FoundMyFitness - #044 Fasting Q&A with Dr. Rhonda Patrick and Mike Maser

Episode Date: January 9, 2019

This episode features a Q&A session with Dr. Rhonda Patrick. The questions were sourced from social media followers of both FoundMyFitness and also Zero Fasting Tracker, a convenient mobile app used widely in the fasting community for logging. In this 45-minute podcast, Dr. Patrick answers some of the most popular questions related to fasting, including: (00:00) Introduction (03:46) What effects do coffee, supplements, and amino acids have on fasting? (12:29) Should you consume electrolytes on a fast? (14:50) What evidence is there that one method of fasting is more beneficial than others? (24:01) What effect does the consumption of exogenous ketones have on fasting? (29:30) Are there downsides to exercise during fasting? (34:31) What role does fasting play in the growth-longevity tradeoff? (49:48) What's the ideal way to break a fast? If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Hello, my friendly fasters. A little bit about today's episode. Today's host is, not me. The reason is because this episode was originally put together for the benefit of the Zero Fasting Tracker audience. Instead, today you'll find CEO of Zero, Mike Mazur, relating many of the questions submitted by some of you following either me or Zero on social media. Zero was created by a mutual friend of ours and prior guest of the Found My Fitness podcast,

Kevin Rose, and offers a simple solution for users to track their fasting times, whether we're talking about time-restricted eating or longer fasts. If you previously checked out Zero, they've since added Apple Watch support and are looking to add a host of other great features, so make sure to visit their website at ZeroFasting.com or give them a follow on Twitter at Zero Fasting. That's at Z-E-R-O-F-A-S-T-I-N-G. In this 45-minute episode, I answer some of the most popular questions related to fasting, including what affects coffee, supplements and amino acid have on fasting, whether one method of fasting is more beneficial than another. What effect consumption of exogenous ketones may have on fasting? Whether it is good to exercise while

fasting. The ideal way to break a fast. How fasting affects muscle mass. How fasting plays a role in the growth-longivity trade-off, and so much more. As you might expect, much of my expertise in these areas is derived from the great conversations I've had with leading experts in the field, such as Doctors Valtralongo, Ruth Patterson, Guido Kromer, and Satchin Panda. These episodes are amazing resources, and I strongly encourage anyone listening to check those out at foundmyfitness.com forward slash episodes. Once again, that's foundmyfitness.com forward slash episodes. Now off to the Q&A.

Hey, everyone. I'm Mike Mazur. I'm the CEO of Zero. You can find us at Zerofasting.com. And I'm really excited to be here today with Dr. Rhonda Patrick. Hey, Rhonda. Hey. So we're here today because we received a ton of questions from the Zero community and Rhonda's community. It found my fitness. And it was about all things fasting.

So you submitted almost 500 questions to us, a great turnout. And while we can't get through all 500 today, we went through them and found themes of certain topics around fasting and related topics. that you want to hear about. So without further ado, we'll get into the questions, but Rhonda, before we do that, let's talk a bit about your background for folks that might not know. So you did your PhD work at University of Tennessee. And then you went on to do your research at St. Jude, which of course is doing great work trying to solve childhood cancer. That's right. Yeah. So I did all my graduate research at St. Jude Children's Research Hospital, which is affiliated with the University of Tennessee. And while I was there, I studied the interface between mitochondrial metabolism and cancer

and cell death. And so there's sort of, you know, I did, became this expert in mitochondria, and, you know, cancer metabolism and how cells die or don't die. And that was sort of my focus during my graduate research there. That's phenomenal. I've actually been working with St. Jude more on the fundraising side since 2011. So that's a cool connection that we have for just what's an amazing organization. Very amazing. Just cutting edge research going on there. Absolutely. Well, let's get into the questions. We'll get through as many as we can. And given that it's bright and early in the morning here in San Diego, we got a ton of questions about coffee and caffeine and how it may or may not impact the beneficial effects of fasting. So let's get right into it if that's

cool. Yeah, let's do it. Okay, great. So I've got my cheat sheet here on my iPad. The first question from John Phillips is, can you discuss in further detail why you recommend a water-only fast versus consuming coffee or amino acids while in a fasted state? I'm looking to optimize my morning workouts with amino acids or a caffeine boost and want to know what benefits I am potentially missing out on versus the benefits I likely still receive. So coffee, amino acids. Yeah. There's a lot in that question there. Dense.

But the coffee question, as you mentioned, is something that is certainly, it's asked quite frequently. And to sort of address that question, I think people mostly are asking it in the context of a type of fasting called time-restricted eating. Time-restricted eating, it has a fasting component to it, but it also has a circadian biology component to it. And people might go, well, what is circadian biology? And really, you know, just sort of think about the fact.

fact that, you know, you're awake during certain times. So you're awake in the morning, you know, early in the morning, your body produces a stress hormone called cortisol, wakes you up, you're alert, you're active, you, you know, do all your activities. And then as the day progresses, and nighttime comes on, you get sleepy, you're making, your body's making melatonin, helps you with, you know, getting tired and you go to sleep and things sort of shut down, right? All these natural pathways. Right. It's just sort of sort of this rhythm, this circadian rhythm. That's what, that's why they call it, you know, circadian rhythm. So, um, It turns out, you know, every cell in our body has one of those and including, you know,

pathways like metabolism. So it's really important to make sure that you're consuming food when, you know, the metabolic pathways are active. You know, you don't want to eat when they're not active. And so a lot of this work has been done by Dr. Sachin Panda at the Salk Institute and some of his colleagues, you know, they've shown that what activates metabolism is, you know, basically when you take in your first food, you activate those metabolic pathways and then they'll be active for a certain amount of time. And then as the day goes on, they become less

active. For example, if you look at men who eat the same meal early in the morning and then they eat the same meal later in the evening, same calories, same macronutrient content, everything, they're more insulin sensitive in the morning and they're less insulin sensitive in the evening. Fatty acid metabolism is the same way. So you may think, well, maybe I'll just just eat some fat in the evening. Well, it turns out your fatty acids and being able to use those as energy is also on a circadian clock and it's less active in the evening as well. So with that said, where does coffee come into play? You know, coffee, if you're just, if you're talking about coffee with cream, you know, obviously cream is got calories and fat and that's, you know, something that

would be considered, you know, food, right? Cream. If you're talking about coffee, you know, about just black coffee, coffee without, you know, any... Or espresso, like a shot of espresso. Exactly, or espresso, something without any calories, essentially. Right. Then the question becomes, does that count as, you know, starting your clocks? And, you know, there's no real direct data that has addressed that question. A couple of my thoughts are, for one, we do know that caffeine itself changes the circadian

And so if you, you know, give someone a cup of coffee later in the day, it actually shifts the body's circadian clock, that natural rhythm, by like 40 minutes. So coffee itself is changing the circadian clocks. It's extending it essentially. Yeah, it's delay. Yeah, exactly. Right. And additionally, you know, caffeine is metabolized by the gut.

It's also metabolized by the liver. So the question is, does that, you know, activating those metabolic pathways, does that start your clocks. We don't really know if it's enough to or not. What we do know is that, you know, there have been some studies, for example, a study done by Dr. Ruth Patterson at UCSD. She looked at time-restricted eating in women that had previously had breast cancer, women that ate all of their food within 11 hours and they fasted for 13 hours. During that 13 hours, they were allowed to consume caffeine. So black coffee or tea without cream. And Even though they consumed the coffee during their fasting period, they still had a 36% reduction in breast cancer recurrence.

So they had positive benefits along the same lines. There's been some pilot studies in people with type 2 diabetes where they've done time-restricted eating for anywhere between a six to eight-hour window. So they're eating within a shorter window and they're fasting for 16 or more hours a day. They're also allowed to consume caffeine or tea. and they had positive effects on blood glucose regulation, insulin sensitivity, weight loss. So clearly there's evidence in the scientific literature that if you consume black coffee within that fasting window, there's still positive effects happening. So if I can paraphrase, while coffee or caffeine may slightly interrupt the circadian window,

the metabolic benefits from black coffee or tea without additives are, maintained? It seems as though, you know, at least according to these studies, that, you know, it's not negating those metabolic benefits. Okay. However, the question becomes, if you were not to consume it, would you have a more robust effect? We don't know.

We need to study on this because this is like one of the most common questions we get, but I guess the early directional research is, and for a lot of people, coffee, including myself, coffee is crucial. Okay for right now. and we'll learn more about the detail level of what's happening maybe. Well, and I also think that if you're talking about just, you know, like I mentioned, time restricted eating, this is something that you're practicing on a daily basis, right? This is you're eating your food within an eight to, you know, 12-hour time window.

Right. And you're fasting, you know, for 16 or and or up to, you know, 12 to 16 hours, right? There's other types of fasting, which we can talk about, you know, where you're doing it longer. Yeah, we're going to get into that with another question with different modalities of fasting. Yeah. And in that case, research has also shown if you consume black coffee or tea without any calories that there's still benefits. Great. And what about the amino acid aspect? Right. That's a great question as well.

And this sort of touches on another aspect of the fasting literature. And that is, you know, there are many benefits that occur during a fast and there are many types of fasting. And when you're actually fasting, some of the things that are occurring are you're lowering different, you're deactivating pathways that are typically like a grow pathway. For example, it's called IGF1. It's a grow, grow pathway. MTOR is another grow, grow pathway. Both of those pathways are activated by amino acids.

And so if you're limiting your amino acid intake along with your calioling, you're calioling, oilic intake and everything else, you're going to deactivate those pathways. And the deactivation of those pathways, IGF1 will go down, and TORB will go down. And those are essential for the activation of some of the benefits of fasting, including a process called autophagy, which is basically when your cells start to recycle. And interestingly, they seem to recycle damaged components of themselves. So like mitochondria, which are, you know, they're the powerhouse of energy in your cell, damage mitochondria can be cleared away.

So spring cleaning is the process of autophagy within your body. You know, pieces of protein, dead cell things are just in there, it gets rid of them. But MTOR has to be deactivated, IGF1 has to be deactivated for that to happen. And then there's other things as well, which we can talk about when we get into more of a prolonged type of fast. Those things also need to be deactivated. So amino acids would be something that would sort of negate that. Interrupt that natural reduction of IGF-1, which may interfere with some ontophagy. Right.

Got it. Okay. Great. Well, that's certainly important for a lot of folks in our audience. I'm going to move on to the next question. Still caffeine-related, we'll do. We have a ton of coffee questions, but I think we can probably dovetail off your last answer.

This one's from Maruna Heckman. I've got that name right. First of all, thanks for all that you do. That's for you, Rhonda. You've changed my life. Wow, that's awesome. Is there any more evidence yet surrounding if having coffee, tea, supplements, et cetera, while fasting disrupts the benefits of fasting?

I think you just answered most of that. I think so. So it sounds like if you keep it to caffeine only, you're not really interfering with IGF1 and MTOR, but maybe not trying to add anything on top of that. What about electrolytes, though? Because we get a lot of questions, you know, electrolytes are I guess technically a supplement. You're supplementing your natural biochemistry with, you know, magnesium or salts. Any thoughts on that?

You know, I do think that if for time restricted eating, you know, I personally like to try to take everything within my eating window. But I don't think it's really key when you're talking about things like sodium, potassium, magnesium. As far as I know, that's not really changing any of the circadian rhythm. But when you're talking about a prolonged fast, when people are fasting for, for example, maybe 48 hours or more. And by the way, as you get into a more prolonged fast, that's something that you may want to do under medical supervision. Yeah, absolutely. I should just say now that while you're a PhD, you're not a practicing clinician. And so none of what we talk about today should be construed as medical advice, but research findings.

Exactly. Yeah. Information. So basically the electrolyte stuff, I think that, you know, there is evidence in the literature. You look at someone that's doing a prolonged fast. You do start to deplete things like sodium and potassium immediately. Those things sort of taper off as the fast goes on. But I do think it, you know, there is some evidence that it's good to take an electrolyte supplement.

Right. Particularly with a prolonged fast. And if you're doing water only, even more important, right? Yeah. So, and there's a variety of like mineral and electrolyzed supplements out there. Cool. So. Okay.

Great. I think we've covered most of the coffee and caffeine questions, which is great to get started. You talked a little bit about time restricted feeding. Next question, I think, will build on that, which is from Sam Reyes. The question is, has there been any evidence suggesting one method of fasting is more beneficial than others? Right. I think that's a really good question. It's a very broad question.

It's a very broad question, but it sort of gives me a chance to describe some of the different types of fasting, which I kind of touched on already. But, you know, you hear in, like, popular culture, you hear everyone say intermittent fasting. Right. And intermittent fasting is this, like, blanket term for all things fasting. Like, Walter Longo, like, doesn't like that term because it's just so general. Right.

Dr. Volta Longo, from USC, who is really an expert, he does a lot of research on fasting. He has mentioned how intermittent fasting can be considered in humans fasting up to about, you know, 24 hours. And then prolonged fasting happens when you get into like the 48 hour mark, so two days or longer. And then of course there's time restricted eating, which has an intermittent fasting component to it, but it also has that circadian biology component to it. You want to eat within the time when your metabolism is optimal.

And when you're not eating, you're obviously fasting. And so, you know, people end up doing up to 16-hour fasting period. So if they're eating within an 8-hour window, they're fasting for 16 hours. And that's time-restricted-based. Of course, colloquially, it's called 16-8. Yeah, exactly. Right. So that would also be time-restricted eating.

That's something that you're doing on a daily basis. And so, as I had already mentioned, with the time-restricted eating, you know, there's, you get the benefits of the fasting part. So you're fasting for 16 hours. Part of the benefits, you know, with that are things like you do start to have. have repair processes that are activated in order to repair damage, whether it's damage to your DNA or damage to proteins or just damage, like I mentioned, mitochondria, or just pieces of, you know, dead cells floating around. That stuff is cleared away and repaired during a fasting state.

So you get that with the intermittent fasting and time-restricted eating, which has a fasting component. In addition, the time restricted eating, you have the benefits, and this has been shown by Dr. Sachin Panda, Ruth Patterson, others, that you're eating within your circadian biology in terms of when your metabolism is its most optimal. So you don't want to, you know, for example, if you eat your first, you know, bite of food at 8 a.m. in the morning, and then you're eating dinner at 8.30 or 9, you're basically, you've already gone past 12 hours, your metabolism at 830 or 9 isn't going to be very good. And so, and what may end up happening is you're not going to be as insulin sensitive. So your blood glucose

levels are going to be higher. Your fasting blood glucose is going to be higher. Your fatty acid metabolism's not as good. So you're going to start to store fatty acids and adipose tissue rather than using them as energy. So you'll start to like gain more fat mass, which has all sorts of problems. In addition to that, you may also, your body, because you have been going, it's been like over a 12-hour mark, when you eat that food in the evening, you may be resetting the clock and your body thinks it's resetting the start time of metabolism. So the whole time you're sleeping is when your metabolism is at its best, and then you wake up in the morning and it's completely misaligned.

So everything is misaligned in terms of your metabolism. So that means that you're always going to have higher blood glucose levels. Your fatty acids are going to be more likely to be stored in adipose tissue rather than use as energy. So that misalignment. So that's the benefit for time-restricted eating or time-restricted feeding, as it's called, with animal studies. And then, as you mentioned, Dr. Volta Longa's research, he does a lot of research on what's called

prolonged fasting, typically 48 hours or longer. Again, as you get into that, you may want to do that under medical supervision. Now, he has done a lot of research in animals showing that, you know, if you do a prolonged fast, not only do you have this atophagy start to activate, which we talked about. about, as the fast becomes more prolonged, you actually start to get the clearing away of cells, damaged cells, seems to be preferentially damaged cells that are cleared away. And in the process of that happening, you actually activate stem cells and sort of replenish those damaged cells with new, healthy young cells.

Wow. He's shown this in animals where literally during the fasting period, organs will shrink. And then during the refeating period, which we'll talk about a little bit later, they regrow. So you're basically getting rid of the damaged cells, mostly it seems, and then you're replenishing them with healthy new young cells and they're regrowing. That's all been done in animal studies. He has some preliminary evidence in humans where it seems as though looking at various markers of like stem cell activation, for example.

That does seem to be happening. But he's got some ongoing studies where they're going to look at that in much more detail. So, you know, that's a benefit of the prolong fasting, which you don't really get from a shorter fast because you need to really have a stronger stress. You have to have your IGF-1 levels really dip down. That takes time. I think they're probably prolon, which, you know, we won't get too much into, but it has some calories per day, but that's like a five-day regimen.

So are you really looking at kind of five days to get most of those benefits you discussed? So pro-lon is, that's the name for their fasting. Mimicking Diet, which was developed by Dr. Volta Longo, and it's a very specific, has a very specific macronutrient content, so a specific amount of fat and protein and carbohydrates, and a total calorie cap. So, you know, I think that like the first day it's up to a thousand calories and then the second, the fifth day, you're getting a little bit, a little over 700 calories a day. And he has shown, again, he's shown in animal studies, the same benefits with the organ shrinking

and then regrowing. And then he's done some clinical studies in humans. showing a variety of metabolic benefits. You're getting, you know, of course, improved glucose levels, insulin sensitivity. He shows IGF-1 does go down and, you know, cholesterol, like there's benefits with your cholesterol, metabolism, things like that. Right. So that's also another sort of part of fasting.

So the same idea of a prolonged fast that you mentioned where you're getting the autophagy and the stem cell production over a multiple day fast, except. in his case, bring low calories into the equation ostensibly to probably make it just easier for people to stick with than a water-only fast. Definitely seems like it's easier for people to stick with or at least try out. You know, in animals, he has shown that you do get a lot of the same benefits as a water fast. But you have to remember, you know, animals have a much faster metabolism than humans. In fact, if you fast a mouse, a rodent, for 48 hours, they lose 20% of their body weight.

A human loses maybe 2%. I can tell you from experience that doesn't happen for me. I've tried, but no. So the question then becomes, well, you know, how much of the organ shrinking, regrowing you get with just a fasting, mimicking for five days versus, you know, actually not eating? So there's lots of little nuances that aren't quite figured out yet. But certainly there are benefits, and he's shown that in humans. So just to wrap up the question, it sounds like,

you know, the question is a fasting type more beneficial than other. It sounds like there are different instruments, different tools for different outcomes. And, you know, maybe combining some of these modalities, maybe doing, you know, timer-stricken feeding, circadian more regularly, and then periodically to kind of get those cleansing benefits. Metabolic cleansing, you do maybe a longer one. Again, if your doctor says it's okay and you're cleared for it, Could that be a good sort of sequencing for people?

Yeah, and I think that's a good summer, and I think I should probably also mention another benefit that comes from both intermittent fasting and certainly prolonged fasting is your body shifts from glucose metabolism, metabolizing carbohydrates to fatty acid metabolism. Ketones. And you get the production of ketone bodies like beta-hydroxybutyrate, which is in and of itself been shown by people like Dr. Eric Verdon to be, anti-aging, in a sense, where it's a signaling molecule that's been shown to activate genetic

pathways in the body that are known to delay age-related diseases that are known to help increase repair processes. It's been shown to reduce damage that's generated by your mitochondria, which are basically what's generating most of the energy inside of your cells. But that whole process of generating energy, what we know as metabolism, generates a lot of, you know, very harmful reactive byproducts, and beta-hydroxybutyrate lowers that. So it kind of makes your mitochondria more efficient. Got it. That's another benefit with the intermittent fasting and certainly prolonged fasting fasting. Cool. Well, I'm sure you could spend a whole day talking about different fasting types, but we don't have that much time because we have other questions. So let's move into, actually,

you talked about ketones a bit in that last answer. So let's move on to a question about ketones from Austin, will consumption of exogenous ketones disrupt a fasting state? And I know that there's been a lot of work in producing ketone supplements. So that's the question, I think, is, will that disrupt a fast? It's certainly a question that I've had myself. I've actually tried a beta-hydroxybutyrate ester. So beta-hydroxybutyrate is the major circulating ketone body that's generated when your body starts to go into ketogenicis. A lot of things do happen when you're fasting, and that's one of them. So basically, anywhere between, it takes anywhere between, you know, 12 to 36 hours for your liver to deplete the glycogen.

And once that's depleted, what ends up happening is you immobilize fatty acids from your adipose tissue. They go to the liver, and they're actually used to make ketone bodies. So you're oxidizing the fatty acids now, using them to make ketone bodies like beta-hydroxybeterate. those ketone bodies can then be used as an alternative energy source themselves. Which is incredible. I mean, just on that point, the fact that, you know, the analog I've heard is, you know, you're basically turning your body from, you know, burning gas to diesel. It's like a completely different fuel, glucose to ketones.

It's amazing that our bodies can even do that. And in some ways, you know, it's a preferred fuel for different organs in our body, right? It seems as though it might be. It certainly seems to be. metabolically efficient, you know, so it takes less energy to use a ketone body compared to glucose. So it's energetically favorable in that sense, which is nice. So it doesn't, sounds like it doesn't really interrupt a fast. It's sort of part of the natural Well, so yeah, let me, so I'll let me continue. So that is, that was the natural phenomenon

I was explaining, right? Okay, got it, got it. Now, what, what ends up happening, so there's been about five clinical studies that I've, that I've, um, read that have, they're mostly clinical studies with exogenous ketone esters. And just for, for the audience, exogenous, meaning, um, not produced in the body. Exactly. You're taking it externally. Exactly. You're taking a like a supplemental form of it. Yeah. Thanks for clarifying that. So the, the exogenous ketone esters, um, that are taken, basically a lot of the studies that have been done have been looking in the context of like athletic performance. But they also look at other metabolic parameters, which is interesting because that's

kind of where you can find some of this data if you look carefully. And within these five studies, there have been, it seems to be that what's been shown is that the exogenous, consuming, for example, the exogenous beta hydroxybutyrate, the supplemental beta hydroxybutyterate ester, it ends up, it increases the blood levels, you know, beta hydroxy hydroxybutyrate pretty high. But it also seems to decrease circulating free fatty acids, which suggests you're not immobilizing fatty acids from your adipose tissue to be used to make your own, which means you may not be getting the benefit of what you would call fat loss, right?

And that's a regulatory loop that occurs in the body. So when your beta-hydroxy beta-hydroxy beta-rate levels get high enough, your body says, okay, we don't need to make any more of these, so it stops the immobilize. What's called lipolisis, the cutting of the fatty acids from the adipose tissue, right? Interesting. So your body's stopping you from making too much, right? So that does seem to happen. Okay.

But then again, the exogenous ketone esters don't last for that long. And if you're exercising or doing physical activity, it's dose-dependence. So the more active you are, the quicker you use up those ketone bodies. Yeah, it's interesting because, you know, I know that when I'm practicing fasting, which gets my ketones way up. And then I'm doing a ketogenic diet, which does the same thing. And then I go for a big workout. I'll come back and measure my ketone bodies and they're way down.

And I guess it's because I've been using my ketones during the workout. For energy. Yeah. Exactly what happens. Yeah. So that's kind of one caveat that I would be aware of with, you know, consuming the beta hydroxybutyrate supplemental esters or salts if you want, but salts don't work that well. A good point is that they've also been shown.

consuming the exogenous beta-hydroxybutyrate has been shown in humans to prevent the use of amino acids from muscle. So it stops, which also makes sense during a prolonged fast. Your body has mechanisms at play that help prevent you from using muscle, using proteins and amino acids from your muscle as energy. And one of those is that the ketone bodies prevents that from happening. So that's a good thing. So there's a trade-off potentially. And again, this is something that, you know, I don't know how much of a difference it makes, but it's something to keep in mind. Yep. And if you're an athlete and you're needing fuel, maybe you're a better candidate than someone that's just looking for purely metabolic body-based ketone production.

And that's a maybe, but it's a factor. Well, that's a great segue actually to another question related to exercise and growth. So let's see. So I practice, this is from Angel or Anhell. I hope I got the name right. So I practice a simple 12-hour eating window and a 24-hour fast once a week. So there's intermittent fasting with a 24-hour fast per week. My question is, are there any downsize to training fasted, as I usually do?

The exercises involved are heavy weight training and moderate cardio afterwards. Just wanted to know if I'm metabolically doing harm or having adamantialial. adverse effects of the intended goals. Thanks and love your work. Great question. There have been meta-analysis of studies done, so that just means there's lots of studies that have been, that have looked at, for example, doing physical activity, either aerobic or anaerobic activity in a fasted state versus pre-exercise feeding, so you eat before exercise. And a meta-analysis just kind of aggregates all those studies that have been done and looks at what the data says. And so meta-analysis that have been done on that topic have shown that pre-feeding before

exercise improves, it seems to improve long duration aerobic exercise, so duration is longer than 60 minutes. Got it. But it doesn't seem to really have much of an effect on performance if it's aerobic exercise less than 60 minutes. On a similar note, it's also pre-feeding, eating before you, exercise has also been shown to improve anaerobic exercise. So like run till exhaustion, but it doesn't really seem to have much of a significant effect on high intensity interval training.

So there is a little bit of a performance enhancement with eating before you work out in terms of long duration aerobic exercise. Traffle, it's long distance running, things like that. Right, right. Which actually makes sense. But for weight training, sounds like if you're keeping it within 60 minutes. So even less than, yeah, even running less than 60 minutes or a high intensity interval training class. But what's really interesting is those meta-analysis showed that eating before you exercise,

so if you fat, if you're training fasted, you get really robust enhancements in glucose, you know, sensitivity, but really robust enhancements in your mitochondrial adaptations to using fatty acids. So you're basically, your mitochondria become really primed for fatty acid use, which makes sense. If you're in a fasted state, you're going to have, you know, you're depleting your glucose and you have more of these fatty acids that are available for energy. There's a lot of increased activity in genes that regulate fatty acid metabolism. That's really expressed when you train in a fasted state.

Interestingly, when you feed before you train, those adaptations are blunted. With respect to the fatty acid. Right. Uptake. Yeah, like the really priming your mitochondria to be like robust to use fatty acids as a source of energy. You still get glucose, you know, effects and enhancements and stuff even when you're training, when you're, you know, eat something beforehand. But it seems as though those fatty acid adaptations that the mitochondria shift to are blunted somewhat. So it sounds like for on hell or Angel, that, you know, if you're doing kind of a weightlifting with cardio shouldn't be a dramatic effect.

I will add to that because I think even one of the previous questions you were asking, someone was asking about the amino acids, wanting to amino acid take before they train, and they were wanting to like, for hyper, like hypertrophy, you know, so basically wanting to grow more muscle. I will say that there have been studies looking, there's been a lot of research that has been done looking at, you know, is there this anabolic window that you have to take in amino acids and protein to like, you know, increase muscle growth? And I think over the past few years, studies have, it's been pretty consensus that there's a lot longer time that you have.

It used to be thought like there's this one hour window. You have to down this protein shake immediately or you're going to miss it. I don't think that's the case. I think that there's been a lot of research that has come out showing that you actually can take an amino acid or, you know, protein hours after. workout. However, if you are doing, if you're going into your workout fasted, let's say you've been fasting for 16 hours. You don't, you aren't, you aren't storing proteins. So in that case, if you are doing a fasted strength training workout, you may want to consume protein within an hour after that. Got it. Good distinction. Yeah. If you're in a fasted state. If you're in a fasted state,

like a pretty fasted state. I think that's a great, a great recap for, for, for, for Angel. Not sure. Okay, moving on to the next question. I think we have time for maybe one or two more because these are, they require a lot of explanation. Let's talk about longevity, because that's a lot of the reason that our audience and your audience, you know, is doing fasting. So this is from Nina.

Can you elaborate on the growth longevity tradeoff? So, and you talked a little bit about the beginning with IGF1 and longevity. So the growth of longevity tradeoff, by fasting, we downregulate the aging pathways such as mTOR, growth hormone, and IGF1. Clearly, Nina's done her homework and listened to you. But in order to build muscle through resistance training, we need to eat protein and have these pathways activated in order to maintain build muscle. Is there a way we can get the best of both worlds? It's a great question. Is the tradeoff overstated?

How so? Thank you, exclamation point. That's a meaty question, but it is. to a lot of what you talked about already. It does. And I think I will try to keep it as brief as possible. I think, you know, I do need to kind of just briefly explain, you know, the role of IGF-1, MTOR in, you know, aging and in the field of aging research, there have been many, many, many studies that have shown that higher IGF-1, particularly higher IGF-1, is associated with higher cancer incidence.

And this has been shown, you know, if you look in humans, you know, humans that have a mutation in genes that regulate IGF1 that make them have like a higher IGF1 level all the time. They kind of, they have actually higher cancer incidents than people that don't have those. And the idea there is that if your IGF1's high, it's a growth mechanism and it's could promote tumors to to grow. Yes, exactly. So because IGF1 is a growth signal, as you mentioned, it allows basically, you know, So when you have accumulated damage in your cells, whether that damage comes from the mitochondria,

you know, genomic damage, there are signaling pathways that are activated that say, look, this cells too damage to repair. I need to kill it. I need to get rid of it because I may acquire a very dangerous mutation that could allow cancer to survive. And so your body has this beautiful way of doing that. And it's called program cell death or apoptosis, basically, kill the cell. But IGF1, if IGF1 is around and express at a high level, it's kind of around going, no, no, no, grow, grow, grow.

You're cool. You can stay. I'm here. Forget about the damage cell. Yeah, forget about it. Yeah. So it basically overrides those checkpoints. Got it says die. And so it can become very dangerous because it can allow us one cell to then grow, which then replicates and makes more cells. And then you eventually get the formation of a tumor.

Sometimes this takes several decades to happen. And then, of course, you know, it bypasses immune-point immune cells and things like that that are also involved in killing the cells. But that is one important way that IGF-1 plays the role in cancer. Humans that have more of it have a higher cancer incidence and the vice versa. So humans that have mutations that make less of it, have less cancer incidents. It's been shown in many, many animal studies. Dr. Volta Longo has shown this and others, so many others, that, you know, IGF-1 can override.

If you basically inject human tumor cells into a mouse and increase their IGF1 by a variety of modalities, including high protein intake, you can actually allow the cancer cells to grow faster. And just real quick on the high protein intake, I mean, the latest diet trend, I think it's waning. It's just been protein, protein, protein, right? And so, I mean, we have yet to see the impacts, you know, long term of all that protein uptake, which is, I think, interesting. I don't want to concern people, but, you know, protein does upregulate IGF1, correct?

Yeah, it does. Yeah. You know, and to address the good part of IGF1, I mean, so we talked about this bad part where it's definitely... Yeah, and you know, about that tradeoff. Exactly. Yeah. And, you know, IGF1, in addition to the cancer, it also deactivates a very important

longevity pathway, a gene in the body called FOXO, which is really, really associated with, It regulates all sorts of genes that are involved in repair and stem cell production, atopathy, all those things. So high IGF1 turns that off. Turns that off. Turns that off. So it turns off atopathy, turns off all that stuff. Interesting.

Okay. So she's feeding no protein? No, no. So the trade-off is that IGF1 has a really good, it's also very important. I mean, obviously during development, it's part of the growth pathway. You need to grow. Right. But it's also an important grow pathway.

muscle to repair muscle to grow muscle, which is also important for longevity. I mean, there's multiple studies that have come out even recently showing that muscle mass is really important for lowering all-cause mortality and preventing frailty and things like that. It also gets into the brain as an important growth factor for neurons. It actually helps you grow new neurons that's called neurogenesis, and it actually helps prevent neurons from dying. So it allows the existing neurons to keep living. So it's an important signaling pathway in your brain.

into muscle. I've seen a handful of studies in mice and in humans that have shown exercise, being physically active, helps bring IGF1 into the brain, so it crosses over the blood brain barrier and gets it into the brain where you want it and also gets into the muscle. So as opposed to having your IGF1 around in your bloodstream where then goes to other tissues or stays around and is being a gross signal for potentially damaged cells, you actually want it to get into your brain into your muscle. So I think exercise in physical activity is a really good way to make sure that IGF1 that you're getting is going to the right places. And in fact, there have been studies looking at protein intake and all-cause mortality that have shown that higher protein intake

does increase all-cause mortality and cancer mortality as well. However, in people that have none of the unhealthy lifestyle factors that are looked at, for example, they're not obese, they are physically active, they don't smoke, they're not drinking excessive alcohol. they're, and they still have high protein intake, they have the same mortality in cancer mortality rate as someone that has a lower protein. That's a great recap. Yes. And I guess intuitively, you know, if you're going to give your body all this fuel and growth,

use it. Exactly. Use it for what it's designed to do. And then, but if you're giving you all that fuel and you're not using it, it can be left to do not so great things. Yeah. Yeah. But to sort of, I went on the tangent there to kind of get to her, the second part of her question,

Yeah. Which was, you know. Is there a happy medium? Yeah. What's the golden rule here? Where is the sweet spot? You know, for a long time, it was thought, you know, this process of what's known as caloric restriction, which does lower IGF1, but you're doing it all the time.

You're constantly eating like 30% less than what you would. And it's not as, you know, some people are kind of miserable doing it. You're chronically lowering your IGF1. Is that good? Because you want IGF1 for some things. And in fact, I had a conversation when I talked to Volta Longo. And he has even talked about the fact that, you know, the prolonged fast seemed to be a good sweet spot. Because during the, you're doing a prolonged fast, you actually drop your IGF1 during that fasting period.

And that is what is critical for the apoptosis, the clearing away of the damaged cells. It's important to activate the stem cells. But once you get to that point and you then refeed, you actually, you actually, want IGF1. You want IGF1 because IGF1 then allows the stem cells to grow and make more cells and replenish that population and regrow. So you actually, there's this balance and it's like IGF1 is important in that. It plays an important. You want it lowered to get that whole clearing away and atopaginia. And then the rebuilding. And then the rebuilding you want it. So there's this nice sweet spot. And I think that's the beautiful machine of our body that it goes through modalities of

cleansing. And it's the reason that I think fasting has become rightly, very intermittent fasting, and caloric restriction has become so popular because, you know, that's kind of how ancestrally we were brought up. I mean, we didn't have, you know, 7-Elevens and supermarkets and coverage full of food all the time or constantly eating. We had these natural breaks where we were hunting for food or gathering for food and we weren't eating all the time. Our bodies were repairing and then we got to refeed when we, you know, caught the, the deer and ate it and then, you know, brought ourselves to that rebuilding phase. Exactly.

Replicating what for millennia we've been as humans designed to do. Exactly. Exactly. Yeah. That's an awesome, awesome question and a great, great answer. Do we have time for one more or how are you doing? Yeah. Let's do one more.

Okay, we'll do it. We'll try and make it quick. Let's see. Okay, this hopefully will be pretty quick. Let's do post-fast feeding. So we get a lot of questions about this. What's the ideal way to break a fast? So you talked a little bit about this.

Is there a method to the madness with macro timing? And this is from Brian Avchin. Is there a method to that madness with macro timing? and as it pertains to glycogen levels, or is it fine to eat anything in particular once you reach your, or once you break your fasting window, once you end your fasting window. So what should we be consuming ideally after this fast? Well, I think we kind of address that. You know, if we're talking about the prolonged fast or someone that's doing a fast for greater than 48 hours, you know, you're basically at that point after your IGF1 has gone lower and you've done some of the

atophagy and clearing away of the damaged parts of the cell and also apoptosis, the damaged cell itself, you want that IGF1 active. And what activates IGF1 are amino acids. So, and particularly essential amino acids. So eating some protein actually to break a fast seems like it would be a good idea because you want that IGF1 higher. The other thing that actually regulates IGF1 bioavailability, is carbohydrates.

So carbohydrates allow IGF1 to be more bioavailable. So most of the time you're wanting to have less IGF1, but in the sense you want to have that regrow signal. So eating, you know, eating a balanced diet. But, you know, when people are breaking a prolonged fast, some people have sensitivity, you know, their guts a little more sensitive if you haven't eaten for a few days. You know, so you really have to sort of listen to your body. Kind of a soft landing out of it.

Yeah, some people, you know, I don't. I've had people talk to me about taking like, you know, making a shake with some blueberries and they add a little bit of, you know, protein powder. Right. They eat like a little small piece of salmon. Right. And some fruit. Other people like to kind of ease into it with some soups or bone broths and then eventually

kind of make it, make it a small piece of protein or something. And if you're talking about more circadian or like 168s, I mean, the thing I sort of want to emphasize here is that, you know, a lot of people use fasting as a license to kind of binge, which obviously is not a good idea. Like when you're breaking a fast, especially a longer fast, giving your body a chance to adjust back to a feeding state is important in eating, you know, non-processed foods is super important. Would you agree? Yeah, absolutely. You know, I think that eating a healthy diet with, you know, lots of vegetables and, you know, healthy meats and fatty acids and things like that is important. Avoiding processed foods, avoiding refined sugar,

those things. I mean, if you're constantly eating refined sugars and all that, you're going to have a hard time. Your body is going to have a hard time switching over from metabolizing glucose to fatty acids. It's going to make that transition more difficult. So that's another thing to keep in mind as well. Cool. I did want to mention a couple of things because I forgot to mention on some of the other questions. I think there were some questions about like autophagy and a caffeine, some caffeine. I know if that, I I talked about breaking the facts a little bit, but... Does caffeine interfere with that?

Yeah, and I thought that that was an important point because research by Dr. Guido-Grito Kramer has shown that actually the polyphenols in coffee, and it can even be decaf coffee. You know, it can be tea, decap coffee coffee. It's not the caffeine, it's the polyphenols that are in the coffee bean. They actually activate atopagy. He showed that in animals, but they actually play a role in activating atopagy itself. I think you just made a lot of people's day because now I can drink black coffee

and I get even more benefits to autophagy. It's unclear if you're getting more benefits. But yeah, I think there does seem to be a caveat there where it seems as though while drinking the black coffee may actually enhance the atophagy. Awesome. Well, this has been great. I know we only got to a fraction of the questions.

I hope we can do this again because the science is evolving. I know there's tons of new studies coming out. I mean, in 2019, I think you're on top of a bunch of new science, you know, coming out related to fasting and human studies, et cetera. Yeah, there's like at least four or five new clinical studies on time restricted eating and then another handful on prolonged fasting that Dr. Baltolong is doing that's, you know, that's ongoing. So it's really exciting.

Yeah, it's a very dynamic world that we're in, which is exciting and more data coming out. But I want to thank you. And again, for everyone. who submitted questions. Thank you. I'm sorry we couldn't get to them all, but hopefully we'll be back soon with more updates. And again, Rhonda Patrick found my fitness and check out Zero fasting. And if you haven't downloaded it or listened to Rhonda's podcast, please do so. We'll put links in the show notes. And from San Diego, that's it. Cool. Thank you. Thank you. Thanks for listening. If you're interested in tracking your fasting and time restricted eating,

make sure to check out Zero on the Apple App Store or head over to their website at Zerofasting.com. One last mentioned before we go about the Kevin Rose connection. I would be remiss if I didn't share that I recently was invited to talk to Kevin's wife, Dr. Darya Rose, on her podcast. We talk a lot about my recent paper on DHA in phospholipid form and its relevance potentially for the prevention of Alzheimer's disease. We also talk about some fun pregnancy-related topics and more. You can find that episode by looking up Darya's podcast and grabbing it right off her feed. The name of her podcast is Foodist Podcast. Once again, that's Foodist F-O-O-D-I-T podcast.

Alternatively, you can also head over to her website, which is www. www.summertomato.com. Once again, that's www. www.summertomato.com. Thanks for listening. More episodes coming soon.