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Speaker 1:
Welcome to The Dr. Gundry Podcast, where Dr. Steven Gundry shares his groundbreaking research from over 25 years of treating patients with diet and lifestyle changes alone. Dr. Gundry and other wellness experts offer inspiring stories, the latest scientific advancements, and practical tips to empower you to take control of your health and live a long, happy life.

Dr. Steven Gundry:
As many of my longtime listeners will know, I’m always on the top of latest research regarding exciting compounds that support your health. And as soon as the research is available, I like to bring it to you right here. I also like to try it out on myself and my patients.
Today, I want to talk about some of the best supplements that are available right now, but not very many people have heard about. So number one is spermidine. Now, I’ll give you one guess where that compound was first discovered. And it’s a naturally occurring compound in the body, but it plays a crucial role in cellular function and survival. In fact, spermidine is one of several polyamines, including putrescine. These actually regulate cellular function.
Now how does it work? Well, spermidine is very critical for the process of autophagy. Now, you may remember the word autophagy. I’ve talked about it a lot, I’ve written about it in my books. Normally, cells die. And when cells die, one of two things can happen. One is that the cell literally explodes and it’s called apoptosis. Apoptosis is really bad for you for multiple reasons. I’ve written about this in multiple of my books. Among the other really bad things about your cell exploding is the mitochondria in the cell also explode. And mitochondria, you might recall, are actually containing bacterial DNA and your immune system views this mitochondrial DNA as bacteria and produces inflammation. SO cells dying by apoptosis is a bad thing.
On the other hand, the other way cell death can be accomplished is what’s called autophagy. Autophagy basically means self-eat. That says that the cell recycles its components to build a new cell, including recycling mitochondria, so that none of this debris is sprayed out and none of this debris is looked on with inflammation in mind.
So autophagy is a great thing, apoptosis is a terrible thing. So the more you can produce autophagy, the better. Just so happens that fasting happens to be a great way to produce autophagy, but you can ignite the process in many other ways. So spermidine is one of those agents that activates autophagy.
It does that in two ways. First of all, it inhibits the mTOR pathway. Now, you’ve heard me talk about mTOR many, many times. mTOR was originally called the mammalian target of rapamycin. It was discovered during the time we were developing transplant drugs, including rapamycin. And rapamycin, we test transplant drugs to see if it doesn’t kill animals before we use it on human beings.
And rapamycin was fascinating because giving rapamycin to animals made them live longer. And people said, “What the heck?” Well, they found an energy sensor called the mammalian target of rapamycin, mTOR. And subsequently, it’s been found in all life forms, not just mammals. But mTOR had kind of stuck in our heads, and so now it’s called the mechanistic target of rapamycin, just to keep that M in your head.
So what? This senses energy. If it senses that there’s not much energy available, what it tells every cell in your body is to look at itself and see if it’s pulling its own weight, see if it looks a little odd, seeing if it’s doing the job. And if it’s not pulling its own weight or not doing its job or looks a little different, it tells it to recycle itself to not take any more energy. And that’s actually a good thing, it’s kind of like pruning a tree for winter.
The other thing it does, like spermidine, activates the AMPK pathway. Now, you hear this word a lot, and I’m going to talk about it in this lecture. So the AMPK pathway is another system to utilize energy properly and to also activate the release of fatty acids from fat cells so that they can be used for fuel. And if you follow some of the GLP-1 agonist drugs that are now incredibly popular, one of the ways they work is also activating the AMPK pathway. So the great news is you can activate it with fasting, you can activate it with spermidine, and oh, by the way, a great way to activate it is exercise. So spermidine is kind of exercise, fasting in a bottle.
Now, how does it support longevity? Well, since autophagy has been shown to increase longevity, the more autophagy you accomplish, up to a point, the better. Also, spermidine is shown to be anti-inflammatory. Spermidine has been shown to improve fat metabolism through what I went through before. And the other great thing, it appears that spermidine actually inhibits cell proliferation in a good way. Think about cancer cells. The last thing you want to do is tell cells to grow if you have cancer. And we know that mTOR stimulation or rather suppression of mTOR tells cancer cells not to grow.
Now, there’s a neat study back in 2018 looking at the link between dietary spermidine and mortality rates. And it turns out that cultures and people who have more spermidine in their diet actually live longer. Now, that may explain why traditional fermented sausage eaters live a long time. In fact, as I wrote about in Gut Check, the folks with the longest life expectancy in the world by a country are people who live in this tiny country between Spain and France called Andorra.
And they had the longest life expectancy of any country in the world by far, and they just so happened to be sheep herders. And they eat a lot of sheep and goat cheese. And interestingly, they have sausages every day. And it just so happens that sausages, fermented meats are one of the richest sources of spermidine. Fun fact, chicken skin is loaded with spermidine, as are chicken livers. So don’t have a boneless skinless, chicken breast. Have the skin instead. I believe in spermidine so much that it’s in several of my compounds, including my new gummy Active Amines. And that’s how Spermidine works.
Spermidine also has been shown to improve gut health. And if you’ve been paying attention, Hippocrates said 2,500 years ago that all disease begins in the gut. And I happen to believe that all disease can be reversed in the gut. Spermidine actually improves the gut barrier integrity, and it is protective against the gut endothelial damage. And as you know from Gut Check, and now coming up in my next book, The Gut-Brain Paradox, the integrity of the gut wall determines what’s going to happen to you and to your brain going forward. So anything you can do to improve that gut wall integrity is going to improve your lifespan, your health span, and your brain span.
Okay, hydrogen, molecular hydrogen is called H2. You may remember from the periodic table from high school that hydrogen is the smallest molecule. It’s so small that one of its unique properties is that it can be swallowed as molecular hydrogen water and be absorbed through the wall of your intestinal tract and be absorbed through cell walls.
Now, hydrogen has been shown in literally now 15,000 separate papers to be really important for multiple cellular functions. One, it activates the Nrf2 pathway, sometimes called the Nrf2 pathway. It also is fundamental for regulating nitric oxide production and hydrogen sulfide production. Now, I’ve written a lot about these postbiotics, hydrogen sulfide, the so-called rotten egg smell.
We used to think that hydrogen sulfide was a toxic gas, but we now know that there’s a Goldilocks effect of hydrogen sulfide gas. And that is a little dab will do you. A bit of hydrogen sulfide is very protective to the walls of our blood vessels, it’s very protective to your brain, and it’s also very protective to your gut wall integrity.
So where do you get hydrogen sulfide? Well, you have to have hydrogen gas and you also have to have sulfur molecules. The best source for sulfur molecules in our diet are the cruciferous vegetables, the brassica vegetables like broccoli, cauliflower, bok choy, arugula, cabbages. Those are rich in sulfur-containing compounds.
Fun fact, you probably know I’m a big fan of Sanpellegrino water. And no, they don’t sponsor me and pay you to tell you this. They happen to have the highest sulfur content of any mineral water. So hydrogen and sulfur get hydrogen sulfide gas. Good for you in the right amount.
Now, exercise also is good for you because it’s bad for you. Nietzsche once said that what doesn’t kill you makes you stronger. So a lot of these compounds actually have exercise mimetic effects. And who doesn’t want exercise in a bottle? And we’ll get to that in just a minute because there may be such a thing as exercise in a bottle.
But back to hydrogen gas. In a swim test on rats, rats who were given hydrogen water performed better and recovered faster than rats who did not drink hydrogen water. Now, what does this have to do with gut health? Well, it turns out that a lot of us, most of us should have gut bacteria that produce hydrogen gas. And that hydrogen gas is really important for brain function. Unfortunately, a great number of us, because our gut bacteria had been killed off, don’t have hydrogen gas producing bacteria.
In one Japanese study, they found that people with early Parkinson’s disease had a gut microbiome that didn’t produce hydrogen gas compared to control people without Parkinson’s disease who did have gut bacteria that produced hydrogen gas. And the amazing thing is when they took these individuals with early Parkinson’s and gave them hydrogen water, their Parkinson’s symptoms reduced, again, showing the huge benefit of this postbiotic hydrogen gas production.
Now, I have an entire episode on this with Alex Tarnava, the mind behind the groundbreaking hydrogen tablet. And I have a hydrogen tablet, it’s called H2 Restore. All you do is pop it in water, it fizzes, and you drink it. Sadly, as he points out, most of the hydrogen water producing machines don’t produce a lot of molecular hydrogen enough in these forms dissolved in water. So you’re actually better off using hydrogen tablets to make hydrogen gas water.
Okay, so in part two we’re going to talk about exercise in a bottle. You don’t want to miss this one.
All right, let’s go on to part two of some supplements you probably never heard of really should know about. First of all, there’s some really exciting new probiotic strains. Probiotics are friendly bacteria. And with each passing year, we’re not only discovering these strains thanks to the Human Microbiome Project, but we’re also learning how to grow them.
So one of them is called Puf1, P-U-F1. Now this was first found in the feces of breast milk fed infants. Now, it turns out that Puf1 is one of the keys to breast milk supporting health benefits in infants. There have actually been five preclinical studies show that the strain may protect against tissue damage in the colon by mitigating pathogen induced inflammation. Data also shows that Puf1 may regulate immune cells. It’s also been shown to stimulate the growth of beneficial gut bacteria. And it also produces large amounts of vitamin B12. I was so excited to find Puf1 that I actually incorporated it into my formula GI Renew for that reason.
Now, there’s another really exciting strain that you may have heard about, akkermansia muciniphila. Now, it’s one of the keystone species in our gut and maybe one of the keystone species for good health overall. Now, it was first identified in 2004. Literally, it translates into mucus loving and it’s a species of bacteria that helps maintain our gut lining. Now, Akkermansia fosters the growth of butyrate and other short-chain fatty acid producing bacteria. And the more, to a point, Akkermansia you have, the more you produce and invite, if you will, the growth of the short-chain fatty acid bacteria. And bonus, the more you produce bacteria that produce GLP-1 agonists. And everybody knows about GLP-1 agonists, those are the injectable weight loss drugs, and I’ll get to that in a minute.
So these all work together to improve the gut wall health, mitochondrial health, the immune system’s health, and your brain health. Now, Pendulum Life was the first company to offer living Akkermansia in a pill form. I have multiple interviews with them right here on this channel, and please check those out. They’re really interesting. And even how the founder, Colleen, decided to investigate this based on the health of one of her daughters is actually very heartwarming. It’s a great interview.
All right, now let’s talk about some of the new postbiotic strains. Tributyrin, this is a derivative of butyrate, butyric acid. And I just mentioned butyrate is one of the holy grails of short-chain fatty acids. Now, a study investigated the effect of a three-week tributyrin supplementation on the gut microbiome in 20 healthy adults. 32 participants were given either tributyrin or a placebo daily. The results show that tributyrin increased microbial diversity, that’s a good thing, and the abundance of beneficial bacteria producing, spoiler alert, short-chain fatty acids. Participants also exhibited improved gut health markers, including reduced inflammation. Good stuff.
Another study investigated the effects of tributyrin on gut microbiota and inflammation in antibiotic-treated mice. The study found that just this supplementation alone helped repair intestinal damage by restoring gut microbiome balance and reducing inflammation. Interestingly, the mice treated with tributyrin showed improved gut barrier integrity and reduced levels of inflammatory markers. Knowing all this, this is why I put this compound in my best-selling Bio Complete 3 formula, and that’s one of the reasons that people have experienced such great result with that formula.
Urolithin A. Now, Urolithin A is one of the new darlings of postbiotics. Here’s the deal, we’ve all heard that pomegranates and raspberries are really good for you because they have some compounds called oxalic acid. And okay, so far so good. What we didn’t know is that only about 17 to 20% of us have a set of bacteria that can take these compounds and turn them into the active compound, which is called Urolithin A. Interestingly enough, 50 to 70% of super-agers, turns out, have the set of bacteria that make Urolithin A from these compounds. So the point of all that is you could eat all the pomegranates and raspberries that you want, but most of us won’t turn it into the compound that we actually need for good health, which is Urolithin A.
So why do we need it? Well, it turns out that Urolithin A is one of the first compounds that has been shown to produce mitophagy, which is basically the recycling of damaged mitochondria, and mitochondrial biogenesis, making new mitochondria. That’s a good thing.
Number two, studies using Urolithin A have shown that it enhances muscle function, muscle strength, and endurance, particularly in older adults and sedentary individuals without a change in an exercise program. It’s exercise in a bottle, of all things.
Now, cognitive function, preliminary research has suggested in animal models that Urolithin A improves memory and cognitive function. Immune function, Urolithin A appears to enhance immune cell function and actually may help in maintaining immune health in individuals who age. Finally, there’s really cool anti-inflammatory effects for overall improved health.
Now, there’s some animal studies in worms. See, the C. elegans model, which I refer to in all my books. [inaudible 00:21:54] a little worm, Urolithin A supplementation of C. elegans resulted in a 45% increase in lifespan. Now, why is that so important? So what if a worm lives longer? Interestingly, this animal model has always correlated, the results have always correlated to higher animal models all the way up to rhesus monkeys. In other words, what works in this little worm will almost certainly work in us.
Now, in human trials, daily supplementation with Urolithin A significantly improved muscle strength and endurance. In fact, one study reported a 10% increase in leg muscle strength after four months of supplementation in middle-aged, overweight, and sedentary individuals. Nice stuff. Now you should really check out my episode with Chris Rinsch, the co-founder of Amazentis, which is the company behind Mitopure. The company is called Timeline Nutrition, by the way.
Finally, berberine. Now, Berberine has gotten a lot of interest as the natural alternative to prescription weight loss drugs like Ozempic, like Wegovy, and like Metformin, the diabetes drug. Now, you probably heard that two of the major weight loss companies have decided to market these miracle weight loss prescription drugs as part of their program.
Now, I won’t go into how these work, but I will provide a warning. So far, it looks, from clinical studies, that 40%, maybe 50% of the weight loss that individuals experience on these drugs is muscle mass. And the last thing you want to do is lose muscle on a weight loss program because muscles are what eats the calories you eat. And sadly, placebo controlled trials show that once you stop this drug, even if you think you’re getting the drug, your weight comes back rapidly because your muscle mass is not there to eat it.
Now, there is some evidence that berberine can act as a GLP-1 agonist, but it’s so much more than that. I’m a huge fan of berberine for many reasons, and it’s in actually many of my formulas. It’s a polyphenol. It’s one of the most potent mitochondrial uncouplers that has ever been discovered. It’s also known to activate AMPK. It reduces insulin levels and it controls blood sugar. It’s absolutely amazing. If you want to know more about this, read Gut Check and Unlocking the Keto Code because it’s all in there.
All right, those are some of the exciting new supplements that you need to know about. That’s all for today.

Speaker 1:
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