Dr. Gundry: Hey there. Welcome to another exciting episode of the Dr. Gundry Podcast, the weekly podcast where I give you the tools you need to support your gut, boost your health, and live your youngest, healthiest life. I’m Dr. Steven Gundry, father, husband, cardiologist, cardiac surgeon, medical innovator, and author of best-sellers, including The Plant Paradox. Each week, I’ll be sharing the latest in cutting-edge health information, interviews with experts in the field, and intimate discussions with real people who have turned their health around. I’m excited to be a part of your unique health journey. So let’s get started.

So welcome, everybody. It’s really my great pleasure to talk to Dr. Valter Longo, who has recently published a book, The Longevity Diet. And it’s a pleasure of mine because I’ve been a big fan of his research, and you’ve probably read in The Plant Paradox that I definitely reference your work. So it’s great to have you here. What compelled you to write The Longevity Diet?

Valter Longo: The Longevity Diet is really the result of 25 years of work, starting back in the days with Roy Walford, who was my mentor. He was, at the time, I think, the leading figure in the world for nutrition and longevity, and he has written some books on the topic, of course. And I just thought that it was … 25 years went by, and at that time, there was really not much genetics available. We didn’t know what genes controlled aging, what genes prevented diseases, and certainly we …

Calorie restriction, which was the intervention that he was really promoting, which is the chronic reduction of calories, didn’t work very well. It taught us incredible … It gave us incredible findings, but at the same time, it just showed us this is probably not the way to do it. People are not going to be willing to do it, and even the monkeys did not live that much longer. So there was time to really do it differently, and I think that’s … The Longevity Diet … I waited until I finished clinical trials, and then I felt that, okay, now we can go out and tell people to do something that has been clinically tested in randomized trials and is safe. Of course, you can always do additional studies, but I felt that it was enough to really make a difference.

Dr. Gundry: Yeah, and so what … You and I think probably long-term calorie restriction is not the way to go. I’ve read all of your mentor’s work a long time ago, and it has actually influenced a lot of my work, but I agree with you that long-term calorie restriction, it’s not the answer. Most people won’t do it. And certainly it, in a way, didn’t work out for Dr. Walford in the way he thought it would, but there’s lots of mitigating circumstances. So give us a little bit of the background of your studies, first in mice and in people, that kind of led you to your current thinking.

Valter Longo: Yes. The original studies were mostly genetics. The first was the identification of the TOR, a sis kinase signaling pathway, and showing that, if you mutated that, that you would get extraordinary effects on lifespan and also on protection. Then we went on to show … This was what we called the protein aging pathway, so it responds to high levels of amino acids in proteins. And then we identified the PKA, the Ras PKA in yeast and the PKA probably only in mammals, that responds to sugar. So if you eat lots of sugar, these genes are turned on. And so we think that the protein pathway and the sugar pathway together they’re really pushing systems to age more quickly. And the master regulator, or one of the master regulators in mammals and humans, we think, is the growth hormone receptor axis, meaning they’re the set of genes that are controlled by growth hormone.

Eventually, we were able to start studying these populations in Ecuador that is lacking the growth hormone receptor, so they’re about three-and-a-half feet tall, and just like mice that lack the same receptor, are long-lived, protected from cancer, protected from diabetes, and protected from age-dependent cognitive decline. We show that these people probably are just a little bit longer lived, not big effects, but very much protected from cancer, from diabetes, and the latest paper we show that … We were doing fMRIs here in Los Angeles … that they seem to be protected … They seem to have a younger cognitive profile, so the type of learning and memory abilities that you see in somebody that is younger.

Dr. Gundry: Yeah, that’s fantastic. Yeah, I got interested in TOR many years ago as a transplant immunologist and surgeon, and we were actually researching rapamycin and became fascinated. Back in those days, you actually had to have animal studies that showed how lethal it was and, lo and behold, to everybody’s surprise, the rapamycin, if given in the proper doses, these animals were living an incredibly long time. That’s my background in that.

But we both really kind of focus on two things that the average person can take home with them and that is that sugars are bad for the aging pathway, and unfortunately, certain amino acids that are more prevalent in animal protein than they are in plant proteins, this is kind of the one-two punch. I grew up in Omaha, Nebraska, in the center of the United States and a meat capitol of America, and so when people say, “Well, gosh, I really don’t want to give up my meats and animal proteins, and I really don’t want to give up my sugars,” can you say why you think both of those things are probably equal in importance in producing longevity?

Valter Longo: In accelerating aging?

Dr. Gundry: Yes.

Valter Longo: In accelerating aging. I probably think that it has to do with reproduction and growth, right? To grow, you need fairly high levels of both, and to reproduce you need high levels of both. And you cannot have a baby. It wouldn’t make any sense to have a baby if you did not have sufficient … Well, also, because evolutionarily, that would be an enormous investment of energy wasted. So I think that’s probably where all of this comes from. You need enough protein, enough protein reserves, enough sugar, enough sugar reserves to face the nine months to have a baby.

But, of course, you do it as a sacrifice, Not of course, but probably because there is just not enough energy to go around for everything, and also it wouldn’t make sense that you have put so much energy into not aging at all. There is probably no benefit of keeping somebody not aging, or at least we haven’t gotten there yet. And so I think it makes perfect sense that now you sacrifice repair and protection for the sake of growth and reproduction.

This is pretty consistent in many different organisms, and I think it’s a pretty good … It’s very clear in a cell. We’ve done a lot of work, for example, with chemotherapy resistance, and you see very clearly if you push the … If you starve a system and you reduce the glucose and the proteins, it becomes protected, but it doesn’t divide. It sits there. It becomes smaller usually in size, and it doesn’t divide. As soon as you give the amino acids and the sugar, it becomes larger and it starts dividing and it can divide very rapidly like cancer cells, but when they divide very rapidly, they’re very much unprotected, very sensitive.

Dr. Gundry: Yeah. That brings us actually to a good point. You and I are both fans of fasting. I know you and Joseph Mercola have talked about this. I think he’s probably more on the Jason Fung side of things that a four or five-day water fast is a great idea maybe once a month. You, on the other hand, have the fasting mimicking diet. So could you kind of talk about the benefits, the drawbacks, of both of these systems?

Valter Longo: Well, we started with the water-only fasting, and we started it with cancer patients 10 years ago or more, and I have to say it was a disaster. It was a disaster for compliance. It was a disaster for potential safety issues, and it was a disaster also, or certainly problematic, for doctors’ compliance. Doctors really felt that they were exposed, and they were doing something that they didn’t feel comfortable with, and so did the patients. So this is how we started. Then we went to the National Cancer Institute and basically said, “This is the problem we have. What about a diet that mimics fasting?”

I think I speak from experience having done this for so long and really talked to thousands and thousands of people and hundreds of doctors. The water-only fasting seems like a good idea because it’s free and you feel like, “Oh, I want to give it for free to everybody.” But when we did that in Europe, for example, it was also a disaster when people weren’t allowed to improvise the fasting mimicking diet, because people go home and do all kinds of wrong things. People are not pharmacists. They’re not trained to make their own drugs or medical food, and of course, whereas, let’s say, if you take 100 people, maybe 90 will be fine at any given cycle. And so if you look at it from 30,000 feet, you think, “Well, no big deal,” but if you really get down there, you realize how a lot of people have problems with the water-only fasting, and they’ll have problems even with improvised diets.

And so I basically gave up all the financial benefits from the diets. I don’t make a penny out of any of it and never will, but I felt that … And it was the right call. Do something that you’ve clinically tested in patients that doctor … that it’s always the same. Now over 25,000 people have done it with thousands of doctors, and it was tested in a randomized clinical trial, so we really feel very, very positive about the safety. And also, I have to say, a lot of the funds eventually will go back to research in universities and institutional, so even buying the kit is really benefiting the research, and it’s a good cause, and I think, yeah, for all those reasons.

Now, water-only fasting can be done in a clinic, in a specialized clinic. Now the TrueNorth, for example, in northern California does that. Absolutely. And the Buchinger Clinic, Wilhelmi Clinic in Germany is another good one, and so if somebody can go to those clinics, by all means, they’ve shown a lot of good effects. Now, when it comes to disease prevention and disease treatment, et cetera, then you have to prove it. And even in those cases, the clinical trials have been very few for those diets. We’re doing many with the F and D. So I think everybody else has got to just do clinical trials and show their results, both mouse work and clinical trial, and then I think it’s ready for recommendations.

Dr. Gundry: For the purpose of people who either haven’t read your book yet or haven’t read deeply into The Plant Paradox, can you give us a nutshell of what the fasting mimicking diet does and why you think and, quite frankly, I think that this is a really good way to go about things?

Valter Longo: Yes. The main thing mechanistically, I think, if you look at how it works, is the breaking down … I like the analogy of a wood-burning train, an old wood-burning train that does not have enough fuel to make it to the next train station, so it starts burning the damaged chairs, the damaged walls, and then makes it to this train station and then, of course, it’s lighter, and it can make it there, and now it can rebuild. It can rebuild the chairs, rebuild the walls. So now you have a … not a completely new train, but certainly a train with new chairs and newer walls, and that’s what the body does. Now, after many papers, we have a pretty good idea that this is very consistent.

Whether it’s the liver, the pancreas, the hematopoietic system, the blood system, the nervous system, and probably the muscles, probably everywhere, the fasting shrinks the system because it’s trying to get lighter and it’s trying to use either intracellularly by autophagy or cellularly by just destroying cells and saying I don’t need … For example, white blood cells go down. Well, you don’t need … You’re starving. You don’t need all the white blood cells that you normally have, so you slowly get rid of some. And you don’t need all the muscle that you normally … So day by day, some of the muscle is going to be utilized for fuel.

Then, in that moment, what we discovered a few years ago was the stem cells are getting activated, and the cell is getting ready also to rebuild. So now in the re-feeding moment is when most of the incredible programs occur, and you see embryonic and developmental genes that are being expressed at fairly high levels, genes like NANOG and probably even ALC 4, although it’s been a little bit trickier. Some of the genes are involved in pluripotencies. They have stem cell ability to make almost anything, and you see them turned out in a very high level. So at that moment then, you re-feed; you have the amino acids. So the same things that are bad for you before now have become essential for you to rebuild, IGF-1, TOR, and PKA, et cetera. And then you rebuild, and that’s what I think is really the foundation for a lot of the positive effects.

Dr. Gundry: I think the interesting thing that you’ve shown is that this is something that you don’t have to do a modified fast for every day of the month. You found that, in fact, the people can do this for five days a month or seven days a month and eat normally the rest of the month and act as if they had been restricting calories every day. Is that putting it safely?

Valter Longo: Yeah. So what we’ve been saying … What we’ve been seeing is that … First of all, the diet works by far much, much better in subjects that have lots of problems, right? If you have high cholesterol, high blood pressure, or high triglycerides, fasting glucose, are you pre-diabetic, that’s when it works the best. And then in the clinical trial, the people returned to their normal diet, and what we saw was that many of the effects were long lived, and so the five-day restriction seems to reprogram somewhat.

For example, IGF-1, if you look at one week later at the third cycle of the fasting mimicking diet, and then you even look at three months later, you still see the IGF-1 be much lower in the people that started with a very high IGF-1. Now the people that started with normal IGF-1, it comes down a little bit and not so much long term. So, of course, this is very good news because, whereas calorie restriction, chronic calorie restriction, drops everything gradually, including the muscle, the IGF-1, the blood pressure, so it keeps coming down.

If you look at the Biosphere 2, when my boss Roy Wolford was there, after a few months, their blood pressure reached … They started with 110. They were very healthy, and then it reached 85. It was like 85 over 55, so the blood pressure keeps dropping. In our case, we don’t see that. If you have a high blood pressure, you go back to normal. If you have a low blood pressure, you stay there. That’s really interesting because it tells you that it’s probably fixing problems rather than just blocking pathways that are involved in blood pressure maintenance or glycemic levels.

Dr. Gundry: Fantastic. One of the things that you write about in the book is that you spend summers visiting one of the oldest living villages in Italy. What have you learned by observing these people? And the second part of that is how do you compare this village to the other blue zones? So maybe one at a time.

Valter Longo: Yes. Italy, Calabria is one of the villages we spend a lot of time with, and the other one is Sardinia now. I’ve been spending more time with Gianni Pes and others in Seulo and Villagrande. There are these very world-record towns in Sardinia. And, of course, I visited Craig Willcox in Okinawa several times, and I visited the people in Loma Linda several times. And I think it’s just surprising how similar … Everybody has their own version of these vegan/plus-some-fish or sometimes plus some meat, but very little, and most of them seem to have this in common.

Now an interesting thing in Molochio in Calabria, where I really grew up, was that we published a paper a few years ago showing that if you look at up to age 65, a low-protein diet is associated with a reduced risk for cancer, a reduced risk for overall mortality, but after age 65, that sort of turned around, right? And so I started thinking could it be that these people, whether they’re in Okinawa, Loma Linda, or Calabria, or Sardinia, they’re doing the same. And it turns out, we think, and it’s a little bit of speculation, but it’s very clear where it’s happening, lots of times, they either go to a nursing home, let’s say, in Loma Linda, or they go live with their sons and daughters in Calabria or Sardinia, and they start eating a lot more, right?

So we think that because of this somewhat of a coincidence, they do the exact … the optimal phase-specific diet. So they under-eat up to age 70, 75, and then they slowly start eating better. Maybe they eat some meat, et cetera. So we started … I mean, at least the evidence is now suggesting that maybe that’s the best way to go. For example, IGF-1 is very high up to age 45, 50, 60 even, and then it drops down dramatically in somebody who’s 85. And so we saw, for example, that people who had a low-protein diet and people that had a high-protein when they were over the age of 65, did not have any difference in IGF-1.

This would be consistent with this idea that you may not need anymore to be restricted that much, and, in fact, you need to do the opposite once you get to age 65, and that’s exactly what you see in almost all of these groups. Not all of them, but many of these very long-lived groups tend to have these two phases of life, where they now start eating more at a certain age, just because they’re in a place that sort of forces them to eat more.

Dr. Gundry: Yeah. Have you had any chance to look at the folks in south of Naples and Acciaroli?

Valter Longo: Yeah, yeah. I went there. I went there a few months ago. I spent a few days talking to the dieticians and the scientists there. They’re in many different places. The data is still not very well developed, so I think they need to do more work in trying to figure out how many … There are certainly a lot of centenarians in the Cilento area, and they seem to be at a prevalence that is higher or much higher than many other areas. It’s not as high as it is in a little town, but that makes sense. Cilento is a large area. So I think there are several scientists that are doing work there, and they’re bound to come up with some very interesting findings.

Dr. Gundry: Yeah. I …

Valter Longo: And again, the diet is the same. When I interviewed many of the centenarians, you keep hearing the same story. Some fish, not very much, and lots of vegetables they could get in the back yard. And sometimes, they would maybe use meat to make minestrone-type, vegetable-type soups tastier. And different from what people think, these people did not have huge dishes of pasta and bread. They had some pasta, but even pasta, when you ask them, they say, “That was expensive, so we’d rather put green beans and all kinds of other vegetables and then put a little pasta to make it taste good, but we did not want to do what now everybody in the world does.” And it’s extremely damaging, is to have these 120 grams of starches and nothing else.

Dr. Gundry: Yeah. I was very impressed. They really … I found the same thing. They didn’t really have pastas and breads like other parts of Italy. I was also impressed with their use of rosemary, which has fascinated me as really an anti-aging, brain-protective compound, so … Well, that’s great to hear. We’re kind of running out of time. What are you working on now, and where do you see the future of longevity research going?

Valter Longo: Now we’re doing a lot of work, I mean, many more diseases, and so we just published a paper on pancreas damage. We damaged the pancreas of mice, and then we did the fasting mimicking diet, and we showed that we could reverse the lack of insulin production, so essentially we reversed both Type 1 and Type 2 diabetes in mice. And we did the same for multiple sclerosis in mouse models, and we have some data on people, in clinical trials, but now we’re really systematically going through many clinical trials.

We have received funding for Type 2 diabetes now. We’ve received funding for Alzheimer’s. We have about five trials for cancer ongoing right now. We’re going to do a large one with metabolic syndrome. Yeah, so I think in the next couple of years, we’re probably going to have five, six, seven clinical trials published on the use of the fasting mimicking diet. They’re not always the same. Some of them are lower calories. Some of them are higher calories. Some of them are longer. They last a week. For example, for autoimmune disease, we’re going to test a fasting mimicking diet that are a week long just to get more effects on autoimmune cells, to have more killing of autoimmune cells, and more activation of stem cells. Yeah, these are some of the things that we’re going to be doing in the next few years.

Dr. Gundry: All right, great. Well, that’s been fantastic. Keep up the good work. Like I say, I’ve followed you through the years. I followed your mentor, and we should stay in touch because I love what you’re doing, and thanks for spending time with me today.

Valter Longo: Yeah. Thank you, and thanks for the great book you wrote.

Dr. Gundry: And folks, get Dr. Longo’s The Longevity Diet. You can, I’m sure, find it at Amazon, Barnes & Noble or your local book store. It’s a very good read, and he’s truly one of the great experts on longevity there is, so listen to this guy, okay?

Valter Longo: Thanks a lot.

Dr. Gundry: All right, thanks a lot. Thanks for listening to this week’s episode of the Dr. Gundry Podcast. Check back next week for another exciting episode, and make sure to subscribe, rate, and review to stay up to date with the latest episodes. Head to drgundry.com for show notes and more information. Until next time, I’m Dr. Gundry, and I’m always looking out for you.