Spermidine: The Longevity Supplement I Take Daily
Spermidine is one of those compounds I've known about for a while, but it doesn't get much attention. It sits in this weird middle ground. Not quite a normal supplement like fish oil or a multivitamin, and not quite a peptide either. I take it daily, and I want to walk you through why.
What Spermidine Actually Is
Spermidine is a polyamine. That means a small, positively charged molecule found in nearly every cell in your body.
It helps with cell growth, stress response, immune signaling, and gene activity. Your body makes it and breaks it down, and that balance matters. When it gets disrupted, usually from oxidative stress as we age, it correlates with chronic diseases like cancer and heart disease.
Fun fact on the name. It was first discovered in semen, hence "spermidine." But it's found throughout the entire body. If it had been discovered in the finger first, we'd be calling it fingerdine.
How It Works
There are three main mechanisms.
Autophagy (cellular cleanup). Spermidine triggers your cells to clean out damaged parts, like a recycling program. It does this by blocking a protein called EP300, which normally puts the brakes on cleanup. Less EP300 activity means more cellular recycling and better cellular energy.
Protein production control. Spermidine activates a molecule called EIF5A, which boosts production of TFEB. TFEB is a master switch for the cell's recycling centers. This chain reaction shows up across many species.
mTOR dialing. Spermidine dials down mTOR, the sensor that tells cells whether to grow or clean up. Lower mTOR puts the body in cleanup mode and longevity mode. Higher mTOR puts you in anabolic, muscle-building mode.
That last point matters. Spermidine basically mimics a fasting and caloric restriction signal. Spermidine levels naturally rise during fasting, and that rise appears required for the longevity benefit.
If your only goal is putting on as much muscle as possible, spermidine might not be the right tool. But if you've already got muscle on your frame, your hormones are dialed in, you're training hard, and you're using peptides, spermidine fits well into the longevity side of the equation.
What the Human Data Shows
Human evidence falls into two buckets. Observational studies and intervention trials.
Observational. People who eat more spermidine in their diet show around a 24 to 26% lower risk of dying from any cause. They also show lower cardiovascular risk and slightly lower blood pressure. That's a meaningful correlation.
Intervention trials. Here it gets murkier. A small three-month memory trial showed promise. A larger 12-month trial at 0.9 mg per day showed no significant memory benefit, and blood spermidine levels didn't change in either group.
The problem is the dose was tiny. I'd argue 5 to 10 mg is closer to where you'd notice something. Higher dose studies up to 40 mg per day showed more benefit and no safety issues, but blood levels still didn't rise much. The body may just be using it up.
Dosing
Here's how I think about it.
Low dose (0.6 to 1.2 mg per day). Typical wheat germ or plant extract amount. Well tolerated, probably too low to do much.
Moderate dose (5 to 10 mg per day). This is my sweet spot. Some cognitive improvements reported here.
High dose (15 to 40 mg per day). Purified spermidine. Safe in short-term trials in healthy men. I personally wouldn't go to 40 mg.
I notice a benefit in energy and clarity in that 5 to 10 mg range.
Side Effects and Cautions
Pretty reassuring so far.
The minor signal is muscle and joint issues. Some people in supplementation trials reported joint stuff slightly more than placebo.
There's also a possible B12 depletion signal, similar to metformin. In the dementia food trial, the higher dose group showed a decrease in vitamin B12. Not proven causal, but worth mentioning. Just keep B12 replenished.
Who should be careful. Pregnant or breastfeeding women. Anyone with active cancer or high cancer risk. Polyamines are elevated in many cancers. That doesn't mean polyamines cause cancer, it could be the body's reaction trying to fight it off, but it's worth flagging.
How It Fits With Hormones and Peptides
Androgens affect polyamine pathways, so there could be some synergy with TRT.
With HGH and IGF-1 peptides, you're stacking an anabolic signal against an autophagy signal. I'd time them apart. Take spermidine in the morning, take your GH at night. You don't want two opposing signals fighting each other.
Immune peptides like thymosin alpha-1 might pair well with spermidine since they're doing related things on the cellular health side.
My Take
Spermidine has strong mechanistic science behind it and promising observational data. The clinical trial signal isn't overwhelming the way it is with, say, a GLP-1 peptide. You can't say definitively "this does X."
But higher spermidine levels correlate with better longevity, period. The supplement is low risk and potentially very beneficial long term.
I use the capsule form. The one I take is BioStack Labs NAD Regen, which has 5 mg per serving along with a few other ingredients. Works really well for me.
If your priority is living long, staying strong, and performing well for decades, spermidine earns a spot in the stack. I've never had a day where it crashed my energy, and it feels like it's doing real work on the autophagy side. That's good enough for me to keep taking it daily.
Full transcript click any paragraph to jump video
Hey everybody, this is Hunter Williams. I hope you're doing amazing wherever you might be in the world. Today's video is going to be all about a little compound known as spermidine. This is one that I've actually known about for a while. And honestly, it kind of lays more on the normal supplement side of things. As you guys know, I tend to talk more about peptide stuff, but in a spirit of doing more content around things that I'm passionate about in the supplement world. This is one thing that i've kind of been geeking out on lately. One, just because I use it on a daily basis and two, because i think it's something that not all the people know about.
It doesn't get a ton of love because it kind, of it,s in, the biohacking world but it exists kind. Of like not so much with the normal supplements like your multivitamins and fish oils but, it is also not, so, much, with, a peptides but I think there's benefits to taking it Obviously in the clinical arena, we don't see as much because it's relatively a newer compound compared to some of the other supplements like creatine and fish oil that have been around for decades. Nonetheless, I think it is very important for people to know about it.
And so I'm going to make a video today on it, but it exists kind of like in this longevity slash autophagy side of things. So it was going be less on the performance, muscle growth, fat loss side of things and more on the autophagy, resilience, longevity, kind of life extension side things, which is really cool because I think we can get a good mix of both and we have so many different compounds that allow us to do so. So that's what we're going to talk about today. As always, make sure you are on email list and I don't say that just to spam you. Honestly, at the time of this video, the week that I'm filming this, my Spotify was actually taken down earlier this week.
Fortunately, I was able to get it back within 24 hours. but it was taken down for quote, harmful and dangerous content. And so just make sure you're on the email list because if I get taken on off of every and any platform, that's the way that I can communicate you and communicate with you. and it's, the one channel that, I owned that. I, can't at least for now get taking down off. So make, sure on email lists, obviously to check out the Accion Collective from my private group. You have access to me in there to be able to ask me any questions you want. Obviously much more important than that you have, access the community. so without further ado, i'm going to share my screen and today we're going, to talk and learn about spermity.
Alright, today we're going to talk about spermidine. What it is, what it does, and is it worth taking, or is just another supplement that you're gonna waste your money on? We'll find out. Just go over, we'll talk what speridine is. We're gong to go through some of the animal studies, then we go to some human studies. There's not so many human study, but we do have correlative evidence around sperminate intake and what that can do for longevity. And we can kind of extrapolate from there, at least from what we know. Now, going into the background on spermidine, what is it? It's actually a type of molecule called a polyamine, which means that it's small, positively charged, and found in nearly every cell in the body.
And so we have speridine just about in every single cell of the What it does, it helps with cell growth, stress response, and immune signaling, as well as gene activity. So it has a host of different functions in the body. And our body basically balances how much sperm need it makes and how it breaks down. When this balance becomes disrupted between how we actually make versus how many we break down and utilize, its linked to aging and diseases like cancer and heart disease. Basically, with the oxidative stress that comes from aging that we all experience, We come to this point to where the body doesn't have a balance of how
much it's making versus how it is breaking down and ultimately that leads to, not leads directly, but it has correlated with some of the chronic disease that most of us all suffer from. And then we look at the bigger picture. It actually did get his name, uh, because it was found in semen first. And so a lot of people think like, Oh, spermidine that has something to do with sperm. Not really, but that's where it came from. Cause it's first discovered in Seamen. Then we actually found it through the whole body. So it'd be kind of if you had like fingerdeen because of this discovered it in the finger first, But it is actually in other areas of the body,
that is where It comes from And it's less of a single target supplement and more of dial to dial in our body stress response system. And, it is one that is heavily regulated and hard to shift with a pill. So that's what makes spermidine unique to some other oral compounds, especially in the supplement world, is that it tends to move the needle more when we look at the body's stress responses than a lot of adaptogens or herbs or things of that nature. Now, let's get into how it actually works. And so there's three main pathways when you kind of look at the mechanistic nature of sperminine and how they play out in the body.
The first is going to be the autophagy. Everybody loves the buzzword autofagie. You've heard that probably on every podcast that you listen to. What does that actually mean though? Well, I call that cellular cleanup. So When we look at spermidine, it triggers your cells to clean out damaged parts like a recycling program. It does this by blocking a protein called EP300, which normally puts the brakes on cleanup. And so think of this protein EP 300 as something that's going to naturally tell your body to say, hey, stop doing autophagy.
Well, spermidine removes this protein. It blocks it. Doesn't remove it, but it blocks that. And then in doing so, it's going to lead to better cellular cleanup and better cell recycling. So when we have less EP300 activity, and it results in more cellular recycling and cellular energy. Now, when we look at protein production control, spermidine helps activate a molecule called EIFSA, which in turn boosts production of something called TFEB,
a master switch for the cell's recycling centers. This chain reaction is found across many species, but basically that's the next way it works. And then it also works on nutrient sensing around mTOR. So spermidine often dials down mTOR, which stands for mammalian target of rapamyosin. But this mTor, probably heard that too on a lot of podcasts, is a key sensor that tells cells to grow or clean up. The lower amount of mtor we have, the more the body's gonna be in cleanup mode and longevity mode.
And the, more mtor we, have the higher m-tor, we the have more it's going to be an anabolic mode, growth mode putting on muscle mode And so that's the balance we walk with longevity is having lower mTOR for longer lifespan or higher mtor for muscle growth, which in a way, if you think about it, is going to lead to longer life span too. And, so we don't want it to be too high. We don' want to it be to low. You've probably heard of something called rapamycin. This is also something that inhibits mTor and in doing so is in theory, A lot of times in practice too, helping with longevity.
But when we look at spermidine, it connects to mTOR because it basically is signaling to the body to be in a state of fasting and caloric restriction. Now, does that mean it's going to cause a ton of fat loss? No. When we take spermidine it is very analogous or very similar to fasting. to doing the things on the autophagy side of the equation, they're going to drive longevity. And one of ways it does that is by dialing down mTOR.
So it kind of inhibits mTor, not all the way, but to the point to where we will notice that there is less mtor in the body, to which we then kind exist more in this autrophagic spectrum. Probably you're thinking, is this something that I really want to do if I want put on muscle? Maybe not. And if putting on muscle is the most important thing, spermidine might not be something that you want to take all the time. However, I think if you kind of get to the point where you have the muscle on your body, you're hormonally optimized, or using peptides, your resistant training, and you are doing all those things, then spermodine absolutely exists and has a place in the world of longevity.
Looking at the mechanisms step by step, we have obviously spermidine intake. It blocks the protein EP300, activates EIFSA, and then that leads to TFEB, which then results in autophagy. And so from the time we take spermidine through those pathways, We are then getting autofagie. This has been confirmed across multiple species and lots of different research. The fasting connection is especially important because spermadine levels naturally rise during fasting. and so we're fasting. We're actually just endogenously raising sperminine levels and the rise in spermi appears required for lasting longevity benefit.
So we need this rise to get the benefits. It can't be something that we are just doing once every three weeks. Now, let's look at some of the benefits. Where do we see tangible benefits of sperminine? Because it's great to talk about it mechanistically, but what does it look like in a practice? Human evidence falls into two buckets. We have observational studies and then intervention trials. So let us look some at the data on observable studies first. This was done through dietary intake of spermidine, so it wasn't around spermidine supplementation, but people who eat more spermodine have around 24 to 26%
lower risk of dying from any cause. They also show lower cardiovascular risk and slightly lower blood pressure. So interesting there around spermidine that people just consume more in their diet, have around a 25% lower risk of dying from all-cause mortality, which is pretty cool. Now, let's look at actual supplementation. A small three-month memory trial showed promising results. but a larger 12-month trial of spermatine supplementation at 0.9 milligrams per day, which is not a lot.
We're going to see, we're gonna talk about the day. I think the dose is probably somewhere around five milligrams, but 0,9 milligram per, day but no significant memory benefit in blood sperminating levels didn't change in either group. And so again, through dietary supplementations, We didn' see blood levels change. In the smaller one we didn''t see significant memories benefit, It's a really low dose. Some people are taking up to 40 milligrams per day. I probably won't ever do 40 mg per Day, but 5 to 10 mg, definitely, absolutely. But that was one intervention study. Again, just to sum those up, when we do look at the higher dosing group, there was a little bit more benefit.
So 3.3 mg and then upto 40mg per-day. And up the 40 mgs perday, There was no safety issues, which is pretty cool. Now, when we talk about doses, the 0.6 to 1.2 milligram per day is the typical weep germ or plant extract supplement amount. It's well tolerated, but maybe too low to have any strong effect. The more moderate dose is going to be in the, you know, like five to 10, I would say at least two to ten. milligram per serving. And then you can get this from obviously food or supplementation.
There are some cognitive improvements seen in those moderate doses, but no placebo comparison. The high dose is going to be 15 to 40 milligrams per day of purified spermidine. It's been shown to safe in short-term trials in healthy men, blood levels didn't rise much. And so again, we probably would say 10 milligrams is the upper limit per day. But again it's still hard to measure blood spermidine levels. Then again the body may be using it and so it is harder to necessarily track that because it being metabolized. We look at side effects.
Very reassuring with side-effects so far. Minor signal is muscle and joint issues. So there have been people in the trials that use supplementation. They reported slightly more often to have joint issues than in placebo groups. This is one thing, you see this in metformin, probably some other longevity supplements too that we might not even realize is going on, higher depletion of B12. And so in the dementia food trial, the higher dose group showed a decrease in vitamin B-12, It's not proven causal, but worth mentioning alongside, you know, things like metformin.
Just make sure you're replenishing B12. And then again, at the high dose short term at 40 milligrams a day for 28 days in a healthy order of men, there were no adverse events. So we're probably good to go there. But again the question is at what dose can you get a benefit? And I personally notice a benefits in energy levels and I would say overall just kind of a feeling of clarity and feeling good around that five to 10 milligram. per day dosing. And then who should be extra careful? Obviously, I wouldn't take it if I was pregnant or breastfeeding. If you have active cancer or high cancer risk, polyamines are also elevated in many cancers.
Now, does that mean that poly amines cause cancers? No. It could be a reaction of the body to try to stimulate the immune system to fight off those cancers, however, when we look at spermidine, it is one of those compounds that exist with the polyamine. So Most likely we don't see anything that would cause a cancer but polyamines are correlated with higher higher levels of poly amines or correlated With cancer and we dont have a lot of data around drug interactions with spermidine, but I think you should be fine when you're taking it now, how does it fit with hormone and hormone replacement therapy and peptides.
There's not really any evidence of like supplementing with hormones or peptide, but I would just say androgens also affect polyamine pathways and growth context. So be aware of that. It could be synergistic with your androgen supplementation via TRT. Same thing with HEH, IGF-1, HE-H peptids, similar thing. Now, when we look at HE and IG-F1 that's going to be more on the anabolic side of the equation. And so just beware, okay, if I'm timing my spermidine, maybe I take my spermidine in the morning, and my HGH at night because they're going to have shorter half-lives.
And so when we look at how we don't want to, have two counteracting signals, because on the GH side, we're getting the muscle growth and the anabolism. On the spermidine side we are getting autophagy. So that's what I would do again. That's just me kind of spitballing how I sector this together. But there could be also, when you look the immune peptides, there can be a synergistic mix of those, or they could be redundant. And so they're doing similar things. If you look at like thymus and alpha one and thylalanine, they are doing some other things I think they find to take together. But as always, I know most of you guys are into the peptide and hormone scene.
So I wanted to throw that in there. But where does spermidine stand? We have strong mechanistic science behind it, promising observational studies. The clinical trials are kind of weird, and so I don't think the signal is strong enough to say there's an overwhelming amount of evidence like you would with a GLP-1 peptide. There's no debating that that's going to cause weight loss, right? But when we look at spermidine, some of the supplements, it's very hard to gauge. Like, is it doing something or is not? Anecdotally, I can say it is doing some thing. I think when you look the data we have, we can see it probably doing somthing. But also too, you don't have long term use of this.
So what we do know is that higher spermidine levels correlate with better longevity for a fact. And so as a supplement, it looks very low risk to take, but also potentially pretty beneficial in the wrong run. And, so it definitely has a research back to autophagy candidate. We can't, you know, definitively say like other things we have, again, It's not really been studied and put through a micro, micro like some of these other. So. That is it for the slides. And that is my overview of sperminine. So not a super comprehensive in-depth video, but it's pretty straightforward.
Most of the time you can get it in the form of a capsule. I do think there are some companies that sell it as a liquid that you could do it like a sublingual dropper or whatever, But I've used it In the Form of A Capsule. Believe the one I used is, it comes from BioStack Labs and it is in their product NAD Regen. There's a couple other ingredients in there, one serving that has five milligrams of and it seems to work really, really well when I've used that through the years. So I love spermidine, I think it's one of those things, probably something you would just, unless you're really really focused on muscle growth,
muscle grow, you could add in spermidine if you are much more in the camp of, hey, just want to live long, want live strong, good performance, be healthy for the long term. I would say, maybe you'll notice like a benefit within the first week or two of taking it and it probably will subside. But I will say, I don't think I've had a day that I have taken spermidine where I was completely crashed from an energy perspective. So it does seem to help there and seems like it's doing a lot from the autophagy side of the equation.
Thank you guys so much for tuning into this one. I just always want to make sure that you know at the end of these videos, even if you watch every single one, that my heart goes out with gratitude to you guys to get to do what I do as a dream come true to me. And especially with all the censorship and all of the weird stuff that happens, because I feel like my videos are pretty boring. To me, it's like I don't feel I'm saying anything super sensational that is censorship worthy. But hey, I guess it is one of those things we just exist in the world to which when you say something common, is a threat,
a guess. Just all the people that support me. Thank you guys so much that, support the work, you know, use my coupon codes at places, share this with friends and family, being on the email list. And obviously too, if you support through being through the private group, thank you, guys, so, much. Again, I plan on doing this for a very, very long time to come. So thank,you guys and I will see you in the next one. Peace.
