ZOE Science & Nutrition - 3 intermittent fasting mistakes that cancel fat loss and stop you seeing the benefits | Prof James Betts

Starting point is 00:00:00 Welcome to Zoe Science and Nutrition, where world-leading scientists explain how their research can improve your health. An annoying sensation of hunger overwhelms your mind, pushing aside all other thoughts. A deafening rumble emanates from your stomach, as your fridge calls your name. How can fasting possibly be good for you when it feels so wrong? In the not-so-distant past, going hungry was a necessity rather than a choice. But today, fasting is entirely optional, yet everywhere. From intermittent fasting apps to wellness influencers promising fat loss, longevity and cellular cleanup. But what actually happens when we fast?

Starting point is 00:00:49 And can it really improve our health? Although fasting is wildly popular, it's still hugely misunderstood and questions about. Does breakfast kickstart your metabolism? Does coffee, olive oil or a splash of milk break a fast? and are the supposed benefits something unique to fasting or simply the result of eating fewer calories? Today, I'm joined by James Betts, professor at the University of Bath where he carries out fasting studies on humans. He's published dozens of papers on fasting and is one of the world's leading experts on meal timing and its metabolic effects. By the end of the episode, you'll know what you have to do to be in the fastest state, what you can eat while fasting,

Starting point is 00:01:32 and whether fasting is something you should try or just another nutrition. myth, waiting to be debunked. 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 quick fire round of question, decided 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-sentence answer.

Starting point is 00:02:01 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.

Starting point is 00:02:21 With 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.

Starting point is 00:02:58 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 meal patterns, ultimately as a physiologist, we back up to think about nutrient timing

Starting point is 00:03:30 because we're ultimately focused on time here. as I often say to our students, it's the most study 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-test and post-test. 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 met,

Starting point is 00:04:12 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, but in 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.

Starting point is 00:04:41 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 rats. But we do have to accept that their metabolism is faster than ours in relative terms, and they eat pretty much continuously.

Starting point is 00:05:09 Whereas we're 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 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 all 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

Starting point is 00:05:47 be some things that are really different for humans that, therefore, maybe we don't understand. Absolutely. So I definitely don't want to disparage 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, 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 broadly nocturnal animals, and we're diurnal, we're awake and active in the daytime. And we know all sorts of other aspects of how circadian rhythms

Starting point is 00:06:28 and metabolism are managed, and our behaviour, 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 behavioural 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

Starting point is 00:07:09 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 sheer body size if you compare kind of elephants and mice. But also with these animals, we know that they have a really 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.

Starting point is 00:07:44 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.

Starting point is 00:08:16 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 talk about today. Can we start right at the beginning? Because 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 are fasting.

Starting point is 00:08:51 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're 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 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 post-pranthal state.

Starting point is 00:09:36 So your post-pranthal 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 post-absorptive. 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.

Starting point is 00:10:16 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 there's going to be increases in metabolism as those nutrients arrive. And there's a cost of storing them, 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

Starting point is 00:10:58 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 in the... 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 five to eight hours to capture that full response and have it come back to the fasted level. So on that basis, if, if

Starting point is 00:11:42 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, 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 a.m. onwards until you're breakfast. And we really don't hit the fasted state. So you could say that most people eating a typical meal pattern are actually in the Fed state, this post-pranial state, for their entire waking lives. And many people actually 24 hours a day are in the Fed state.

Starting point is 00:12:23 They never get a fasted state. So if I eat my last meal at 9 p.m., then that was eight hours later. It could be like five 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 two and a half hours in the fastest 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, as you could say, is that life? 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

Starting point is 00:13:25 activity would have to precede food. We often think about fueling your day. But of course, 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 genome would have 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,

Starting point is 00:14:09 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 in hand that may be, again, coming back to timing, it's not just about having an active lifestyle and eating well,

Starting point is 00:14:44 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 a.m. or 1pm. 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 farses that exist and how to understand them? Because this is also like very confusing. People talk about time restricted eating and intermittent fasting.

Starting point is 00:15:17 They talk about water fasting. There's five, two diets. How would you think about these different fars 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. And sometimes that means a complete day, as in 24 hours 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 there at the beginning or end of that time. Then there is the 5-2 diet, which has been very well publicised.

Starting point is 00:16:13 So 5-2 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. And some studies just say 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 time-restricted feeding or time-restricted 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 o'clock in the afternoon and miss their evening meal.

Starting point is 00:16:55 And all of those get you into the fasted state, which you talked about before has been sort of 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 5-2 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 fasting-based diet is 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,

Starting point is 00:17:52 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 a hundred 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 the gains with that. So that's the first thing to say is yes, 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

Starting point is 00:18:37 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've 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 percent off your calorie intake,

Starting point is 00:19:25 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 experience 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.

Starting point is 00:20:00 And 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 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,

Starting point is 00:20:33 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 farded from Monday morning to Friday evening. Until Friday afternoon. Friday afternoon. You personally felt less hungry after you got past the first couple of days? Yeah, so I do every study

Starting point is 00:20:56 that 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, the hunger went away and I can say that, so it was always Monday morning to Friday afternoon. And I remember on the Thursday, I felt amazing.

Starting point is 00:21:14 I ran to work, I came home, washed the car, mowed the lawn, and just how it was so energized. And from all the monitoring we were doing, I happened to know that my blood sugars were down at kind of one or two millimol 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 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. there was one or two had trouble during a cold snap. And it's kind of well documented that if it's

Starting point is 00:21:51 very cold, it was a kind of snowy spell in the winter that actually doing that kind of long-term fasting can be a bit more challenging. You can start to get almost like flu-light symptoms if you're that fasted and it's cold. But if it's warmer, then like I say, I felt quite energized by the whole thing. What can you consume on a fast? I think you've already answered the question that I can't eat calories. But what else? else. Yeah, so I think if we're going with this more scientific or physiological definition that 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.

Starting point is 00:22:34 So carbohydrates, fats and proteins and alcohol too are off the table by that point 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 all that's consumed in those studies. If you do do a longer fast, you do have to think about certain micronutrients,

Starting point is 00:23:26 vitamins, minerals, electrolytes that you may be missing out on in that time. And in particular, you can have a problem if you're missing phosphate, magnesium, sodium, sodium, potassium. So when we do those studies, they were plain water only, but we give people some vitamin tablets to take during the time. Otherwise, when you eat afterwards, you can get something called refeating 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 first 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,

Starting point is 00:24:09 although we think that's awful, I mean, many of us have probably just been unwell for two or three 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. But actually, 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 their 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,

Starting point is 00:25:04 not least because some of those caffeinated beverages have some of the phosphate and so on that you wouldn't want to be missing. 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 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 what it's almost sort of been invented by Kellogg's.

Starting point is 00:25:46 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 body weight? Is that going to. going to change your metabolic health. And so we did that using a method called a randomised control trial where we recruited a load of people. We had them have breakfast every day for six weeks. And the other group had to skip breakfast every day for six weeks. And it was quite an extreme difference. 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

Starting point is 00:26:52 within a couple of hours of waking up. So we had quite a clear difference between our breakfast consumers and non. So in terms of health, there wasn't 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 treat on the bench top 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

Starting point is 00:27:39 a breakfast and a lunch meal based on 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.

Starting point is 00:28:10 So there was some evidence for weight change there, but it certainly wasn't in favour 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 a be able 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

Starting point is 00:28:35 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 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, a bit of the physical activity in their lifestyle. And I think people could use that information to say, well, therefore I'll have breakfast because it will make me more active. If you're trying to help your dog lose weight,

Starting point is 00:29:20 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 combination. Could we start to talk about what's happening in the body when we fast? Because I think that's tied into this theory about the health benefits. Could you help us to understand this?

Starting point is 00:29:56 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. All of us are sitting here now pretty much using a mixture of carbohydrates and fats. 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.

Starting point is 00:30:32 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 lunch time 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 seven, eight hours without food, you're going right towards the fat end of things

Starting point is 00:31:02 and we can actually understand why that is from the availability of them. So on your body stored right now you probably have one or two 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 fat available.

Starting point is 00:31:28 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 have 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,

Starting point is 00:31:58 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?

Starting point is 00:32:44 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 a lot of the poor metabolic health conditions that we see in society today are really due to excess, right? This not just this permanently post-pranial 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

Starting point is 00:33:20 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 ketogenicis and make the... 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

Starting point is 00:33:57 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. I mean, that's part of the process, too, that there's a...

Starting point is 00:34:33 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 increasing 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. And then a related process that I think I've mentioned the term already, autophagy, which means self-eating. Cells seem to activate this process after a day or so without food, so consistent with when the ketones start to increase.

Starting point is 00:35:11 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.

Starting point is 00:35:47 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 a person is trying to lose weight or improve the 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,

Starting point is 00:36:37 I guess my first question was going to be, 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 one's up to six months, but in the first month or two, people can be losing, say, four 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

Starting point is 00:37:22 six months or six 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 weight loss and for health gain. So any of the different diets you're looking at, if it's 5'2, go for the two consecutive days. If it's time restricted 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.

Starting point is 00:37:50 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 describe that for a lot of people, basically, they're never getting into this sort of sense of being fasted at all because they're eating at 9, 10, 11 p.m. and then eating again at 7 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 day-to-day.

Starting point is 00:38:31 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 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 until now as we're thinking about advice,

Starting point is 00:38:59 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 on-off 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.

Starting point is 00:39:27 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 could be that just having a break from processed food for periods of the day is really what your gut needed to recover. And so do you, in general, as you're looking beyond just the gutting into these other things, do you see improvements in metabolic health for people who didn't need to lose weight?

Starting point is 00:39:52 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

Starting point is 00:40:27 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 there 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, all the benefits are so small, it's just difficult to detect them with 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 on those health outcomes, if you're looking at people who are not metabolically so healthy, whereas the weight change side is as effective

Starting point is 00:41:10 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,

Starting point is 00:41:30 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 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. One of the things I've learned running a data-driven health science company is this.

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Starting point is 00:42:20 Okay, let's get into it. 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 do exercise in the fastest day, 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.

Starting point is 00:42:47 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. So then the big debate is, but would I have trained as hard? So I think the way to look at that is if you're going to just be doing your kind of routine training,

Starting point is 00:43:32 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 the Fed state or at least have some caffeine before because then you might actually push yourself harder

Starting point is 00:43:50 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,

Starting point is 00:44:05 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 lift something heavy or any 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.

Starting point is 00:44:25 There's a real synergy there that we're talking today about the benefits of effects of fasting and then layering on exercises. Well, maybe if you exercise 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. 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.

Starting point is 00:45:00 They're stuck in their muscle and 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, you're going to eat for six hours. Do we know what happens if those eating windows aren't exactly the same?

Starting point is 00:45:29 So let's say, rather than saying I'm going to start eating at 11 in the morning and finish at 7 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 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,

Starting point is 00:45:56 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.

Starting point is 00:46:25 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 o'clock, 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. And then incidentally, that's one of the reasons that time restricted eating might be favorable because if you're doing a 5-2 or alternate day fasting, you're kind of working against

Starting point is 00:46:59 that physiology that your body wants to see repeating cycles day after day, whereas if you did time-restricted 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 of circadian rhythms and how we know there's rhythms in our body. And so being very regular with things and having a routine is really important. I've started to question that idea. Yes, you could

Starting point is 00:47:42 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 long haul 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 irregularly so that your body, yes, has to be strained to adapt to the new feeding pattern, but maybe straining your body and training it to adapt to different things isn't the worst thing either. What do you make of olive oil during a fast? And I ask that because a lot of influences on social media are saying it can boost this autophagy that you would describe

Starting point is 00:48:28 and it's 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

Starting point is 00:49:03 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 and during the fast is that some of those processes that we were talking about as maybe important, like ketogenesis and autophagy, may not be as disrupted by that as having sugar. But 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.

Starting point is 00:49:47 There are certain considerations. One I alluded to earlier is if you've 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 more routine 5-2 alternate day fast-type meals, in which case we know that if you've 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

Starting point is 00:50:31 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 result in a deficit and illicit 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,

Starting point is 00:51:11 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 because you're clearly motivated to do this fast. you're probably feeling good about choose making a good choice, whereas the person you are by the end of an extended fast probably isn't the best place to choose the foods. James, thank you so much. I'd like to try and do a quick summary.

Starting point is 00:51:35 So the first thing that I'm struck with is this idea that we do so much of our science based upon looking at what happens with 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 these big gaps between them. And that as a result, there's some really important things we're only just starting to understand

Starting point is 00:51:58 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

Starting point is 00:52:21 the food that they've eaten and they're not back to their sort of fastest 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.

Starting point is 00:53:01 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 fastest state might actually be good for you. Like that very strain 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.

Starting point is 00:53:36 And I think this analogy a bit of like, you know, going to the gym, lifting something heavy hurts at the time, but is good afterwards. Then I think we talked a bit about the specifics of the fast. 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, there'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 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 time-restricted 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

Starting point is 00:54:38 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 really. one right fast is what I took away from this and that there are a range. You have an ability to fast for four 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 what you're eating. Maybe the benefits probably start with about a 10-hour eating window. You were saying, I think, for that could start to have an impact if you're thinking about weight loss.

Starting point is 00:55:18 If you can get to six-hour window, that's probably like the most effective. It's 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 as 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.

Starting point is 00:55:58 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, shall 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, 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. Cool. I'll end this episode with something I think you'll like, a free Zoe gut health guide. If you're a regular listener, you know just how important it is to take care of your gut. Your gut microbiome is the gateway to better health, better sleep, energy and mood. The list just goes on.

Starting point is 00:57:05 But many of us aren't sure how to best support our gut. I wasn't sure before doing Zoe, which is why we've developed an easy-to-follow gut health guide. It's completely free and offers five simple steps to improve your gut health. You'll get tips from Professor Tim Specter, Zoe's scientific co-founder and one of the world's most cited scientists, plus recipes and shopping lists straight to your inbox. We'll also send you ongoing gut health and nutrition insights, including how Zoe can help. To get your free Zoe gut health guide, head on over to zoe.com slash gut guide. Thanks for tuning in and see you next time.

ZOE Science & Nutrition - 3 intermittent fasting mistakes that cancel fat loss and stop you seeing the benefits | Prof James Betts

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