C (3:34)

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 actually have to starve yourself for five days before that would happen?

B (3:47)

Yes, 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 you know, fasting, mimicking diets and other things come in. But, but, but yes, normally a person will have to do, say water only fasting for three, four or five days before they see this. At least some of the cells. Now we, 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.

C (4:19)

So if you're not willing to fast yourself for five days, is there any positive impact on your body from fasting more rapidly? Because 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?

B (4:43)

Yeah, 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 restricted eating, something that Satchin Panda and others have worked a lot on. In time restricted eating, like with old things, people started abusing it and started doing 16 hours of fasting per day or 18 hours or 20 hours. And 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 gallstone problems. But the worst one is the association of breakfast keeping with increased cardiovascular mortality. Increased overall mortality. Right. So there's meta analysis and this meaning 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 hour time restricted eating is the one that I never met a doctor or anybody that argued with it. And yet most people eat in America, and I'm assuming in the UK for about 14 to 15 hours a day. So that means they fast for only, let's say, nine hours or so. I think that going back to 12 hours of fasting and 12 hours of feeding, which most people say, well, it's a normal eating pattern, fine, call it whatever, but that seems to be very, very good.

C (6:18)

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?

B (6:26)

I mean, the mouse studies will indicate yes, and I think there, and we're starting to see some studies indicating reduced biological age, but I don't know if anybody's ever tested the, say, 11, 12 hours of eating. Most studies have looked at longer ones. So longer interventions, of course, are going to have more benefits and might even reduce biological age more dramatically short term, but doesn't mean that they're going to make your life longer. If in fact there is, you know, this association with, you know, increased mortality is correct. Right.

C (7:04)

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.

B (7:21)

Yes, and I think this is the concern with lots of drugs and lots of interventions, you know, like say GLP1. 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, 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, to the 16 hours.

C (8:02)

Tim, I'd love to bring you in here both because I know this is something that you study 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 you know, what we found there. But also more broadly.

D (8:18)

Yes. So we did what we call the Zoe big if study 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 lab which are not generalizable. How easy would it be for people to do? So we had 140,000 people 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. I 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, about that. So we were asking people to do fairly 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 alone for six months. And those people got real benefits in mood and energy. They lost weight and.

D (9:40)

Waist circumference improved and they actually had less hunger by doing that. So they really liked it. A third of people never found it too, 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, 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 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 stricter time restricted eating, but it not necessarily for everybody. We didn't try the 12 hours. So it could have been that most people it'd be even easier to do the 12 hour.

B (10:31)

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 Satin Panda, it tells them 10 hours, but then it's about 11. Right. So it gets closer to 12. So do you know what they actually was that they did?

D (10:46)

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. But 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, people are more likely to adhere to it long term and get benefits than really going for some superhuman effort.

C (11:20)

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?

B (11:41)

And 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 without 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 making diet cycle. So they did monthly. So these diabetics with doing fasting, making diet once a month for 12 months, by the end of it they saw.

D (12:36)

How many days per month?

B (12:37)

Five days.

D (12:38)

Five days per month?

B (12:39)

Yeah, 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. And then year two you may 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 control fasting, making diet once every three months and then fasting, making diet every three months plus what I call the longevity diet. And so we'll see. We're now at patient 400, 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. But 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.

C (13:58)

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?

B (14:11)

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.

C (14:20)

Let me just play that you're saying that you did it three times and your measured biological age improved by two and a half years.

B (14:26)

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.

C (14:39)

Tim, what's your reaction to that?

D (14:41)

It's very exciting that you might be able to trick the body into this, into this state. And I think the question is whether this is sustained over time.

D (14:54)

Because you might get a temporary change in your, 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. And 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.

A (15:48)

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