[Angel Foster] (0:00 - 0:18)
When you formulated the five-day fasting mimicking diet, and this has been shown to stimulate autophagy, what's the benefit of doing it that way as opposed to somebody doing a water-only fast, for example? These have become quite popular for three days or five days.

[Dr. Valter Longo] (0:18 - 5:05)
Yeah, I mean, well, first of all, it became quite popular for one in a thousand people, right? I always say it's very difficult, if you think about it, to take somebody that is drinking three coffees a day and say, from now on, I want you to drink two. If you start telling people you got to do a four or five days of water-only fasting, good luck, right?

So, you know, because we are, especially, this is why part of the reason of developing the fasting mimicking diet, people just are, we are just slaves of those meals for hormone reasons, right? This is not just a, you know, a decision that we make rationally, it is our body is telling us, you need to have breakfast, if you always have breakfast, right? Or you need to have lunch.

So, yeah, so you remove it all, you got a problem. Then you got potentially hypertension, hypoglycemia, you know, so this is why, you know, there are saline solutions, right, for patients that, you know, the body needs salts and it needs lots of things, even if you're not eating, for many reasons, right, that the fasting mimicking diet is a bad idea. Then when I developed the fasting mimicking diet many years ago, 20 years ago, I basically also thought, why don't I make it with the healthiest food from all over the world that I can think of, right, nuts and olive oil and vegetables.

And so that turned out to be a very good idea. I wasn't necessarily thinking about, I was just thinking about why not, right? I can do it with vegan, very healthy food, why do I have to get lard instead, right?

So there's a lot of fat, for example, in the fasting mimicking diet. And it was a good idea because then eventually we showed and Stanford just published a paper, so did the University of Miami, one on colitis and one on Crohn's, but we had shown that in mice, when we gave mice a water-only fasting, the gut became leakier. We gave mice a fasting mimicking diet, not only the gut became less leaky, but we could reverse or partially reverse inflammatory bowel disease in the mice, right, both, you know, Crohn's and colitis-like symptoms.

So, and then we showed that it probably was the microbiota modulation, meaning that the prebiotic in the food, in the fasting mimicking diet, we're feeding the bacteria, lactobacillus, we feed the bacteria, and we actually showed that in the paper. They were growing this population of protective bacteria and they were protecting the gut and reversing inflammation and the autoimmunity. So the water-only fasting was partially effective.

It was not bad for the mice, but it was only partially effective. I mean, the new data from Stanford is just beautiful. You know, this is a paper in Nature Medicine by Dr. Sinha, and it's just remarkable effects of three cycles of fasting mimicking diet. And, you know, this is about a 100-patient trial at Stanford. So I think that we got it right, you know, and for many, many different reasons. I mean, I just talked about a few, but another one is the fasting mimicking diet as carbon source reserves, right, glycerol.

So we use glycerol as a gluconeogenesis reserve, which is gonna, you know, prevent the body from going to amino acids and potentially muscle mass to generate glucose, right? So it's just a lot of biochemistry in there, you know, that then is, to people, it's just food, you know, maybe not what they like to eat, but this is why pretty soon we're gonna publish on a study from Southern Italy of overweight, obese people with lots of risk factor, and this is 500 patients, and we're doing there the FMD once every three months, right? So we'll see, right?

We haven't published it, but we're analysing the data now. Like, is it possible that you don't even need to do it once a month, as we've done in many trials? What about every three months?

What about every, potentially, every six months? The most important one, the fact that the fasting mimicking diet usually comes with some type of supervision. Now, I don't know what the companies are doing, but, you know, this is also very important to be screened and maybe see a nutritionist or a physician, or at least, you know, talk to a dietician before you do it.

So that's another important reason for doing the FMD.

[Angel Foster] (5:06 - 5:43)
Yes, interesting, because I think it sounds, from what you're saying, like it's much easier for people to be compliant with it. But I have, you know, I have friends, for example, who work with a functional medicine doctor who is a big proponent of a water-only fast, and they seem to enjoy it. But what you're saying is that early rodent studies show that, actually, that may contribute, that water-only fast may contribute to things like leaky gut, alongside potentially losing muscle during that five-day process.

But using the fasting mimicking diet helps promote a healthier gut and also preserve muscle mass throughout that process.

[Dr. Valter Longo] (5:43 - 8:04)
Yeah, and this is now demonstrated clinically, right? And I'm not saying water-only fasting is bad for you, because it's not, right? But it doesn't seem to be as good, and it's not as easy, and it's not as safe, and, you know, for all those reasons.

But, yeah, somebody, and a lot of people in Germany, for example, do water-only fasting, you know, and I wouldn't go and say, oh, you know, your family's been doing this for 200 years, now you stop and do the FMD. I mean, you know, some people are used to it, and they've used it, and they want to use it. But, you know, this is why we have an FDA, and we have a lot of regulatory agencies all over the world, and medicine wants to see randomised trials, large randomised trials, and also long-term data.

And, you know, this is what we're trying to do, instead of making it like it's always been, like fasting, water-only fasting, and all these practises have always been a niche, you know, very, very few people, again, maybe one in a thousand, right, that are doing it. And the medical community rejects it, and the science community rejects it. Yeah, at some point, we're going to have to face that reality, right, that, you know, to convince doctors, to convince scientists, to convince big universities and journalists, this has to be tested thoroughly, and we have to think about all things.

You cannot say, well, yeah, but I like it that way better, and so I'm just going to recommend that. It doesn't work like that, right? And, yeah, so, and the doctors are going to be the biggest factor, right?

So, once the doctors embrace whatever type of fasting, that's going to be a big deal, but they're not going to be easily convinced. This is why now we're escalating from, you know, 100 patient type of trials to now 500 patient type of trial. Pretty soon, we're going to see the thousand patient trials, you know, multi-centre.

So, we're trying to, you know, and by me, a lot of it, like Stanford, I was just a middle outer, so I was not, I had nothing to do with the trial. So, by me, I really mean lots of, you know, university hospitals that are testing it independently of companies and independently of financial interest, and if it works, they say it works, and if it doesn't work, they'll say it doesn't work, you know? So, that's very important.

[Angel Foster] (8:05 - 8:10)
And what would be a suitable age for someone to start doing something like the fasting mimicking diet?

[Dr. Valter Longo] (8:10 - 10:01)
Well, we're now testing it in 14 to 18, right? So, in Naples, in Southern Italy, and so we'll see what happens, but the idea, and of course, people shouldn't do that now. We'll see, this is 330 people trial with teens in one of the worst regions of Europe for, you know, children, obesity, and overweight.

So, we'll see, right? But our idea, you know, in the 14 to 18 is that, you know, is it possible that at least in portion, I think we're going to have a lot of dropouts, right? A lot of these teenagers are just not going to be able to do that.

But we're hoping that, you know, maybe in 50% of them, can we just train their brain, you know, and without telling them, oh, you got to change your diet and, you know, drop everything you're doing, and now here's the new plan, which is very, very difficult for them, say, okay, don't worry about it, just do this for five days, and then go back, and then slowly they'll, that's what we see with adults, right? They'll slowly start eating better, right?

They don't, you know, they don't feel as obsessed with whatever bad food, you know, like ultra processed food or lots of, you know, bread or potatoes and starches. So, we'll see. But for sure, let's say 20, 25 years old, right, that, you know, it may be good to start doing it like once or twice a year, even though you're fit, and then eventually, you know, if there is a reason to increase it, you increase it.

So, I still do it only once or twice a year, but I skip lunch every day, you know, I do everything else, I do the 12 hours, and so, in my case, you know, probably not necessary to do it, you know, three, four times a year.

[Angel Foster] (10:02 - 10:40)
And what about when we're looking at, for example, the stress or the output of somebody's life? Do you take that into account? So, for example, I work a lot with high performing midlife women, they're also very into their fitness, they're pretty lean, they have a lot of stress in their life, because they're kind of in leadership positions, they've got young families, they're pushing their bodies already quite hard.

Would they, would that still be applicable to do this a few times a year? And would they need to kind of down regulate some of the other things they're doing in order to make space for that? Does it add extra stress, for example, that if you were, you couldn't necessarily maintain that same output?

Or is it always good?

[Dr. Valter Longo] (10:40 - 13:03)
I will say that be careful with men always maintaining that output, right? I will argue for the exactly the opposite, right? And this is why some of these fasting clinics, I think are good, right?

For more for psychological reasons than anything else, right? So it's a way for people to say, okay, stop, right? Yes, I think, you know, especially if you're talking about a couple times a year, stop, right?

So it's okay, right? You know, do it when you can just feel better, feel good, and dedicate those five days to a reset, a true reset, you know, also psychological. Now, somebody could say, hey, I don't care, you know, I gotta work 365 days a year, and I gotta be high performance.

People do it all the time. And that's okay. You have to be careful, but that's okay.

I don't think it adds stress. I think, if anything, even if you're high performing, and you're continuing, it will sort of reset. And that's what we see with a lot of high performing people.

It will help you feel better psychologically. And, you know, this has been tested at the University of Palermo for depression, and the patients did better when they did the FMD. And now, you know, I know there's several clinics are using it with a lot of their patients that are depressed, and they have psychological issues.

And yeah, so I think that, you know, best would be to stop. But if that's not an option, I think that it probably, it's okay to also do it with the high performance. I wouldn't do it with a high performance in sports, right?

I mean, I wouldn't combine it with, you know, strenuous exercise, because then your blood glucose can go very low, and you could have problems. You can be physically active, but no strenuous exercise. Some people feel really energetic.

It's really interesting, right? Some people feel really energetic and say, I never had all this, so much energy in my life. And some people say, I couldn't finish work.

I couldn't, you know, get to 5pm. I say most people, when I do it, I do everything, you know, that I need to do. So I think it can be done.

[Angel Foster] (13:04 - 13:20)
It sounds like though, from what you're saying, it's quite a nice opportunity to take a bit of a break, right? A pause, which I think we all need in modern life for a week or so, maybe even do it in combination with some friends doing it alongside you, spend some time in nature, doing nature walks, make it a little bit of a spiritual practise, right? For a reset.

[Dr. Valter Longo] (13:20 - 13:44)
That's the best, right? And so, you know, yeah, of course, it'd be great to be able to afford a clinic somewhere in the world that you can go to and do it there. But for most people, this is not an option.

So I say, you know, if this comes to your home, or wherever you are, and you can do it there, yeah, with your friends and use it as a reset period, I would say it's fairly inexpensive, and anybody can do it. Yeah.

[Angel Foster] (13:44 - 14:05)
And what about your thoughts around you mentioning earlier that on a daily basis, we should look at a 12 hour overnight fast. What about fasted exercise if it's within that 12 hour period? Do you see that as a positive or is it more down to preference of the individual, whether they train in a fasted state or in a fed state?

[Dr. Valter Longo] (14:05 - 14:47)
Yeah, you know, we're looking into it. I'm not an exercise expert. So yeah, I would say probably you can pick based on the data that is available and published data.

I will read up on the papers and see if there is a better time to do it, you know. So now we're collecting data, so I don't want to come up with, until we have a chance to review, you know, many, many papers, come up with recommendation on when is best to train. But yeah, there's a lot of data out there.

I think most of the training is going to be good, no matter what.

Longevity expert Dr. Valter Longo dives deep into the science behind the Fasting Mimicking Diet and why it holds a significant edge over traditional water-only fasting. 

Dr. Longo explains how the FMD is engineered to trigger cellular cleanup while providing essential nutrients that protect muscle mass and maintain gut integrity—avoiding the leaky gut risks seen in water-only trials

WHAT YOU WILL LEARN

• Safety and Compliance: Unlike water-only fasting, which can cause hypotension and hypoglycaemia, the FMD is designed to be safer and much easier for the average person to complete.
• Gut Health Protection: Emerging research suggests that water-only fasting can actually increase leaky gut symptoms in mice
• Muscle Maintenance: The FMD utilises specific carbon sources like glycerol to support glucose production, which prevents the body from breaking down muscle tissue for energy during the fast.
• Psychological Reset: Beyond the biology, the five-day protocol serves as a powerful psychological stop sign