Rapamycin For Age Reversal: Everything You Need To Know (& Why Most People Are *Wrong* About True Gut Health!)

My name is Ben Greenfield. And on this episode of the Ben Greenfield Life podcast.

Most people have a total misunderstanding of probiotic bacteria and what they do and how they function. The job of your probiotic bacteria is to digest components in your food and break them down and produce secondary molecules that we call postbiotic metabolites. And it's these smaller metabolites that the probiotic bacteria produce that have a wide range of biological activity. So it's not the probiotic bacteria themselves, it's the compounds that the probiotic bacteria produce, these postbiotic metabolites, that regulate not only your microbiome ecosystem, but they get absorbed systemically and influence every single organ system in your body, especially your brain and your immune system. And the problem, Ben, is that most people are not feeding their gut microbiome well, and if you don't feed your probiotic bacteria well, they will not thrive and survive. They won't be able to produce the postbiotic metabolites that regulate your health. So what are the types of foods that your probiotic bacteria require? They are dietary fibers and polyphenols.

Faith, family, fitness, health, performance, nutrition, longevity, ancestral living, biohacking, and a whole lot more. Welcome to the show.

Alright, folks. So, you've probably heard me talk about rapamycin a few times in the past several weeks if you've been listening to the podcast as any loyal podcast listener should be. Anyways, it's because I've been taking a deep dive lately into this kind of darling in the anti-aging longevity sector. I had some reservations about rapamycin for the longest time. After reading the book written by today's podcast guest, I learned a ton about it. The book is called Rapamycin, mTOR, Autophagy, and Treating mTOR Syndrome. If you don't know what mTOR syndrome is, don't worry, we'll clear that up. And, my guest is Ross Pelton. Ross is extremely intelligent when it comes to all things related to anti-aging and longevity. He's a pharmacist, he's a nutritionist, he's an author of this fantastic book and some other titles. This book again is called Rapamycin, uh, and he's a health educator, and, and he, he has a lot of knowledge as well in the microbiome and in drug-induced nutrient depletions. He was actually named as one of the top 50 most influential pharmacists in the United States, and, uh, runs a fantastic website, social media profile, and is a really great follow. So, I'll link to all his stuff. If you go to the shownotes over at BenGreenfieldLife.com/Rapamycin. And if you don't know how rapamycin is spelled, I'll tell you right now because you want to know. You're going to see it all over the place in the next 10 years, I guarantee. BenGreenfieldLife.com/Rapamycin. It's R-A-P-A-M-Y-C-I-N. Ross, welcome to the show, man.

Ben, great to be here.

Yeah, I've been looking forward to this interview and I think even alluded to it on a few other podcasts. And, one thing I have to ask you before we jump in, I was actually in preparation for our show today listening to an interview with a guy who's in the longevity sector down in, I believe, He's in New Zealand. I don't have it pulled up in front of me right now. You might know who this guy is. And, it was a whole podcast episode about rapamycin and the longevity-enhancing benefits of rapamycin. They got to the end of the interview and the interviewer said, "Well, do you take it?" And, he's like, "No, no, no, no, no, not yet." And so, I suppose I should just lead this interview off rather than waiting to the end to ask you, do you actually take rapamycin?

Absolutely. Been taking it for about 2.5 years now.

Okay. Yeah, me too except for about 2.5 weeks now. So, I'm a little bit behind you and we'll get into why, of course. But before we start, I think the story of rapamycin is very interesting, this whole idea of Easter Island and the soil. And I believe Rapa Nui is the name of the island or something. Can you tell that story?

Sure, you bet. So, back in the 1960s, a group of Canadian scientists made a scientific expedition to Easter Island. And, the goal of that expedition was to look for potential sources for new antibiotic and antifungal drugs. They took a lot of soil samples around Easter Island. And, when they got back to their labs and started looking at things, one of the soil samples had a compound that produced by a strain of Streptomyces bacteria. So, One of the things I like to emphasize, Ben, is this is something that's naturally produced in nature by a strain of soil bacteria. It's not some weird molecule that the pharmaceutical companies have produced that's never been seen on planet Earth or in any human's body before. But, this compound that is produced by this strain of soil bacteria was named rapamycin after the indigenous people's name for Easter Island, which is Rapa Nui. So, that's how it got its name. And interestingly, they started to develop rapamycin as an antifungal drug and then they discovered that it suppresses the immune system. So, all this research came to a screaming halt. But then, in September of 1999, the FDA approved rapamycin for people that get kidney transplants because people who get an organ transplant need to be on immune suppressive drugs for the rest of their life. So, that was the way that rapamycin got its original FDA approval. Well, samples of rapamycin were sent off to the National Cancer Institute and they went crazy over it. They discovered that rapamycin is the first example of an entirely new class of chemotherapy drugs. Most chemotherapy drugs are called cytotoxic. They kill rapidly dividing cells like the tumor cell, but they also cause a lot of side effects because there's other cells in your body that divide rapidly. Like the epithelial cells that line your gastrointestinal tract and liver cells and the bone marrow and so forth. So, that's where all the side effects come from. Turns out that rapamycin is not cytotoxic, it's cytostatic. It stops the cancer growth, but it doesn't have all these side effects. So, in the early 2000s, rapamycin got FDA approval for treating two different types of solid tumor cancers. These FDA approvals, Ben, have been an impediment to getting rapamycin accepted as a life extension drug because most functional medicine docs and health-oriented physicians are not going to write a prescription for a life extension enthusiast for chemotherapy or something that suppresses the immune system or something that's generally a cancer drug. But, Joan Mannick, is a scientist that worked for one of the big multinational drug companies, Novartis. And, she had the enviable position of being able to research anything she wanted. And, she was interested in aging, she decided to research rapamycin and she devised a really interesting clinical trial that really changed the landscape for rapamycin and opened up the floodgates for our understanding of it as a literal revolution, a real breakthrough in life extension therapy. So, Joan Mannick's trial, she selected elderly people age 64 and older, divided them into 4 groups of people. One is a placebo group, and then the 3 other groups took a different dose of a rapalog, a rapamycin-type drug that has exactly the same effects of rapamycin. One group took 0.5 milligrams every single day. Second group took 5 milligrams once a week. Third group took 20 milligrams once a week, and they took their dose or the placebo for 12 weeks. And then, there was a 2-week washout period, and then, she subjected all these participants to the seasonal flu vaccine. Then, she did blood work and measured how their immune system responded to this challenge of the flu vaccine. Turned out that the people taking 5 milligrams once a week, that was the sweet spot. These people got a 20% boost to their immune system.

Now, just for comparison's sake, how much would people be taking if they were using it as an immunosuppressant or as, say, like a cancer chemotherapy agent?

You bet. So, if you're taking it for chemotherapy or for immunosuppression, you take it every single day.

Same thing, 5 milligrams every single day or more than 5 milligrams every single day?

Different doses. It's not one set dose, different doses, but the difference is rather than taking daily, Joan Mannick's trial discovered and announced that if you take rapamycin episodically, in this case once a week, there's tremendous health benefits. So now, I want to kind of morph into an explanation of why taking it once a week provides such unique and important health benefits. And to do that, Ben, I need to get into the other topics in the title of my book, um, mTOR and autophagy. And right at the beginning of my book, I say there are two main themes in my book. One is the drug rapamycin, which is a very interesting story in and of itself. But to my way of thinking, mTOR and autophagy are a much more important topic in my book than just the drug rapamycin, because this understanding of mTOR and autophagy has opened up a whole new understanding of cellular metabolism, of health, and the aging process. So, let me break this down and describe these terms and what they mean. In 1994, David Sabatini discovered the mechanism of rapamycin. When rapamycin gets absorbed across the cellular membrane, it goes into a cell and it binds to an enzyme. And this is an enzyme that is a master sensor of when nutrients are available. And when nutrients are available, this particular enzyme sends out signals to the cell that says, "Use these nutrients to build and grow. Make new proteins, make new enzymes, build new cellular components." And because this is the enzyme that rapamycin binds to, David Sabatini named this enzyme mTOR, which stands for the mechanistic target of rapamycin. So, it's just the term that Sabatini gave to the target where mTOR binds to.

I think a lot of people hear that term mTOR because it gets thrown around a lot these days, they don't even realize the R stands for rapamycin.

Yeah. And, if you look in PubMed, there are thousands and thousands of published studies and articles on mTOR. And now, I need to discuss and explain the other side of the equation. So, I mentioned mTOR senses when nutrients are available. If there are no nutrients available, then a process of autophagy gets activated. And Japanese scientist Yoshinori Ohsumi won the Nobel Prize in 2016 for his discovery of autophagy. When no nutrients are available, autophagy is the process where cells are able to target old misfolded proteins and enzymes and cellular components and break them down and get them out of the cell for detoxifying the cell, or they're reutilizing the components like the amino acids in misfolded proteins, breaking them down to their amino acids, and then reutilizing these amino acids to build healthy new proteins and healthy new enzymes and healthy new cellular components. So, autophagy is detoxification, and it's also the rebuilding and the revitalization and the renewal of your body. And for hundreds and hundreds of thousands of years of evolutionary history, mTOR and autophagy were in balance. And when I use the term balance, and I— mTOR and autophagy, and I— when I say they're in balance, that doesn't mean equal parts. And I use the analogy of the gut microbiome. A gut microbiome that's in balance is about 85 to 90% good bacteria and only 10 to 15% bad bacteria. That's a healthy balance in the gut microbiome.

Right. So, it's not like it's a 50-50 split is what you're saying. Right.

It's not a 50-50. When the good bacteria vastly outnumber the bad bacteria, the bad ones aren't causing problems. So, a balanced microbiome is vastly overpopulated by good bacteria. So, back now to mTOR and autophagy. For hundreds and hundreds of thousands of years of human evolution, people did not get up in the morning, and go to the kitchen and open the refrigerator and start making breakfast. Ancestral humans did not eat 3 meals a day. And these days we've got people eating breakfast, lunch, dinner, in-between meal snacks, desserts, evening cocktails. Relative to our ancestral humans, relative to the way our bodies developed for hundreds and hundreds of thousands of years, these days people are eating all the time, which means nutrients are always available to the cell. MTOR is always getting expressed and autophagy is not getting expressed. So, this is a fundamental cellular mechanism that is out of balance for most people alive today. And, what's the effect of this? Well, these days, mankind is experiencing what I call an epidemic of epidemics. We've got an epidemic of heart disease, and diabetes and obesity and inflammatory conditions and autism. And all of these things are off the charts compared to where they were 50, 60, 70 years ago. Back in the 1960s when I was a kid growing up, none of these were epidemics.

Yeah, but at the same time, by the way, it is a lot more fun to watch the National Football League because now the players are like 400 pounds rather than being 250. You know, the rampant societal anabolism has certainly had payoff in some cases in the case of something like professional sports. And, it's kind of funny, I don't want to totally derail, but I think this is one reason why perhaps people who are still in a highly anabolic phase such as my own 15-year-old teenage boys, I'd never tell them to go take the rapamycin I'm currently taking because I kind of want them in a pretty pro-anabolic state for a lot of the time. But, I was explaining to them last night at dinner, actually this conversation came up, I told them, look, you see Dad doing things like intermittent fasting, rapamycin engagement in autophagy-related activities, cold thermogenesis, et cetera. But I started really focusing hardcore on those when I was about 35 to 40 years old because at this stage in my life, anabolism and fertility is not quite as important as longevity and autophagy. So I think some of this stuff, you know, it's, it's, it's age age-related context, right?

You're right. And you bring up a good point. Who should take rapamycin and when should you start taking it? I'll first admit that we don't have all the answers. This is a very new field. But we do know these things. You would never give rapamycin to a child because mTOR senses when nutrients are available. It's a primary anabolic process. So, you don't want to inhibit anabolism or the building process in an infant. I don't think that teenagers or even young adults in their 20s and 30s should start taking rapamycin yet. And, a pregnant woman should never take it because you don't want to interfere with the building processes when the fetus is growing. Yeah. But, somewhere around late 30s, early 40s, 50s, that's when people can start to consider taking rapamycin. And again, we don't have all the answers. Maybe a healthy exercising person at age 50 should think about taking it, but maybe an overweight obese person in their 30s would be beneficial to start taking it. We don't know the answers to these things.

Yeah, someone who's like overweight or obese or might have an increased need for cellular autophagy might start taking it earlier in life. And I actually do want to get back to the dosage and timing a little bit later. And, by the way, my dose right now is 5 milligrams once a week. My wife, after hearing me talking twice in the past 2 weeks at dinner table conversations about rapamycin, now started herself last week on 5 milligrams once a week. And, if you get my wife to take a supplement, that's pretty darn impressive. But, when I interrupted you, you were getting into this issue with excess societal anabolism and this constant pro-growth state. I assume that that's related to this mTOR overactivation syndrome that's part of the title of your book.

You bet it is. In fact, I, I coined the term mTOR syndrome, which is the constant overactivation of mTOR, and autophagy is not getting its due. It's the appropriate time for detoxification and rebuilding. And aging is a complex process. There are many, many things that, that contribute to the aging process. But, I think this imbalance between mTOR and autophagy is a fundamental cellular mechanism that's out of balance in most people today and it's actionable. People can do something about this to improve their health. Rapamycin is not a magic bullet. If you got bone-on-bone arthritis, rapamycin is not going to fix that. But, when you start taking rapamycin, every single cell in your body is going to start working better. You're gonna get better detoxification, but more importantly, you're gonna start to effectively rebuild and renew your body. And the analogy I like to use here, Ben, think about a car that has a flat tire. You can't change that tire, you can't put that new tire on until you take the old tire off. That's the same way it is with proteins and enzymes in the body. They're huge molecules consisting of hundreds thousands of amino acids linked together in unique shapes and forms. But over time, these proteins and these enzymes undergo stresses and it changes their structure, it changes their shape. And when the shape of a protein or an enzyme changes, it loses its functionality. But it still is in place. You can't get a new protein or enzyme to take its place until you detoxify and break down and get rid of that old protein. So, that's what autophagy does. It's breaking down damaged cellular components, misfolded proteins and enzymes that are not functioning, and rebuilding healthy new proteins and enzymes. So, it's really critical that people understand that autophagy is the number one process for detoxifying every cell in your body, but it's also the rebuilding and the renewal of your body. And, people age faster when they don't activate autophagy and they're not getting this renewal process going on on a regular basis.

Yeah. When you talk about the host of chronic degenerative diseases that are addressed by rapamycin, metabolic syndrome, type 2 diabetes, neurological diseases like Parkinson's, MS, inflammatory conditions like rheumatoid arthritis, systemic lupus, macular degeneration, hearing loss, periodontal disease, cognitive decline, Alzheimer's disease, I mean, you treat each of these in your book with more justice than we could do on the podcast. I at least want to give a head nod. To all these different conditions that rapamycin seems to prevent or treat. But it got me thinking, this is something I don't know if you've ever been asked this, but you mentioned that originally even before it was used as a cancer chemotherapy agent or immunosuppressant that they were looking at it for its potential as an antifungal. How confident are you or other researchers that some of these systemic effects or these system-wide effects related to chronic disease are not necessarily to autophagy and mTOR inhibition, but perhaps to, you know, controlling fungus, Candida, yeast, things like that. Because I realize that's also a big concern in modern society, people consuming excess sugar, alcohol, etc. Have you ever thought about that?

Sure, you bet. And though, as I say, aging is a very complex process, and there's a lot of things that people do, lifestyle and environmental factors, that are contributing to aging. I mean, we know about environmental toxins, things like glyphosate, we're poisoning the planet, and sedentary lifestyles and poor dietary choices. And so, there's lots of things that go into aging processes and there's a lot of things that people can do to slow down their aging process. I'm just saying that this mTOR autophagy ratio is so critically fundamentally important to cellular metabolism, I think it's a one of the foundational concepts that is contributing to the poor health of mankind right now. And, this is such an important process that in the second edition of my book, Ben, I proposed the mTOR autophagy theory of aging to try to draw attention to this, to try to get more recognition of the significance and the importance of these two terms and what people need to do to balance these things. And, of course, one thing I wanna emphasize for our viewers today, The natural way to balance mTOR and autophagy is fasting, intermittent fasting. Condense your food window into a smaller period of time so you go longer periods without nutrient intake. And some people do the 16:8 protocol and some people do 2 days a week 24-hour fasting. Anything you do to do some type of fasting is going to be very beneficial for your long-term health. I advocate doing virtually everything. I take rapamycin, I do intermittent fasting, I exercise, I have a fanatical adherence to a healthy diet. So, I recommend that people do all of these things.

Ben Greenfield: It's interesting because you still get some pushback on this. Now, we've already established the fact, I think, a little bit earlier that the use of rapamycin as an immunosuppressant or cancer chemotherapy agent is at volumes much higher than the amount, this 5 milligrams-ish or so amount that's used every week, or I've even seen some cases 5 to 6 milligrams every 2 weeks. And so, that's no longer a concern of mine, the immunosuppression. However, I also get some pushback from people who I've been talking to about this that they're concerned about the loss of muscle mass or perhaps the, the, the potential triggering of almost like a sarcopenic, a muscle wasting type of state if we're inhibiting mTOR too much. And of course, we know that things like grip strength and muscle mass are, are protective and associated with decreased all-cause risk of mortality. So how do you, how do you think about that question, like whether or not rapamycin could be excessively inhibiting mTOR and causing someone to, say, not gain muscle in response to exercise in the same way that metformin, another popular off-label drug, for diabetes and blood glucose management seemed to cause a little bit of an impairment in mitochondria and VO2 max. A lot of people weren't taking that. But, what do you think about mTOR when it comes to excess muscle loss or inability to put on muscle?

The key here is that when you take rapamycin, you partially inhibit mTOR, which allows autophagy to get activated for a period of time. And, I've had a lot of discussions with a lot of bodybuilders and weightlifters. And, early on, probably 2, 3 years ago, A lot of the weightlifters are saying, "I don't wanna get into this. Inhibiting mTOR is gonna prevent my ability to build muscle mass." But, it's really not the case. It's actually the opposite of that. You need to have periods of autophagy in order to effectively build new muscle mass when mTOR gets reactivated. You've gotta get those old damaged proteins and enzymes out in order to build the new ones. And so, we find out that Taking rapamycin is not detrimental to bodybuilders and people who are trying to increase their muscle mass and their strength. It actually is beneficial because you've gotta have this period of autophagy in order for the mTOR process to work appropriately. And when mTOR is always getting activated, when people are eating all the time and autophagy's not getting activated, it's kind of like driving a race car with the pedal to the metal forever. You can't do that. Or, you've got a sprinter who's really a good track and field performer, but they can't run fast forever. You've gotta have periods of rest, relaxation, and rejuvenation. And, I like to compare autophagy to sleep. During the day, we're active all the time. That's the mTOR phase. We're taking in nutrients. But, We think about sleep as a rest phase, kind of like autophagy is a rest phase. But, sleep is not a rest phase in terms of nothing going on. There's a tremendous amount of activity going on during sleep. You activate the glymphatic system, which detoxifies your brain. And so, sleep is very important for detoxification and rebuilding and renewal of your body just like autophagy, or at least there's a thread of a metaphor there that's similar. So, autophagy is just critically important for long-term health.

Ben Greenfield: Here's the way I've been thinking about it. I'd love to hear your feedback on this. I generally lift weights Monday through Friday. My weekends are primarily devoted towards things like frisbee golf and pickleball and walking and hiking and being with the family. And Sundays tends to be even more of a recovery day. So, Based on that logic, I've actually been taking my rapamycin on Saturday morning because I figure, hey, if it's inhibiting mTOR, I know the half-life is closer to 4 days, but I think it kind of begins to wane in the system after around 48 hours if I'm not mistaken. By consuming it prior to a couple of days of lighter activity and a couple of days for which mTOR activation is not as important to me as autophagy, that I'm timing my rapamycin dosing in such a manner that if there were any risks to an inadequate muscle response to a weight training workout, I'm kind of mitigating those by getting most of that rapamycin out of my bloodstream before I start weight training again on Monday morning.

I'll give you a maybe on that. Nobody's done the studies. We just don't know all these things. And so, those are things that need to be researched. And, you're Your theory there has got some validity to it, but I just have to say nobody has really looked into this. We don't know the best timing for rapamycin. And so, we don't know if once a week is best, maybe once every 10 days is best. Instead of 5 milligrams once a week, maybe 10 milligrams every other week is better. We really don't know the answers to these things. And, you know, there's biochemical individuality. When we really dive into this, we'll probably find people have different methods or different capabilities of absorbing rapamycin, of metabolizing it. We'll be able to individualize doses at some time in the future, maybe 5 years or so. But right now, what we know is 5 or 6 milligrams once a week is extremely safe. In fact, I think that taking rapamycin appropriately once a week is safer than over-the-counter drugs like acetaminophen and ibuprofen, which is, I think they have far more potential side effects than rapamycin. Acetaminophen is the number one cause of liver failure and liver transplants in the United States, and you can buy it without a prescription. So, I think that people should have access to rapamycin. The upside is tremendous. The side effects are minimal. The most common side effect from rapamycin are these little aphte, ulcers, little mouth sores. Maybe 5% of people get those when they take rapamycin. They generally go away fairly quickly and don't recur. But, um, some people get elevated triglycerides. Some people have a drop in their iron or the hemoglobin levels. These are minor side effects. Most people don't have these effects. I do encourage people to get a baseline set of labs before they start taking rapamycin. And then, 3 months or so later, get a second period of set of labs and do your comparisons. So, you can have a before and after to look at. But, the side effects from rapamycin are very, very minimal. They're manageable. And, the upside is tremendous. Rapamycin, to my way of thinking, is a revolution in lifespan increases. And, I like to emphasize it's not just increasing life extension, it's increasing healthspan. In fact, back in the 1960s or so, a doctor by the name of James Fries wrote a paper they got soundly criticized for, but now it's pretty well generally accepted. What we're trying to do with life extension and anti-aging is called rectangularization of the aging curve and the compression of morbidity. So, you age healthfully for a much longer period of time. And, at the very end of life, whether it's at 95 years or 127 years, wherever, your infirm years are very small at the very end of your life. And, that's what we're doing. That's what rapamycin does when you take it appropriately and exercise and healthy diet and all of the other things. If you're taking metformin or any of the other AMPK inhibitors. This is all designed to actually slow down your aging process to get activity in autophagy so that you are balancing this mTOR autophagy ratio. And so, when we talk about diet, Ben, for a long time, people have always been concerned about the quantity, how much you eat, the quality, what's the quality of your food, are you drinking, eating organic foods and drinking filtered water? But, the thing that has been missed is the timing of food. And, that's what's addressed here in the mTOR autophagy ratio, leaving more time without nutrient intake. So, autophagy gets activated to rebuild and revitalize your body and detoxify your body. So, it's not necessarily consuming less, it's just narrowing the window of your nutrient intake so you have more time to activate autophagy.

Right. The metabolic effects and healthspan effects of a prime rib consumed at 1:00 a.m. is a lot different than prime rib consumed at, say, 10:00 a.m. after a weight training workout or something like that. I absolutely agree. Or any breakfast with a decent amount of protein used as a circadian rhythm management tool like a zeitgeber. Yeah, timing, that's a lot of Satchin Panda's research, of course, that food is not just about quality and quantity, it's also about timing. And you're absolutely right when it comes to that. Now, you mentioned about other agents that people take for longevity. I've been very impressed with peptide bioregulators. I've been very impressed with what I've seen on NAD, increasingly impressed with C60 and astaxanthin. And, there's a few others out there, but when it comes to rapamycin in some of the digging around and discussions that I had leading up to this interview, I saw people doing a few other different stacks. I think one that came up repeatedly was, I don't know if I'm pronouncing this right, Ecarbose or something like that, like people taking— acarbose with rapamycin. Are you familiar with this?

Yep, it's, it's one of the blood sugar regulators. It's an AMPK activator. And, um, another one is metformin, um, and they all have some benefits. But, but though all the other life extension drugs I'm aware of have significant individual benefits, rapamycin and regulating the mTOR autophagy ratio is a fundamental mechanism. And so, I think all the diseases of aging are related to this imbalance of mTOR and autophagy. And, in animal models, every single age-related disease responds to rapamycin, metabolic diseases, cardiovascular diseases, neurological diseases, everything in animal models responds to rapamycin. They all have a slowing down of the process. Some of them actually reverse some of the processes, I mean, cardiovascular disease in animals with rapamycin. And, the research thus far in humans is certainly all encouraging. It takes a lot of money to get clinical trials going. There are a few clinical trials with rapamycin, but it's so safe for people to take. I think the downside of not taking rapamycin is much more detrimental than taking it. I guess I'm a proselytizer when it comes to rapamycin.

But, I got to ask you, the wholesale price, you talk about this in your book, wholesale price to pharmacies for a bottle of 100 2-milligram, I think it's called Sirolimus, I believe is the brand name.

Sirolimus.

Sirolimus.

Sirolimus is the brand name.

Yeah. Yeah, it's over $3,000. And in many cases, of course, if it's for longevity, that wouldn't be covered by insurance. So I'm curious what your personal strategy is because I think you talk about in the book, like, you're paying something like a $20 copay or something like that. So tell me about how you're getting your hands on this stuff.

You bet. So, um, when I first got my prescription for rapamycin, I took it to my local pharmacy, Ashland Drug. Pharmacist looked up, he said, "It's available, but I'm not going to order it for you. It's well over $3,000 for a bottle of 100 tablets. My prescription is just going to get filled for a few tablets, so he's going to have a lot of money in his inventory tied up that's not turning over." Right. So, I took it to the local chain drugstore. They don't have nearly the controls that independent retail pharmacies have. They ordered it for me and they fill it for me and I for a long time, for a couple of years, I've gotten it filled for $20 a month copay on my insurance program.

Right, your mom-and-pop pharmacist, the one with the soda fountain and the cameras. Right. Yeah. And, I know the type you're talking about. Now, I went a different route because you talk about this generic form called Rapapro, which is a product made by— actually, I think you can get it through this Anti-Aging Systems website, which is interesting because I interviewed another guy named Phil Micans about peptide bioregulators. And that's where I've been sending a lot of people, that same website, to get peptide bioregulators, which are a discussion for another day, but I also think are a fantastic life extension agent. But so, so for me and my wife, you know, if we're taking, uh, 1-milligram tablets, 5 of those once a week, those boxes of RapaPro are, I believe, about $69.99. So, that means we're paying about $30 a month each as a couple to take 5 milligrams, the dose we've been talking about of rapamycin once a week. So, we are not talking about expensive supplement. I mean, that's pretty affordable.

Yep. I'm showing the box of Rapapo on the screen here.

Oh, yeah, you got it held up.

Yeah. And, it's available from International Anti-Aging Systems. They are a company that's been around for quite a number of years. They specialize in making hard-to-obtain life extension drugs available. A couple of years ago, they got interested in rapamycin, and they contracted with an Indian pharmaceutical company to produce their generic proprietary brand of rapamycin that's called Rapapro. And this Indian pharmaceutical company uses a new nanotechnology for the production of Rapapro. So, the particle size is extremely small, which means it has very good absorption. So, I got excited about this because as you mentioned, Ben, the price is really reasonable. It's $69.95 for a box of— Yeah.

That's dirt cheap for a supplement with this many systemic effects. Yeah.

51-milligram tablets. And so, you're getting 100 tablets for $70 roughly. It comes out if you're taking 5 or 6 milligrams once a week, it's about a 2-month supply. For $70, about $35 a month. That's a very reasonable price.

Yeah. If people want to see the video of what the box looks like, if you go to BenGreenfieldLife.com/Rapamycin, R-A-P-A-M-Y-C-I-N, you can see Ross holding up the box here. But yeah, that's the exact box that's up in my pantry right now.

Yeah. So, I did my due diligence. I started ordering RapaPro and I started doing my sirolimus blood test. And, this is another thing I want to talk about, Ben, because I'm strongly encouraging people who take rapamycin to get their plasma serolimus blood test done to find out how well it's absorbed and what their plasma levels are. So, when I started taking Rapamore Pro, I did my blood test and I found it is very well absorbed. My plasma levels are right up there in the range where they should be. So, I just verified for myself that this is a really quality product. It does gets well absorbed and for a very reasonable price. And so, a lot of people can't find a doctor who will write a rapamycin prescription for them. Many people don't have insurance programs that'll cover it. This is a way people can get rapamycin for a very reasonable price. And the International Anti-Aging Systems people have actually said that people use my discount code of ROSS-10, they'll get a 10% discount on their initial order.

There you go. Cool. I'll put that information in the show notes for people and I'll link to interview with Phil Micans on peptide bioregulators as well. Where are you getting the sirolimus test?

Okay, that's a good point to bring up. So, the sirolimus blood test is made available by LabCorp. Big national company that does labs for all across the United States. So, I found out that Life Extension allows people to order the sirolimus blood test for $95.

You mean the Life Extension Foundation?

Yeah.

Okay.

Bill Fallon and his group. So, if you call Life Extension and order the sirolimus blood test, you pay them, They send you the order, you take the order to LabCorp, and you get their blood draw. That's $95. The same blood test is available directly from LabCorp for $54. Oh. But, that requires a physician's prescription. Well, I've educated my doctor about rapamycin. So, I went to her and said, "I want to be getting my sirolimus blood test so I can check my absorption and availability." She wrote out a prescription for the sirolimus blood test for me, and on it she put, "Good for 1 year." So, I can now go to LabCorp anytime I want and get my blood tested. I was taking rapamycin for well over a year, and when I did my blood test, the plasma levels were not nearly as high as I wanted them. So now, I've upped my dose to— I'm taking 10 to 12 milligrams once a week, and the blood levels are up as high as I want them. But, that's why I'm encouraging people, if you don't test, you don't know. And so, I really encourage people to do the blood test and check and make sure that they're getting adequate blood levels up in the levels that they want.

And, you haven't had any muscle loss or any noticeable decrease in strength from doubling your dose once a week?

I have not. The only thing I've lost is a little visceral abdominal fat. Huh.

Well, you can't complain about that. I'm just curious. You know, when I talk to guys like you or I don't know, this other guy I spoke with a few weeks ago, Bryan Johnson, who has this pretty extensive Blueprint protocol or Phil Micans or any of these other guys in the anti-aging sector, I kind of like to know anything else that you're doing. I mean, you mentioned you do some intermittent fasting. It sounds like you weight train, you take rapamycin, but is there anything else in your protocol that you think is particularly effective or that you swear by whether it's supplementation or certain parts of your daily routine?

I got a lot of things I can talk about. First of all, I just wanna emphasize that number 1 on everybody's list should be a healthy diet. And I'll say a few words about a healthy diet in just a couple minutes. Second thing is exercise. That's just gotta be number 1 along with diet. Diet and exercise, number 1 and number 2. In fact, on my website, I've got a study that I summarized, a group of Italian scientists a number of years ago studied a fairly large group of elderly people between the ages of 94 and 105. And, they were trying to figure out what's the number one thing for healthy aging. And, they examined a huge number of parameters. Turns out the number one thing for healthy aging, maintain your muscle mass. So, you have to do regular strength training or resistance training. Things like cycling and swimming and jogging, those are great aerobic exercises, but you're not building muscle mass. So, people need to understand the importance of doing strength training. And, I especially emphasize this for women because far more men do strength training than women and everybody needs to do it. And, I think there's tremendous benefit for most people to boost their glutathione levels. Most people have low levels of glutathione levels for a variety of reasons. Although—

Although, Ross, I got to interrupt you real quick with a caveat. I mean, obviously, as you age, you see a remarkable decrease in glutathione, same thing with NAD, for example. But many people do not do well from a genetic standpoint. I have an entire podcast with Dr. Kashif Khan about this with supplementing with straight glutathione and instead need to take precursors like N-acetylcysteine or selenium because they can actually, I believe it's excess methyl depletion that can occur with glutathione supplementation in someone who has poor glutathione absorption SNPs. So, just something to consider. I would recommend you listen to that podcast and make sure because I'm a guy who doesn't do as well glutathione as I do with N-acetylcysteine, selenium, and some glutathione precursors.

Those are all great precursors. I'm in favor of them. But, when people take glutathione orally, it's not well absorbed. It gets broken down and destroyed. Some of the liposomal delivery systems are a little more effective.

Yeah.

But, I happen to work for my day job. I'm the scientific director for a Dallas-based company named Essential Formulas. And, we have the sole rights to import a product from Europe called Reg'Activ is the brand name, R-E-G-'A-C-T-I-V. And, these products contain a unique strain of probiotic bacteria called Lactobacillus fermentum ME-3. And, we call it ME-3 for short. And, ME-3 synthesizes glutathione.

Ben Greenfield: Oh, interesting. So, that's the way that you'd be bypassing any issues with exogenous supplementation, just getting your body to make more of its own. I like that.

I'm going to look into this. Human clinical trials showing tremendous benefits. So, this is a real breakthrough in my mind because people can naturally boost their glutathione levels on a daily basis.

That is, especially with the increasing difficulty securing N-acetylcysteine. I think this is great. I didn't know about this. I'll look into it.

Yep. I'll send you stuff afterwards on all of this so that you can consult this.

I'll put it in the show notes for people too. Yeah, yeah.

Perfect. And, next item on my Life Extension formula list is crystal-free Coenzyme Q10. A lot of people know about Coenzyme Q10. Many people don't realize that the melting point of CoQ10 is 10 degrees higher than body temperature, which causes it to crystallize. When it crystallizes, it forms clumps. We cannot absorb clumps of CoQ10. It has to be single molecules in solution. And, if most of the CoQ10 products on the market have horrible rates of absorption, literally only 1 or 2%, there's a company out of Denmark, Pharma Nord, that has a patented process for keeping their CoQ10 in solution. They've done clinical trials. They get 3 to 10 times higher plasma levels than most of the commercial products on the market. So, I'm I'm a big proponent of crystal-free coenzyme Q10.

And, that's very good information too if someone's on a statin because of the CoQ10 stripping properties of statin and the associated muscle soreness and mitochondrial deficits. I know a lot of people on statins are taking CoQ10, but I don't think many of them are aware of this temperature issue and the availability of crystal-free. So, I'll get more information from you and put this in the shownotes too. Okay. So, that's super interesting. Crystal Free CoQ10 and Rejactiv.

Yep. The information I send you on CoQ10, Ben, from Pharma Nord, they've agreed to give people that order it with a discount code that I have a 20% discount. So, I'll send all that for your show notes so that your viewers will be able to get a 20% discount on Pharma Nord's CoQ10.

Okay.

Next topic I'd like to talk about, which I think is critically important, I am a microbiome guy. Yeah. My company, Essential Formulas, markets premium probiotics and I'm trying to reeducate the world about how the gastrointestinal tract and the gut microbiome really function. Most people have a total misunderstanding of probiotic bacteria and what they do and how they function. The job of your probiotic bacteria is to digest components in your food and break them down and produce secondary molecules that we call postbiotic metabolites. And, it's these smaller metabolites that the probiotic bacteria produce that have a wide range of biological activity. So, it's not the probiotic bacteria themselves, it's the compounds that the probiotic bacteria produce, these postbiotic metabolites that regulate not only your microbiome ecosystem but they get absorbed systemically and influence every single organ system in your body, especially your brain and your immune system. And, the problem, Ben, is that most people are not feeding their gut microbiome well. And, if you don't feed your probiotic bacteria well, they will not thrive and survive. They won't be able to produce the postbiotic metabolites that regulate your health. So, what are the types of foods that your probiotic bacteria require? They are dietary fibers and polyphenols. Those are the two primary food groups for your postbiotic metabol— for your probiotic bacteria.

Right. And by the way, I want to emphasize, you didn't just say kefir, kombucha, yogurt, kimchi, sauerkraut, even though some of those have those fibers in them. You're specifically talking not necessarily about fermented products but the polyphenols and the fibers themselves whether fermented or unfermented.

Exactly. You bet. I mean, fermented foods are great, but the fundamental mechanism of how the gut microbiome works is that probiotic bacteria digest and ferment dietary fibers and polyphenols to produce these postbiotic metabolites. Over 99.9% of the bacteria in your gastrointestinal tract reside in the colon. That's where all the action takes place. That's an anaerobic environment. And so, when we take dietary— when we ingest dietary fibers and polyphenols, humans do not have the enzymes to digest dietary fibers, so they pass totally through your digestive system. And the similar situation with polyphenols, most of them are massively large molecules. We do not absorb most polyphenols efficiently, so they will also pass through your digestive tract. But when these dietary fibers and polyphenols reach the colon, they are the food for your probiotic bacteria, And, that's when the bacteria will ferment these products, break them down, produce the smaller postbiotic metabolites that regulate your health. The problem, Ben, is that I've got multiple studies that report from 90 to 95% of American children and adults do not consume adequate amounts of dietary fibers and polyphenols. So, nobody's feeding their gut microbiome the way they should. And consequently, everybody has gut problems. And so, now, take a little time to dive into what it means to have a dysregulated gut microbiome, what we call dysbiosis, too many bad bacteria, not enough good bacteria. The reason bad bacteria are bad is because they produce compounds that are inflammatory. So, you get gut inflammation. And, when you have inflammation in the gastrointestinal tract, that causes a substance called zonulin to be produced. And, I don't know if your listeners are familiar with zonulin, but a physician by the name of Alessio Fasano who's a pediatrician at Harvard discovered zonulin. I hope he wins the Nobel Prize. I think it's one of the most important health discoveries of all time. Paralleling mTOR and autophagy. But, zonulin gets expressed when you have gut inflammation and it degrades and breaks down the tight junctions in the epithelial cells in the lining of your gastrointestinal tract and creates leaky gut or intestinal permeability. And, that allows lipopolysaccharides to leak through into systemic circulation. A quick explanation or definition of lipopolysaccharides, They are components of the cell walls of gram-negative bacteria in your intestinal tract. Everybody has them. They're supposed to stay in your gastrointestinal tract. But, if you have leaky gut, these lipopolysaccharides leak into your systemic circulation. They are highly inflammatory and they create systemic long-term chronic inflammation which accelerates your biological aging. So, it's critical for people to understand how to create and maintain a healthy microbiome with predominantly good bacteria. And, the way you do that is to feed your microbiome and your probiotic bacteria well. And, the key here, Ben, is that not just the quantity of dietary fibers and polyphenols, the thing that's important is the diversity. Most ecosystems are more functional and stronger and more resilient when they have a high level of diversity. And, the only way you can get a diverse microbiome with lots of different strains of probiotic bacteria is by consuming a wide diversity of different types of fiber-containing foods and polyphenols.

Ben Greenfield: I agree. I'm looking out my office window right now, and by the way, I've got right out in the garden, there's rosemary and thyme beyond that. Wild nettle, wild mint, dandelion, Oregon grape, and Oregon grape root. So, I do a lot of plant foraging. And, one reason for that, I make this fantastic wild plant pesto. Head nod, shameless plug for my cookbook. The recipe is in my "Boundless Cookbook." But, I go out of my way to eat a lot of these plant varietals. I got to ask you though, when you look at these postbiotic metabolites produced in the colon, are you primarily referring to short-chain fatty acids or things like butyrate?

That's just one. That's just one class of postbiotic metabolites. There's— we're just at the tip of the iceberg of this understanding of how this microbiome works. In the future, we will probably discover that probiotic bacteria are capable of creating thousands of different postbiotic metabolites. We know that some of them have a wide range of anti-inflammatory activity. Some of them directly kill pathogens. One of the most important things that postbiotic metabolites do is regulate the acid-base balance in the gastrointestinal intestinal tract. A healthy microbiome has an acid-base level that's just slightly acidic. When you have a slightly acidic acid-base level in the gut microbiome, you support the growth and the proliferation of your probiotic bacteria and it suppresses or inhibits the growth of bad bacteria. When people have dysbiosis, too many bad bacteria, not enough good bacteria, You become 10 to 100 times too alkaline. You have to get bound to that slightly acidic condition to have a healthy microbiome to allow your good bacteria to proliferate. And so, here's how you maintain this. You create this slightly acidic pH in the gut microbiome with postbiotic metabolites like short-chain fatty acids, which are propionic, acetic, lactic acid. And nucleic acids and organic acids and amino acids and folic acids, many of the different types of postbiotic metabolites are slightly acidic. And, that's how you create and maintain the slightly acidic pH that allows the good bacteria to thrive and it suppresses the growth of the bad bacteria.

And, that all comes down to diversity of fiber and polyphenol sources, it sounds like you're saying.

Exactly. Diversity, diversity, diversity. Yeah, yeah. Many people think that just taking a probiotic, there's, Americans think more is better. My probiotic's got 50 billion. Mine's got 100 billion. Mine's got 200 billion. When you take high doses of a single or several strains of probiotic bacteria like that, you're working against balance and diversity. And it's the same with prebiotics. Now, a lot of companies are putting some prebiotics in their formulation so they can get the term prebiotic on the label. Large amount of inulin, large amount of fructooligosaccharide, that's just one. You're working against balance and diversity. So, I try to get people to understand the importance of eating a little bit of as many different types of fruits and vegetables on a daily basis as you can to get this diversity of fibers and polyphenols. I want to encourage people to to Google my 8-minute YouTube video. If they Google Ross Salad Buzz on YouTube, I've got an 8-minute YouTube video that teaches people how to make a microbiome-supporting salad. I call it Ross's Salad Buzz, B-U-Z-Z.

You sent me the video. I didn't watch it. Maybe I'll watch it during lunch today while I have a salad. You know, by the way, it's interesting, Two things. One, I should mention because I just interviewed Colleen Cutcliffe yesterday at this company called Pendulum that makes a blood sugar-controlling probiotic that contains high levels of Akkermansia that they put inulin into, but I was pleased to hear her describe to me this secondary polyphenol supportive compound that they encourage people to take along with it. So, I don't want people to think just because a supplement has inulin, it means it's bad. It just needs to be accompanied. By their polyphenols. The other thing that's interesting, you know, is that it's concerning to me unless it is for the purposes of a short-term immune-friendly diet for healing the gut and eliminating a host of diverse plant defense mechanisms from entering the gut that so many people these days are on, a very fiber and polyphenol-poor carnivore diet or low-fiber keto diet I also think this is why many of the people I talk to follow that diet for some period of time wind up settling back into, in the case of a carnivore diet, some pretty significant fruit and avocado consumption. In the case of a low-fiber keto diet, a lot of them return back to a low-fiber keto Mediterranean type of diet rich in herbs and spices and polyphenols, which I think is an intelligent move. And again, I think there's a time and a place for an autoimmune-friendly diet like a short-term carnivore stint, if you need to give the diet a break from plant defense compounds. But long term, I think it's very important that people hear the message that you're sending, Ross, which is the importance of these gut postbiotics and the fact that you need diversity and polyphenols to get them. You know, we're running up kind of short on time, but you have that Salad Buzz video. You also have like a, a course or something like that about these postbiotics that you're talking about, don't you?

Yeah, I I've got a booklet that I can make available to all of our viewers free of charge. This is a booklet I wrote, Dr. Ohhira's Probiotics and Postbiotic Metabolites. And I'm the scientific director with Essential Formulas and we have the sole rights to import Dr. Ohhira's probiotics from Japan into the United States. This is a probiotic that's made in a multi-year fermentation process. They've got large 80-gallon fermentation vats in a sterile warehouse They put in a wide range of Japanese fruits and vegetables and mushrooms and seaweeds and 12 starter strains of bacteria. The bacteria get to digest these foods for 3 to 5 years before they encapsulate the product. And the final product has got over 500 of these postbiotic metabolites. Wow. So this is the fastest way to institute positive changes in the gut microbiome because you're directly ingesting these postbiotic metabolites. When people take a commercial probiotic, even if those bacteria survive transit through the harsh acid in the stomach, when they reach the colon, those bacteria have to locate dietary fibers and polyphenols, which most people aren't consuming enough of, and then start the process of converting them into the postbiotic metabolites, which takes time. Take Dr. O'Hare's probiotics and you are directly ingesting over 500 of these postbiotic metabolites. So you're directly getting— anti-inflammatory activity, rebalancing the acid-base level, reestablishing gut-brain communication, balancing your immune system. So, there's nothing else in the world like Dr. Ohira's probiotics which directly delivers these 500 postbiotic metabolites.

Are you saying Dr. Hairs or Dr. Harrows?

It's Dr. Ohira, O-H-H-I-R-A.

Oh, H-H-I-R-A. Okay, cool.

Yeah, he was a visionary microbiologist that took him 10 years to develop the system. He was initially a Buddhist monk, and then after he left the monastery, he became a landscape architect. He had a worldwide reputation as a landscape architect, and in 1976, the country of Malaysia invited him to put a large freedom park and design the architectural design, which he did. 1980, he went back to Malaysia for the grand opening ceremonies. He ingested some bad food and got violently ill. There was a shaman at these grand opening ceremonies that saw O'Hara lying on the ground writhing in discomfort and vomiting. He pulled some black syrupy stuff out of his leather satchel and started spoon-feeding O'Hara with this stuff, cured him right away. And he's a curious individual, so he finds out the stuff the shaman gave him gave him was made from locally fermented Malaysian fruits and vegetables. He takes it back to Japan, he plays around with it, he doesn't— he can't study it the way he wants to because he doesn't have the scientific education. So, at age 49 with a very successful landscape architect career with an international reputation, he walks away from that career, goes back to school, gets a degree in microbiology and starts this whole process of developing Dr. Ruhia's probiotics.

Wow. Well, this has been a wealth of information, Ross, and I'm super happy I had you on the show. I didn't even know we're going to go this deep into the gut, but this is just as interesting to me as the rapamycin piece. So, uh, yeah. All right, well, um, so bengreenfieldlife.com/rapamycin, R-A-P-A-M-Y-C-I-N. I'll have all the show notes over there. I'll follow up with Ross to get links and everything else for all this stuff. And, in the meantime, you can also leave your questions, your comments, and your feedback over there for Ross, for me. And Ross, thank you so much for doing this, man.

You bet, Ben. My website for people that want to know is naturalpharmacists.net. And, to get a free copy of this book, go to naturalpharmacists.net/OHIRABOOK, O-H-H-I-R-A-B-O-O-K. Ben, love being with you.

Cool. Thanks for doing this, Ross. Alright, folks. I'm Ben Greenfield with Ross Pelton. Natural pharmacist signing off from BenGreenfieldLife.com. Have an amazing week.

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