The metabolic expert: 3 intermittent fasting mistakes that cancel fat loss | Prof James Betts

Can fasting improve your long-term health? >> Yes, but actually most of us really don't hit the fasted state at all. Having caffeinated drinks absolutely is

breaking your fast. Although caffeine isn't even a nutrient and there's no calories in there, it quite clearly perturbs metabolism. >> What do you make of olive oil during a fast?

>> That small amount of olive oil has interrupted you getting into that state and therefore the person technically didn't fast. What can you consume on a fast?

James Betts is a professor of metabolic physiology at the University of Bath and is one of the world's leading researchers on meal timing, energy balance, and metabolic responses to food. We did a study over the last

couple of years where hadn't eaten from Monday to Friday. By day two, I was really very hungry, but actually that just completely went away by Wednesday morning. I felt amazing. That's because

if you've been fasting a while, you've certainly shifted to using fats rather than carbohydrates to fuel your day. >> Why would I want to do any of this? >> Because a lot of the metabolic disease,

diabetes, pre-diabetes are really due to excess body fat that can cause some problems. And having a window of hours without food is probably where you need

to be to start accumulating that benefit of missing calories dayto-day. Is there a best meal to break a fast with?

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subscribing is how you can give a little bit back and we'll keep showing up every week to return the favor. Okay, let's get into it. James, thank you so much for joining me

today. >> Well, thank you very much for having me on the show. >> It's a pleasure. And we always start the show with a quickfire round of questions designed to be very hard for scientists

because we have these rules where you can say yes or no or if you have to you can give us a one-s sentence answer. >> Okay, that's scary, but let's go. >> All right. Is breakfast the most

important meal of the day? >> No. >> Is the time when you eat a meal important for good health? >> Yes. Can some forms of fasting improve your

long-term health? >> Yes, with a in brackets it depends. >> Can intermittent fasting help some people lose weight?

>> No, within brackets it depends. >> What's the most common myth that you hear about fasting? >> Probably something about the body going into starvation mode. People seem to

think that their body will just stop burning calories if they fast. Well, look, I'm both fascinated by the answers and slightly confused. And so I suspect a lot of our listeners are in

the same boat and probably coming in also a bit confused about fasting because there's so much talked about it. There's so many different people who have been telling us different stories over the last few years like what is it,

how do you do it, which form is best and of course does it actually work and give you health benefits. I know you're really interested in something called nutrient timing. Can you explain what

that is and why you think it's so interesting? >> I believe then that when we really start getting into the weeds about fasting and and meal patterns, ultimately as a

physiologist, we back up to think about nutrient timing because we're ultimately focused on time here. As I often say to our students, it's the most studied variable in all of science. Whether

you're into nutrition or biology or physics, time comes into all of our experiments because most parameters are not stable and we need to do pre-ests and post- tests. We don't eat continuously like rodents which teach us

a lot about our physiology and yet our metabolism and our requirements just march on variable but continuously and somehow our body beautifully manages to

match up these chunk meals with the things that we need in between meals as well. So I would say nutrient timing is about how that kind of flux or balance

is is met. How the body sees nutrients arrive at one time and either stores them or uses them or excretes them so that you have them available when needed. >> You're saying as humans we tend to eat

like discrete meals and in quite a short period of time we get a lot of like nutrients in and then long periods where we're not eating anything and then another meal. And that might sound normal, but actually you're saying even

when you think about like mice or whatever, they're actually just sort of eating all the time. And so that's very different because our body is needing to use up nutrients, energy, whatever sort

of continuously. So we've sort of got this mismatch that our body somehow has to be designed to solve. >> Yeah, that's absolutely true. So a lot of what we know about physiology and metabolism comes from rodent models.

They've been very informative studying mice and and rats, but we do have to accept that their metabolism is faster than ours in relative terms and they eat pretty much continuously. Whereas we

humans, we have this relatively slower metabolism and our meals just naturally seem to occur in kind of chunks at a certain time of the day and then in these lumps we call meals. So our

physiology has to has to cope with that and we know that our fuel use can be slightly different as a result. >> I definitely want to get into all of that, but I'm really intrigued by this idea that a lot of what scientists

understand about sort of human metabolism and physiology actually comes from sort of studying, you know, mice and rats. And you're saying therefore

there's useful information, but also because of the way that they eat in this very different way, there might be some things that are really different from humans that therefore maybe we don't understand. >> Absolutely. So I I definitely don't want

to disparrage any colleagues who do cell studies or studies in non-human animals because these have been so instructive, but we need to look at well what parts of this may not translate so well

between species. And I do feel that this meal timing area, we know that literally just the pattern in which animals eat, uh, these smaller animals we've studied,

is different to humans. We know the time of day they eat is different because of course they're they're broadly nocturnal animals and we're dial. We we're awake and active in the daytime. And we know

all sorts of other aspects of how circadian rhythms and metabolism are managed and our behavior, our responses to not eating are very different. So I do think there's a number of areas

really relevant to practical guidelines where we would want to see human data really here. Even at a behavioral level, if you fast a human, we tend to get a bit lethargic and not do so much. You

fast a rodent and they get hyperactive and start to scurry around trying to forage and scavenge for food. Even at that level, we see a very different response. And if we just based our understanding on rodents, we'd say,

well, do a fasting diet and you'll suddenly become more active. And it doesn't seem to be quite like that in human beings. >> Brilliant explanation of how we're different. You also said something about how they have a fast metabolism and we

have a slow metabolism. Could you help me to understand that? >> Yeah. So, this is a general rule in physiology. So, we know metabolism doesn't quite scale with with sheer body size if you compare kind of elephants

and mice. But also with these animals, we know that they have a relatively large surface area and a fast metabolic rate considering their size. So

ultimately you could look at it that a rodent really has this relentless metabolic rate that means it needs to eat. They have a relatively large gastrointestinal tract as well and large liver. So much greater capacity to

absorb nutrients. So that's all consistent with the fact that it's really imperative for a rodent that they're eating all the time because they need to feed this relentless metabolic rate. Whereas we humans are quite good

at having not so much food. We're arguably better at fasting than those animals. It's fair to assume that throughout evolution, we've had to learn to deal with intermittent food

availability and uncertain food availability. So having the capacity to cope with those periods without food and then still being able to function is going to be heavily kind of positively

selected for. Of course, we're not the kings in the animal kingdom on this. There's other animals that famously will have a meal and then wait weeks for the next one. But compared to the species that teach us so much about our

metabolism, we certainly can manage with kind of larger more infrequent meals than rodents can. And I think we've moved quite naturally really from

nutrient timing to fasting. And I think that's what I would really love to to talk about today. Can we start right at the beginning? cuz you'd think it was obvious like what is fasting but

actually I think that if I went on the internet I would see almost like 10 different definitions even of what a fast is you know for you doing all of these studies on humans what does it

mean to be in the fasted state >> yeah so you finished by saying fasted state I think if someone just says fasting that's ambiguous enough to say that we are fasting because we are not

actively eating now so in that sense you could say you're fasting between meals meals or between courses or between bites. So I don't think it's too helpful just to say fasting is the act of not

currently eating. So then we move on to the fasted state. We're really asking is your body in a state of being fasted as in there is no external influence of

ingested nutrients anymore. When you've eaten you're in the postrandial state. So you're postandial means after eating. But the equivalent term for a scientist for fasting would

then be post-absorptive. Meaning that if you presented to my laboratory and we did all the tests that we do to test the effect of a meal, all of the organ systems which would be

upregulated to process that food, if all those responses are absent, we would describe you as postabsorptive. You have finished absorbing the food and there's no trace that that's increased.

absorbative is not something I've ever thought I've ever heard about food but I do remember like often I think particularly when I was younger saying like you know have you finished digesting so digestion would be part of

it when we think of all the responses all the things that perturb your metabolism increase your metabolism and can be measured in your tissues after eating the process of digesting and

absorbing the food through your gut and intestinal tract is part of that but then we're going to see in other tissues like your muscle and your fat that there's going to be increases in metabolism as those nutrients arrive.

And there's a cost of storing them, um, metabolizing them, oxidizing them, or getting rid of them. And so all of those processes go into this word absorptive. You've finished doing whatever it was

you were going to do with the food. And how long that lasts after a meal is the logical follow-on question would be, well, that really depends on the meal. So carbohydrates have quite an acute

spike in response. So if you eat sugars, we get a big hit from that sugar, but within a healthy person, it would only be a couple of hours and you're back to baseline and it would look to all

intents and purposes like you hadn't eaten. For somebody who's not so fit and healthy, then it might take an hour or two longer. For fats, it can take many more hours to actually be recovered from

that. If you have a fatty meal, then your blood fats, your blood lipids will be increased for many hours. Sometimes when we do feeding tests in the laboratory, we have to test for 5 to eight hours to capture that full

response and have it come back to the fasted level. So on that basis, if if listeners out there are thinking, well, I have my breakfast, lunch, and dinner, and dinner or tea would be normally a

couple of hours before bedtime. It's thought that many of us then are not truly post-absorptive until the early hours of the morning. So most of us, if unless you're practicing intermittent

fasting during the day, are probably only really fasting in the early hours of the morning from maybe 2 or 3:00 a.m. onwards until your breakfast. And we really don't hit the fasted state. So

you could say that most people eating a a typical meal pattern, are actually in the fed state, this postprandial state for their entire waking lives, and many

people actually 24 hours a day are in the fed state. They never hit a fasted state. So, if I eat my last meal at 900 p.m.,

then that was 8 hours later, it could be like 5 in the morning before I'm finally into this fasted state. And then if I get up and have some breakfast at 7:30

in the morning, I've actually only been like 2 and 1/2 hours in the fasted state and all the rest of the time I'm in this fed state. >> Fed state. Yes. Most people grab their

breakfast straight away and then the way that we have a snack an hour or two later and lunch an hour or two later means that we really spend the entirety of our waking lives in this permanently

fed state. And so this is when it's a bit more speculative is you could say is that likely what our ancestors experienced? We know that our ancestors

throughout evolution didn't have a refrigerator available with fresh food in abundance available all day every day. they probably woke up and had to go and do something to procure the food. So

that's one thing already that physical activity would have to preede food. We often think about fueling your day. But of course the the more natural way of things arguably would be you don't eat

to fuel your day. You have to go and do the activity to procure the food in the first place. So I do think if I was speculating that the more natural thing that our uh genome would have uh adapted

towards would be not just uncertain availability of food but certainly gaps between meals and periods of our lives and our days where we are not in the fed state.

>> So interesting. So you're saying rather than like oh well you can't possibly achieve anything unless you've like had a really good breakfast there's a lot of work you have to do in order to then fuel yourself. So it's like almost exact

opposite of I feel like the you know the sort of the Kellogg's thing about you know breakfast is the most important meal of the day. >> Yeah. And I mean part of that might be a story for another day but some of those

benefits might be increased by doing that in a fasted state. And then we also know that often we have quite a lot of carbohydrate at breakfast time. And one of the things you can do to really

mitigate any big increase in your metabolites like your blood sugar is to be active in advance of the meal. So the two kind of go hand inand that maybe again coming back to timing. It's not

just about having an active lifestyle and eating well. But the sequence of those things on a daily basis is so important. When you eat isn't just a question of time of day. Should I eat at

10:00 a.m. or 1:00 p.m.? It's about where that eating occasion occurs relative to other things like activity, sleep, previous meals, and so on. Can we

now start to talk about the sorts of fasts that exist and how to understand them because this is also like very confusing. People talk about

timerestricted eating and intermittent fasting. They talk about water fasting. and there's five two diets. How would you think about these different fasts

and which of these are probably relevant as we're trying to think about improving our health? >> Okay, in broad terms, I would say intermittent fasting is the overall

umbrella term for just not eating for a prolonged time at some time in your waking period. Then we have alternate day fasting. So as the name suggests

this means eating one day and not eating the next day. Uh and sometimes that means a complete day as in 24 hours or or in fact more. Right? If you choose to

eat on Monday and not on Tuesday and eat on Wednesday that of course results in over 24 hours of fasting because you had sleep on the at the beginning or end of that time. Then there is um the 52 diet

which has been very well publicized. So 52 infers the week and simply means having two days in a week when you don't eat. And some studies have done that on

two consecutive days. Uh and some studies just say they they can be non-consecutive days. So you can kind of recover from one fast and eat again. And then the next broad category I would say

is timerestricted feeding or timerestricted eating. It's just like a type of intermittent fasting, but where we very specifically define the time of day when a person

won't eat. So it might mean that they miss the early part of the day and they can't have breakfast or lunch or they say fast from 4:00 in the afternoon and miss their evening meal.

>> And all of those get you into the fasted state, which you talked about before as being sort of the the definition >> as defined there. They do. Some of the issue I have with some of the research

that's out there is there will be a paper that is ostensibly labeled as a study into alternate day fasting or 52 fasting. But often to allow a diet to be

practical, the authors of the study will then say, "Well, of course you're allowed to have 600 calories on your fasting days or the parts of the day when you're fasting." But if the whole

rationale for this diet was based on physiology that says you will be in a fasted state and that small amount of food has interrupted you getting into that state then why would we expect any

special fasting related benefit if the person technically didn't fast. The benefits we're trying to go for with a fastingbased diet it's kind of asymmetrical that it takes a long time

to build them up. So, if you've managed to go most of a day without fasting, the thing you can pat yourself on the back about is that some of the mechanisms, which I'm sure we'll talk about, like ketosis and autophagy, these things take

a long time to gradually come up with your fast and you can ruin that in a second by eating something. So, while I completely accept the practicality of saying to someone, well, you can have

100 calories or so several times throughout the day, while it doesn't feel you've broken your fast to a large extent, your physiology has then interrupted that gradual process. So,

you're kind of offsetting um the gains with that. So, that's the first thing to say is yes, um I'm saying that that small amount of food while it seems harmless has probably interfered with

the proposed benefit of fasting. But a related point to make there is having the 600 calories feels like it's helping and going to make this easier. But strangely for many people I think having

the absolute fast is weirdly an easier thing to do because you haven't got to think about what you eat for those snacks. You haven't got a kind of gray area about well how much am I allowed?

It just simplifies the whole diet and makes it more objective just to say I don't need to know about calories or types of food or anything. I just need to be able to read my watch and know can

I eat at this point or not. I know from a lot of our research participants that's what they found useful. And there is some objective evidence in the literature to support that that if you cut your diet significantly so you take

a 25 30 40% off your calorie intake you really feel hunger. Whereas if you go even further, paradoxically you'd think that would be even harder, but cutting

your calories even further sometimes actually can bypass the hunger response. So it's easier to stick to a diet that's more restrictive. Strangely, I experienced that often when I just start

to eat something, then I actually end up being hungrier than I was before I ate anything. Which sounds crazy as I say it. Is that just me, James?

>> No, this is what I say. it can be quite paradoxical that it's kind of the opposite of what you'd think. And um uh the best kind of personal account I can give to that is we did a study over the

last couple of years where we had people fast from Monday to Friday. Now I'm quite good at fasting. I just I've always missed meals. But by day two without the food on the Tuesday, I was

really very hungry. That just completely went away by Wednesday morning. And even though I hadn't eaten by that point by three, four, and then on day five, the hunger had gone. So you do get these

strange quirks where at first you're very hungry. Your body's telling you it's lunchtime and then it's telling you now it's dinner time and you didn't have lunch. But by the next day and the next day, it seems to just reverse and

actually you don't feel hungry at all. >> You did a study where you fasted from Monday morning to Friday evening >> till Friday afternoon. >> Friday afternoon. you personally felt less hungry after

you got past the first couple of days. >> Yeah. So, I do every study that uh we're going to ask people to do. I go and do the intervention myself and do all the measurements to see what it's like. But

yeah, that the hunger went away and I can say that so it was always Monday morning to Friday afternoon. And I remember on the Thursday um I felt amazing. I ran to work. I came home,

washed the car, mowed the lawn and just had was so energized. And um and from all the monitoring we were doing, I happened to know that my blood sugars were down at kind of 1 or 2 millm mole per liter by that point. But critically,

my ketones had kicked in by then. So my alternative fuel when you're fasting is these ketone bodies. And and that's what my body and particularly my brain would have been running on by that point.

>> That's amazing. And did you manage to get your participants to stick with this Monday to Friday fasting when you went to do this? >> Yeah, the volunteers did it. Um, there was one or two had trouble during a cold

snap and it's kind of well documented that if it's very cold, it was a kind of snowy spell in the winter that actually doing that kind of long-term fasting can be um a bit more challenging. You can

start to get almost like flu-l like symptoms if you're that fasted and it's cold. But if it's warmer, then uh like I say, I felt quite energized by the whole thing. >> What can you consume on a fast? So I

think you've already answered the question that I can't eat calories, but what else? >> Yeah. So I think if we're going with this more scientific or physiological definition that uh fasting or being in

the fasted state means there is no evidence in your physiology that you have eaten recently. That would certainly mean no calories. So no what

we call macronutrients. So carbohydrates, fats, and proteins and and alcohol too are off the table by that point. Um for a few hours before if it's for carbohydrate and for five, six,

seven, eight hours before if it's for fats. Then in some of our studies, we allow caffeinated drinks too. But equally, I would say strictly speaking, this although caffeine isn't even a

nutrient and there's no calories in there, it quite clearly perturbs metabolism. So some of our studies we would also then say no caffeine, no metabolically active substances. So most

of the time in the physiological literature we would say it means water fasting. We wouldn't dehydrate a person. So water only plain water is is all that's consumed in those studies. If you

do do a longer fast, you do have to think about certain micronutrients, vitamins, minerals, electrolytes that you may be missing out on in that time. uh and in particular you can have a

problem if you're missing um phosphate, magnesium, sodium, potassium. So when we do those studies, they were plain water only, but we give people um some vitamin

tablets to take during the time. Otherwise, when you eat afterwards, you can get something called refeeding syndrome if you've eaten the wrong thing after fasting. So it's worth mentioning

that. But yes, short answer is for me fasting is plain water only. Well, so firstly, I'm definitely picking up that fasting from Monday to Friday is not something to try at home without some

careful supervision. Is that what you're saying, James? >> Yes, I think so. I mean, I mean, many people actually, although we think that's awful, I mean, many of us have probably just been unwell for 2 or 3 days where you haven't been able to eat

for two or three days. And some people say, I couldn't miss a meal. I couldn't skip breakfast. Um, but actually like like we said at the very start, human physiology is actually quite well

adapted to periods without food. So we do surprisingly well without that. >> When we talk about people fasting for their health as opposed to for your

studies, do you feel that coffee and tea needs to be excluded during these fasting periods to get the health benefits? >> No, I don't think so. It's really useful

from a scientific perspective to control things. So we try and separate the fast from the weight loss, from the energy deficit, from caffeinated drinks. But actually, when we do come to talk about

what you would actually recommend someone does, then I wouldn't see a reason to exclude those. Not least because some of those caffeinated beverages have some of the phosphate and

so on that you wouldn't want to be missing. Uh, but caffeine of course can also help energize us without the calories. So, if you were concerned that you might be a bit lethargic by fasting and reduce your physical activity, which

we've seen in several of our studies, maybe the caffeine would help avoid that. Can I move on now to your answer about breakfast which is I've decided highly divisive amongst scientists

including like quite cutting edge nutritional scientists and that's because I think there's this message about it's the most important meal of the day and then other message about

well it's almost sort of been invented by Kellogg cuz I've heard both of these things and that it kickstarts your metabolism. Is there any truth to any of this? Everyone's grandmother, doctor,

everyone else has always told them breakfast is the most important meal of the day and it's just so common in the public psyche. We all believe it. And so we went ahead and did a series of experiments called the bath breakfast

project where we really tried to take that apart and understand is breakfast actually causally linked. So if you decided to start having breakfast if you didn't already or if

you decided to stop if you already had breakfast, is that going to change your body weight? is that going to change your metabolic health? And so we did that using um a method called a

randomized control trial where we recruited a load of people. We had them have breakfast every day for 6 weeks and the other group had to skip breakfast every day for 6 weeks. And it was quite

an extreme difference. Our our fasting group couldn't have a single calorie until midday every single day. and our breakfast group had to have 700 calories

by lunchtime and 350 of that had to come within a couple of hours of waking up. So we had quite a clear difference between our breakfast consumers and non.

So um in terms of health there wasn't a big uh a big difference. We saw some slight evidence using continuous glucose monitors that maybe glucose control was

slightly better in the afternoon when people have breakfast. And we took some samples of fat from people's tummy, just a few fat cells, which we could then um

treat on the benchtop and see how sensitive to insulin they were. And there was some evidence that the breakfast consumers had fat that responded to insulin better. But all the standard stuff that your GP would

measure your cholesterol, your glucose, and insulin, and including with repeated meals. So we tested people with a breakfast and a and a lunch meal at baseline and follow-up. no difference

between groups. And the big thing people are interested in is body weight. Then they would wonder if you have breakfast, are you more likely to lose weight? And we repeated the experiment in lean

people and obese people. And we found kind of opposite responses in a way. So with the lean people, if they started skipping breakfast, they lost weight. And with the obese people, skipping

breakfast did nothing, but having breakfast caused a gain in weight. So there was some evidence for weight change there, but it certainly wasn't in favor of having breakfast, it wouldn't say that having breakfast is a good way

to lose weight. >> So you're saying that people living with obesity actually if they skipped breakfast, >> they stayed pretty much the same. So what it shows there is that those people

are more likely to compensate for that. So if you take away the breakfast, they would eat more later in the day and become less active to maintain their balance. whereas if they were having the

breakfast then they would gain weight. And so that link to physical activity was actually one of the really interesting findings that we had was that um skipping breakfast for both

groups causes people to become spontaneously less active in the morning. So one of the benefits if you like of having breakfast could be that it just makes you naturally slightly

more active during that period. So, we've seen that in a few studies now that prolonged fasting periods do tend to make people just lose a bit of the movement, bit of the physical activity

in their lifestyle. And I think people could use that information to say, um, well, therefore, I'll have breakfast cuz it will make me more active. If you're trying to help your dog lose weight, you

could just do it that way. But, of course, we're more intelligent than that. So if a person is saying, "Well, I'd like to skip breakfast because it might help me lose weight, but my concern is I'd be less active." We'll

just make the simultaneous decision to try and be more active. Decide to park that bit further away from the building and to take the stairs rather than the elevator and so on at the same time as fasting, I think, would be the

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Are you ready to join the gut health revolution? If so, go to zoe.com. Could we start to talk about what's happening in the body when we fast?

because I think that's tied into like this theory about like the health benefits. Could you help us to understand this? >> So, I think a good place to start is to recognize that, you know, anyone sat

here now listening to this to think about what fuels you're using for your metabolism. Now, although there's several places in our diets where we can derive energy, including protein, we

don't actually get a lot of energy in our diets from protein. Now, all of us are sitting here now pretty much using a mixture of carbohydrates and fats. Uh,

if you've been fasting a while, you might be more using fats. If you've been very active and eaten lots of carbs recently, you might be using pure carbohydrates. But most of us are somewhere in the middle using say half

fat and half carbohydrate. If we then start a day and start to fast, so we miss breakfast. even by lunchtime that would have shifted more towards the fats and you're using fewer

carbohydrates for your energy. And then certainly if you miss lunch too and you're getting in so now you've been fasting for not quite double figures of hours yet but maybe kind of 7 8 hours

without food you're going right towards the fat end of things and we can actually understand why that is from the availability of them. So on your body stored right now, you probably have 1 or

2 thousand calories worth of carbohydrate if we add together. And this would be in a full state. So adds up to less than a day's worth of energy. Whereas we have vastly more calories

stored as fat on our bodies. Even for a lean person, this could be 75 to 100,000 calories worth of of fat available. So I think that's the first step to say then

is within that first day when it's coming through to bedtime without eating, you've certainly shifted to using a different fuel. So I'd say that's day one, you've increased your

use of fats rather than carbohydrates. If you continue to fast, then now as your body's becoming depleted a little of its limited store of carbohydrate,

you start to see some other responses. As you go into that second day, you then need to metabolize your fatty acids a bit differently. So instead of just using them as a fuel, some of them are

converted at your liver into ketone bodies. And this is what people may have heard of ketogenic diets or keto diets. It simply means that your bodily carbohydrates are running out. And

because key tissues like your brain need glucose, the one other thing that they could run on there is ketones. So you could turn some of your fat into ketones. And you start to see those

elevate just a little on the second day. So now you're seeing that you haven't just shifted from carbohydrates to fats, but this third fuel source kind of comes into play on day two or three.

Why does anyone think that any of this would be good for you? Because these all sound like clever ways to deal with like our ancestors, you know, facing famine,

but I've got a fridge, so >> why would I want to do any of this? >> We know that um a lot of the meta poor metabolic health conditions that we see in society today are really due to

excess, right? This not just this permanently postprandial state, but a lot of people have got excess body fat. they've got fat deposition in their muscles. And so there's an excess in the

body that can cause some problems. What the proposed mechanism is for part of the benefits of fasting is that you actually remove some of your stored carbohydrate. So you know you don't have

certainly a liver but also muscles that are just brimming with carbohydrate. And because that's depleted, you've shifted to using fats even to the point where you're using fats to undergo

ketogenesis and make these ketone bodies. And that's the signal that you've managed to persist with a long enough fast for that shift. And so that then by degrading those fuels means that

it's proposed that you get greater benefits for insulin sensitivity so you can control your blood sugars better. There has also been some suggestions that that would mean that you lose more

weight. And in particular, not so many nowadays, but there was always some suggestion that maybe not only do people lose more weight, but they lose it more from body fat and less from losses in

lean mass, like reductions in muscle availability. >> And what about inflammation, which I think has come up a lot on this podcast over the last couple of years.

Can fasting help there? >> The studies that have been done don't show such clear effects there. I mean that's part of the process too that there's an idea that you need to fast

for kind of 14 to 16 hours or more. But once you switch to those lipid derived fuels, the sign there that you've achieved that is that you have this increase in ketones that actually a lot

of processes like that that are arguably either something that if you've got low-grade inflammation that's believed to be bad for health, you could suppress that. Um and then a related process uh

that I think I've mentioned the term already autophagy which means self-eing cells seem to activate this process after a day or so without food. So consistent with when the ketones start

to increase and this is a way that cells kind of recycle and regenerate which is believed to be good for health. So yeah, there's a few processes like that in

terms of systemic inflammation and autophagy in cells which are believed to be good for health and there's some evidence that they might increase with fasting. But the studies that have been

done using the kind of diets that people might be recommended, we can't clearly say yet whether the fasting is what does that because we know that a lot of those things will change favorably just with

weight loss and fasting diets do tend to elicit weight loss. >> What are the reasons that someone listening to this might consider fasting? What are the benefits that

might cause them to think about fasting in the first place? I think that would come down to their goals. If if a person is trying to lose weight or improve their metabolic health or usually both,

if those are someone's objectives, then intermittent fasting in its various forms is broadly effective. You know, almost all studies that have used it do

show that people lose weight and get some health improvements. The question in the scientific community is how much of that is specifically to do with fasting or is it just that fasting is

one good way to reduce overall energy intake. >> So James, if I'm listening to this and I would like to lose some weight, I guess my first question was going to be like, well, how much weight do people lose

with intermittent fasting? >> How much would they lose? This does seem to be a diet that people can adhere to for longer periods, but certainly the majority of studies have been done over

say a month. Some of the longer ones up to 6 months, but in the first month or two, people can be losing say 4 to 10% of body weight depending on how extreme the fast is. But even if people are only

losing half a kilo to a kilo a week, this is sustainable. So you don't want to suddenly lose weight and then pile it back on again. I was going to say, James, could you describe to us actually

what would be a good pattern if you wanted to do that intermittent fasting in a way that I can sustain for 6 months or 6 years? >> So, if you want the more effective ones,

it is the case that having a greater number of hours back to back without fasting have been more effective for for weight loss and for health gain. So, any of the different diets you're looking at, if it's 52, go for the two

consecutive days. If it's timerestricted eating, having a bigger window without food in the day, they're going to be more effective. And then that's down to personal preference. The person would

know that the longer the fast, the better, but there'll be a point where that would break them and they can't stick with that. So having the kind of longest intervals between meals that you can sustain over time,

>> what is sort of like the longest eating window that I can have that could still be beneficial? Bearing in mind the way you described that for a lot of people

basically they're never getting into this sort of sense of being fasted at all because they're, you know, eating at 9, 10, 11 p.m. and then eating again at 7:00 a.m.

>> Having a window of 10 hours or more, whether it's early or later in the day is probably where you need to be to start accumulating that benefit of missing calories dayto-day. You're

saying that if you have a 10-hour eating window, which means sort of 14 hours that you're not eating on either side, that's probably the starting point of where you would expect to see benefits

in terms of weight loss. >> Yeah, more or less. There's variability around that in the literature, but that's the that's the kind of numbers you see. Most of these studies ask people to stop eating at some point in

early mid afternoon time. I think up till now as we're thinking about advice, you've been talking very much about weight loss. If someone is thinking about health and long-term health, what

should they be thinking about this? >> There's a handful of studies now really showing that not being in this permanent delivery of nutrient state, but having onoff times might theoretically be kind

of more natural for us, if we can use that word. I mean it's highly variable outcomes but does seem to be that the diversity in the gut seems to benefit from having that kind of thing. We know

that a lot of things in our diet are not good for our gut. So any diet which is going to restrict those things and have long periods without them it it could be that just having a break from processed food for periods of the day is is really

what your gut needed to recover. And so do you in general as you're looking beyond just the gut and into these other other things, do you see improvements in metabolic health for people who didn't

need to lose weight? >> So if there are people with metabolic disease, diabetes, pre-diabetes, it does seem fairly clear that actually some of these intermittent fasting diets can

improve those aspects of their metabolic health and make them slightly more insulin sensitive and so on. Then if we're thinking about people who don't have any metabolic disease as such but

are concerned about their health, there are several studies showing improvements at a really mechanistic level when we've looked at things like insulin sensitivity

where that seems to improve. But generally the actual profile of their metabolism as your GP might measure the standard things just looking at glucose control at a whole body level don't seem

to measurably improve. But that's mainly because you're dealing with people where they there already wasn't a big problem there. So there might be a bit of a flaw effect where it's either there's no potential to improve or the benefits are

so small it's just difficult to detect them with a a noisy intervention like this. None of these studies are perfect, but when you look overall, I think that's the pattern that there are some

specific parts of metabolism that can improve in otherwise healthy people. Generally bigger effects if on those health outcomes if you're looking at people who are not metabolically so

healthy, whereas the weight change side is as effective as any other form of caloric restriction. Even if you do a 24-hour fast, so fast for an entire day,

the next day people only eat 10, 15, maybe 20% more, not the 100% more they'd need to eat to fully make that a waste of time. So people don't really make up

for what they missed. That is, by the way, one of the issues with some of the studies that are out there is that it's really not clear whether participants in those studies were told to eat more or not on the fed days. So I think um

that's something I'd like to see more of in future studies where we're actually told what the research participants were understood about what they were supposed to do on the fed days.

Can I ask you this question about exercise and fasting? And you said that you've done some research >> and there's been this open question like is it a good idea to go and you know do

exercise in the fasted state or actually is it a terrible idea and it's really important that you eat first. When you exercise, you use fuels, you deplete fuels, and that gives your body a signal

to adapt and you can get benefits in terms of improved insulin sensitivity and fat oxidation and so on if you exercise to deplete fuels. If you then

exercise in a fasted state, you start already without all those ingested fuels. If you and I went for a run in the morning and you've had breakfast and I haven't, we both run the same distance

for the same time, the alarm bells at a cellular level in my body are going off earlier so that my liver, my muscles are sending out the signals like I've trained harder and I might get more bang

for my buck by doing the same amount of training. And so then the big debate is, but would I have trained as hard? So, I think the the way to look at that is if you're going to just be doing your kind

of routine training and you're going to go for a run with a friend where you know how far you're going to go, where you're going to go, and how fast, maybe do that in a fasted state and you'll get more benefit. But if you're doing your

high quality training where you want to push yourself, maybe do that in a fed state or at least have some caffeine before because then you might actually push yourself harder and some of the

benefits then will be greater because you push yourself harder and you did run further or faster. I've been trying this a bit and doing like one of my gym sessions first thing in the morning

before I've had anything to eat. And the first time I did it, I was convinced that I would fall over. it would be impossible because obviously I'd need to have food before I was going to try and like lift something heavy or the rest of

it. And interestingly, as soon as I get into it, I do not notice any difference. And it's quite the opposite of what I sort of imagined. >> Yeah, these things kind of go hand in

hand. There's a real synergy there that we're talking today about the benefits of or effects of fasting and then layering on exercise as well. Maybe if you exercise it, it can facilitate the

effects of fasting. The two go hand in hand because they're both aiming for the same thing to deplete some fuel stores more rapidly so that then you get the benefits of having depleted them and

turned over your glycogen. Um this is the stored form of carbohydrate in the body. So again, you could look at that philosophically that a sedentary person who eats all the time with this

permanently fed state, their carbohydrate stores are just kind of stagnating. They're stuck in their muscle and in their liver. Whereas what you really want to do is turn those over, use them up and replace them on a

daily basis is a much healthier approach. >> One thing we haven't touched on is eating consistency, like eating your meals at the same time versus maybe moving them around. And we've been

talking about eating windows. You said, you know, you're going to eat for 10 hours or you're going to eat for 6 hours. Do we know what happens if those eating windows aren't exactly the same? So, let's say rather than saying I'm

going to start eating at 11 in the morning and finish at 7:00 p.m., I like moving around because I'm going to do that at the weekend, but maybe during the week I'll start eating at 8 and I'll

finish at, you know, 4 or whatever it is. Do we know anything about where the consistency matters? >> When you eat is important, not just in terms of time of day, but time relative

to other meals, sleep, activity. It's most important that it's relative to when you usually do those things because your body, your physiology becomes

entrained to a certain pattern. There's so many rhythms throughout tissues in your body and these are really helpful because it means that your body essentially learns. Your tissues learn.

They have these literal molecular clocks within tissues so that they know when light appears when the first meal tends to appear. So your cells across your

different tissues in your body know if you're a breakfast consumer or not. They know if there's going to be a big wash of sugars and fatty acids at 8:00, an hour after you woke up, or if that

doesn't normally happen until lunchtime. So you can definitely condition your body to anticipate and expect nutrients to be there or not to be there at

certain times of day. Um, and then incidentally, that's one of the the reasons that timerestricted eating might be favorable because if you're doing a 52 or alternate day fasting, you're kind

of working against that u physiology that your body wants to see repeating cycles day after day. Whereas, if you did timerestricted eating where you say, well, this is every single day. I'm now

going to eat at that time and not at that time. That's something that your body could become more accustomed to and then work more effectively with. So the consistency is likely to be better whether I've got a health goal or a

weight loss goal than sort of moving it around every day. >> Yes. So that is the conventional wisdom and you hear people all the time talk about kind of um circadian rhythms and

how we know there's rhythms in our body and so um being very regular with things and having a routine is really important. I've started to question that idea. Yes, you could do the exact same

thing at the exact same time every day and then be very happy with yourself that you're aligning with your rhythms and you're all in synchrony and then real life gets in the way and you travel

on a longhaul flight or just you go somewhere and can't eat at a certain time of day. I'm also then wondering whether there could even be some value in occasionally doing things um

irregularly um so that your your body yes has to be strained to adapt to the new feeding pattern, but maybe straining your body and and training it to adapt

to different things isn't isn't the worst thing either. >> What do you make of olive oil during a fast? And I asked that because a lot of influencers on social media are saying

it can boost this autophagy that you're describing this like killing of cells and also reduce inflammation. As we covered at the outset, I think the hard line as a scientist as a

physiologist is that fasting means no disruption of your metabolism by ingested fuels and olive oil is lipid is fat. So you are taking calories in. I

think the rationale behind that would simply be that we know that there's a much more profound acute response to sugars. So if you have sugars, you get this episode of a load of hormones like

insulin increasing and a really acute disruption of metabolism that's quite measurable and rapid. Whereas with lipids, it's a more slow and steady response. So there would be a change in

metabolism, but not as clear. And maybe I think the reasoning behind having olive oil in during the fast is that some of those processes that we were

talking about is maybe important like ketogenesis and autophagy may not be as disrupted by that as having sugar but um it absolutely is breaking your fast. The

question is just whether it's completely disrupting the objective of doing the fasting. And finally, is there a best meal to break a fast

with? >> There wouldn't be a single best meal. Um, there are certain considerations. One I alluded to earlier is if you fasted for a very long time, you could

have some electrolyte imbalances. So, if someone's fasted for multiple days, you do need to think much more specifically about what to eat. But I think here we're talking about the the more routine

52 alternate day fast type meals in which case we know that if you fasted for a shorter period you'd be very insulin sensitive. So it wouldn't be

like sugars are a huge problem there. If you've fasted for a couple of days you get this a bit of a paradox where your insulin sensitivity goes you become less

insulin sensitive. So you wouldn't want a very high carbohydrate load at that point because your control of those sugars wouldn't be as good. Generally within a day though I think the main

practical advice would be to acknowledge that you have banked this fast. You've got a period of calorie restriction which you're hoping for many people will result in a deficit and elicit

physiological responses that could be good for health. So I think the main thing is then just to recognize that you're probably feeling quite hungry by that point and maybe your dietary

restraint won't be amazing. So you would make not some of your best dietary choices and maybe eat quite a lot. So I think while there's no one best meal, I

think the trick would be to have decided before you did the fast what you were going to eat and how much of it ideally then choosing something healthy cuz you're clearly motivated to do this

fast. you're probably feeling good about choos making a good choice whereas the person you are by the end of an extended fast probably isn't best placed to choose the foods. James thank you so

much. I'd like to try and do a quick summary. So the first thing that that I'm struck with is this idea that we do so much of our science based upon looking at what happens with like mice

and rats and then infer it for ourselves. But actually, mice eat constantly and humans are designed just to eat a few times with like these big gaps between them. And that as a result,

there's some really important things we're only just starting to understand as we think about the way that we really eat these discrete meals. And we therefore don't have all the answers that we thought we had. What we also

know is that most people today, you know, living in, you know, in the western world eating modern food are in this sort of fed state all the time. So

in other words, they're still just trying to metabolize the food that they've eaten and they're not back to their sort of fasted state they would have been when they when they first woke

up. And that's really very different from the environment that probably our ancestors were in and has a lot of implications probably for our health and what's going on. And that for you the interest in fasting is like how could

you start to be spending a lot less of your day in this sort of fed state and more of the time in this unfed state because that has a bunch of benefits.

Our ancestors didn't eat to fuel their day. they had to like go out and do a bunch of things to get the fuel and then they would eat it. So this idea that you

like have to get up and have to eat food before you do anything else because we just can't function otherwise is simply not true. And you gave this example with exercise where potentially doing this

exercise in this fasted state might actually be good for you. like that very strain is is actually helping out and that in the same way one of the reasons that fasting might be good is we have

these sort of stores of glucose or something that can be turned into blood sugar really fast and if it's never used up it's just sort of sitting there but if we can from time to time sort of deplete that and replace it again it may

be like helpful and I think this analogy a bit of like you know going to the gym lifting something heavy hurts at the time but is is good afterwards then I think we talked a bit about the specifics of the fast I I think the really big message I got is you can't

eat on a fast. There's no cheating. You can't have a bit of olive oil or anything else. Like it's got to be a fast. Like it can't be anything that is actually going to be giving you any

calories. In your experiments, you go so far that you can't even have like tea and coffee, but actually saying for normal people, you know, that's fine. And and maybe the caffeine can help a bit to counteract some of this sense of

being tired that you say happens in a fasting period and that you therefore potentially do less exercise. And that for anyone doing the sort of timerestricted eating, which we see a

lot of, I think being aware that you might be less willing to do physical activity before you cut into your eating window, is really interesting. And so you probably need to think a bit more about what am I doing to make sure that

I am walking or I am going to be doing some physical activity in that period because otherwise potentially I just sort of do a bit less and I'm maybe counteracting the benefit of this

window. In terms of what fast there is, I think there isn't one right fast is what I took away from this and that there are range. You have an ability to

fast for 4 days which sounds pretty amazing. I know that I can't do that. But if we're thinking about this sort of probably most sustainable end of something you're doing daily, then you

would say think about this window of work you're eating. Maybe the benefits probably start with about a 10hour eating window. You were saying I think

for that could start to have an impact if you're thinking about weight loss. If you can get to 6h hour window that's probably like the most effective is a short period of time but sort of most effective for weight loss. And then

finally, I would leave it with this is relevant for people who are not worrying about weight loss but thinking about health benefits that I think probably doesn't push it as tight on the windows

is my takeaway. And that all of this is still relatively early in terms of the amount of science and studying. You know, we don't have this data going back

50 years understanding people who, you know, restricted their window for 10 hours every day versus not else. But you're pretty bullish about the benefits

of some sort of fasting even as we don't yet have all of that data. >> Yes, I'm bullish on the benefits of it relative to doing nothing. So, if someone's saying, "Should I do this, yes

or no?" I'd say yes. But if they're saying, "Well, I'm choosing between this diet and any other one." It hasn't been shown to be more effective uh certainly for weight loss and for generally

healthy people for health gain. Not hugely better than just cutting calories at every meal. So if someone's thinking, "Oh, I really struggle with fasting as you've said," then there's no reason to try it. You could just say, "Well, I'll

reduce my calories at every meal." But yeah, if it's relative to shall I fast or not fast, there are benefits to doing that for many people. >> If you've enjoyed today's episode with

James Betts, I know you'll love watching this episode with Professors Sarah Bry and Tim Spectre. In it, they discuss Zoe's fascinating research into the benefits of intermittent fasting.