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Maurice Castelijn

You’ve been asking for fasting and you wanted to understand things like time-restricted eating, Ramadan, intermittent fasting, mimicking, prolonged fasting and so on. So we’ve got a fantastic set of slides that Alex has lined up for us. Alex, over to you. 

Alex Ruani

Thank you so much, Maurice, for that amazing introduction and welcome, welcome, welcome. You may or may not have seen me in the news in the past few weeks. I don’t know why there’s been an explosion of media requests for fasting. So our former Prime Minister in the UK has 36-hour fasts starting on Sundays. We’ve seen new research coming out. We have hundreds of millions of people around the world following Ramadan fasting. We’re going to talk about that today. 

So again, fasting has been in the news, but also in a sensationalised manner. You may have seen a whole email rant from me about this sensationalised headline. I’m not going to go further into that. There is a whole email that I’ve written on that. When you see a headline, don’t take that for, you know, granted. Just, you know, make sure to look into the nitty-gritty. So it’s when we don’t eat, essentially. And there are many different types. So you have time-restricted eating, one meal a day, Ramadan, alternate day fasting, weekly 24-hour fasts, fasting-mimicking diets, the 5-2 diet popularised by late Dr. Michael Mosley, whom we had here at The Health Sciences Academy telling us all about that not too long ago, prolonged fasting, breakfast keeping, intermittent fasting in any way that people do it, right?

Alex Ruani

If controlling restriction requires extreme willpower in a way that starts causing eating anxiety or extreme hunger that may disrupt our normal functioning. And we are not isolating ourselves to take a break from life whilst we do something really extreme. We need to be mindful of that. And just a red flag for you and your clients or whoever you’re working with, that’s overwhelming psychological distress from either breaking a fast, so naturally in prolonged fast, although hunger comes and goes in waves, there may be a reduction in appetite, and breaking a fast may cause some anxiety in some people, or maybe guilt from not fasting or not doing it right. 

So this is drastically affecting someone’s life, their mental health, mental well-being, their physical well-being, their work activities or social activities, family commitments, looking after their little children, or their ability to function as usual. That’s when we just need to make sure we refer this person to get some support. Now fasting on its own, is fasting an eating disorder? 

Alex Ruani

Probably 10 years ago, if I would have told you well I’m fasting today, you would have said, “Alex do you have an eating disorder?” 

But fasting today has been more normalised, yes, our former Prime Minister is fasting on Sundays and Mondays. So fasting on its own is not an eating disorder, but it may increase the risk for eating disorders or even worsen or aggravate an existing eating disorder. And I’m mostly worried about young populations, young boys and girls who are more vulnerable to some of these risks. So children and adolescents should not engage in planned multi-day fasts unless it’s for medical reasons, as part of the recovery from some kind of surgery or something like that. So again, very important to mention because we want to get this out of the way and make sure we’re all on the same page, that fasting is not an eating disorder but it may increase the risk, especially if we get anxious around eating. Now with that aside, good to have that, you know, touched on, let’s talk about the main types of fasting. 

My goodness, there are so many types. So I thought, there are so many different types, how can I categorise these? So when you look at the scientific literature, you’ll probably come across these two buckets, regular fasting schedules or sporadic fasting, like a one-off type of fast. Like one of you said you are fasting for eight days once a year. Regular fasts will be, for example, within one day or within a 24-hour cycle, all of us fast when we’re sleeping. So we’re doing it. Fasting is a natural process. We just stop eating and we sleep. So regular fast within each day may be prolonged. So, okay, I’m extending my non-eating window before or after I wake up and you may do that within a 24-hour cycle. 

Alex Ruani

Or you may have a fast in between weekdays or in between weeks, for example once a month. Like some of you said I do a 24-hour fast once a month. So again there is that rhythmicity. Now within a 24-hour period, we have for example Ramadan and time-restricted eating is another form of fasting. Some of us do it spontaneously, some of us do it in a planned manner. So we have for example early time-restricted eating with early eating windows, delayed time-restricted eating where we start eating after midday or later in the evening, and one meal a day, and that one meal a day can be any time, right?

Alex Ruani

Depending on where you allocate that meal. We then have in-between weekday fasts. So here you’ll see alternate day fasting or once or twice weekly short fasts, like the former UK Prime Minister has a once-a-week short fast. And he does this regularly, allegedly. So usually either in alternate day fasting or in once or twice weekly fast, what we see in research, the investigations that we normally see, is periods of eight weeks, 12 weeks, where individuals on the fasting days will probably just have water or unsweetened beverages like tea and coffee. Or other protocols may actually include some calories. So usually 25% of normal caloric intake or required caloric intake as for example, the 5-2 diet. So eating as you would eat on five days of the week and restricting your intake on two days of the week. So again, this has mapping and categorising fasting. So we are all talking about the same thing and we can compare like for like and not make crossover comparisons that may not be relevant. And then you have sporadic fasts, one-offs.

Alex Ruani

For example, a prolonged fast, which is usually considered to be longer than 48 hours, or short under 48 hours, one-offs here and there. Not planned or planned. And of course, behind all of this, there may be some fasting mimicking diet. So essentially researchers, especially in the field of cancer research or chemotherapy treatments, where there are fasting-mimicking diets, trying to minimise any kind of muscle loss in patients or nutrient deficiencies. So they are developing food supplements and soups or blends with some macronutrients in them, essential vitamins and minerals and essential nutrients to make sure these efficiencies are mitigated while still providing the benefits of fasting. So you eat on one day, you don’t eat on the other. You eat on one day, you don’t eat on the other. Yes, alternate day fasting or the five-day diet. So here we have alternate day fasting or once or twice weekly short fasts. Now this is a very interesting review. You have the link to the abstract in there if you want to read the full paper.

Alex Ruani

So essentially researchers analyse differences between different kinds of fasts and I think that’s very interesting so if you want to read more on that this is a very good resource. So between-day fasts usually involve a fasting day where no energy is consumed, no caloric intake is there, or the researchers may use some form of caloric intake. But then, on your eating days, you will have ad libitum eating, which means eat all you want.

Alex Ruani

You don’t need to restrain yourself. And then scientists will measure what happens, right? So you have days where you’re restraining your eating or not eating at all, and days where it’s just like, go ahead, eat whatever you like, whenever you like. And then they will observe what happens and they will report the benefits and detriments. So let’s say we start with a fasting day. Are we going to eat less the day after? Right, after this fasting day. What’s the effect of this fasting day on hunger hormones? Yeah, so we’re completely restricting our intake. How might our hunger hormones change? And it’s very interesting because to see this, ideally you wouldn’t look at one day in isolation, we need to look into a longer period of time and follow hunger hormones and see how they may fluctuate. But in essence, especially for individuals who are susceptible, it feels like a very effortful restraint to do something that is not, doesn’t feel as spontaneous.

Alex Ruani

Yeah, so we may have a fasting day and the following day if a scientist tells me, eat anything you want, all you want, whenever you want, I’m like, yeah, I’m going for it. So that ad libitum eating day, we may see some compensatory eating and our appetite levels may be increased. And then I think, okay, I’ve eaten so much yesterday. I’m still full. I’m gonna slow down today, and now I have a moderate intake day. But tomorrow I go like, oh, okay, another ad libitum day.

I think I’m starving. Why am I so hungry? Why is this? And I keep eating and I have all these crazy appetite levels. The next day I may moderate again, either out of guilt or because I’m so full from yesterday. The following day I may go again into this binge eating cycle to compensate or because my hunger hormones are completely through the roof and confused or my brain is not detecting any stop signals at all.

Alex Ruani

And then I say, okay, done. I’m done. I’m gonna go on a fasting day. Extreme willpower. I’m gonna fast. I’m gonna stop all these nonsense fluctuations on my hunger hormones, and I’m gonna fast. Again, this is just an example. Now, what does the research say? That’s where we’re more interested. So fasting days, yes, we see and we can measure extremely beneficial short-term effects.

So we see reductions in CRP and other inflammatory markers. We see increased insulin sensitivity, meaning that our muscles, our liver, and our tissues are better receptive to insulin and we can uptake glucose in a much better way without storing it as fat.

Alex Ruani

And yes, more glucose uptake in muscles rather than fat storage, so on and so forth. You can keep going with a list of short-term benefits. They are measurable, we see them. But how shortlist are these benefits? Right? So that’s another question that we often want to ask. So when you see research that only focuses on the day after fasting or just on the fasting day, and doesn’t look beyond that, that research is usually looking at the mechanism itself as opposed to long-term effects. Always be mindful of that. 

Now how do these fasting days and bingeing day cycles affect hunger hormones and satiety signaling? Is it good or is it bad for long-term appetite regulation? Now, hunger hormones in these instances are all over the place. And I’m not just saying their production, but also their signaling, the receptivity in the brain is more erratic, is more unpredictable. There is that disruptive 24-hour rhythm, the body loves predictability, and the body loves to work in rhythms that are similar day after day.

Alex Ruani

Here, we have no rhythm day after day. Now, for some individuals who are more susceptible, I’m not generalising to everyone, but some of you may be doing great on this. But for other individuals, these unpredictable intakes may hugely dysregulate hunger hormones and they may over-activate the hunger response. And again, I’m not generalising, this can happen. So long-term overeating drive, when you look at alternate-day fasting or twice-weekly fast, we may reinforce a decreased sense of inhibition toward food. to work full. And this may result in more dysregulated appetite, more dysregulated satiety signaling and receptivity. So our brain may be doing a poorer job at recognising, start eating, you are hungry but I’m not recognising it, or stop signals. So there is a de-sensitivity, and sensitivity is decreased, right? So there is this interesting review, this systematic review and the meta-analysis looking at alternate day fasting, the 5-2 diet, amongst others, and they looked at 17 randomised controlled trials.

Alex Ruani

And what they found is that there is an increased cognitive restraint in this kind of less consistent or less regularised ways of eating. So there is an extreme inhibitory effect that we have to exert. Some of you say you got used to that later on and yes we actually see contradictions. So if you look at this systematic review you’re going to see studies where it goes up, hunger goes up, hunger goes down, very variable fluctuations in appetite. We are all different.

Alex Ruani

The drive to eat was not mitigated and the prospective food consumption, that overcompensatory eating was not mitigated. So again, we cannot generalise, but speaking of this, we have to be mindful that hunger levels may go a little bit all over the place or the signalling or the receptivity.

Alex Ruani

And this is a very important point, especially if you’re advising patients or clients on this, make sure to mention this caveat. Now, what about within-day fasts? So fasts that occur in a 24-hour cycle. So these are periodic, non-eating hours within a 24-hour period. And you have in here Ramadan, of course, which occurs in a 24-hour cycle, and you also have time-restricted eating. So we’re talking about fasting and different fasting types, and we were talking about alternate-day fasting and within-week fasts that lasted 24 hours or a couple of days. So what about those fasts that are actually more regular, more periodic, and that they occur within a 24-hour period? So let’s look into those.

Alex Ruani

So we have Ramadan and we have time-restricted eating. And let’s talk about Ramadan. Now there are many religious diets. Some of you today mentioned different religious diets that you have followed before, fasting diets.

So there is a review that I find very interesting. They have this table with different religious fasts. It’s a fantastic review because it compares them and you can read on them. It’s really, really interesting. 

But let’s talk about Ramadan because it falls within a 24-hour cycle. So Ramadan is an Islamic religious journey lasting about a month, and what happens is that those who observe Ramadan, and I have so many friends observing Ramadan right now, many of you who have mentioned that as well, there is a dry fast so no liquids no fluids no water not even a drop of water no oral medications from dawn to dusk so it’s not from sunset or from you know when the Sun goes down and the Sun comes up it’s literally from the last light, the last twilight, so the first twilight in the morning. Observers will do this for about a month. So within that 24-hour cycle, there is a restriction of food and fluids. So right now, in March, when those of you who started Ramadan, you were fasting for about 13 hours. But then towards the end of Ramadan in April, you’re going to be fasting for 14 and a half hours. So it’s going to get a little bit more extended.

Alex Ruani

And it really varies depending on the geographical location, the time of the year. So for example, summer, Ramadan is a lot harder here in the UK because your fasting period is just so long. Daylight lasts so much longer. But there are millions of people around the world observing it. However, some people are exempt from observing it. Even Islamic teachings exempt some individuals. And it’s really contraindicated for those who have serious medical conditions like heart disease, kidney disease, severe diabetes, pregnant and breastfeeding women, those who are hospitalised or taking prescription oral medication during fasting hours, and anyone really where fasting could be a health risk, like for example really little children. So feasting by night, fasting by day. We may turn Ramadan into an unhealthy feast in this guise, but of course there is this cultural-religious celebration that we cannot ignore this journey. Naima, I remember you shared some of the more poetic elements of Ramadan. So yes, it’s a celebration as well. And depending on what is eaten, how much, and how long overnight, there may be some weight gain. So many studies have reported weight gain during Ramadan. So you can click on the three links here, you have three examples. So it does raise a little bit of an eyebrow. I thought after all these restrictions, I should be losing some weight. What’s happening here? What explains, what do you think explains Ramadan fasting weight gain? Why may that happen? Is it the night overeating, or excessive intake to blame?

Alex Ruani

Is it poor diet quality? Like one of you mentioned more sweets are being produced and consumed. Is it hormonal changes or something else? What do you think maybe behind this weight gain? It can be any of these or all of these combined. And hormonal changes are the ones that I want to focus on because we can go on overeating and poor food choices forever, but I want to go into the more interesting ones. So let’s look at hormones and specifically, why don’t we look at leptin? 

So leptin is this appetite suppressant hormone produced by our fat cells. And it has a huge number of homeostatic regulation functions in our body. But leptin may somewhat be behind, besides all these other culprits, leptin may be behind some of the potential weight gain. So when we start engaging in Ramadan, we may start going a little bit against our usual leptin rhythm.

Alex Ruani

So essentially, if you can see on the right-hand side of your screen on the top graph, there’s a typical nighttime leptin release. So it’s essentially suppressing appetite so we can sleep. There’s appetite suppression during sleep, so that facilitates sleep and is part of that. But because we’re starting to eat most of our calories later in the day and very close to bedtime and sometimes even past before bedtime, especially in summer when days are so long here in the UK, this may disrupt metabolism initially and result in weight gain. Especially we see that in the first two weeks really coincide with research highlighting slight weight gain in many, many people during the first two weeks of Ramadan. With gradual weight loss after that, it can be possible, and some, for others, not. What happens during those second, third weeks of observing Ramadan is that leptin starts shifting and it becomes more adaptive to a later time.

Alex Ruani

And leptin shifts to, you know, five or even six hours later. That peak is delayed. So you can see on the second graph on the bottom of the screen on your left-hand side. So, leptin starts shifting to diurnal hours, so daylight hours. So, you can see that instead of picking at night, as we usually see, or late in the day, before bedtime, or in our first hours of sleep, that pick is actually in the early morning. So by having leptin levels that are greater in the morning instead of nighttime, we have enhanced appetite suppression and enhanced satiety, and it may help us better maintain the fast during the daylight hours. That shift takes time. And if you look at research on changing our meal times and moving to late-night meals, you most likely, if observed in the long term, you are most likely going to see a shift in leptin peaks more towards the early morning hours, suppressing appetite regardless of quantity eaten and meal composition. So I thought this was fascinating because it may in part explain some of that initial weight gain. But it’s nice because the body is very intelligent and it readjusts and I love that. I love that about adaptation in the body.

Alex Ruani

But doing it right, so for example, when I have friends observing Ramadan, some of them may restrict their sleep or sleep fewer hours, and there is a lot going on. So perhaps not just looking after, you know, a healthful, really healthy eating and hydration, but also timing the meals in a way that doesn’t really disturb sleep too much, especially in summer days, and not rather than eating all night long for an unlimited time, having a little bit of bandwidth for sleep as well. We know that sleep deprivation, so sleep debt, can result in increased levels of hormone? 

Ghrelin. And ghrelin – what kind of hormone is that? It induces appetite. So ghrelin increases appetite. So when we have sleep deprivation and we sleep fewer hours or our sleep quality is compromised, we may have higher levels of leptin and we may feel a during our fasting hours. Now when we think okay great, that’s very useful to know. Now Alex, can you tell me if Ramadan fasting is helpful for my health or not? And the answer is yes, if you are eating in a way that doesn’t compromise sleep, you maintain physically active, like one of you actually mentioned, reduce physical activity, Ramadan fasting can be extremely, extremely favourable to your metabolic health. For example, which is, you know, and again, click on this hyperlinks because there are so many amazing research studies on lower levels of bad cholesterol, lower levels of triglycerides, reduced fasting blood glucose, reduction in inflammatory markers, reduction in oxidative stress, and many, many other benefits, like for example, improved gut microbiota composition, better liver function, genes that actually help with antioxidant defences.

Alex Ruani

So you see this cascade of effects that tend to happen when we do Ramadan in a way that doesn’t compromise our sleep too much, that ensures adequate hydration, good diet quality, and all of these things that we need to keep in mind, like keeping physically active, which is not so easy, right? It’s not easy. But again, these benefits can be cancelled out depending on what we eat, how much we eat, and how long we eat, so on and so forth. But very, very helpful to know that it can be extremely beneficial, but the results are very mixed. So if you see a scientific paper saying Ramadan is not beneficial, take that with a pinch of salt because literally it really depends on what kind of behaviours were taking place during that Ramadan period. Now how does Ramadan compare to other fasts? Is it superior in terms of metabolic effects and health benefits?

Alex Ruani

Well, when, you know, again, you have another literature review here, so you can click on that link when you get the slides. When you stack Ramadan fasting against different types of intermittent fasting, for example, time-restricted eating or modified fasting regimes, sadly, the other methods tend to have more pronounced effects on fat loss and body composition, especially in the long term. It doesn’t mean that Ramadan is not beneficial, but usually when you look at long-lasting effects compared to Ramadan.

 So in Ramadan we see a weight regain that may occur within the first month after finishing Ramadan. Now I don’t want to generalise because the reason why we see mixed results as well is really whether those eating windows are really short and in the night or if they are extended like in winter. So if you have fasting windows that are so long in summer with very short eating windows in the night when you’re supposed to be sleeping, then we see mixed results. So it depends on the time of the year, the variations in eating windows, the geographical locations. For example, think about Finland, Norway, Sweden, you know, where you literally have daylight all day long. And yes, you know, there are extensions where they can follow Ramadan timing compared to other locations, but, you know, it becomes really challenging. So there is a lot of, in scientific research, a lot of variation in the methods. So we cannot really compare like for like, I would like to compare for example, all winter Ramadan fast. How do they compare to each other? Summer Ramadan fast, how do they compare to each other? 

But we don’t have enough science. We need to make more science and learn more about all this.

Alex Ruani

Really, really good. All right, so the majority of us do this. So we eat during the day and we fast overnight when we sleep. So is that more doable? Well, most of us are doing it, right? We literally stop eating so we can sleep. But what’s the research on time-restricted eating?

Now, time-restricted eating, for those of you who haven’t heard of this, is a form of intermittent fasting within a 24-hour period. So we literally look at a 24-hour cycle. And it seems to accentuate our 24-hour metabolic rhythms and nutrient sensing. So there are metabolic benefits, there are reduced risks for certain conditions, and each day we’re going to make sure that the eating window is somewhat restricted at the same time, so there is a level of consistency day after day. It doesn’t mean that we’re going to eat non-stop for that eight-hour window. So, for example, if you have an eight-hour eating window and a 16-hour fasting window. So an eight-hour window doesn’t mean that we’re going to eat non-stop for eight hours, usually what happens if you look at the research done on time-restricted eating is that scientists will time maybe two or three meals within that period. You also have shorter windows of six hours, and four hours. Sometimes if you see a restricted window to two hours, that may be like one meal a day because if you are eating, even if it’s just two meals within those two hours, there is a level of reducing it.

Alex Ruani

The metabolic effects may be very, very close to each other. Our typical eating windows for most of us are 12 hours, 14 hours, you may skip breakfast, you may skip dinner. But again, in time-restricted eating, it usually starts from eating windows of eight hours.

Usually, it starts on windows of 10 hours, but usually eight hours, six hours, or four hours of eating, not non-stop with meals timed within that period.

Alex Ruani

What are the benefits?

The amount of papers that you’re going to find on the benefits of time-restricted eating is enormous. But there is a lot of inconsistency as well in the way these studies operate on things that they are measuring. There’s abundant research on time-restricted eating. And you can see in here a summary. I just picked this visual representation because I thought, okay, great, let’s just put everything on one slide. So a number of benefits. You’re going to see, for example, increases in bile acid production. Who knew? Protection against nutritional challenges.

Alex Ruani

For example, maintaining nutritional balance, regulating energy state, enzymes, DNA, RNA, protein repair mechanisms, reducing cellular stress, maintaining insulin sensitivity or improving it, improving glucose uptake in muscle, liver, and peripheral tissues, enhancing all kinds of metabolic pathways, liver pathways as well, for example, inhibiting cell apoptosis or reducing certain liver enzymes that may not be as beneficial. Then you also go into fat metabolism, burning excess body fat, we see that in many studies, reducing certain detrimental lipids or fats in the body that have become, that have sedimented in certain parts of the cardiovascular system, regulating energy expenditure, and reducing inflammation. Many of you have mentioned that you’re super interested in the reduction of inflammatory markers. So fasting is very stressful on the body, especially when we extend it beyond a certain period where the body starts metabolising fats for energy. There may be a switch depending on how long you’re fasting.

Alex Ruani

And because of that activation of, you know, it’s quite stressful for our systems, there is this feedback loop where it challenges the body, you know, it can activate or increase all of these beneficial counteractive measures. So it’s pretty fascinating when you read the research on fasting and what it can do. Metabolic effects. Here you have a table, again, a fantastic review that you can look into. Weight loss, reduction of type 1 and type 2, prediabetes, sorry, and type 2 diabetes risk, fatty liver disease, cardiovascular risk, cancer risk, neurodegenerative conditions like Alzheimer’s and dementia, mixed results on sleep, some may sleep better, some may not. We’ll talk about sleep in a moment. And muscle mass, we’re also going to talk about muscle mass in a few moments because we’re seeing mixed results in there. So when these time-restricted windows are usually aligned to your chronotype, whether you’re an early bird, an intermediate chronotype, or a late-night owl, we are seeing more of those benefits. 

Alex Ruani

Weight loss – what happens with weight loss? Normally you have mixed results if, in the design of the studies, individuals are told to eat as little. So eat anything you want, how much you want during your eating window, we tend to see mixed results in there. Whereas if there is some form of caloric restriction, even if mild, a few hundred calories, a couple of hundred calories, that’s where results on weight loss tend to be more consistent across studies. So is the ideal eating window starting in the morning, midday, or evening? What I’m gonna tell you is many scientists, not all, not all, but many scientists, have a hypothesis that early eating windows may result in better cardiometabolic effects.

But is that so? Well, there are so many studies that actually contrast that hypothesis and smash it to pieces, right? We actually see better results in other studies with delayed windows and I saw better effects with early windows and midday windows. It’s really messy right now and I really scratched my head and I went all over the place. There are so many systematic reviews as well, not just studies, that this is highly debated right now. Let me give you an example. Is an early eating window always best?

Alex Ruani

Well, if you look at this meta-analysis, not always. For some people, yes. For others, no. So, for example, in this one, this example you can see on the screen here, the first example on the table actually, a six-hour delayed window, eating window, with no caloric restriction, so participants were not even limiting their calories, they were eating as a lipid. They had an eating window starting at noon until 6:00 PM, and that was not an early eating window, it was more like a midday-ish eating window. Fat oxidation increased from 9:00 AM to 12 noon, so that was before eating, before breaking the fast they were burning more fat and Carbohydrate oxidation or using glucose as an energy fuel was reduced but then Carbohydrate oxidation was increased after eating from 6:00 PM to 9:00 PM. And fat oxidation, fat burning was reduced. So you normally kind of see this trend when you look at different eating windows, fat oxidation may occur at a different time, depending on how long you have not eaten.

Alex Ruani

So mixed results all over the place and not just on effects on fat oxidation, but all kinds of things, insulin sensitivity, glucose, uptake in muscle, liver, so many parameters. There was an eight-week time-restricted eating, delayed time-restricted eating, with aerobic exercise and supervised resistance training three times a week. So I had a personal trainer, really. The resistance training sessions took place between 1:00 PM and 7:00 PM. So literally, the participants chose a time in between there. Aerobic training was also performed between 1:00 PM and 7:00 PM, so depending on the participants’ schedules. Now, the participants ate all of their calories between 12 noon and 8:00 PM. And they had a mild caloric restriction on top of that of 300 calories. And guess what? Their lean muscle mass actually increased. Not only they didn’t lose muscle, they gained muscle mass.

Alex Ruani

It may be true for some individuals and it may be linked to skipping breakfast, it may be linked to other factors that we cannot generalise because in the research we see mixed results. For some people yes, for some people no. The factors surrounding our eating like exercise and so on also need to be taken into account. Another study, delayed time-restricted eating. So three meals, really, one at 1:00 PM., the second one at 4:00 PM, and the last one at 8:00 PM.

Alex Ruani

Very doable, right? And the participants consumed 100% of their energy requirements. What I love about some of these studies is that they follow the exact energy requirement or caloric requirement calculations needed for activity levels, so very personalised.

And they did this eating window for eight hours, as you can see here, for eight weeks. They had a standard resistance training program, but each major muscle group was trained only once a week. Can you believe it? Only once a week. It’s not like in these three resistance training sessions they trained all muscles. No, they only trained one group of muscles. So major muscle groups were trained only once a week.

Alex Ruani

The researchers analysed fat mass and fat-free mass before, during, and after and they saw that of course there was some decrease in fat mass, and again the participants were not restricting calories and they saw a decrease in fat mass, and then what happened to muscle mass? Well, the muscle area of the arm and the thigh and free fat mass were retained. So based on the measurements that they undertook in the study, there was no muscle loss per se.

Alex Ruani

And also maximal strength was maintained. So again, delaying these eating windows does not mean that it will cause muscle loss for everyone, especially when we’re timing the meals quite strategically, we are having the right proportion of carbohydrates, protein and fats in the diet, making sure that we take advantage of that optimal eating window after resistance training and so on. So again, you can see right here in the table what happened with free fat mass and so on muscle.

There was even in our muscle a slight increase after the eight weeks. So a slight increase in our muscle mass. So again, it varies per person. For some of us delaying our eating window may have no effect on muscle mass. For others, for example, older populations, we need more research. There is not enough research on older populations.

Alex Ruani

And just because one influencer happened to say, oh, I’m losing muscle because I’m skipping breakfast. And the same influencer was saying 10 years ago, skip breakfast. And now this influencer changed their mind. It doesn’t mean that all of us should start having our early eating windows and shift to that side.

Yeah, so again, very important. Now, let’s go back to the big question. Which eating schedule is more effective? What do you think? Should it be this morning schedule of eating, midday or evening? And the answer is the one you can stick with, the one that feels less forced. We don’t want to generate eating anxiety or cognitive restraint that is exceedingly effortful. So, the meal times that you may be accustomed to, if we can start at least there, and then of course things can be adjusted. But the eating window that you find the easiest to follow. And usually, I’m going to share a table with you later, but usually, if we are to work with a client or a patient like you, Dr. Paula, on time-restricted eating, we first need to know what kind of eating window our client normally has. Let’s say 14 hours, so then we can reduce it to 12 hours and see how that goes.

And then 10 hours and see how that goes. Is your client doing great? Fantastic, no need for further reduction, right? Oh, no results yet? Okay, maybe we’ll do eight hours of eating, planning the meals within those eight hours.

Alex Ruani

So rather than going from 14 hours of eating windows to four-hour eating windows, which are extremely short, we can do things more gradually. We’ll look into safety precautions, contraindications and risks in a few moments. But I want to talk about something very important. So all of us have clock genes and these clock genes, which have variants that you know have that have been inherited from mom and dad, have a huge influence on our sleep and wake cycle. And these clock genes are central in the brain, but also peripheral. So in our liver, in our kidney, we have clogged genes. In our brown fat, in our hearts, we have clogged genes. In our adrenal glands, aorta, white fat, in our muscle tissue, we have clogged genes. In the cerebellum, the brainstem, and the hypothalamus in the brain.

Alex Ruani

So essentially, here you can see all of these Circadian logs and our genetic predisposition to certain sleep schedules and wakefulness and eating schedules and so on, activity levels, are largely influenced by these inherited genes. When you look at research on genetics and their association with chronotypes, the influence of genetics on our chronotypes is huge, it’s really, really big. Can we override our circadian rhythms? Of course, we can shift things around, but we still have these clock genes that are not going to change. Their expression may change because we change our sleep. Because I love chatting with you. What’s your natural wake-up time? And again, think about a good night’s sleep with no alarm clock, on a day off, no children waking you up, you have little children, you know, they don’t have an off battle. Our sleep is so disruptive when we have little children. So what’s your natural wake-up time?

If you have little children, I think before you had the little children. So what’s your natural wake-up time? And again, your natural wake-up time on those three days where you have no sleep deprivation, you feel sleepy really well, you don’t have an alarm clock, you don’t have children waking you up, that may somewhat indicate a self-reported chronotype. But we can also find out about our chronotype if we do a genetic test. So a genetic test, when they analyse around 350 genes, they may with really, you know, fairly good precision, whether you are an early chronotype or a late chronotype or somewhere in between. About 30% of the population is morning type, although societal structures like school time, working hours, so on and so forth, are really structured around early times. 40% of the population in evening time. Now this is important because there is something called the optimal position of sleep for your chronotype. So what’s the optimal position of sleep for your chronotype? The optimal sleeping hours, or the midpoint of your sleep, in your case.

Alex Ruani

So mostly influenced by genetics, we can shift our circadian rhythm, but the genes remain the same. And when you position your sleep in alignment with your genetics, and again, some association studies, there is a variability risk, we may not always get the exact time in our DNA tests, but genetically it’s there, even if we cannot accurately measure it. When you position your sleep in a 24-hour period, in a way that matches your chronotype, your sleep architecture is optimal. Essentially, those 90-minute sleep cycles and within those sleep cycles you’re going to see more deep sleep in the first half of the night. You’re going to see usually an increase in REM sleep, the dream state of sleep, in the second half of the sleeping time. But for example if you have a late chronotype and their genetic predisposition is to go to bed at 2:00 AM and wake up at around 10 AM, and then we force this person to actually not go to bed at 2:00 AM, and maybe the person has little children or work commitments and this person is trying to go to bed at let’s say, 11:00 PM, this person may not be able to fall asleep easily. And I’ve seen some misattribution of insomnia, and researchers are talking about this more now, misattribution of insomnia to late chronotypes, which I find fascinating. And these late chronotypes may not fall asleep as easily, but they still wake up early in the morning. So they train themselves to almost go against their natural tendency. So it’s a very, very interesting field of research.

Alex Ruani

Now, what does all of this have to do with time-restricted eating? So, of course, chronotypes are mostly genetic, but there are lifestyle-driven circadian rhythms. We can override our chronotype and shift our hormones one way or another if we align our sleep hours, our meal times, our activities, and so on and so forth. But we may still go against our natural genetic clocks. And that’s called circadian misalignment. And there is a lot of research on that.

Alex Ruani

I find it fascinating. But when it comes to time-restricted eating, the early types may want to go to bed before 9:00 PM and may want to wake up before 5:00 AM, whereas the late types may want to go to bed after 2:00 AM and wake up at around 10:00 AM, if not later. And you can see the difference between these two rhythms. very, very far apart to say to a late chronotype starts practising early time-restricted eating because I saw a scientific paper that is amazing, may backfire. It may not be the right thing for them. So are we eating against our clock genes or are we aligning our eating patterns to our clock genes? And again, if you can take a genetic test on this, I think it’s one of the most accurate ways of somewhat guessing if you’re an early bird or a night owl, but you can also self-determine based on your natural tendencies. So eating times aligned to your chronotype tend to have the most favorable outcomes. 

Alex Ruani

So in time-restricted eating, chronotype considerations are fundamental. So favoring early day windows with early breakfast, generalising benefits to everyone with any regard for midday or late chronotypes, that’s not ideal. And especially since, let’s say we stop eating at 2:00 PM or 3:00 PM, and we don’t fall asleep until like 10-11 PM., are we going to get hungry? And that can also impact sleep. 

Sleep, the delay of sleep onset, and the sleep architecture, it can have a knock-on effect on sleep. So it’s not all roses for early time-restricted eating. So at the moment, it’s very mixed, and if you ask me, as we see more research coming on chronotypes we’re now going to understand ah that’s why we cannot generalise we need to start investigating the effects of time-restricted eating on different chronotypes and how that works so it’s not that difficult but research is very expensive and very difficult to recruit different chronotypes and even check for them. But there are studies out there checking their genetics, whether the chronotypes are somewhat mentioned by genetic tests. So the cleaning up of cells, yeah? So this is a housekeeping mechanism to recycle exhausted materials and dispose of damaged organelles and proteins and so Can individuals extend their non-eating hours?

Alex Ruani

In general, we see from animal studies and human studies that there is an increase in autophagy and even longevity in eukaryotic cells. Does it happen during long fasting windows or shorter ones? ones. So tell me if you think that autophagy only takes place in longer fasts, yes or no? What do you think? When we say autophagy only takes place in longer fasts, the answer is no, and I’ll tell you why. Can you believe it? Autophagy is a 24-7 process. Right now, as I’m speaking, there are cells in my body, whether I ate or not, cleaning up the house. So autophagy happens in a 24-7 manner. It’s a regular, ongoing process.

Alex Ruani

So a more precise language is to talk about the increase in the rate of autophagy. So it’s not an activation or an initiation per se, it’s more like we are increasing each flux. So it’s happening but we are increasing the rate at which it happens. And the more we extend our non-eating hours, the greater that rate. So there is no cutoff that says after 17 hours, after 24 hours, after 3 days. By the way, I didn’t know this. I really wanted to look into this.

It’s very important that we know that, yes, that rate increases the longer we don’t eat. So the rate of autophagy likely increases with any extension of the usual non-feeding period, whether that’s 12 hours of not eating or 16 hours of not eating. And yes, the more you extend a fast, the more autophagy flux we can measure. So especially when it’s combined with either complete caloric restriction or some caloric restriction or longer fasting periods, we see more repair. So when some influencers say, well, you need to activate autophagy, so don’t eat for three days, otherwise, it’s pointless. Listen, let’s be precise with the language. Autophagy is occurring 24-7. We’re talking about increases in the rate. Yeah, I just thought it was an important one because I’m out there on time-restricted eating, influencers saying, well, 16 hours of fasting or restriction are not enough for autophagy. And I’m thinking, well, autophagy has already increased by not eating for 16 hours.

Alex Ruani

So there is no precision in that language. Yeah, so be mindful of that. Now, fasting, there are many mechanisms in which fasting also helps with, for example, diseases like cancer or even during chemotherapy. So fasting can actually increase patients’ tolerance to chemotherapy injury because there is more cleaning up of the house. So of course there are other mechanisms and deactivation or increased expression of certain genes in here but generally speaking, that’s what’s happening. Now do prolonged fasts alter the gut microbiome? So we see research, for example, when we’re talking about Ramadan, there are some studies showing beneficial effects on gut microbial composition, diversity, and so on and so forth. Also in time-restricted eating, you’re going to see some benefits. But what about prolonged fasts, when we’re fasting over 48 hours for a few days, a week, or even 10 days? 

Alex Ruani

And this is a question that one of you asked me in our last webinar, and these are the slides that I didn’t include in my last webinar because it was so long already. So there are some effects of a 10-day fast that were measured by some scientists. And this, again, was a small to recruit participants in long-term fasts because of ethical reasons, right? It’s not just because they are expensive and you have to monitor the participants and their health, but also because there are considerations on the health status of those participants. 

Is their health going to decline from not eating? Are they more prone to injuries, accidents or adverse health effects? And yes, they are. 

Alex Ruani

So yes, more difficult to run these studies. But there are a few of them, not too many. And this is the first one on microbiome composition in a 10-day fast. So what happens? What do you think happened to these participants who fasted for 10 days? What happened to their microbiome? Interestingly, okay before we talk about the microbiome, let’s look into inflammatory markers. So after they finished the fast, when they reintroduced food, there was a little bit of a shock for the system, but then it gradually improved. Even when food was reintroduced after 10 days, there was an exaggerated post-meal inflammatory response. All eating is pro-inflammatory.

Alex Ruani

Whenever we eat and consume calories, there is a pro-inflammatory effect in the body. We cannot escape that. But in this case, these effects were exaggerated compared to pre-fast levels. So several inflammatory markers after the reintroduction of food were twice as high three days after reintroducing the food compared to pre-fast. So although inflammatory markers reduced significantly during those 10 days, they were twice as high in the days after. But then they normalised, and they decreased over time.

Alex Ruani

This is important because the reintroduction of food needs to be planned in a way that is going to help the body as opposed to challenging it too much. So very interesting research because it makes us think, okay, the reintroduction of food needs to be reconsidered. What about the gut microbiome? What happened in those 10 days? I was a little bit surprised to see a complete depletion, like literally they could not find plant-eating bacteria. So essentially the good gut bacteria that generally digests fibre, or prebiotics. So depletion of very healthful species that use plant foods as an energy source.

So that’s a flat line that you can see in this graph. However, they saw an increase in Bacteroides. Now, these Bacteroides are associated with weight gain, especially when there is an overgrowth in that population. So again, when we reintroduce food after those 10 days, we really need to be considering how are we going to help repopulate the gut in a healthful way. And it really took three months for gut microbiota to repopulate and recover compared to the pre-fast levels. 

So the protocols followed after a long-term fast are very important. We really want to repopulate our gut with a good batch and reduce the chances of bad bugs or unhelpful bugs to overgrow. So I thought this was fascinating. There is a lot more that this study found, so you can look into it, and I think it’s just fantastic.

Alex Ruani

Okay, let’s move on to side effects, contraindications, and caveats. So you can see here fasting types. You can read these at your own time. So we have different fasting types and the contraindications for each of them, the adverse effects for each of them, the side effects, the safety precautions, the caveats and exceptions on beneficial effects, the limitations and some tips. So this is my attempt to try and summarise all of these things to watch out for.

So let’s take one of them. For example, the one we learned today about, early time-restricted eating, contraindications, shift workers, who’re working at night, those with evening exercise routines, night owls, so late chronotypes. What are the adverse effects of early eating windows?

Alex Ruani

Well, potential for bedtime hunger and delayed sleep onset. What are the side effects? Sleep disturbances, especially in the adjustment period. What are the safety precautions of early time-restricted eating?

If you are not used to eating early in the morning, or if you often skip breakfast, a gradual shift, rather than sudden, of your first caloric intake to earlier daylight hours, not five hours earlier, not four hours early, maybe half an hour earlier, one hour earlier, something like that, is more gradual and doable. What are the exceptions to the beneficial effects of early time-restricted feeding? We saw it. Very challenging and less beneficial for late chronotypes. 

They’re just not hungry first thing when they wake up because they had a late-night meal. If they are usually following their normal chronotype, they may not be hungry. Like in Ramadan, their left-in may be shifted to early morning hours, suppressing appetite in the morning. What are the limitations? It may require an early dinner, which might not be something that is helpful for the family, for work schedules, or for social activities. Some tips, monitoring hunger levels in the evening to adjust earlier meals. So for example, instead of going to bed hungry, how can we adjust the last meal so it’s larger maybe or lower glycemic and so on, so we are not going to bed hungry and we cannot fall asleep? 

So that was just one example of early time-restricted eating. And here you have chronotype-aligned time-restricted eating at the bottom, which is the one that I think the direction of research is going to go to, where we adjust our eating windows to our natural chronotypes. So you can read all of this. If that wasn’t enough, another table for you. So you have fasting types and all the benefits. So on the first column on your left-hand side, you have different types of fasts, and at the top, you have benefits on autophagy, oxidative stress reduction, inflammation reduction, short-term weight loss, long-term gut health, cardio, metabolic health, cholesterol levels, blood pressure, immune function, cancer risk, and longevity. And I also put in there the strength of the evidence. 

So you’re going to see in between brackets, low strength, moderate strength, high strength, usually in a combination of the number of scientific papers available going to see in between brackets, low strength, moderate strength, high strength, usually in a combination of number of scientific papers available and how well-powered those papers were.