3 intermittent fasting mistakes that cancel fat loss and stop you seeing the benefits with Prof. James Betts

Intermittent fasting may help with blood sugar, appetite, fat loss, and energy. But many people do it wrong. 

In this episode, Prof. James Betts, one of the world’s leading experts on meal timing and its metabolic effects, explains what fasting actually is, how long you need to fast to see changes, and the key mistakes that can stop the benefits.

Today, we break down what happens in your body when you stop eating, and explain why it may support weight loss and blood sugar control, but also why fasting doesn’t work for everyone. You will learn why breakfast may not matter, why the 5:2 diet often fails, and why eating even small amounts can stop a true fast.

If fasting can work, but is not magic, what actually makes the difference: the timing, the consistency, or simply eating less?

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Jonathan: James, thank you so much for joining me today.

James: Well, thank you very much for having me on the show.

Jonathan: It's a pleasure. And we always start the show with a quick fire 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 sentence answer.

James: Okay, that's scary, but let's go.

Jonathan: Alright. Is breakfast the most important meal of the day?

James: No.

Jonathan: Is the time when you eat a meal important for good health?

James: Yes.

Jonathan: Can some forms of fasting improve your long-term health?

James: Yes, with a, in brackets, it depends.

Jonathan: Can intermittent fasting help some people lose weight?

James: No. Within brackets, it depends.

Jonathan: What's the most common myth that you hear about fasting?

James: Probably something about the body going into starvation mode. People seem to think that their body will just stop burning calories if they fast.

Jonathan: 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've 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 are really interested in something called nutrient timing. Can you explain what that is and why you think it's so interesting?

James: 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 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-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. 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.

Jonathan: You're saying as humans we tend to eat like discreet 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.

James: 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. Whereas we are 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.

Jonathan: I definitely wanna 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 for humans that therefore maybe we don't understand.

James: 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 and metabolism are managed in 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, we'll do a fasting diet, and you'll suddenly become more active and it doesn't seem to be quite like that in human beings.

Jonathan: 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?

James: 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 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. 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.

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Jonathan: 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 a fast is, you know, for you doing all of these studies on humans, what does it mean to be in the fasted state?

James: 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 are 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? There is no external influence of ingested nutrients anymore. When you've eaten, you're in the postprandial state, so postprandial 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 it's increased.

Jonathan: Absorptive is not something I've ever thought I've heard about food, but I do remember like often, I think particularly when I was younger, saying like, you know, have you finished digesting?

James: 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, 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 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 are 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 five to eight hours to capture that full response and have it come back to the fasted level. So on that basis, if listeners out there are thinking, well, I have my breakfast, lunch, and dinner. 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 2:00 or 3:00 AM onwards until your 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 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.

Jonathan: So if I eat my last meal at 9:00 PM 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 fasted state, and all the rest of the time I'm in this fed state.

James: 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 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 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 adapt 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.

Jonathan: 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.

James: 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. It's 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, 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 AM or 1:00 PM? It's about where that eating occasion occurs relative to other things like activity, sleep, previous meals, and so on.

Jonathan: Can we now start to talk about the sorts of fasts that exist and how to understand them? Because this is also very confusing. People talk about time-restricted eating and intermittent fasting. They talk about water fasting. There's the five: two diet. 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?

James: 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 add sleep on there at the beginning or end of that time. Then there is the five two diet, which has been very well publicized. So five two 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 parts of the day and they can't have breakfast or lunch, or they fast from four o'clock in the afternoon and miss their evening meal.

Jonathan: And all of those get you into the fasted state, which you talked about before, as being sort of the definition

James: 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 five two fasting, but often to allow a diet to be practical, the authors of the study will then say, well, of course you allowed to have 600 calories on your fasting days or the parts of the day when you are 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. 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 are 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 are 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 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 gotta 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.

Jonathan: 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?

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 the best 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 dinnertime 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.

Jonathan: You did a study where you fasted from Monday morning to Friday, evening

James: till Friday afternoon. Yeah,

Jonathan: Friday afternoon. You personally felt less hungry after you got past the first couple of days?

James: Yeah, so I do every study that we're gonna ask people to do, I go and do the intervention myself and do 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. I ran to work, I came home, washed the car, mowed the lawn, and 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 millimoles per liter by that point. But critically, my ketones had kicked in by then. So my alternative fuel when you are fasting is these ketone bodies and that's what my body and particularly my brain would've been running on by that point.

Jonathan: 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?

James: 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 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-like symptoms if you are fasting and it's cold. But if it's warmer, then like I say, I felt quite energized by the whole thing.

Jonathan: What can you consume on a fast? I think you've already answered the question that I can't eat calories, but what else?

James: Yeah, so I think if we are 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. 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 then for 5, 6, 7, 8 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, 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 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 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.

Jonathan: 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?

James: Yes, I think so. I mean, many people actually, 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's like, 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.

Jonathan: 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?

James: 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. 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 this.

Jonathan: Can I move on now to your answer about breakfast? Yeah. 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 what's, it's almost sort of been invented by Kellogg's. I've heard both of these things and that it kickstarts your metabolism. Is there any truth to any of this?

James: 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 a method called a randomized 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 within a couple of hours of waking up. So we had quite a clear difference between our breakfast consumers and non-breakfast consumers. 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 a breakfast 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. I wouldn't say that having breakfast is a good way to lose weight.

Jonathan: So you're saying that people living with obesity, actually if they skipped breakfast, they stayed pretty much the same.

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James: 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, 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, therefore, I'll have breakfast because 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 or 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.

Jonathan: 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. Yeah. Could you help us to understand this?

James: So I think a good place to start is to recognize that, you know, anyone sat here now listening to this. So 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 using more 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've 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. 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 2000 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 a vastly more calories stored as fat on our bodies. Even for a lean person, this could be 75 to a hundred thousand calories worth 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 have certainly shifted to using a different fuel. So let's 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.

Jonathan: 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 wanna do any of this?

James: 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 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 just 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.

Jonathan: 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?

James: 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. 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, 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.

Jonathan: 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?

James: I think that would come down to their goals. 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?

Jonathan: So James, if I'm listening to this and I would like to lose some weight, I guess my first question was gonna be like, well, how much weight do people lose with intermittent fasting?

James: 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 six 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.

Jonathan: I was gonna 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 six months or six years.

James: 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 five, two, 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, 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.

Jonathan: 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 pm and then eating again at 7:00 AM.

James: 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.

Jonathan: You're saying that if you have a 10 hour eating window, which means sort of 14 hours that you are not eating on either side, that's probably the starting point of where you would expect to see benefits in terms of weight loss.

James: 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.

Jonathan: 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?

James: 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. 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.

Jonathan: Do you in general, as you're looking beyond just the gut and into these other things, do you see improvements in metabolic health for people who didn't need to lose weight?

James: 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 there already wasn't a big problem there, so there might be a bit of a floor 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 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 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 a hundred percent 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, That's something I'd like to see more of in future studies where we're actually told what the research participants understood about what they were supposed to do on the fed days.

Jonathan: Can I ask you this question about exercise and fasting? Yeah. 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?

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James: 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 way to look at that is if you are going to just be doing your kind of routine training and you're gonna go for a run with a friend where you know how far you're gonna go, where you're gonna 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.

Jonathan: 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 gonna try and like lift something heavier and 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.

James: Yeah. These things kind of go hand in hand. There's a real synergy there that we are talking today about the benefits of, or effects of fasting and then layering on exercises. 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. 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.

Jonathan: 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 gonna eat for 10 hours, you're gonna eat for six hours. Do we know what happens if those eating windows aren't exactly the same? So let's say rather than saying, I'm gonna start eating at 11 in the morning and finish at 7:00 PM I like moving around because I'm gonna do that the weekend, but maybe during the week I'll start eating at eight and I'll finish at, you know, four or whatever it is. Do we know anything about whether consistency matters?

James: 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 what 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 gonna be a big wash of sugars and fatty acids. At eight 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 five, two, or alternate day fasting, you're kind of working against 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 gonna 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.

Jonathan: 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.

James: Yes. So that is the conventional wisdom. And you hear people all the time talk about kind 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 do the exact same thing at the exact same time every day, and then be very happy with yourself that you are 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.

Jonathan: What do you make of olive oil during a fast? And I ask that because a lot of influencers on social media saying it can boost this autophagy that you're describing as like killing of cells and also reduce inflammation.

James: 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 it absolutely is breaking your fast. But the question is just whether it's completely disrupting the objective of doing the fasting.

Jonathan: And finally, is there a best meal to break a fast with?

James: There wouldn't be a single best meal. 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 five two 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're 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 a. 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 are 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 a. 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. 'cause you're clearly motivated to do this fast. You're probably feeling good about 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.

Jonathan: 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 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 discreet 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 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've been 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 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 actually helping out and that in the same way, one of the reasons that fasting might be good is we have these sorts 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 helpful. And I think this analogy a bit 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, and 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 gotta 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 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. Yeah. And so you probably need to think a bit more about what, 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 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 that could start to have an impact. If you're thinking about weight loss, if you can get to a six-hour window, that's probably like the most effective. This is a short period of time. Yeah. 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, which 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. But you are pretty bullish about the benefits of some sort of fasting, even as we don't yet have all of that data.

James: 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.