Speaker 1 (00:07):
You know, there’s a really interesting compound that occurs in nature, that occurs in several foods, and maybe one of the kind of hidden secrets to longevity that you need to know about. And I’m talking about spermidine. You may recall a term called autophagy. Autophagy actually means self-eat. In aging, there are essentially two ways a old cell is destroyed. One is called apoptosis. It literally explodes and spews everything all over the place. That’s actually a bad way. On the other hand, the opposite is called autophagy. An atophagy basically means, okay, everything in here is worn and old. Let’s recycle these components, buff them up and reuse them again. And it turns out the more you can induce autophagy and the less you induce apoptosis, the longer you live and the longer you live well. What does that have to do with spermidine? Spermidine promotes autophagy, not apoptosis.

(01:43):
So I wanna talk about spermidine. Now, stay with me for a few minutes because we’re gonna get a little nerdy and it’s gonna be kinda sciencey, but I promise you it’ll be worth it because you really wanna know about spermidine. Okay, spermidine is a naturally occurring compound. We actually make it. It’s part of a class of compounds called polyamines. In mice, oral administration of polyamines has been shown to repair their intestinal mucosa and reduce inflammation. In fact, if you’ve read gut check, polyamines increase intestinal alkaline phosphatase. That’s a really good thing to have. Here’s the fun part. Spermidine was discovered in human semen. Yes, that’s where it got its name. In 1678 by Anton Van Leyvanhok. Now it’s known to be present in all body cells. It can be created in tissue, but here’s the good news. It can be created by bacteria in our gut.

(02:48):
Now, as I mentioned, spermine’s cool thing is it, it induces autophagy. That’s the natural way we recycle cellular components. Now, fasting, if you’ve read my books, is a phenomenal way of creating autophagy. But spermidine will do this without fasting. How? Well, spermidine inhibits acetyl transferase. Now, this reduces acetylation, and it also inhibits MTOR, or the mechanistic target of rapamycin complex one. This activates the AMPK pathway, and actually starts up atophagy. So spermidine activates atophagy by inhibiting MTOR and activating AMPK. That’s how it works. There are a lot of other compounds that activate AMPK. One of them that you may have heard of is berberine. Another one that you may have heard of is metformin, the diabetic drug. But spermidine does it too. Now, how was this identified? Well, a study was done in yeast, and they found that if they gave yeast spermidine, it was correlated to the upregulation of autophagy genes in these yeasts.

(04:19):
It also increased the lifespan of these yeast. And if the yeast lacked autophagy genes, then it didn’t work. So they figured out the mechanism of how spermidine did what it did. So what does that have to do with the aging process? Here’s the good news. Spermidine has great anti-aging properties. So autophagy’s role in inflammation and lifespan is really important. It reduces apoptosis cell death. It actually changes lipid metabolism. It’s crucial for regulating lifespan. It’s affected by spermidine. There’s a university of GRAT study that showed improved mitochondrial function in the brain due to spermidine-induced autophagy. Spermidine actually produces mitophagy, which is the turnover and recycling of mitochondria. And if you’ve been following any of us, you know that brain aging is directly related to mitochondrial dysfunction in the brain. So the better your mitochondria are, the better your brain. It increases ATP production by the mitochondria, and it has the potential to actually reverse cognitive decline.

(05:48):
Here’s the good news. Spermidine crosses the blood-brain barrier. Unlike many other combines, spermidine can get to the brain to do its cool thing. What about lifespan? Well, these have been primarily done in mice, but old the fourth, there’s a human study coming up. Mice, age mice were given spermidate for six months. It had notable anti-aging effects. It reduced liver and kidney damage. It preserved cardiac tissue, which usually gets older and older in mice. And it actually robustly restored their hair growth. They got furrier and more radiant. Now, human studies, there was a 2018 study. There was a link between dietary spermidine and reduced mortality rates in humans. Yes, believe it or not, some humans eat a lot of spermidine and some humans don’t eat a lot of spermidine containing foods. And so these groups were compared. There was an independent predicting value. The association held true even after adjusting for factors like age, BMI, alcohol aspirin use, diabetes, metabolic syndrome, physical activity, sex, socioeconomic status, and diet quality.

(07:11):
And the study showed that there was lower cardiovascular and cancer related deaths, and the mortality rates were dramatically statistically lower in the study group that had more spermidine in their diet. So that sounds good. How about another cool study this time in mice? They wanted to know what would happen to mice if they were supplemented with spermidine in their water. So they took age mice and gave them spermidine for six months into their water versus normal water for the other group of mice. The mice age-related bald spots improved, their heart health improved, their telomeres shortening stopped, and the treated mice telomeres looked like younger mice telomeres, and telomere linked is another sign of aging. So lots of cool stuff, but the take home point is people who had a lot of spermidine in their diet did better than age match controls who didn’t have a lot of spermidine in their diet.

(08:21):
That’s pretty cool. Now, everybody has heard about rapamycin, and there’s a lot of folks trying out rapamycin for anti-aging effects. And just to be clear, rapamycin works on the same MTOR pathway that spermidine works on. Could you take them both? Since I was around doing heart transplant when rapamycin was developed, I can tell you that there is a risk benefit ratio with rapamycin. And quite frankly, I’m not willing to take that risk benefit ratio, and quite frankly, the dose of rapamycin for humans that safe has yet to be determined. And since I don’t have a heart, lung, kidney, or liver transplant, I don’t need to take rapamycin to keep rejecting my heart. Fasting has the same effect. Now, the combination of fasting and spermidine, now that’s what I’m interested in. So what are the practical applications behind all this? First of all, the bad news, as we age, spermadine production gets lower and lower.

(09:39):
So as we age, it’s more important to acquire spermidine from external sources. Now, there’s actually some rich sources of spermidine. Mushrooms are probably number one. Cauliflower and broccoli are right up there. My favorite is actually aged cheeses, like, for instance, aged Parmesan or aged pecorino cheeses. For example, in one gram of mushrooms, that’s not much. There’s 160 micrograms of spermidine. In comparison, one gram of meat, and quite frankly, that’s not very much. Gives you just 20 micrograms of spermidine. So gram for gram, pound for pound, you’ll get about eight times more spermidine from mushrooms than you will from beef. Interestingly enough, there’s lots of spermidine in chicken skin. So my advice, find yourself a good pasture raised chicken like FarmerDansLectinLitechicken.com, and order the whole chicken and eat the chicken skin. In fact, I have a patient who daily dines on large amounts of baked chicken skin that he buys from his butcher because they sell boneless, skinless chicken breasts, and they basically throw the skin away, and that’s where the spermidine is.

(11:16):
Fun idea. You do absorb spermidine from the gut, and the absorption rate is anywhere from 40 to 80%, so eating spermidine goes a long way. Here’s an interesting clinical trial. There was a randomized placebo-controlled trial carried out for three months. During that trial, 1.2 milligrams of spermidine were administered to one group while the other group was administered to placebo. At the end of the trial, it was found that spermidine was completely safe to take. The additional benefit is the spermidine group actually had increased hair growth. Listen out, guys, it grows hair. All right. So spermidine is now generally recognized as safe, which means the FDA has basically said, “Because of this clinical trial, we’ll let people have it, we’ll let people take it in supplemental form.” And what you gotta do is make sure you get quality ingredients, know who your supplier is, and think about adding spermidine to your diet, either through food, a great way, or supplementation.

Speaker 2 (12:44):
I hope you enjoyed this episode of the Dr. Gundry Podcast. If you did, please share this with family and friends. You never know how one of these health tips can completely transform someone’s life when you take the time to share it with them. There’s also the Dr. Gundry Podcast YouTube channel, where we have tens of thousands of free health insights that can help you and your loved ones live a long, vital life. Let’s do this together.