 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? 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?

Speaker 2:

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.

Speaker 2:

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 if you were to supplement with natural as 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?

Speaker 1:

No, I haven't heard. Heard, I don't know, 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 a higher dose you get a completely opposite effect.

Speaker 1:

It reminds me of what happens with the mTOR inhibitor rapamycin which, at low dose, what happens with the mTOR inhibitor rapamycin which, at low dose basically a weekly dose which is what longevity enthusiasts do you know 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 powerful, most powerful immunosuppressants. So it's FDA approved for organ transplants and renal cell.

Speaker 1:

So it's interesting with that and that's obviously it's not specifically autophagy, but it's clearly a dose response effect that has completely different, uh, different things going on with that.

Speaker 2:

That's why I would always recommend to stay, say, for example, spermidine. Just to go back to, because those are the numbers, I know more. A daily dietary intake of spermidine can range between 6 to 15 milligram per day in diet right, yeah, depending on what you eat.

Speaker 2:

Right, like, say, blue zone, eat very healthy, you're going to get probably around 15 milligram, 15 not great diet maybe around six milligram, five, six milligram, so um. So from the data we have and the studies that have been done in human again like specifically in human, I would not go over daily supplementation of spermidine above six milligrams. Some people you probably can go safely up to 10 milligrams 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 gonna look like, and and we do know from pre-clinical 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 let don't do it too much. Do it in in the range of maybe two, two times the dietary intake. That that would be the cautious way I would.

Speaker 1:

I would go yeah, and there's no, no evidence or value or variation, and doing um weekly doses rather than daily doses like rapamycin, is there any so?

Speaker 2:

actually the probably there is no data to compare both, but again, it's very different from rapamycin because you're they, you have daily needs of spermidine and you produce it constantly. So the 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 D3, k2. As your vitamin D3K2. It's a daily need that you have to tend to, like your daily water and your daily calories. You need to provide it constantly, at a reasonable level, to your cells to maintain a healthy, efficient autophagy process.

Speaker 1:

I mean 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. So 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. That's what stuck, and it sounds like it's similar with with spermidine. In other words, we can't measure autophagy. So we 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, dose that we know is required from nutrition, and then the fall off with aging of the gut and you know we're we're not able to harvest, even if we eat enough. We don't, we don't get enough. So kind of projecting from that.

Speaker 2:

Is that what you're saying? Yeah, a hundred percent. And to your point about uh going back from the daily dietary intake, the origin of why people even started looking into spermidine and its power 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 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 spermatin and actually supplementing it, uh, we've we always recommend to follow those uh dietary amounts. But again, like in all in uh modern organisms, uh, they don't follow exactly the dietary amounts. Also, the the food is different from animals but, like in mice, in flies, in worms, uh supplementing with spermidine in those organisms has definitely shown an extension of lifespan in all those organisms from 5 to 20 percent. So it does extend lifespan in model organisms and it's correlated in epidemiological studies in humans to an increased lifespan as well.

Speaker 2:

So it's um, 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 a 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. That's what we're like, uh, driven by. Like, this is the data that gets the the amount we recommend and you're talking about animal longevity studies.

Speaker 1:

I always love the interventions testing program that we've talked about on this show a little bit with the three mouse populations. They're wild type mice and they, you know, famously rapamycin is the one that you know, blew it out of the water. But they've tested all sorts of things. I wonder if spermidine been tested there.

Speaker 2:

So OK, 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.

Speaker 1:

Yeah, and Matt Kaperlein up in Washington has this WormBot project where they do sort of like an ITP intervention testing program, but instead of using mice they use worms, flatworms 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 so maybe I should, maybe I should reach out and look yeah, definitely yeah, tell him.

Speaker 1:

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 can 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?

Speaker 2:

I think it would be more. 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.

Speaker 2:

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 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 Again. It's all dependent on how healthy you are in the first place, right.

Speaker 1:

Again, it's all dependent on how healthy you are in the first place, right, 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?

Speaker 2:

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 that would be your high.

Speaker 1:

What is it witcher? What is that?

Speaker 2:

wheat witcher germ from wheat oh wheat germ.

Speaker 1:

Okay, sorry, I'm sorry, I got it. I blame the accent that would be the highest source.

Speaker 2:

Second higher source is going to be, uh, 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 a high level in in soybeans, in nuts cruciferous. Uh, you're going to find it in aged cheese quite a bit too. Um, again, in all 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 to to add to your list of things to eat all good things to eat, but to your point, um, as we age, uh, even if we eat all those spermidine rich foods, our gut may not be able to take it up, and we can still.

Speaker 1:

With aging, we we get lower and lower levels of spermidine and we may not be able to overcome it with with diet alone, and thus the need for supplementation.

Speaker 2:

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.

Speaker 2:

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 the plants are not going to produce as much. It's also a stress response for the plants, so 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.

Speaker 1:

And said 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 when they purchase uh, spermidine for supplementation definitely the first thing.

Speaker 2:

I would not advise people to use synthetic spermidine um just because the amount is uh not very well controlled, the way it's done. Also, it's only spermidine. What we do is we extract um from with germ, a water soluble extraction that doesn't use any um 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 group, hence the name. But he actually comes with two other mainly that are always together, which are putrescine and spermin.

Speaker 2:

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, of that, a lot of the um, the effort that we put in the company is um constant um analysis, uh screening whether it's from the wheat germ we use to extract the spermidine, but also uh the final product. So we ensure the amount of spermidine in the supplement and and we just by experience with 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?

Speaker 1:

Yeah, yeah, it just kind of dropped off.

Speaker 2:

Oh sorry.

Speaker 1:

It's going to come back. Sorry about that, no worries.

Speaker 2:

I think I must have bumped my camera, no worries.

Speaker 1:

We'll edit it out, or maybe we won't, I don't know. We'll leave it in.

Speaker 2:

It's okay. As long as you can still hear me.

Speaker 2:

Yeah, yeah, oh, okay, there, okay, I'm back so yeah, just be mindful out there of um 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 spinoff of the University of Graz, where Professor Frank Maddow, which is this professor that really has a ton of 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 testing behind it that we're really proud of and that we always feel confident to stand behind that's nice.

Speaker 1:

So 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 extracted from natural ingredients? Are there any labels? Or how do we tell? How do we recognize that?

Speaker 2:

If it doesn't say from wheat germ or algae. You can also get some spermidine from algae, but it's not as efficient, so most people are going to make it from wheat germ. If you don't see from wheat germ, then you most likely are looking at a synthetic form of it. Another thing is 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.

Speaker 1:

Make sure it comes from a good source of wheat germ 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?

Speaker 2:

no, it's not. Also because, um, I mean, it's it's most internal data for us to stay up to date of what others do and like, compare our production, um, uh, 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. Um, actually not, not currently. But yeah, maybe that's something that could be, that could be done in the future for sure. But again it comes into a, a gray area where you, like you know you start becoming in a negative lens of the brands directly it.

Speaker 2:

It's kind of a bit of a yeah you don't want to trash other people certainly, and that can be negative in itself.

Speaker 1:

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?

Speaker 2:

Or too little for that matter. Right, our very first supplement starts at one milligram 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 one milligram is your entry dose. That's a minimum.

Speaker 2:

I would recommend people to start at least two or three milligram 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 20s, and 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. I would recommend anyone to start supplementing to to get beneficial effects. But the best thing I can, uh, that people could do would be to go up to six milligram daily. And 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 and also because, uh, so we manufacture in europe and we have the european food safety agency, novel food approval, so it's the equivalent of um grass, the grass status, let's say, and it's the. In the novel food approval they uh recommend the maximum dose of supplementing on top of a daily diet at six milligrams. So technically we shouldn't tell people to go above six milligram. Definitely should be safe up until 10 milligram, 12 maybe. But I would recommend someone to kickstart their journey in supplementing to start at between 3 and 6 milligram daily dose.

Speaker 2:

I think you should start seeing benefits after a month, a couple of weeks. Some people start seeing effects almost the very first day about sleeping, and we're not exactly sure what would that would be. Could be related to um, to cortisol levels, because spermidine helps decrease cortisol levels, um, when that's not really clear. 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.

Speaker 1:

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 start at 30, let's say, with three milligrams, um, how do I know if it, if my spermidine available bioavailability becomes less and less due to dietary sources, over age, when do I change that, that three milligram? Do I wait till I'm 40, 50, 60, 70 or we don't know?

Speaker 2:

right it's yeah, we don't know. And again I would say three milligram for someone that just want to kick start. But in reality, because it's safe, because it's in the dietary limit, the best thing you can do is start at the maximum dose allowed by the european union. At least it would be six milligram daily. There is no negative side effects known for supplementing with spermidine at this level, so you could definitely start at six milligram and stay at it all the time yeah, and I want to be respectful of your time.

Speaker 1:

One, one last question I have to ask about, uh is, um, uh, the the interesting use of these, these fasting memetics, or these, these, 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, 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, they might increase something like spermidine on there to do. Are you seeing that in your population, are you?

Speaker 2:

You mean of people that would take Ozempic and start.

Speaker 1:

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 agonists?

Speaker 2:

We don't really have that. I know of people that have done both or used spermidine to transition out, but I would highly recommend someone to give it a go to transition out of a Zempik. Spermidine has been shown in many studies to actually support weight loss because it promotes thermogenesis. It promotes, it limits fat accumulation as well by 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 gonna stop your uh, 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 who is trying to get off Ozempic to maintain the health benefits of autophagy and just weight loss for sure, and it supports metabolism.

Speaker 1:

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?

Speaker 2:

Oh, not sure. No, I think. Uh, 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 to to go through it all during my lifetime.

Speaker 2:

So just go look at the data. It's the best thing you can do to find your information. And yeah, just look out there for new paper. We have clinical trials 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 vaccine. So let's just look up, for the data is coming up and pouring out every week, with spermidine research for sure and melissa, tell people how they can uh reach you and reach your company.

Speaker 2:

Yeah, so you can show notes as well, but go ahead.

Speaker 2:

Yeah, thank you uh, so you can find our products and uh, we have a lot of um scientific um 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 at spermidinelifeus. You can order there also the supplements. You can also find our products on amazon, but definitely check us out on spermidinelifeus and spermidinelife on instagram as well. We have, like some, some posts regularly, I think, coming up, so and to.

Speaker 1:

To be clear, I want to emphasize even though the company is out of switzerland and and the eu, this product can be, it's available in the us also so our us audience can order it as well.

Speaker 2:

Yeah, see that's where I'm. Not that I'm not a good uh, I'm not a good sales rep, I'm like the scientist of the house.

Speaker 1:

Yes, the company is based in Austria.

Speaker 2:

The company is based in Austria, but we have a little branch here in the US 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 US to talk about it.

Speaker 1:

So yeah, Well, this has been a wonderful conversation. You've been a great guest. Melissa, now this will be your third podcast, right.

Speaker 2:

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.

Speaker 1:

We'll definitely have you back again and thanks so much for talking with us and thanks for the work you're doing.

Speaker 2:

Thank you so much for having me. It was a pleasure.