Are You Ready To Join The Life Extension Revolution? The Most Promising Life Extension Drug With Dr Ross Pelton

Lisa: Well, hey everyone, and welcome back to Pushing the Limits. Today I have an exciting guest for you. I've always managed to pull out the best of the world. I have Dr Ross Pelton with me from Oregon. Welcome to the show, Dr Ross. Fantastic to have you.

Dr Ross Pelton: Yeah, I'm really excited to push the limits with you today.

Lisa: Well, you definitely push the limits. Now, you are a pharmacist, but you're also a natural pharmacist.

Dr Ross Pelton: I'm a recovering pharmacist.

Lisa: A recovering pharmacist. I like that. And you've written 12 books, I believe, to date. You're an expert in the fields of longevity and anti-aging, and you've just released a book which we're going to dive into today, along with many other topics, and see how many we can get to. And we're definitely going to have Dr Ross on again, I think. But your latest book — can you just tell us about your latest book and what it's about, and then we'll dive into what you know for these viewers and people on the podcast?

Dr Ross Pelton: Yeah, so it's a mouthful. The title is Rapamycin, mTOR, Autophagy and Treating mTOR Syndrome. So I recognise that's a mouthful, and a lot of people are not familiar with the terms mTOR and autophagy.

Dr Ross Pelton: One of the things I really emphasise is that if anybody wants to become good at anything, whether it's medicine or being a lawyer, you have to develop a literacy for the language of that profession. It's the same thing with health. If people want to really be healthy, they have to study it, they have to work at it. Most of us did not have good role models and good teachers to begin with early in life, and so you have to learn these things.

Dr Ross Pelton: And so mTOR and autophagy are new terms for most people. When you read my book, though, I go over it and over it and explain it in many different ways over the course of the book, and you'll get to understand what these terms mean and the significance of them.

Dr Ross Pelton: And so there's three things here. First, there's rapamycin. It's the most effective life extension drug that's ever been discovered. But to my way of thinking, these terms mTOR and autophagy are even more important than the drug rapamycin, because mTOR and autophagy have given us a totally new understanding of cellular metabolism, the entire aging process, and so the health of every single cell in your body and ultimately the aging process. So we'll dive into all of this for our viewers today.

Lisa: Yep. So rapamycin — let's go into the history of rapamycin. So for people listening who've never heard of rapamycin, which is probably most of the people, it's a drug that was discovered, or a compound that was discovered, on Rapa Nui, Easter Island, back in the 60s. Can you tell us a little bit of the background of that story, and why did these scientists go to Easter Island to find this?

Dr Ross Pelton: It's a team of Canadian scientists in the 1960s that made a scientific expedition to Easter Island, and the purpose of that scientific expedition was to look for sources of new antibiotics and antifungal drugs. So they took a lot of soil samples and brought them back to their labs in Canada, and one of the compounds that was produced by a strain of soil bacteria was this compound that they named rapamycin, which is after the indigenous people's name for the island, which is Rapa Nui.

Dr Ross Pelton: And so rapamycin originally was being developed as a new antifungal drug, and then they discovered that it suppresses the immune system, so all of that research just came to a screeching halt. But in September of 1999, the FDA approved rapamycin for people to get kidney transplants, because people that get organ transplants need to be on immune-suppressing drugs for the rest of their life.

Dr Ross Pelton: And then some samples of rapamycin were sent to the National Cancer Institute, and they went crazy over it. They discovered that it is the first example of a totally new type of chemotherapy. Most chemotherapy is what we call cytotoxic — it kills rapidly dividing cells, and in addition to killing tumour cells, it kills a lot of cells in the body. Your bone marrow and the cells lining your intestinal tract, the epithelial cells, have very rapid rates of turnover, and so that's where all the side effects from these cytotoxic chemotherapy drugs come from. Rapamycin is not cytotoxic. It doesn't treat cancer by killing. It's cytostatic — it just stops the cancer growth.

Dr Ross Pelton: So the National Cancer Institute elevated rapamycin to priority status for rapid research, and in the early 2000s it gained FDA approval for treating several different types of solid tumour cancers. These FDA approvals have actually been a large hindrance to rapamycin being accepted as a life extension drug, because you usually don't give chemotherapy to people that are healthy and want to work on life extension.

Dr Ross Pelton: But what scientists have found is that instead of taking rapamycin every single day, which will suppress the immune system, if you take it just episodically, like one dose once per week, you get some significant health benefits. So let me explain why that is. This is the mechanism of action, how rapamycin works.

Dr Ross Pelton: When rapamycin gets absorbed across the cellular membrane into a cell, it binds to an enzyme that's named mTOR, and that stands for the mechanistic target of rapamycin. They just named it that because that's where it binds. But this protein — it's a protein slash enzyme — its primary function is that it's a master signalling molecule that recognises when nutrients are available to the cell. So when nutrients are available, mTOR sends out signals and says, use these nutrients to build and grow, make new proteins, new enzymes, new cellular components. And by the way, David Sabatini is the scientist that is credited with discovering mTOR and naming it.

Dr Ross Pelton: So the other half of the equation is autophagy. Excuse me, a little cough here, catching my throat. So in 2016, Yoshinori Ohsumi won the Nobel Prize in physiology and medicine for his discovery of autophagy. So autophagy is the other side of the equation in cellular metabolism.

Dr Ross Pelton: And so the other side, autophagy, gets activated when nutrients are not available to the cell. And when nutrients are not available, your body and individual cells are able to target old, damaged, misfolded proteins and enzymes and under-functioning cellular components. You can break them down and either detoxify them, get them out of the cell, or re-utilise the innate ingredients, like amino acids, to rebuild healthy new proteins and healthy new enzymes.

Dr Ross Pelton: So it turns out autophagy is a major detoxification function for every cell in your body, and it's also the major process of rebuilding your body. And this is one thing a lot of people don't understand: you have to constantly be rebuilding your body, and if autophagy is not activated, you're going to suffer long-term health consequences.

Dr Ross Pelton: And most of humanity is suffering now. We have what I call an epidemic of epidemics. We've got heart disease, cancer and diabetes, and Alzheimer's, and autism — I mean, off the charts. And 50, 60, 70 years ago when I was a kid, none of these things were an epidemic. So I think the health of humanity is in a significant decline, and I think this mTOR-autophagy function, these two cellular functions that are terribly out of balance now, I think it's a fundamental problem that is contributing to many of the health problems.

Dr Ross Pelton: This is why this has gotten out of balance. Remember, mTOR senses when nutrients are available. For millions of years of human evolution, people did not get up in the morning and go to the kitchen and open the refrigerator and start to make breakfast. People didn't eat three meals a day for almost 99.9% of human evolution. And these days people eat all the time relative to our ancestors: breakfast, lunch, dinner, in-between meal snacks, dessert, evening cocktails. And that has taken the mTOR-autophagy ratio and thrown it way out of balance, because when nutrients are available, mTOR is always getting activated, and people are eating and activating mTOR all the time, and autophagy's not getting its due.

Dr Ross Pelton: And one of the ways I express this is that if you're driving a car, you can't drive that car constantly with your foot to the metal, pedal to the metal, racing. You have to slow down, you have to take breaks, you have to have rest periods. And the other way I talk about autophagy is that if you have, for example, a flat tyre on your car, you can't put the new tyre on until you take off the old tyre.

Lisa: Yeah, that's a good analogy.

Dr Ross Pelton: Autophagy is so important because you've got to get those old damaged proteins and enzymes and cellular components out, so that when mTOR gets reactivated, you'll build healthy new proteins and healthy new enzymes. And so this is one thing I really emphasise to elite athletes and to people that are doing strength training on a regular basis: you've got to do something to activate autophagy so you can continually rebuild your body, and you'll be a better athlete with more strength and more stamina and more endurance if you activate autophagy appropriately.

Dr Ross Pelton: And that's what rapamycin does. Rapamycin goes into the cell and binds to mTOR, so it partially inhibits it so you can activate autophagy. So that's really what this is all about. It's learning how to activate autophagy and rebalance this mTOR-autophagy ratio. And I got so passionate about this that in the second edition of my book I proposed the mTOR-autophagy theory of aging. I think this is critical for people to understand.

Dr Ross Pelton: And people often ask me, well, isn't there a natural way to do this? Yes, there is: intermittent fasting. When you fast, you go for longer periods of time without nutrients coming in, and you condense your daily nutrient intake into a smaller period of time. And so yes, that's the natural way to do it. But most people aren't going to discipline themselves to do intermittent fasting. I advocate doing everything to promote your health, so do some intermittent fasting and take rapamycin. And there are some other anti-aging life extension drugs that are good, and there are many other different types of activities and therapies that have life extension activity, different antioxidants and so forth, and we can get into that. But initially, on rapamycin, here we are.

Lisa: Yeah, this concept is just mind-blowing, actually. I've known about mTOR and autophagy for a long time, because obviously I've been in this space for a long time. But when you said this is the breakthrough, this is the information, this is the thing that we need to be paying attention to — because it's counterintuitive in a way. You'd think we want mTOR all the time, which is the building, the making of the new components. But without the clearing out of the garbage, which is the autophagy piece of the puzzle — my analogy is you bring the groceries into the kitchen, you cook your dinner and then you don't clear the garbage, you just bring the new groceries, cook the dinner, and so on, and pretty soon your kitchen is full of garbage and you can't operate in there. And that's exactly what's going on with this mTOR-autophagy piece.

Lisa: And autophagy — can you explain to me one thing that I've struggled with? You have autophagy and then you have senescent cells and then you have apoptosis. Can you explain the difference between autophagy and apoptosis to me, because I'm struggling with that concept? Senescence is when there's a natural process when cells reach the end of their lifespan, the body can get rid of them, recycle them. Well, senescence is when old cells don't go away, that recycling of the old cell stops, and they keep on producing inflammatory markers, and so it's a major source of chronic inflammation, these senescent cells that have not been recycled. And there is a similarity, because autophagy is recycling old damaged cells — not cells, but...

Dr Ross Pelton: And that's the difference. Senescence is cells; autophagy is cellular components.

Lisa: Okay. And then apoptosis, that's when the senescent cell has imploded on itself, which we also need it to do, and that's the body's process of getting rid of these old cells. And when apoptosis isn't working, the senescent cells stay there, the old cells become senescent and instead...

Dr Ross Pelton: ...of going away, they keep doing some level of biological activity, which is really putting out inflammatory markers. And rapamycin decreases senescence.

Lisa: Wow. So it's doing autophagy and it's killing off senescent cells.

Dr Ross Pelton: And so we have this family... You're not killing them off, but it's decreasing senescence because you're turning over things in the cells and keeping your cells healthy.

Lisa: Okay, so they're not reaching a senescent state. Ah, gotcha. And because we have these senolytics as well in the anti-aging space — the things like fisetin and quercetin, and there's many, many ones — so that's working on a slightly different pathway than the rapamycin is, right?

Dr Ross Pelton: Right. And one thing I want to really emphasise here for people: David Sabatini discovered mTOR and named it in 1996. Yoshinori Ohsumi won the Nobel Prize for discovering autophagy in 2016. These are relatively newly understood scientific concepts, and it's a foundational thing that regulates every single cell in our body, and metabolism and health and the entire aging process. So in terms of scientific terms and our history of biochemistry and the knowledge of how the body works, this is really new stuff.

Lisa: Yeah, yeah. This is a game changer. This is a game changer when you get this concept.

Dr Ross Pelton: Yes. And I really emphasise to people, rapamycin is not a miracle cure. If you've got bone-on-bone arthritis, rapamycin is not going to cure it. If you have an aneurysm in an artery and that artery is ready to blow and give you a heart attack or a haemorrhage to the brain, rapamycin is not going to correct that. Rapamycin is a slow, day-by-day improvement of your health. When you start taking rapamycin and activate autophagy, every single cell is going to start to work better in your body over time.

Dr Ross Pelton: And in animal experiments, virtually every single type of age-related disease responds — metabolic diseases, cardiovascular disease, things like Parkinson's disease and Alzheimer's disease. In the animal models, these things all improve. You're slowing down the process of biological aging. In some cases, like cardiovascular disease, the animal experiments show they're reversing it.

Lisa: Wow, wow. You don't reverse things very often. And so this is cellular rejuvenation. This is really the renewing and remodelling of your body. You're building new proteins and new enzymes and new cellular components.

Dr Ross Pelton: And so yes, it is actually the process, on a regular day-to-day basis, of rebuilding your body.

Lisa: Now, when people go to the doctor — say, healthy people who are interested in life extension and health span and the things that you and I are very much interested in — they are likely to run into a blank wall. When you ask the doctor, "Can I get rapamycin, please?", they're going to look at you and either they don't know what rapamycin is, or they'll know it as a cancer drug or an immune suppressant drug, and then they'd look at you as if you've got two heads. How is this going to change? How are we going to get access to these amazing things?

Dr Ross Pelton: My book lays it all out. I'm a scientific guy and I've got all the scientific references, and the other thing I say in my bio is that I'm bilingual — my two languages are English and science. I can talk about the science so normal people can understand it. And so my book is really designed to accelerate people's learning curve about rapamycin. Many people buy a copy of my book and give it to their doctor, or they loan their copy of my book to their doctor and say, "Please read this, this is safe and this is healthy and I want to take it."

Dr Ross Pelton: And the next thing is, if you can't find a doctor who's willing to write a prescription for you, there are some physicians that are so supportive of rapamycin and understand its benefit, they will do telemedicine visits for people. You can be on a phone call with a doctor for 20 minutes or so and they'll charge you for that, but then they'll mail you a prescription for rapamycin that you can get filled.

Lisa: So that's exciting options, yeah.

Dr Ross Pelton: I get my rapamycin prescription filled at my drugstore for a twenty dollar copay on my monthly medical insurance. So people that have medical insurance — it's an FDA-approved drug — so many people can get it on their insurance.

Lisa: You're lucky in the States. I think they want to mention here...

Dr Ross Pelton: I'm glad you brought this up. This is a very new breakthrough.

Lisa: Yes, I've got that. Yeah, so I had Phil Micans on the show last week.

Dr Ross Pelton: Wonderful.

Lisa: Yeah, he talked about peptides.

Dr Ross Pelton: That's right.

Lisa: And so this is a way — yeah, explain to people. And I've got links to Phil's links in my show notes, so I'll put those in these show notes as well.

Dr Ross Pelton: I'm actually going to do a little video or a little educational PowerPoint slide presentation on this so I can explain it better to people and send it out to people. But this is a generic form of rapamycin that a company named International Antiaging Systems has developed, and they have a very high quality, well-respected drug company in India make this. And that company is using a new nanotechnology, so the particle size is very, very small, which makes it much better absorbed. And rapamycin traditionally is a very difficult molecule to absorb. It's a fat-soluble molecule — we don't absorb fat-soluble molecules very efficiently. If you take rapamycin with a meal where you have fat in the meal, you're likely to get better absorption.

Dr Ross Pelton: But anyway, back to Rapa Pro here. So you can order Rapa Pro from International Antiaging Systems and get it sent to you in the mail, and it is legal. Now, a lot of people question, how can that be legal? You're getting a prescription drug without having a prescription. On International Antiaging Systems' website they say you should have a doctor and should have a prescription for it, but they don't check that. So you can go on the website and order Rapa Pro and get it sent to you.

Dr Ross Pelton: A couple of other things I want to say about this. Because of some international banking regulations, they do not accept payment on credit cards. There's two options: you can pay with a bank draft, or what's called an e-check. When I went to pay with a wire transfer, I found out that my bank wanted to charge me $45.

Lisa: Yeah, it's a rip-off. I totally...

Dr Ross Pelton: So I have been ordering Rapa Pro using the e-check option. At the checkout you put in your bank routing number and your account number, and there's no extra charge for that, and it comes through just fine. You can also use Bitcoin, by the way — you might not know that.

Dr Ross Pelton: International Antiaging Systems does not sell this to the general public; it's a membership organisation. How did they do that? One cent of your first order, your initial order, is your membership fee. So that's how they make this a membership organisation, and that makes it legal for them.

Dr Ross Pelton: And in 1988, I think, the FDA in the United States made a new ruling during the HIV/AIDS crisis that made it legal for people to import up to three months of their personal medications. And so now people can import up to three months of Rapa Pro for themselves and it's all legal. And so it gives you the opportunity of getting rapamycin without a doctor's prescription — a very high quality product, well absorbed. I've been doing blood tests on myself to test my blood levels and find out it's really well absorbed. And I'll give you something to post on the show notes at the end of the show: if people use the coupon code at the checkout called ROSS-10, they get a 10% discount on their initial order of Rapa Pro.

Lisa: Yeah, no, that's brilliant. And yeah, I've had Phil on, and we're all over International Antiaging Systems because they're doing a wonderful job trying to get us access to things that are going to keep us healthy. And it's been a frustration of mine for years, trying to get stuff for my mum and not being able to get things in the country. So I'm very grateful to him and his team for doing what they do, and also the bioregulators and the other things that they have, which are all cutting edge and well researched and fantastic for us to have access to. So thank you for that.

Lisa: So back to the story of rapamycin. We're now managing to get this. Now, there's decades of animal studies. Can you explain how much is there in human research, and how do we know what dosages to take, and when should we start rapamycin?

Dr Ross Pelton: Although there's a lot of animal research showing the benefits of rapamycin, human studies are not nearly as advanced. We just haven't had the time, and it's hard and expensive to do these studies. And I'd like to talk about the first study that kind of broke open this whole area of rapamycin for humans. A lady scientist by the name of Joan Mannick, who was working, I believe, for Novartis, one of the big multinational drug companies. She had the enviable job — they hired her and told her she could work on anything she wanted, and she was interested in aging, and she decided to work on rapamycin.

Dr Ross Pelton: So Joan Mannick selected a group of elderly people — relatively elderly, they were 65 years old or older. She divided them into four groups. One was the placebo group, and then the other three groups took a different dose of rapamycin or a rapalog, a rapamycin-like drug. There was one group taking, I believe, half a milligram daily, another group was taking five milligrams once a week, and I think the third group was taking 20 milligrams once a week.

Dr Ross Pelton: So they took the drug or the placebo for a prescribed period of time — I think it might have been 12 weeks, something like that. Then she stopped the drug and subjected all of them to the seasonal flu vaccine and measured how their immune system reacted to that challenge of the flu vaccine. It turned out that the people taking five milligrams once a week, that was the sweet spot. Those people 65 years old and older got a 20% boost in the effectiveness of their immune system.

Lisa: That's a huge health benefit. That's huge.

Dr Ross Pelton: 65 years old and older. And so this is the study that identified that taking rapamycin episodically, just once a week instead of daily — you just get a periodic suppression of mTOR so that you can activate autophagy. And that seems to be the sweet spot. We don't know yet. We don't know if it should be a dose once a week or once every 10 days or once every two weeks. We don't know if five or six milligrams is the best dose, or 10 milligrams. And I think eventually we'll be able to fine-tune things, so we'll be individualising dosage and the frequency of dosages.

Dr Ross Pelton: I was on rapamycin for two years, and then I started doing my blood tests, and I found out my plasma levels were not nearly as high as I anticipated and as I wanted them. So I increased my dose from six milligrams a week to 10 milligrams a week, and now my blood levels are up in the range where I want them to be. And because of my personal experience with testing, I think everybody that's going to be doing rapamycin should be testing. If you don't test, you don't know.

Lisa: How do we get that, and what is the test? Because again, once again, I don't think down here we can...

Dr Ross Pelton: Down in New Zealand... Life Extension Foundation, which is international — you can call Life Extension Foundation and order the sirolimus blood test. The generic name for the drug rapamycin is sirolimus, S-I-R-O-L-I-M-U-S. And that drug test through the Life Extension Foundation costs 95 dollars. They have staff, so it's legal for them to write the order for you to get the sirolimus blood test. Then you have to take that order to LabCorp, which is the company that does the blood draw. So I did that for a couple of times, and then I went online and I found out you can get the same

Dr Ross Pelton: ...blood test from LabCorp for 59 instead of 95 from Life Extension, but you have to have a doctor's order to get the 59 dollar blood test. So I went to my physician, who I have educated about rapamycin, and she was very happy — she wrote me a prescription. She said sirolimus blood test, standing order for one year. So I can go in and get this blood test anytime I want for a year.

Lisa: Wow.

Dr Ross Pelton: And so I encourage people to talk to your doctor, ask them to write you a prescription for the sirolimus blood test so that you can get the 59 dollar charge rather than paying 95 to Life Extension.

Lisa: Although that would be just for people in America. That won't be valid for anyone listening in New Zealand and Australia, other Commonwealth countries.

Dr Ross Pelton: I'm sure New Zealand and Australia have different laws, but I think that you have places that will do a blood draw. And so I would call the major blood draw facilities and ask them if they have the same test, and I can give you the information from Life Extension so you can cross reference and tell them how to ask for this and see.

Lisa: Okay, so Mike might be a good person to ask about this also, at International Antiaging Systems. Because it would be good to know, is what you're taking enough? And as you've just found, you actually needed a higher dose. And this is the nuance of that conversation that we don't have all of that information.

Lisa: Now what about people who say, well, are we not suppressing the immune system? That's what it was originally used for. And how is it boosting the immune system when it's...

Dr Ross Pelton: Well, I don't like the word boosting, because you don't want to boost your immune system, you want to modulate it. In fact, that's a very good point, because some of the scientists writing about rapamycin have said that it's not an immune system suppressive drug, it's an immune system modulator. That's a key point.

Lisa: That's key. And when you activate mTOR all the time, you'll suppress the immune system. So you give mTOR a break and allow autophagy to function, and you get a normalisation of that function and modulate the effects.

Lisa: So just going back to the mTOR-autophagy piece. People who are eating all the time — the typical three to six meals a day that we're all told to eat — and they're going to the gym and they're working out and they think they're living healthy, they're activating mTOR and they're not doing that autophagy piece. So how would a young athlete listening to this, or someone in their 40s who's trying to also deal with ageing and stopping ageing — what would be the best combination? Do you take rapamycin on the days where you're not training, or can you take it and it doesn't matter?

Dr Ross Pelton: I take rapamycin once a week and I do the gym almost every day. I mean, at least five times a week, and I do aerobics, and I started doing a spin class which is taking me to the wall, aerobic fitness. But I don't really notice any difficulty exercising after I've taken a dose of rapamycin. And my plan — the first two or three or four days the plasma levels are higher and mTOR is more inhibited, but I have not found that to be detrimental to my exercise at all.

Dr Ross Pelton: There's another thing I want to mention here: who should be taking rapamycin? Because mTOR stimulates growth, you would never give rapamycin to a child, because they're in a period of rapid growth. A pregnant woman should never take rapamycin, because their developing foetus is at a very rapid, maybe the most rapid, time of growth, and so you don't want to inhibit mTOR at all. And we don't know exactly what's the best age to take this, but I think somewhere between age 30 and 50 is a good time to start. And I think that it's going to vary with different types of people. If you've got a 30-year-old person with metabolic syndrome and maybe type 2 diabetes, they might be better off starting at age 30, whereas a physically fit person maybe shouldn't start until 45 or 50. But I also emphasise here, we don't know the answers to these things. We just know from the animal models and some of the human studies that have been done that there's tremendous health benefit over time to rebalancing the mTOR-autophagy ratio and giving autophagy its adequate time to function.

Lisa: Yeah. And that brings in the fasting as well. If you're able to do some periodic intermittent fasting, bringing that into the piece is going to accelerate that autophagy. And then there are some other molecules — I'm designing a formulation at the moment with spermidine in it, which I'm quite excited about. So have you come across spermidine?

Dr Ross Pelton: I know about it. I don't take it. I do take metformin.

Lisa: Yeah, I'm on metformin as well. So there's a number of different things.

Dr Ross Pelton: One other thing I want to say about RapaPro: the people at International Antiaging Systems have done a very good job at bringing this product to people at a very reasonable price.

Lisa: Yeah, it is a pretty expensive drug.

Dr Ross Pelton: I'll tell you a story. When I took my first prescription to my local drugstore here, the pharmacist looked it up and said, "It's available, but I'm not going to order it for you. It costs between three and four thousand dollars, and I'm just going to have a few tablets filled, like 12 tablets, and I'm going to have all that money tied up in my inventory." So I took it to the local chain drugstore and they didn't have such tight inventory controls, and they were able and willing to order it for me, and I started getting it filled. But International Antiaging Systems, the price for RapaPro is about 35 dollars a month US.

Lisa: Yes, it's crazy.

Dr Ross Pelton: Incredibly reasonable price, which is for generally a very expensive drug. And they hope to even bring the price down more in the future. But for somebody that's taking six milligrams once a week, which is probably the most common dose where people start at, one box here of the RapaPro tablets is about a two-month supply. It's 69.95, about 70 dollars, which is 35 a month. That's an incredibly reasonable price.

Lisa: Yeah, they've done really extremely well, and it's just amazing what they do there.

Lisa: Let's go and talk a little bit now about some of the other things, because you're an expert on so many areas. I wanted to dive into some of the other things that you talk about. Now one of them, I heard on one of your podcasts, you were talking about Lactobacillus fermentum ME-3 — a particular strain of probiotic that can help us with glutathione. Open up that box for us.

Dr Ross Pelton: Well, before we shift, I forgot about one thing. I want to tell all our listeners how to get my book.

Lisa: Oh yeah, sorry about that. So to get Ross's book — if you can't see this because you're not on the video, you're on the podcast — you can call the Life Extension Foundation, that's 866-598-6747, and we'll put that down in the show notes as well. And you'll also get, besides Ross's book, you'll get a six-month subscription to the Life Extension magazine, which is fabulous as well. So do ring that number and get that book via that way if you want the magazine.

Dr Ross Pelton: They're open 24 hours a day, so anywhere in the world they can call and order the book.

Lisa: That's amazing. So thank you for that. And now, back to the probiotics, ME-3. It is certainly a fascinating topic. I was just mind-blown when I heard your research on this.

Dr Ross Pelton: Lactobacillus fermentum ME-3 is a strain of bacteria that was isolated from the intestinal tract of a healthy one-year-old child in 1995. And at the time they were testing a lot of different strains of probiotic bacteria for their antioxidant activity. Most of them didn't have much at all. And they tested Lactobacillus fermentum ME-3 and its antioxidant activity was off the charts. They thought they'd made mistakes. They tested it over and over again and they regularly could show that it had incredibly high antioxidant activity.

Dr Ross Pelton: So several years of scientific research to discover the mechanism of action, and they found out that this unique strain of probiotic bacteria synthesises glutathione. And glutathione is called the master antioxidant. It's the most prevalent antioxidant in our bodies. It's made in every single cell. Tissue levels of glutathione are highest in your lung tissue and in the liver. And in addition to being an antioxidant, glutathione regulates a great deal of your detoxification. It's critical for your immune system. It has powerful antiviral effects. So it turns out that glutathione is one of the most important and multitasking compounds in our bodies, and it is so important that I am currently writing a paper titled The Glutathione Theory of Aging.

Dr Ross Pelton: So it's just really incredibly important, and I think that anybody who is interested in healthy longevity, one of the most important proactive things you can do is increase your glutathione levels. There are many things that deplete glutathione, so virtually everybody has sub-optimal levels. Every time glutathione functions as an antioxidant, every time it neutralises a free radical, you're losing a molecule of glutathione. Every time glutathione detoxifies a toxin, like a molecule of mercury, or the toxins in the smoke from these wildfires we've got going on, the glutathione binds with the toxin and gets eliminated. So it's eliminating the toxin, but you're also eliminating glutathione. So glutathione levels are always being depleted as an antioxidant and in detoxifying things. And so I just think it's one of the most, as I said, proactive things people can do, to boost their glutathione levels.

Dr Ross Pelton: So what are the different ways you can boost glutathione? You can take glutathione precursors like N-acetylcysteine and lipoic acid, and several other things can boost glutathione levels. And you can go to a doctor's office — a lot of anti-ageing doctors will do intravenous glutathione. Tremendous health benefits from intravenous glutathione for a lot of people, but it oxidises very quickly, gets used up, so benefits only last for a couple of days. And people that are doing IV glutathione need to go to the doctor about twice a week for the intravenous glutathione infusions, which is time consuming — you have to drive to a doctor's office, you have to sit in a chair with an IV drip in your arm, it's expensive, and you have to pay three or four hundred dollars per infusion.

Dr Ross Pelton: And the third way is taking products that contain Lactobacillus fermentum ME-3, which is the bacteria that synthesises glutathione. And this was discovered, as I mentioned, in 1995 by a microbiologist, Marika Mikelsaar, who's now professor emeritus of the Department of Microbiology at the University of Tartu in Estonia. Estonia is a little country in Eastern Europe, borders on Russia, but they are one of the leading institutions in the world studying the microbiome. And they started studying the microbiome in the late 50s and in the 60s when they started studying the men that were chosen to be cosmonauts for the Russian space programme.

Lisa: Wow.

Dr Ross Pelton: They were concerned that extended time in space would maybe mess up the gut microbiome and cause health problems. So they started studying their gut microbiome and probiotics many decades ago, more than half a century ago. And then when Russian astronauts were put in the space station, they continued to do studies on this. So they've had this long background in studying the microbiome.

Dr Ross Pelton: And then in 1995 there was a joint study between Sweden and the University of Tartu studying children that have skin diseases like eczema and so forth, because the children in Sweden have a very high incidence of these skin conditions and in Estonia they have virtually none. So they started studying these children, looking at the differences in their microbiome, trying to learn what they could about the microbiome of kids that have these skin diseases. Well, Lactobacillus fermentum ME-3 was one of the strains of bacteria that got extracted from that Swedish-Estonian study. And later on, when they were studying antioxidant activity of lactobacillus bacteria, they decided to test this Lactobacillus fermentum ME-3.

Dr Ross Pelton: So fortunately it had already been extracted and been saved in the laboratory, so when they tested it for its antioxidant activity, again, as I mentioned earlier, just off the charts. So this is kind of the history of how this got discovered and developed, and the University of Tartu still owns the patent. And there's a company in France that has secured the rights to market it worldwide. My company, Essential Formulas, in the United States, has the sole rights to import and distribute these products in our country and also Mexico and Canada. But they're marketed under the brand name Reg'Activ. It stands for R-E-G apostrophe A-C-T-I-V. That's an acronym for active regeneration, Reg'Activ.

Dr Ross Pelton: And there are now four different Reg'Activ formulations. There's Detox and Liver Health, Immune and Vitality, and Cardio Wellness. And each of those three products has some other supplemental ingredients along with the Lactobacillus fermentum ME-3 that will support either your liver detoxification pathway, your immune system, or your cardiovascular system. After we had these products marketed in the United States for a couple of years, a lot of naturopaths and functional medicine physicians came to us and said, we want a product that just has the ME-3 in it, because those other three formulations are two capsules a day. So then we produced a product that we now call Essential ME-3, which just contains eight billion of the active Lactobacillus fermentum ME-3 bacteria, and that dose is one capsule daily.

Lisa: That's great. And I've reached out to Dr Ohhira's team, isn't it, today? I reached out to them to see whether we can get that here, so keep an eye on my shop, everyone. We'll hopefully get it.

Dr Ross Pelton: Oh, this is not Dr Ohhira, this is the University of Tartu in Estonia. But I'll get you connected with the people on this product also, so that you can look into it.

Lisa: So both of them, yeah. To have them, yeah. So it's a breakthrough product also to be able to boost your glutathione levels on a regular basis.

Dr Ross Pelton: And here's some examples of why glutathione gets depleted. Alcohol is metabolised by glutathione in the liver, so anybody that's drinking regularly is depleting glutathione levels. Smoking is one of the big ones — cigarette smoking, that's a huge depletor of glutathione. And many people that smoke also drink, so that's a double whammy. And there's a lot of environmental toxins that deplete glutathione, stress levels deplete glutathione. So boosting glutathione levels is really a key anti-aging, life extension therapy.

Lisa: And I study genetics and I know my own genes, and there's a family of genes called the GST, the glutathione GST family of genes. And I've got disastrous genes when it comes to the GST — so GST T1, M1 and P1. I've only got one that's working. These are major detoxification enzymes for the body.

Dr Ross Pelton: And people like you have polymorphisms and detox doesn't work quite as well, and you want to boost your glutathione levels.

Lisa: Exactly. So I'm very excited about hearing this, because I've been wondering how to do that. And as an athlete, of course, I've smashed the heck out of my body, which has also added to that problem.

Dr Ross Pelton: You're right, because you're over-oxidising, you're doing too much oxidative damage, and so on and so forth.

Lisa: So trying to undo some of that damage now in my mid-50s. I'm hoping it's not too late.

Dr Ross Pelton: It's never too late.

Lisa: Exactly, to kind of motivate people that it's never too late.

Dr Ross Pelton: I read a book back in the early 1990s called Biomarkers, and that book — two authors, William Evans and I forget the second author's name — but that book categorised 10 of the most reliable biological markers of aging. Every single one of them is tied into your muscle mass. So once I realised that, I went out and got a universal gym, weight training ever since. But I followed the work of William Evans over the years and he's published multiple studies where he goes into a nursing home and takes frail, elderly 90-year-old and older people. I think one study was eight people from 94 to 105 — a 12-week strength training programme. The gains they make are like science fiction.

Lisa: Wow.

Dr Ross Pelton: So at any time, at any age, if you start working on the body and working on your health, your body will respond.

Lisa: Yeah, I have Mum at the gym three to four times a week, and the weight training is the most important thing. And we have to do cardiovascular, but it's the weight training. And there's a gentleman at my gym, he's 87 years old, and I've been watching him over the last few months, and he's just always on the elliptical and going for it. And I talked to him a few times over the last few weeks about maybe adding in some strength training to his regime, and he was like, well, no one's ever told me that. And I said, well, you know — he was quite sarcopenic as well — I said, look, muscle equals longevity. Cardiovascular is all well and good for the heart and the cardiovascular system, but actually you're breaking down more muscle and you can't afford to do that. You should be doing much more on the strength training side. So I'm a huge proponent, coming from the ultramarathon background, and I have to talk some of my colleagues around to putting in the strength training as the key. I've seen that much.

Dr Ross Pelton: That's a great topic that you brought up, Lisa, because I totally agree with you. I wrote a chapter on sarcopenia for the second edition of my book, and on my website I've got a study that I summarised on my blog. A group of scientists in Italy a number of years ago looked at a significantly large group of people that were, I think, from 95 to 104. And they wanted to research and find out what's the most important thing for healthy aging. They looked at hundreds of different parameters. The number one thing for healthy aging: maintain your muscle mass. So I talk to the cyclists and I talk to swimmers and I talk to joggers and runners and say, yes, aerobics is good, but you've got to do some form of resistance training or you're gradually going to lose it. And that's sarcopenia, one of the hallmarks of biological aging.

Lisa: Yep, absolutely. And actually, when I was talking to Phil Martin last week, he was talking about endurance athletes having much more arterial stiffness. And that makes sense to me as someone with these bad glutathione genes. And I've got a also very poor 9p21 gene, which is about the quality of the linings of the blood vessels and the linings of your gut and all of that. I have the worst quality, if you like. If I was a Teflon can, I'd be the two dollar version, not the hundred dollar version. So when I'm doing extreme amounts of exercise, I'm inflaming that lining. So this, once again, for endurance athletes listening, you have to rest, you have to recover, you have to put in anti-inflammatories, you have to be doing all of this — the glutathione, the Lactobacillus fermentum. Natural anti-inflammatories.

Dr Ross Pelton: Natural, yeah, absolutely. Natural is critical.

Lisa: Thank you for that clarification. Not the other type of anti-inflammatories. Natural anti-inflammatories.

Dr Ross Pelton: And so things like curcumin would come to mind, fish oil.

Lisa: Fish oil is one of those essentials. Actually, on that, now, what is your personal daily routine, or your supplement routine and nutrition and exercise regime? Because you're in your 80s now and you're doing pretty bloody well, amazing, and you're still writing books and you're fully an intellectual powerhouse. And that's a role model for people like me, because most people that get to their 80s, they're not working anymore and they're not able to do a lot of these things, and you are. What's your secret?

Dr Ross Pelton: Well, I got interested in health a lot of years ago. In fact, in my early adult life, when I was a pharmacist, I didn't know anything about health. And finally — as a young adult I ate fast foods and packaged foods, and, you know. But in 1979, kind of as a fluke, I heard some strange music come out of a little neighbourhood church in the little town I was living in in Southern California. I was actually walking home from a grocery store with a loaf of white bread and a half a gallon of milk. And I walked across the street and down the sidewalk, and I stuck my head in the door and I saw a yoga class in session, and I saw 20 people that radiated a level of health that just kind of knocked my socks off. So I got involved with yoga. And in addition to exercising regularly and eating healthfully, these people read health books and health newsletters and health magazines. And with my background in medicine and science and so on, I just started to absorb that information like a sponge, and I'm still doing it. Just go deeper and deeper, and it gets more and more exciting. And so that changed my life. Yoga changed it.

Lisa: Wow.

Dr Ross Pelton: And I will admit I don't do yoga anymore because I have stiff joints and knee replacements and so forth. But my overall programme: I go to the gym almost every morning. I do intermittent fasting. My wife and I, our final meal is usually at six or seven in the evening, and then I don't eat again until like noon or one or two o'clock in the afternoon most days. I'm not fanatical about it — if we have a social event, I'm relaxed and have a good time. For a number of years back in the 1980s and 90s I was a vegetarian for about six years. I'm not a vegetarian anymore. I'm just absolutely fanatical about eating healthy food all the time. And that can get me into a discussion of the microbiome, if we talk about diet, because that's another one of my professions.

Lisa: You've written books on this, so please share.

Dr Ross Pelton: In fact, I'll give you a link for people to get a free copy of a booklet I've written titled Dr Ohhira's Probiotics and Postbiotic Metabolites.

Lisa: That's where the Dr Ohhira came in, yeah. So just going back to that other story, can you help me out with Reg'Activ as well as Dr Ohhira? Can we get those?

Dr Ross Pelton: Yeah. They can get this booklet by going to my website, which is naturalpharmacist.net/ohhirabook. But I'm one of the world's leaders in trying to educate the world about how the gut microbiome really works, and most people have it all wrong. And there's people spending millions and millions of dollars on probiotic bacteria and really getting very little benefit from them. So here's what — in fact, I wrote a scientific article titled Postbiotic Metabolites: The New Frontier in Microbiome Science. I'll send you the link to that so that all of our listeners can get a copy of this. But in this scientific paper I'm describing to people and explaining the job of probiotic bacteria. Their job is to digest and ferment components of your food and produce secondary compounds that we call postbiotic metabolites. And it's these compounds, the postbiotic metabolites, that have a wide range of biological activity. So it's not the probiotic bacteria, it's the compounds they produce that have a wide-ranging biological activity.

Dr Ross Pelton: And I regularly tell people, every time you eat, you're hosting a very big party. You're feeding a hundred trillion guests. Think about that. Learn how to feed them well, or they won't thrive and survive. So what is the primary food for your probiotic bacteria? There's two primary food groups that they require: dietary fibres and polyphenols. And for people that aren't familiar with polyphenols, they're the compounds that give colour to fruits and vegetables. There's over 8,000 polyphenols that have been structurally identified. So we humans do not have the enzymes to digest dietary fibres, and most polyphenols are huge, huge molecules that we don't digest and metabolise well either. So these compounds travel all the way through your digestive

Dr Ross Pelton: ...tract, but when they reach the colon, they're the food for your probiotic bacteria, and your bacteria start metabolising, fermenting them, breaking them down, producing smaller compounds — the postbiotic metabolites — that have a wide range of biological activity. They have anti-inflammatory activity, they have cell signalling activity, the brain communication. One of the most important functions is that they adjust the acid-base balance in your microbiome ecosystem.

Dr Ross Pelton: A healthy microbiome ecosystem needs to be slightly acidic. The way you do that is, a number of the postbiotic metabolites are slightly acidic compounds. There's short chain fatty acids, which is propionic acid and acetic acid and butyric acid, and then there's fulvic acids and organic acids and nucleic acids. All of these slightly acidic compounds create the slightly acidic acid-base balance that's optimal to promote the growth of your good bacteria, and it suppresses the growth of your pathogens.

Dr Ross Pelton: When you have dysbiosis, which is an imbalance between the levels of good and bad bacteria, you end up with too many bad bacteria and the acid-base balance becomes anywhere from 10 to 100 times too alkaline.

Lisa: Wow.

Dr Ross Pelton: Because it promotes the growth of your pathogens. So you've got to get it back down to that slightly acidic level, and it's the postbiotic metabolites that do that.

Dr Ross Pelton: Now, in most ecosystems in the world, greater diversity is a stronger ecosystem. Whether it's the Amazon rainforest or the coral reefs in the ocean or wherever, greater diversity equals greater strength in the immune system of the ecosystem, greater resilience. And the same thing with your gut microbiome. So you want to strive to get greater diversity, which means a wide range of different types of bacteria. How do you do that? Not by taking probiotic bacteria, not by taking commercial probiotics.

Lisa: Not the normal ones, yeah. They don't colonise.

Dr Ross Pelton: They don't stay in your system. The only way you can get a diverse microbiome is by consuming a diverse range of plant-based foods that contain a diverse range of dietary fibres and polyphenols.

Lisa: Why is Dr Ohhira's probiotic different?

Dr Ross Pelton: Thank you for asking. Full disclosure here: I'm the scientific director for Essential Formulas, which is the company in the United States that has the sole rights to import Dr Ohhira's probiotics from Japan.

Lisa: Why did you choose those? Because most probiotics just don't cut the mustard. Explain this whole thing.

Dr Ross Pelton: Dr Ohhira was a visionary microbiologist. In his younger days he was a Buddhist monk and lived in a Buddhist monastery. Then he came out of the monastery and he went to the university and got a degree as a landscape architect, and he developed a very successful career as a landscape architect. He had an international reputation.

Dr Ross Pelton: In 1976 the country of Malaysia invited Dr Ohhira to come and visit one of the major cities, the capital city in one of the states of Malaysia, and they asked him to design what they called a Freedom Park. And Dr Ohhira accepted this job, this consultation and contract job, to do this. Four years later they invited him back to the grand opening ceremony. This is a wonderful nature-type Freedom Park that he created. It had walking paths and meditation benches and water features. It expressed his Buddhist philosophy of harmony with nature.

Dr Ross Pelton: So he comes back in 1980 to this grand opening ceremony, and he ate some tainted food and got violently ill. He's writhing on the ground, and there happened to be a shaman there who saw him in great distress on the ground. The shaman goes over and rests his head in his lap and pulls something out of his little leather shoulder bag and starts spoon-feeding Dr Ohhira some black syrupy syrup. And Ohhira is amazed — in a very short period of time he's cured. I mean, his symptoms are resolved.

Dr Ross Pelton: So he's a curious man and he asked some questions. He found out that the substance that the Malaysian shaman had given him was something that was made from locally fermented Malaysian fruits and vegetables. That's where he got this idea of fermentation. He takes samples back to Japan and it lays around over there for a number of years and he gets totally frustrated, because he's a landscape architect, he doesn't have a background in microbiology. So at age 49, with a hugely successful career as a landscape architect, he walks away from that career, goes back to school, gets a PhD in microbiology.

Lisa: Wow.

Dr Ross Pelton: And starts this whole process of studying this substance from the Malaysian shaman, and over a period of several years he develops Dr Ohhira's probiotic. He created a very unique system, a fermentation system, to create Dr Ohhira's probiotics. In fact, one second here — and these probiotics, everybody can get a free copy of this...

Lisa: So for those watching, he's holding up a book called Probiotics and Postbiotics.

Dr Ross Pelton: This is a picture of the 80-gallon fermentation vats. They start out with 12 strains of starter bacteria and they shred and add a wide range of different types of Japanese fruits and vegetables and mushrooms and seaweeds, all healthfully grown, and the bacteria get to digest and ferment the food components for three years. Three years before they encapsulate the product. And that's called the original formula, that's sold in retail stores throughout the United States. Then there's another product that's called the professional formula that gets an additional two years of anaerobic fermentation in mammoth 10,000-gallon anaerobic fermentation vats. That becomes the professional formula.

Lisa: Wow.

Dr Ross Pelton: But it's this fermentation process in these fermentation vats — it's an external fermentation system that mimics nature's natural fermentation process that takes place in your colon, where the probiotic bacteria break down the food components if you're consuming a healthy diet.

Dr Ross Pelton: And actually, Lisa, there's another thing I'll mention. I've got several studies that I published, and I made slides on these that are used in my seminars, that report that from 90 to 95% of American children and adults do not consume adequate amounts of dietary fibres and polyphenols.

Lisa: Wow, this is scary.

Dr Ross Pelton: Almost nobody's consuming the diet that really supports a healthy microbiome, and that creates inflammation. When you have dysbiosis and a bacterial imbalance, you have gut inflammation, and that causes things called lipopolysaccharides, or LPS, to leak from your intestinal tract into your systemic circulation, which causes chronic inflammation. It's a critical part of the aging process, and it's all based on dysbiosis and a bad diet. So you're not getting a good healthy microbiome. A healthy microbiome should have about 90 to 95% good bacteria and only like five or ten percent bad bacteria. Everybody has some bad bacteria, but when the good bacteria predominate, a few bad bacteria are not going to cause problems.

Lisa: And what happens with things like leaky gut, when your zonulin's high, and calprotectin, secretory IgA and things? Can you explain those things?

Dr Ross Pelton: You bet. In fact, I wrote a paper on this. It was published in January of this year in a medical journal, titled "The Microbiome Theory of Aging". In that paper I'm explaining to people the mechanism of what happens when you have bacterial imbalance, this dysbiosis that creates inflammation in the gut. You just mentioned zonulin, so that's a good topic to bring up. Zonulin was discovered by a physician, a paediatrician, Alessio Fasano. I hope he gets a Nobel Prize for this. It's one of the most important health discoveries of all time.

Lisa: Wow.

Dr Ross Pelton: Zonulin is a protein that gets expressed when you have gut inflammation, and as far as we know, the only thing that zonulin does is degrade the proteins that are the tight junctions that line the cells of your gastrointestinal tract. Your epithelial cells are a layer of cells in your gastrointestinal system, one cell thick, and those cells side by side have proteins on the cell surface that hold them tightly together and allow appropriate things to transfuse, to keep the bad things out. But when you have bacterial imbalance you get inflammation, zonulin degrades these tight junction proteins and allows leaky gut to happen, and that's when lipopolysaccharides and other toxins leak into your system and create chronic inflammation that causes tissue damage, organ damage, accelerated biological aging.

Dr Ross Pelton: So maintaining a healthy gut is a critical thing for people to understand and know about, and it's an actionable thing. You can take steps to create and maintain a healthy gut, but you have to educate yourself on how to do it.

Dr Ross Pelton: Dr Ohhira's probiotics, after that multi-year fermentation process, every capsule in every dose contains over 500 of these postbiotic metabolites. So when you take Dr Ohhira's, these compounds directly start to have anti-inflammatory activity and rebuild and normalise the acid-base level and start to suppress or kill pathogens and re-establish your gut-brain communication — all of these things.

Dr Ross Pelton: When people spend money and buy commercial probiotics, those bacteria have to survive the harsh transit through the gastrointestinal tract, the stomach. The acidity in the stomach is ten thousand to a hundred thousand times a stronger acid than the acid-base level in the intestines.

Lisa: Right. The level of acid is designed to kill pathogens.

Dr Ross Pelton: Yeah, when you're eating, which we need. Bacteria are going to get killed. Some people do have liposomal delivery systems or enteric-coated capsules so the bacteria can survive transit through the stomach. But when they reach the colon, if people aren't consuming a diverse range of dietary fibres and polyphenols, those bacteria can't produce the postbiotic metabolites, and they're close to useless and they just pass on out.

Dr Ross Pelton: So with Dr Ohhira's you're immediately getting these compounds that are rebalancing the whole microbiome ecosystem. But even with Dr Ohhira's you have to eat a diverse range of dietary fibres and polyphenols. You have to concentrate on a plant-based diet — and I'm not advocating vegan or vegetarianism, but when people eat meat products it has to be grass-fed and grass-finished meat, good quality fish, cage-free chickens. It's got to be healthy animals.

Lisa: Yeah. And this is like — I've got a brother who, I'm sure he won't mind me talking, he's got coeliac disease, and then there are other people who have SIBO, and this is where the complications can come in. When you're trying to — you can't put prebiotics, or probiotics sorry, into someone with SIBO. Can you put these type of probiotics in and you're not going to cause more bloating?

Dr Ross Pelton: Let's take them one at a time. First you mentioned coeliac.

Lisa: Yes, yeah.

Dr Ross Pelton: Alessio Fasano kind of discovered this working with young newborn infants that had diarrhoea that was unstoppable, and they discovered that they were sensitive to gluten, which is the protein in wheat, and that's been called coeliac disease.

Lisa: Yeah, that's a terrible thing.

Dr Ross Pelton: No humans have the adequate enzymes to digest gliadin, which is the protein in gluten. No humans.

Lisa: Actually, so we are all getting some effect, but there's different levels.

Dr Ross Pelton: The grains in the United States are more hybridised. I know people in the United States that cannot tolerate eating wheat products, but they go to Europe and they don't have problems because it hasn't been hybridised over time. But I really advocate low intake of gluten-containing products for everyone.

Dr Ross Pelton: And before I go over to SIBO, I want to say something more about gluten and intestinal permeability and zonulin and so forth. Dr Fasano says the two main things that will cause gut inflammation and express zonulin and cause leaky gut are gluten and bad bacteria. Now, there's a number of other things that can cause gut inflammation, but those are the two main ones. So everybody needs to know about this.

Dr Ross Pelton: And so I'd like to also discuss with our listeners, Lisa, a study that will give them some insight into how damaging this leaky gut and lipopolysaccharides can be. Again, lipopolysaccharides are protein fragments from the cell walls of gram-negative bacteria that everybody has in our intestinal tract, but these compounds are supposed to stay in the intestinal tract. You have leaky gut and they leak into your systemic circulation — they're highly inflammatory.

Dr Ross Pelton: So a group of scientists did a wonderful study, taking a group of people, a small group of healthy young adults, and divided them into two groups, and they did a double-blind, placebo-controlled crossover trial. And crossover is important here. So you've got a placebo group and the group getting lipopolysaccharides, and they injected low-dose lipopolysaccharides — so low there were no symptoms. People did not know if they got the placebo or

Dr Ross Pelton: the LPS. And then after a certain period of time, they stopped. There was a washout period, then the crossover: the people that initially got the placebo were injected with low-dose lipopolysaccharides, and the people that had the lipopolysaccharides got the placebo. And then at the end of the trial they did blood work, and they discovered again, people getting injected with low-dose lipopolysaccharide, no symptoms whatsoever, they had a 25-fold increase in their plasma levels of tumour necrosis factor alpha and a 100-fold increase in interleukin-6. These are highly inflammatory molecules.

Lisa: Well, yeah, and we're trying to always get those symptoms. They don't know that they've got chronic inflammation, but those elevated levels of those inflammatory markers are causing inflammation, tissue damage, organ damage, accelerating biological ageing.

Dr Ross Pelton: So it's critically important that people create and maintain a healthy microbiome and don't have gut inflammation, because most people alive today have some level of leaky gut and are not aware of it because of an improper diet and an imbalance between probiotics and pathological bacteria. And so it's a critical problem. Gut problems are one of the most common reasons people go to the doctor, and it's not just gut problems, that advances into accelerated biological ageing and tissue and organ damage. So it's really the root cause of a lot of health problems.

Lisa: And so when we're looking at the microbiome, I do microbiome testing in my clinic and go through everything, and I try and do the north to south sort of model, where we're looking at, are you producing enough hydrochloric acid? That's a key thing that goes south with a lot of older people, or people that have certain problems, that they don't produce enough stomach acid, so that then the parasites and things can get in.

Dr Ross Pelton: You're touching a really good point, because hypochlorhydria, low levels of hydrochloric acid, is a very common problem. And it causes what's called atrophic gastritis, which means an inflammation in the lining of your stomach. It's painful, and so many people misinterpret that. They get that gut pain, they think they have excess acid, so they take acid-suppressing drugs, which is the worst thing you can do. It's not excess acid, it's the low level of acidity that creates the inflammation. So you've got to heal that, and you can take hydrochloric acid tablets or hydrochloric acid drops and build up and recreate a healthy level of hydrochloric acid in your stomach. It's a front line of your immune system, so it's very critical that people do that.

Lisa: Yeah, and doctors put people on proton pump inhibitors for years. I've had clients come through that have been on it for years.

Dr Ross Pelton: Proton pump inhibitors, antacids, Tums and so forth. One of the books I wrote is titled The Drug-Induced Nutrient Depletion Handbook, and in that book I educate the world, especially physicians and pharmacists, about the nutrients that are being depleted by the drugs that people take. And these antacids and acid-suppressing drugs are monstrous. They deplete levels of calcium and magnesium and other minerals, deplete levels of vitamin B12, they inhibit your body's ability to digest protein.

Lisa: I mean, it is diabolical. And they put people on for years.

Dr Ross Pelton: And then another good point: these drugs are addicting. When people — excuse me just a second here.

Lisa: No, no problem.

Dr Ross Pelton: When people take these acid-suppressing drugs and they want to stop, when they stop them, there's a rebound production of acid that goes, "Oh man, that's painful, I've got to get back on my acid-suppressing drug." So you need to gradually decrease the use of those drugs, because it's very difficult to get off them. They've got you addicted.

Lisa: Right. So titrate them down and then titrate up some hydrochloric acid. And can you overdo that? Where do you find that sweet spot?

Dr Ross Pelton: If you take hydrochloric acid and it's immediately painful, you've probably got an ulcer, and you need to heal that ulcer.

Lisa: Yeah, so that's the only time that we should be using proton pump inhibitors really, is if you've got an active ulcer, and then that's a different story, but that's short term. And then there's the digestive enzymes, the pancreas — this is another area that comes in the next part of the process, if you like. The amylase, lipase, protease, it comes from the pancreas. What happens there? Because that goes south too for a lot of people.

Dr Ross Pelton: Well, that's just a very intricate system involved in digestion, and if you have an upset gastrointestinal tract where these enzymes work to break down foods so you can absorb the nutrients, everything's not going to work well. They don't function well in a highly inflamed gastrointestinal environment.

Lisa: And then you've also got — sorry, yeah, well go ahead if you've got something else you want to follow on there.

Dr Ross Pelton: No, no.

Lisa: We'll get there, but let's just talk about the pancreatic enzymes, these breakdowns, like amylase breaks down the carbs and protease breaks down the proteins. And so a lot of older people are protein deficient, and they've maybe got hypochlorhydria plus they haven't got enough enzymes to break down their proteins. And then you've got your gallbladder — that was the other one I wanted to bring up, the sludge in the gallbladder or gallstones, and how does that impact that whole digestive system?

Dr Ross Pelton: Well, many people benefit from taking pancreatic enzymes like lipase, amylase and protease, so they're good supplements, and if you try them and you benefit on them, you need them. They're a good thing. And you mentioned protein deficiency. That's a big topic. I wrote about it in the second edition of my book in the chapter on sarcopenia. I'm not sure what the regulations and recommendations are in New Zealand, but in our country the recommended daily allowance for daily protein intake is way too low.

Lisa: Yeah, dangerously low.

Dr Ross Pelton: And there's a lot of scientific people that are weighing in now saying in the United States we have to change this because we need more protein. And the thing that makes this doubly bad is that as people age, you need more protein.

Lisa: Yes.

Dr Ross Pelton: But as people age, they generally eat less. Most elderly people between age 50 and age 70 or 75 are eating significantly smaller meals and less food intake, but as we age we need more protein intake. And the reason — and I wrote about this in my sarcopenia chapter in the second edition of my book — as we age, there's two processes, there's muscle protein synthesis and muscle protein breakdown, and it's kind of like mTOR and autophagy: these things have to be in balance, and when you're healthy, they are. But as we age, we become less able to do adequate muscle protein synthesis. Muscle protein breakdown stays about the same, but as muscle protein synthesis declines, that means you're breaking down muscle faster than you're rebuilding it.

Dr Ross Pelton: But studies have shown in elderly people that by taking protein supplements and taking in more dietary protein, you can offset this change that happens when you have a decline in muscle protein synthesis. So extra protein intake, you'll boost your muscle protein synthesis and offset this accelerated muscle protein breakdown, which is sarcopenia. Sarcopenia is the term for the age-related disease that is the loss of muscle mass and a loss of strength as you age. And if people don't do some level of strength training on a regular basis, you will gradually lose muscle mass and strength as you age. And it's one of the worst age-related diseases. But again, it's actionable. If you understand it, if you educate yourself, you can do things to slow this down and stop it and in many cases actually reverse it.

Lisa: Yeah, and that's brilliant. What's your take on hormone replacement? Actually, I mean, it's probably another hour, but hormone replacement therapies — I'm on hormone replacement therapy to try to maintain your hormones, to maintain muscle mass, to maintain your bone density, your brain function regulated. I do DUTCH testing, I know what I'm doing, and it has to be done properly and overseen. But are you an advocate of hormone replacement therapy?

Dr Ross Pelton: Good. I recommend that all women about age 40 get a complete hormone panel.

Lisa: Yes.

Dr Ross Pelton: And they need to look at not just estrogen, but progesterone and testosterone.

Lisa: Yes.

Dr Ross Pelton: Many, many women get huge benefits from a small level of progesterone.

Lisa: Yes.

Dr Ross Pelton: And some women get a huge boost from getting just a small level of testosterone. Men have about ten times more testosterone than women do, but many women are testosterone deficient, and oftentimes compounding pharmacists will make it up in a cream, just rub a small little bit on their labia once a day, and it's just tremendous benefits because it gets absorbed very easily. So I recommend that all women be tested. And for men, about age 50 or so onward, many men I think will get a huge benefit from doing testosterone supplementation. And I, for much of my adult life, not knowing it, was low in testosterone, and I started doing testosterone injections, and now probably for 20 years I've been doing testosterone injections once a week intramuscular, just in my butt. And it's easy to do. So that's another one of the replacement therapies that I'm a big advocate of. I've got an article on my blog that people can refer to.

Lisa: Yeah, I'm a big advocate too, done properly and overseen properly. And for me, and for women, I like to look at the whole pathway: how are you methylating, what are your nutrient status, the metabolites of your estrogens, your cortisol as well, and that picture. Because I think once you get that whole picture, then you can optimise, and then you have to tweak, you have to keep an eye on that. You can't just go, "Well, I'll just take the same dose forever" and not look at what you're doing. But it's powerful anti-ageing medicine. That's powerful for maintaining functionality and all of that sort of stuff.

Lisa: Just going back to the microbiome: SIBO, that's one that is a little bit confounding, because you have small intestinal bacterial overgrowth, too much bacteria that has come up into the small intestines. Can you explain that? And probiotics — it's a very unique individual situation and it's not so easy to deal with.

Dr Ross Pelton: Yeah, SIBO stands for small intestinal bacterial overgrowth, and it's a situation where bacteria that are supposed to reside in the colon have backed up into the distal end of the small intestine. So it's not necessarily bad bacteria, it's just bacteria that are living in the wrong place. And those bacteria will ferment foods that you eat and create an enormous amount of gas, which creates a great deal of discomfort. They often cause diarrhoea. And so it's a difficult situation. And there's a lab test that you can do, it's a breath test that people can do to see if they have SIBO. You get a kit with a number of little plastic baggies with a straw, and you just blow your breath into these little baggies and seal it and do it a number of times and send it off to the lab. They're testing to see how much hydrogen and how much methane you have in the breath that you expire, and if either of those levels are elevated, you have SIBO.

Dr Ross Pelton: And so there's a number of diets — and these are easily found on the internet — there's one called the FODMAP diet, there's the specific carbohydrate diet. These are not diets that people should stay on long term, they're therapeutic diets that people should use to try to correct or cure SIBO. They're oftentimes not effective, but I suggest that people try them for a period of time, and if they don't make progress, usually what they need to do is see a physician and take an antibiotic and clear out all the bacteria, and then you have to rebuild a healthy gut microbiome. But also, people who have SIBO have to make diet and lifestyle changes, or the same condition's going to come back again. So you have to become active physically — sedentary lifestyle, you're going to get your SIBO

Dr Ross Pelton: to return. I advocate that the clients that I work with, if they have SIBO — if you have a Fitbit or an Apple Watch, set your watch alarm for an hour and have it go off every single hour, and when that goes off, get up and do some squats and do some sort of exercise for just a couple of minutes, and it'll make a huge difference.

Lisa: I love that.

Dr Ross Pelton: So that's my — but again, healthy diet. And for people that have SIBO and are going to try one of these therapeutic diets, either the FODMAP diet or the specific carbohydrate diet — and there's a couple of others — they advocate that you discontinue a lot of foods that you would normally think are very healthy foods.

Lisa: This is the difficult thing, isn't it?

Dr Ross Pelton: Yeah, it is. And the reason they're telling you to stay away from those foods is because the bacteria that are in the wrong place in your gastrointestinal system will digest those foods and ferment them and create methane or hydrogen gas. So you have to eliminate the foods that kind of starve those bacteria, and that's the therapeutic aspect of these diets. You're starving the bacteria and trying to get them to die off in that distal end of the small intestine.

Lisa: But again, then you're going to affect the other parts too, aren't you? You're going to run out on the other side.

Dr Ross Pelton: And I advocate that people be on Dr Ohhira's probiotics and maybe also take a diverse range of bifidobacteria in a supplement, along with getting on a plant-based diet. Because the real goal, or what you have to accomplish, is to provide the dietary fibres and polyphenols that will allow your own innate bacteria to start to proliferate and populate your colon. That's the way you build your healthy gut microbiome, not by taking commercial probiotics. But Dr Ohhira's probiotics will really accelerate the recovery process, because it's helping to accelerate the return of the gastrointestinal ecosystem to a healthy condition with the anti-inflammatory activity and the rebalancing of the acid-base level with all the postbiotic metabolites that are slightly acidic, and especially butyric acid, which will actually help to rebuild the tight junctions, or help to suppress the breakdown of tight junctions. So that's part of the therapeutic benefit of the short-chain fatty acids in Dr Ohhira's probiotics, or in a healthy gut microbiome if you're consuming the right types of food.

Lisa: Yeah, and this is the difficulty with SIBO, is that everything that's actually good for the colon, it's not so good when you've got SIBO. Probiotics can cause more problems, and fibre can cause more problems. So you have to sort of clear that out, maybe start again, and then repopulate with the right stuff. And so that does complicate things. Now, Dr Ross, I've taken up so much more of your time than I said I would. A lot of people ask me, well, if I've got SIBO, I can't take probiotic bacteria, it'll exacerbate the problem. Can I take Dr Ohhira's probiotics?

Dr Ross Pelton: Yeah. It has some probiotics in it, and it has some of the prebiotics from the fermentation vats, but primarily Dr Ohhira's is the number one product in the world for the direct delivery of the postbiotic metabolites. So most people can take Dr Ohhira's successfully, and I advocate that people with SIBO start out, instead of taking two capsules daily, which is the recommended dose, start out taking one capsule every other day.

Lisa: Right, exactly.

Dr Ross Pelton: For a couple of days. If you're okay with that, then go up to one capsule daily for a couple of days, and if that's not giving you any problem, then jump right up to two capsules daily, and it will accelerate the return of the gastrointestinal microbiome to a healthy condition and create the situation that allows your own innate bacteria to proliferate, if you're eating a healthy diet.

Lisa: Right. Dr Ohhira's got a full range of different products, or just a couple of different ones?

Dr Ross Pelton: They have two probiotic products. There's the original formula, which is the three-year fermentation process in 80-gallon fermentation vats, and then the professional formula gets an additional two years of fermentation in these massive ten-thousand-gallon fermentation vats. But Dr Ohhira also has a product, Dr Ohhira's Essential Living Oils, which is an essential oil product made from a number of different seeds from plant-based products. And then we have Dr Ohhira's Premium Collagen Plus, which is just a phenomenal product providing collagen that's highly absorbed into the system and helps to rebuild healthy collagen and prevent skin wrinkling and so forth. And it's called Premium Collagen Plus because in addition to the collagen, it also has cherry blossom extract, which is widely used in cosmetic products in Japan but not well known outside Japan. And cherry blossom extract is a really great product for stimulating hyaluronic acid and collagen growth.

Lisa: Oh wow.

Dr Ross Pelton: And there's also some hyaluronic acid and CoQ10 and a number of other things in the formulation. So it's Premium Collagen Plus. And also, to emphasise, in the Dr Ohhira's Collagen Plus product, they only use wild-caught proteins from fish. They don't use bovine collagen from cattle that are standing on feedlots for months and months, which is a very unhealthy situation. So they use the marine-based collagen peptides, and specifically they use the tripeptides, which are the low molecular weight collagen, which is much more effectively absorbed. So Dr Ohhira's Collagen Plus is really a great product for the cosmetic language, skin care and rebuilding joints and all the collagen throughout your body.

Lisa: Wow, that's great, that's fabulous. Now, the last thing, because I do need to let you go and Mum's waiting for her coffee — coenzyme Q10. Can you just briefly... and I definitely want to get you back on, Dr Ross, because I feel like you're just a wonderful teacher and I'm just so glad to have found you.

Dr Ross Pelton: One of my favourite life extension nutrients. And can I talk — we talk about life extension too, Lisa. It's not just life extension, it's not just increasing lifespan, it's increasing your healthspan. Most important — you don't want to live more years in a wheelchair with an oxygen tank. I mean, you don't want to die, but you want to have healthy years in your elder years. And so this is all about healthy longevity.

Dr Ross Pelton: And coenzyme Q10 is one of the premium antioxidants in the body. It's the most important, I think, fat-soluble antioxidant. And we don't absorb fat-soluble antioxidants very well, so I encourage people to take it at a meal where there's fat involved. But what we found out is the melting point of coenzyme Q10 is 10 degrees higher than body temperature, so it crystallises, and we cannot absorb clumps of coenzyme Q10. It has to be single molecules in solution. And I have taken many of the commercial CoQ10 products and opened them up and squeezed it onto a white piece of typing paper, which is a clear background, and you can actually see the little clumps of crystallised coenzyme Q10 in the product. And even if a company has a CoQ10 product where they're successful at keeping the CoQ10 in solution in the capsule, when it goes into your stomach it immediately starts to crystallise.

Dr Ross Pelton: And there's another big debate between whether it should be ubiquinone or ubiquinol. Ubiquinone is the natural form of CoQ10. A number of years ago, a company in Japan, Kaneka, came out with ubiquinol, which is the alcohol form of CoQ10. They claim better absorption. Fabulous marketing, bad science, really. When you take ubiquinol, which you pay a lot more for—

Lisa: Wow.

Dr Ross Pelton: —as soon as it gets into your stomach it gets converted into ubiquinone. So people are wasting a lot of money on ubiquinol. But back to the main part of the story: most CoQ10 products have horrible rates of absorption, literally only one or two percent, because it's crystallised, we can't absorb it. A company in Europe, Pharma Nord, has a patented form of keeping CoQ10 in solution. They've done multiple studies showing they get three to ten times higher plasma levels of CoQ10 than many of the other competitors on the market. Most of the double-blind, placebo-controlled scientific trials on coenzyme Q10 from all around the world in the last 20 to 30 years have used Pharma Nord's CoQ10, because it's proven to be well absorbed. And for all your listeners, I'll give you a link at the end for the show notes, and I'll provide a link to an article I've written. People can use the code "ross10", you get a 20% discount on Pharma Nord's CoQ10. And again, I'll send you an article.

Lisa: Yeah, that would be — we're going to have big long show notes this time.

Dr Ross Pelton: People, take crystal-free coenzyme Q10, and Pharma Nord's CoQ10 is the best in the world to my knowledge. And people can get a 20% discount on a regular basis if they use the "ross10" code.

Lisa: Anyway, the link will be in there, we'll put it in the show notes when you send it over to me. Because that's something again that, you know, I've been taking CoQ10, but am I not getting any? Because I know how important it is, as you know, and for people especially on statins, that's a really important one to be on. So yeah, definitely keen to get that link. Dr Ross, you've been so awesome with your time today. I'm so grateful for you. Your work, it's phenomenal, the amount of research that you've done — 12 books, and I don't know how many countless scientific papers and blogs and lectures. Just a phenomenal rate of work.

Dr Ross Pelton: Yeah, my YouTube video on my salad, too, if I send you that.

Lisa: Oh yeah, yeah, yeah.

Dr Ross Pelton: But I really compliment you. You are a health warrior, doing so many wonderful things and being such a motivational person for people. So I really appreciate all you're doing. I'm glad we're friends now.

Lisa: Yeah, and we'll talk again, and we've got other things to talk about, like pulsed electromagnetic frequencies. We didn't even get there. Circulation — we didn't even get to this. So that's round two. Number one is PEMF, because I haven't even done a podcast on that, and it's been on my radar for so long and I haven't got one yet. I'm working on getting one so that I can help Mum. But Dr Ross, thank you so much for your time today.

Dr Ross Pelton: Good to know you and be in touch with you, and we'll do more in the future.