Recap: Is it time for you to try fasting? | Dr Valter Longo & Tim Spector

0:00Hello, and welcome to Zoe Recap, where each week we find the best bits from one of our podcast episodes to help you improve your health. Most of us have heard about the health benefits of fasting, from lowering disease risk to even slowing down aging. The catch? Going without food is tough. Really tough. However, according to Dr. Volta Longo, it doesn't have to be so hard. His pioneering research, including the development of the fast-mimicking diet, is making fasting more practical and accessible for everyone. Today, Volta joins Tim Spector and I to explain how a pause from food transforms the way our cells behave and how you can make fasting part of your life.

0:46I always challenge everyone with the question, find me anything that will revolutionize gene expression more than fasting. And I still haven't got anybody to even come up with something that they think could challenge. Meaning, if you fast a person for, let's say, five days, it'd be hard to find something else that causes more changes in the body than those five days, right? Of course, if you go longer, even more changes, but I say anything you can do in five days. So everything happens during fasting for obvious reasons, right? So you now can no longer rely on energy coming from the outside. You need to rely on energy coming from inside.

1:26And so the body slowly gets into a modality where it starts burning fat and relying on fatty acids and ketone bodies. And ketone bodies are this, you know, you heard of ketogenesis. And so ketogenesis refers to making these ketone bodies that are byproducts of fat breakdown, essentially, breakdown and then reprocessing. So, for example, the brain, after three or four days of fasting, starts functioning both on glucose and on ketone bodies. and the heart can function using fatty acids and other organs use fatty acids, which is basically fat breaking down, fats that are broken down. Then there's something else that's called glycerol that is released and glycerol and amino acids coming from muscle and other systems, they can be used for gluconeogenesis.

2:20So now the body can make its own glucose because of course there is no carbohydrates coming from the outside. So these are just some of the examples or the things that happen in a human body in the fast. Now, a lot of people use words like autophagy and thinking that's going to happen very quickly. So autophagy is this process where cells begin to eat themselves, right? Eat their own components. So they shrink and they start eating themselves. So, Volta, that's a good thing if your cells are eating themselves? It doesn't sound like a good thing. It is a good thing, right? And so these bacteria do it and yeast do it and all organisms do it.

3:00So it's an opportunity to get rid of a lot of normal components, but junk, real junk that accumulate in the cell. So in that sense, it's an opportunity to clean up. And so it's a good thing. Our group that we collaborate with has done a clinical trial showing that the markers of autophagy don't seem to be measurable until about day five, end of day five, in the human blood. But yeah, but that's one of the things that everybody, people fast for three hours and they think autophagy is on, but it probably takes about five days to get there. So just to play back, you're saying that if you got into a state where your cells are actually sort of eating themselves, they're getting rid of sort of damage, that could be good, but you actually have to starve yourself for five days before that would happen.

3:47Yes, of course, and I think we're going to talk about it. So we've been working for many, many years and how you don't have to starve yourself to get some of these effects. And that's where fasting, mimicking diets and all the things come in. But yes, normally a person will have to say water only fasting for three, four, five days before they see this, at least some of the cells. Now, we don't know what other cells do, but let's say the blood cells, they seem to be going into this autophagy process by day five. So if you're not willing to fast yourself for five days, is there any positive impact on your body from fasting more rapidly?

4:27Because you were talking about how it transforms your body in five days. Most people listening are probably not going to fast for five days, but obviously there's a lot of interest in intermittent fasting or all these other sort of things. Is there any impact on your body from shorter periods of fasting? Yes. So there's lots of different types of fasting, and each can have problems and solutions. Now, the one that I like after doing this for a long time is one is called time recited eating, something that Sachin Panda and others have worked a lot on. In time recited eating, like with all things, people started abusing it and started doing 16 hours of fasting per day or 18 hours or 20 hours.

5:08And so I was against that and I'm still against that because those 16 hours and even 14 hours or longer are associated with lots of side effects, lots of problems in the long run, right? And one of them is Goldstone problems. But the worst one is the association of breakfast skipping with increased cardiovascular mortality, increased overall mortality, right? So there's meta-analysis and this mean studies of all studies indicating that this is why I was always against it. And now there is a group that is suggesting that even if you skip dinner, this could be problematic. So I think instead the 12 hours time restricting eating is the one that, you know, I never met a doctor or anybody that argued with it.

5:52And yet most people eat in America, and I'm assuming in the UK, for about 14 to 15 hours a day, right? So that means they fast for only, let's say, nine hours or so. So I think that going back to 12 hours of fasting and 12 hours of feeding, which most people say, well, it's normal. It's a normal eating pattern. Fine. Call it whatever. But that seems to be very, very good. It's come up on various podcasts about various benefits you might get. But does this actually affect the aging processes that you were talking about that could make us sort of stay healthy for more years? I mean, the mouse studies will indicate yes.

6:30And I think we're starting to see some studies indicating reduced biological age. But I don't know if anybody's ever tested, say, 11, 12 hours of eating. Most studies have looked at longer ones, right? So longer interventions, of course, are going to have more benefits. They might even reduce biological age more dramatically short term. but it doesn't mean that they're going to make your life longer if, in fact, there is this association with increased mortality is correct, right? You're saying for people who are fasting for more than 12 hours a day, you're talking 14, 16, 18 hours of fasting, you're worried that although you might see short-term benefits, you're actually concerned that in the long-term, you might actually die sooner rather than actually be healthier?

7:21Yes. And I think this is the concern with lots of drugs and lots of interventions, you know, like say GLP-1. So lots of things are beneficial short-term, but then, you know, medicine is not really set up to think about long-term effects, right? So, yeah. So, and I think fasting, because it is so powerful, is in the same category. But the 12 hours, I've never seen any negative studies, epidemiological or otherwise. So I would say that that's a very good recommendation. It seems to be working for aging. seems to be working from metabolic issues, not as well as the 16 hours, but well. And so I think that's a good, safe option to the 16 hours.

8:02Tim, I'd love to bring you in here, both because I know this is something that you studied quite a lot, and also because Zoe conducted a study on, I think, about 150 ,000 people, didn't it, on intermittent fasting. So I'm really curious about your view and what we found there, but also more broadly. Yes. So we did what we call the zoe big if study um which was time restricted eating not actual fasting but so it was just trying to see what it was when you went to the general population rather than specific you know volunteers in a in a lab which are not generalizable how easy would it be for people to do so we had 140 000 people uh from our zoe database that signed up for this program and we said okay we want you to do three weeks where you're eating in a 10-hour window and you're fasting for 14 hours, which I still think is reasonable.

9:00I think somewhere between 12 and 14 hours, I believe the evidence shows that's still safe. We can disagree on some of the epidemiology, but I think whereas more extreme fasting, I do worry as well about that. So we were asking people to do a modest change. And what was really interesting is that a third of people found it really easy to do this. And they actually carried on well past the three weeks. They went on for six months. And those people got real benefits in mood and energy. They lost weight and waist circumference improved. And they actually had less hunger by doing that. So they really liked it.

9:46A third of people never found it too much and they didn't actually get started. And a third started and sort of gave up. There are certain people that it probably really suits and they feel very comfortable. It feels natural to them and they get into it. And I think they will get benefits. Some people do find it rather hard to go long periods without eating. and that just showing this, you know, as we know at Zoe, all about personalization, that, you know, there are these differences between people that make it harder or easier. So, yeah, I'm all for this not too strict time-restricted eating, but it's not necessarily for everybody.

10:24We didn't try the 12 hours, so it could have been that most people, it would be even easier to do the 12-hour. But what was the, did you actually ask them what they actually did? Yes. You told them to go 10 hours, but did they do, because in the studies of Sachin Panda, he tells them 10 hours, but then it's about 11, right? So it gets closer to the 12. So do you know what they actually was that they did? Yes, we did. And a third did it quite sort of religiously. And there was this middle group that actually went back, you know, and probably managed 12 hours most of the time. But they didn't seem to get quite the same benefits.

11:00But I think, yeah, but realistically, what's more important is that people sustain this for long periods of time. Therefore, I agree the general principle that having more modest goals is more likely to adhere to it long term and get benefits than really going for some superhuman effort. Now, I know you've developed something called the fasted mimicking diet. And so I'd be interested to understand what that is, because I think this ties into this question around how can you do something that's sustainable and something which is trying to get these aging benefits. Could you explain what it is and why you think it's still beneficial for longevity?

11:41And so this is a low calorie, low protein, low sugar, high fat, plant-based diet that lasts between four days and seven days, depending on what we're trying to treat. Then, you know, the patient gets a box and that's a medicine, right? Or that's potential medicine, let's say. And so we tested it now for lots and lots of different things. I think the most advanced ones is diabetes. Now, very clearly, we're seeing regression, diabetes regression, diabetes remission. And the beauty, I think, is with that lifestyle changes, right? So we ask, and the universal laden trial with 100 patients actually looked at lifestyle and saw no difference other than a little bit increase in exercise towards the end of the 12 fasting-mimicking diet cycle.

12:28So they did monthly. So these diabetics with doing fasting, making that once a month for 12 months. By the end of it, they saw... How many days per month? Five days. Five days per month. Five days a month. And then they were allowed to go back to whatever it is that they do. But now the beauty is that they improve so much. 70 % of them reduce drug use. They improve so much. Then we basically think, and we've seen this, we have clinics for my foundations. and so that we can switch them to three or four times a year. That's it, right? So year one, you do a 12, maybe not even 12, but let's say 12.

13:04And then year two, you might be able to go down to four to six cycles. And year three, we're hoping you're down maybe to three cycles. And that's it. So you do it once every four months. And so now we're formally testing that in southern Italy in a 500-patient trial, three-arm, and one is a control fasting-making diet once every three months. and then fasting making that every three months plus what I call the longevity diet. And so we'll see, we're now a patient 400. And so we've got 100 patients left. But yeah, the idea is, yes, we can try to get people to change everything they do, but they're probably either won't change or they'll go back to whatever it is that they used to do.

13:44But maybe if the doctor was on board once every three months, if you have a problem, you can consider doing these five days And once you're done with the five days, you're done for three months. Do you believe that this sort of fasting-mimicking diet, this five days, sort of every few months, can improve the biological age, make you younger on the inside that we were talking about at the beginning of the podcast? Yeah, so we did that in two trials. And in both trials, two and a half years of biological age reduction after three cycles. So this is using what I was telling you earlier. I mean, just play that.

14:20You're saying that you did it three times and your measured biological age improved by two and a half years. Yeah. So subjects that were asked to do the fasting-making diet monthly for three months, they showed a reduction, almost identical in both trials, of 2.5 years on average. Tim, what's your reaction to that? It's very exciting that you might be able to trick the body into this state. And I think the question is whether this is sustained over time because you might get a temporary change in these markers of biological age. But I do think what I like about it is that it's accepting that people aren't going to do long fasts for long periods of time outside a laboratory.

15:10And so it has a pragmatic element to it, which I think is really exciting. So I think the test will be these long-term studies to say, well, at three or five years, have things really changed permanently or is this a temporary, will the body reset itself? I guess this is what we're always fighting in medicine is the body's ability to recalibrate and realize it's being fooled. And the question is, it seems to work short term. The question is, you know, is this going to work long term? But it's very exciting. At Zoe, we never stop being curious about how people respond to food. Recently, we asked thousands of people about breakfast, what they eat and how they feel about it.

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