Spermidine Explained: The Anti-Aging Breakthrough You Need | EP 397.C

Summary

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Spermidine Explained: The Anti-Aging Breakthrough You Need | Dr. Gundry Podcast Ep. 397.C

Overview of the Episode

In this episode, Dr. Steven Gundry dives deep into the science behind spermidine, a naturally occurring compound gaining attention for its potential anti-aging effects. Dr. Gundry explains how spermidine influences key longevity processes like autophagy, breaks down cutting-edge studies in both animals and humans, and offers practical advice for increasing dietary intake of spermidine. The episode is a focused, science-rich exploration designed to help listeners understand why spermidine is becoming a hot topic in the health and wellness world.

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What Is Spermidine—and Why Should You Care? (01:45)

• Dr. Gundry opens by highlighting spermidine as "maybe one of the kind of hidden secrets to longevity."
• He introduces the concepts of autophagy (“self eat”) and apoptosis, noting that autophagy is the optimal, healthy method by which the body recycles old or damaged cellular components.
• Key Insight: “The more you can induce autophagy and the less you induce apoptosis, the longer you live.” (02:37)
• Spermidine, a polyamine present in all body cells and also produced by gut bacteria, stimulates autophagy.
• Fun fact: Spermidine was first discovered in human semen in 1678 by Anton Van Leeuwenhoek, but 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." (03:40)
• Unlike fasting, which is well-known to trigger autophagy, spermidine can do so even without dietary restriction.

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How Spermidine Works: The Science (04:40)

• Dr. Gundry offers a breakdown of the molecular mechanisms:
  • Spermidine "inhibits acetyltransferase," reduces acetylation, and inhibits mTOR (Mechanistic Target of Rapamycin Complex 1).
  • It "activates the AMPK pathway"—a metabolic switch linked to longevity and improved cellular health.
  • Other AMPK activators include berberine and metformin, but “spermidine does it, too.” (05:00)
• Study Spotlight: In yeast, supplementation with spermidine extended lifespan by upregulating autophagy genes. Importantly, when autophagy genes were knocked out, spermidine didn’t show benefits—proving the pathway.

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Spermidine and the Aging Process: Key Findings (07:51)

• Autophagy’s Role in Lifespan: Elevated autophagy (via spermidine) reduces inflammation and apoptosis, improves mitochondrial function, and impacts lipid metabolism.
• Brain Health: A University of Graz study found that "spermidine induced autophagy improved mitochondrial function in the brain," which is key in preventing cognitive decline. (08:23)
• "Spermidine crosses the blood-brain barrier. Unlike many other compounds, spermidine can get to the brain to do its cool thing." (08:47)
• Animal Studies:
  • In mice, oral supplementation for six months led to reduced organ damage, preserved cardiac tissue, and even improved hair growth.
• Human Studies:
  • A 2018 study linked higher dietary intake of spermidine to reduced all-cause mortality, notably lower rates of cardiovascular and cancer-related deaths. (09:24)
  • The statistical relationship held after adjusting for numerous lifestyle factors.

Notable Quote:

"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."
— Dr. Gundry (09:30)

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How to Get More Spermidine: Foods & Supplementation (11:33)

• Aging and Spermidine Production: Natural production of spermidine declines with age, so it's increasingly vital to obtain it from food.
• Top Food Sources:
  • Mushrooms are #1 (1g contains 160 mcg)
  • Broccoli and cauliflower
  • Aged cheeses (e.g., Parmesan, Pecorino)
  • Chicken skin: “Find yourself a good pasture raised chicken … and eat the chicken skin.”
  • Beef is relatively low (1g = 20 mcg, ~8x less than mushrooms)
• Absorption: "You do absorb spermidine from the gut and the absorption rate is anywhere from 40 to 80%. So eating spermidine goes a long way." (14:05)

Notable Quote:

“I have a patient who daily dines on large amounts of baked chicken skin that he buys from his butcher … and that’s where the spermidine is.”
— Dr. Gundry (13:35)

• Supplements: A clinical trial administering 1.2 mg of spermidine daily for 3 months showed it was safe and also led to increased hair growth. Because it's “generally recognized as safe” (GRAS) by the FDA, reputable supplements are now an option.
• Pro tip: Ensure any supplement comes from a trusted supplier. However, whole foods remain the recommended source.

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Spermidine vs. Other Anti-Aging Strategies (10:58)

• Fasting: Both fasting and spermidine work via the mTOR/AMPK pathway, making them natural partners.
• Rapamycin: While rapamycin also targets the mTOR pathway, Dr. Gundry cautions about its safety and suggests he wouldn’t use it outside of post-transplant situations.
• Takeaway: "The combination of fasting and spermidine, now that's what I'm interested in." (11:30)

Notable Quote:

"As we age, spermidine production gets lower and lower. So as we age, it's more important to acquire spermidine from external sources."
— Dr. Gundry (12:11)

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Important Segment Timestamps

• 01:45 — What is spermidine? Why is autophagy important?
• 04:41 — Spermidine's mechanism of action (AMPK, mTOR)
• 07:51 — Spermidine and anti-aging: findings from animal and human studies
• 11:33 — Food sources of spermidine, comparison, and absorption
• 12:50 — Supplementation safety and clinical trial results
• 10:58 — Discussion of fasting, rapamycin, and synergy with spermidine

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Endnotes & Notable Moments

• Dr. Gundry’s enthusiasm is clear: “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.” (10:25)
• Practical advice is down-to-earth, including stories about patients and his own eating habits.
• He cautions listeners about supplement quality and advocates for food-first approaches.
• Anecdote: Baked chicken skin gets a shout-out for its spermidine content and as an underappreciated source.

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Conclusion

Dr. Gundry distills the latest science into clear, actionable takeaways: boost your spermidine through mushrooms, aged cheese, cruciferous veggies, and (for meat-eaters) chicken skin. While supplementation is now safe and available, diet remains foundational. Spermidine works synergistically with other longevity practices such as fasting and offers exciting promise for healthy aging and even brain health. For those seeking natural anti-aging strategies, spermidine-rich foods shouldn’t be overlooked.

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For more, check out The Dr. Gundry Podcast YouTube channel or share this episode with anyone interested in cutting-edge wellness tips.

Transcript

[Dr. Steven Gundry]

A tiny compound is making big waves in the science of longevity. It's got a funny name, but it's no joke when it comes to aging. Well, it's called spermidine. In just a minute, I'll tell you how it works in the body to slow aging. And I'll reveal the best foods with spermidine. I'll be right back after this brief message. Did you know the air inside your home could be up to 100 times more toxic than the air outside? Chemicals from your furniture and cleaning products. Invisible harmful particles from your stove and candles. Mold spores floating through every room. These toxic invaders are silently linked to brain fog, fatigue, heart disease, and more. That's why I created Total Air from my new home wellness brand. Homekind Totalaire uses a true surgical grade HEPA filter, the same standard I trusted in the operating room. Plus an activated carbon layer for chemicals and microband technology to stop mold and bacteria from spreading. Three layers of medical grade protection. One device, Clean air for you, your loved ones, even your pets. Go to homekind.com right now and use code cleanair for 10% off on total air. 180 HEPA, 13 or 14. I built this to protect my family. Now it can protect yours, too.

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 autophagy 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. So I want to talk about spermidine. Stay with me for a few minutes because we're going to get a little nerdy and it's going to be kind of sciency. But I promise you it'll be worth it because you really want to 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 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 Leeuwenhoek. 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. Now, as I mentioned, sperminine's cool thing is that 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 acetyltransferase. Now, this reduces acetylation, and it also inhibits MTOR, or the Mechanistic Target of Rapamycin Complex 1. This activates the AMPK pathway and actually starts up autophagy. So spermidine activates autophagy by inhibiting MTMTOR 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. 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.

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[Dr. Steven Gundry]

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 Graz 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. Here's the good news. Spermidine crosses the blood brain barrier. Unlike many other compounds, spermidine can get to the brain to do its cool thing. What about lifespan? Well, these have been primarily done in mice, but hold the fort. There's a human study coming up. Mice age. Mice were given spermidine 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. 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 aged 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 telomere shortening stopped and the treated mice telomeres looked like younger mice. Telomeres and telomere length 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. 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's 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, spermidine production gets lower and lower. 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 1 gram of mushrooms that's not much. There's 160 micrograms of spermidine in comparison, 1 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 Farmer Dan's lectinlightchicken.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. 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 a 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 got to 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.

Now it's time for the question of the week. A question from JillbertB over on YouTube. On my episode about parasites, they asked, could parasites come from well, water? Well, it's always possible to pick up a funny bug from water, but in general, well water is very safe. In fact, it is so unusual to have parasites. I really don't recommend worrying about it and for goodness sakes, don't do the parasite cleanse. I check for parasites on all my patients and yes, why I do occasionally find them. It's unusual. So don't do it. Now it's time for the review of the week. A review from Monadavids90 on my YouTube short about B12. They said, My gosh, I've been taking B12 with water. I'm going to start under the tongue thing from now on. Thank you doctor With a heart sign.

Well, you're right.

So many people, number one, make two mistakes about B12. They don't take the active form, which is methyl B12. They take plain old everyday B12. And half the people cannot convert regular B12 into its active form. But a lot of people don't realize that they lack a receptor in their intestines to absorb B12 when they swallow it. The good news is, putting it under your tongue in the right form alleviates both of their problems. Easy trick. Thanks for writing.

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[Dr. Steven Gundry]

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