FoundMyFitness - #059 Aliquot #3: Q&A Mashup - Fasting

Episode Date: September 8, 2020

Get a sample of our new premium member's content, known as Aliquots, by listening to this in-depth Q&A mashup on Fasting. What's an aliquot, you may ask? Aliquots are special, curated segments prepared and distributed to premium members via the premium members' podcast feed. In this previous, you'll learn: (00:00) Introduction (01:48) Fasting supports a healthy gut microbiome and reduces autoimmunity (08:28) Increasing autophagy with fasting  (13:26) Reducing protein acetylation with fasting mimetics (18:17) Fasted exercise, water fasting, and a fasting-mimicking diet Learn more about our premium podcast feed The Aliquot by clicking here. 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 again, friends. Today's episode is our third special Aliquot mashup episode featuring a collection of clips on a range of topics related to fasting, including health benefits, associated mechanisms of health span and longevity, and when and how to break a fast. This two-hour episode covers many fasting-related topics, including comparing and contrasting different types of fasting, the effects of fasting on the gut microbiome, The effects of fasting on the immune system. Caloric restriction memetics such as resveratrol and spermidine. Fasting and IGF1. Fasting mimicking diet, the ketogenic diet for autoimmune diseases.

Sensitivity of biomarkers of inflammation and autophagy. Arobic exercise and sauna use while fasting. The effects of fasting on muscle mass. What we know about the minimal fasting time it takes to induce setopoge and apoptosis, refeating after a prolonged fast, thoughts on coffee and other calorie-free substances and breaking a fast, differences between a fasting-mimicking diet versus a water-only fast, and much, much more. This is a special preview of the Alawquot members-only podcast. For a full timeline with time codes for each topic and access to the entire episode, head over to foundmyfitness.com Aliquot. That's A-L-I-Q-U-O-T, Aliquot. If you were a premium member, you can also find this entire episode with a timeline on your private podcast feed. Now, let's dive in. Hope you enjoy.

There are other ways of changing the gut microbiome, for one, actually a pilot clinical trial found that intermittent fasting for 15 days, intermittent fasting, but on the days of their fasting, In this pilot study, people could eat with like up to 500 calories. It's sort of like a fasting-mimicking diet almost in a way. They basically did this for 15 days. So they were fasting for a total of seven days and then not fasting for a total of seven days. And there was an increase in bacterial richness in the gut microbiome in certain types of bacteria that have been shown to promote the production of T-regulatory cells. And basically there's, this was including lactobacillic bacteria, which are commonly used in probiotics as well.

Those have been shown to play a role in promoting T regulatory cell numbers through the production of short chain fatty acids. It also enriched other bacterial species like Previtella, which is another one that's also been shown to play a role in T regulatory cell production in the gut. Interestingly, it was also shown that fasting induced is sort of its own, you know, like ketone body metabolism was happening that was regulating the micro, that basically was facilitating microbiome growth as well. So I thought that was a really interesting study because fasting itself has been shown to also affect autoimmunity through other mechanisms aside from the gut microbiome, which that study. that study I just cited really focused on. But there have been other studies, a lot of studies have been done by Dr. Walter Longo and colleagues that have found either fasting, a fasting mimicking diet or even a ketogenic diet has been shown in animal studies and a very, very small pilot clinical study in patients with multiple sclerosis, again, an autoimmune disorder, where individuals

basically after just one week of the fasting mimicking diet or six months on the ketogenic diet. So much longer period to be on the ketogenic diet versus the week of the fasting mimicking diet. They had an improvement in clinical measures for a variety of clinical measures for multiple sclerosis. And then animal studies sort of confirmed that there was a lot of effects on T regulatory. cells and a variety of different effects on autoimmune regulation from the fasting, mimicking diet, or also fasting. So other studies have found that fasting itself can basically lead to preferentially lead to the death

of dysfunctional cells. And this seems to happen quite a bit in the immune sense. system. So as a fast becomes more prolonged, autophagy starts to happen, and autophagy is basically clearing out damaged stuff within a cell. But as the stressor becomes stronger, if the entire cell is actually damaged enough, the cell will die via apoptosis. And this has been shown to occur in, definitely occur in animal studies. where basically if you take a mouse and fast it for 48 hours, about 28% of the immune cells in the mouse will die off. And this activates stem cells in the blood system and the hematopoetic system where the stem cells increased by sixfold.

And this causes stem cells then to make brand new immune cells, young, brand new healthy immune cells. And interestingly, it's, Volter has shown that they make non, they make, they make functional immune cells. So you can clear out a non-functional immune cell that perhaps was playing a role in autoimmunity and replace it with a healthy functional immune cell that, you know, that basically is not having that autoimmune sort of defect. But it's really, you know, those animal studies were shown to be dependent on IGF1, levels just plummeting going going way down. And it's important to realize the translation of animals studies like that to humans. There's a lot of factors to consider. So for example, a mouse or rodent will lose 20% of their of their body weight after a 48 hour fast, whereas a human will only lose one to two percent. So it's a big difference. And it's also been

shown that within that two-day period, rodents can lower their IGF1 by 50%, whereas it takes a human five days on a water, you know, of basically not eating anything to lower their IGF1 levels by 50%. So big difference is there and with respect to transiting animal to mouse studies. But again, there has been some pilot studies looking at fasting and the effects on auto-imedes. disease like the multiple sclerosis one I just mentioned. There's also been some pilot studies looking at a 48-hour water fast in humans and there was a trend towards the hematopoetic stem cell activation like I just mentioned with the animal studies. So I think that, you know, without

giving any sort of recommendation, I think that, you know, people, people with autoimmune diseases, we may find physicians start to become more familiar with this research. Feel free to share that research, please, with your physician. And perhaps as the research becomes stronger, a lot of it's still in the preliminary phase, perhaps as it becomes more established, we'll start to find things like a fasting, mimicking diet, a low-calorie diet, or even just general fasting,

perhaps even ketogenic diets will start to be used in a, you know, clinical setting. That's the hope. I'm going to, there's a related question that I see people asking in the chat. So let me just skip down to that question real quick. And that has to do with, since we're talking about fasting and I was talking about autophagy a little bit, I know there's been, there's been quite a few questions. One from Xavier and another from Jay, I believe, asking about a few things. One, fasting duration required to activate autophagy in humans as well as biomarkers

and also what are called these caloric restriction memetics, or sometimes they're referred to as fasting memetics like resveratrol or spermidine during a fast to promote atophagy. So let's start off, you know, atopause. I just, I mentioned what autophagy is. It's basically, you know, the clearing out of damage organelles like mitochondria or other other organelles inside of a cell, even damage, even bits of, you know, pieces of DNA floating around or, you know, protein aggregates, things like that. You know, it's just clearing around all that, clearing out all that stuff that could be basically

causing dysfunction. And there are, there are several things that. an activate atopathy exercise is one, a variety of plant polyphenols that are found in coffee and tea, and also some of that are found in fruits like the skins of blueberries and grapes, a resveratrol, for example. Fasting is definitely a major activator of atopagy. There is very limited evidence looking atotagy in humans. There's one study that I like to, to refer to from Dr. Guido Kromer, who I've interviewed on the podcast a few years ago. He's one of the world's experts on autophagy, and he published a preliminary clinical study where they were measuring biomarkers of fasting, which I'll talk about in a minute, that in humans,

to determine what was the soonest time point at which, you know, the biomarkers, markers could be measured and that time point was found to be 24 hours in a human doing a water fast. That doesn't mean that atophagy isn't occurring when you're overnight fasted for 14, 16, 18 hours. Your biomarkers are only as good as the sensitivity of them. And in order to really be able to empirically measure when autophagy starts in humans, you have to have a very, very sensitive biomarker. And that just hasn't been established. I mean, we don't even have that, you know, those types of sensitivity biomarkers for inflammation. I mean, C-reactive protein, high-sensitivity C-reactive protein. You know, my high-sensitivity C-reactive protein comes out as 0.1.

Does that mean I have no inflammation going on in my body? no, it just means that that according to that biomarker, you know, that biomarker is very low for me and, and it's only so sensitive. So, so I don't, I, I, I, I tend to think that, that atopogy, there's a continuum of it and, you know, enough of it, if you have, if you're having, you know, if you measure, you know, you need a certain amount or quantity of cells for, you know, autophagy to be occurring in those cells in order to detect it. So what if it's occurring in, you know, 50% of those cells at, you know, 12 hours? But, but you can't detect that because it's not enough cells for your, for your, for your measurement to detect, right? Doesn't mean that

autophagy doesn't happen after a six, or after a 12 hour fast. It just means that you're not detecting it. So one of the major signals for autophagy to happen is a decrease in what's called protein. acidulation. And that biomarker that I'm referring to that was measured was protein acidulation on lysine residues in proteins. And so basically that that was what was used to detect autophagy. And, and, you know, it is a biomarker. There are other biomarkers that are used, the conversion of, you know, ATG1, ATG2. There's, sorry, LC31, LC32. conversion is another biomarker, but those are not really readily used in a clinical setting. So there's still a lot of development there in terms of the biomarker sensitivity.

The reason the protein acetylation is important to realize is because that happens, acidulation, you know, is something that, you know, happens when you eat food. You make acetyl-CoA and, you know, some of that. that is, you know, acetyl-quase gets used or converted and metabolized into basically acetyl groups that are used in acetylating proteins as well as other things. So that, for that decrease to occur, there needs to be a caloric deficit. There needs to be a decrease in food intake. There are other things that can decrease protein acetylation as well. One of those things is spermidine and another one is resveratrol. And so that sort of was the question from,

from a couple of individuals. We've talked quite a bit about resveratrol. Resveratrol indirectly decreases protein acetylation because it activates certuans, a group of enzymes that are histone deacetylases. So essentially these enzymes are removing acetyl groups from proteins. So that's basically mimicking what happens when you are not eating food. Your protein acidulation is going down. Well, another way to do that is to activate Sertuans. Sertuans then remove these acetyl groups from proteins as well. So resverat trial has been shown to activate atopagy in animal studies as well as

in culture studies as well. Spermene directly lowers protein acetylation. And let's talk a little bit about. spermidine. So spermidine is something, it's a polyamine. It's found in very high concentrations in Natto, which is the fermented soybeans that are commonly consumed in Asian countries, particularly in Japan. It basically inhibits protein acetylation. It inhibits basically the direct transfer of acetyl groups to proteins. So whereas, whereas certuitary, are taking the citil groups that have already been put on off,

spermidine prevents that whole process from even happening. So the seal groups don't even ever get put on. It's spermating has been shown in animal studies or in lower organism studies of yeast and flies and also nematode worms to extend lifespan. It's extended lifespan in an autotopathy dependent manner. So basically, you know, it's been shown to increase a lifespan of these lower organisms. by increasing autophagy. It's been shown,

spermine has been shown to basically, when you give dietary spermidine to mouse strains that are short-lived, so like accelerated aging mouse strains, it can prolong their lifespan. There's been some studies looking at the brain concentration of spermating in flies and that correlates with memory capacity.

There's also been some studies in mice that have the in age, older animals, that giving those older animals, dietary spermene can improve their heart function. It actually has been shown to enhance autophagy and specifically mitophagy, which is the clearing out of damaged mitochondria within a cell. It's been shown to do that within the hearts of mice that were given spermating. And, you know, so mitochondria are extremely important for heart function. The heart is basically primarily using what's called beta oxidation as the energy source, meaning it's using fatty acids, which require beta oxidation occurs within the mitochondria.

So it's not using glucose. And glucose can be used outside of the mitochondria in a process called glycolysis. That doesn't happen in the heart. The heart is using mitochondria. solely as a source of energy. So that's been shown in animal studies in mice. And again, spermine and resveratrial both been shown to basically induce autophagy in basically animal rodent studies and cell cultures. So I think that's sort of in detail, a detailed response to some of these fasting memetics or caloric restriction medics, as they're often referred to. Also, the

atopathy, when does atopathy start and the fasting duration? Again, aerobic exercise in Hillary's mentioning, or sorry, Andrew Bennett is mentioning in the chat about aerobic exercise, being, doing aerobic exercise fasted, can induce autophagy more easily than in a Fed state. There's been many studies looking at a variety of adaptations that occur specifically in mitochondria in response to exercise either in a fed or fasted state. And doing exercise in a fasted state does lead to better and more robust adaptations in general. But most of the studies that were done looking at a fed state were really high, we're simple sugars mostly. So, you know, more of like a refined type of carbohydrate, like toast with jam on it and things

like that. Jay's asking in the chat, are there any human studies with spermidine and autophagy, not that I'm aware of yet. Again, we really have blunt, blunt, you know, tools with respect to measuring autophagy in humans. And I haven't even seen very many studies looking at that. So, you know, until we sort of improve those tools of measurement, it's hard to look at atopathy in humans and whether X, Y, or Z affects autophagy without the actual tools to detect it. And there was also a related question with the autophagy and fasting that had to do with fasting mimicking diet, promoting atopause.

as well as basically, you know, doing the water only fast. And, you know, again, I think that if we look at, you know, even IGF1 levels that go down, you know, it takes five days of a water fast to lower that by 50%. You know, the 24-hour fast that I referred to were after 24 hours. autophagy was detectable in humans. That was, that was, you know, after 24 hours of full fasting. So it's not clear. It is my, you know, opinion that having some calories would basically slow that process.

But, you know, it may still occur. It just may not occur as quickly. And, you know, for some people, some people, fasting is not an option. and a fasting mimicking diet is an option. And so it's, you know, it's nice to have more than one option, particularly for some people that can't do full fasting. But this is all still very preliminary work that is, that needs much more, you know, larger studies to confirm

in order for this to really start to be translated into a clinical setting. And, you know, so I think that as more data comes out, we'll start to have more of that translated into a clinical setting. But until that happens, it's still, it's still difficult to translate this to a clinical setting. And certainly getting the information out to physicians also is another challenge, which hopefully that, you know, I think found my fitness is one of the, you know, platforms trying to reach. physicians in addition to everyone. So hopefully that helps getting the information out there with the podcasts and the variety of episodes that we put out there. And by the way, I guess also there have been some studies looking at atophagy in long-term caloric, people that have been practicing caloric restriction long-term, so for about six years. And there are increased markers of

autophagy found in in those individuals. And so, so that is, that is, I would say, evidence that even a low caloric restriction diet, which is what a fasting mimicking diet is, a fasting mimicking diet is even more than what a caloric restriction diet would be. But, but basically, you know, autophagy biomarkers have been measured in humans that have been practicing caloric restriction for for six years or longer. With respect to exercise, there's quite a few questions in the chat about exercise, increase in autophagy and, you know, what type of exercise is needed. You know, there's just really limited evidence in this field.

A lot of studies were done by the late Beth Levine. She had done a variety of studies in animals looking at atopagy, but I have yet to see really studies that have been done in humans, looking at different types of exercise, you know, and how that can promote autophagy. So again, it's one of those things where we're sort of getting ahead of ourselves by making a statement like, well, autophagy does increase, sorry, exercise does increase autophagy.

But we just don't really know how much exercise, how much atopagy is happening. What types of exercise are some that are better than others? You know, that's, the thing is, is that exercise is a metabolic, it's a type of metabolic stress like fasting. You know, exercise, you are, you are basically putting yourself in, you know, your blood glucose levels are going down. You're, you're sometimes shifting into ketosis. So exercise can sort of kick you into ketosis, something that I've, you know, measured in myself. I wear a continuous glucose monitor and, you know, exercise, you know, is very consistently. I mean, that's the one thing that it does is, you know, takes your blood glucose levels and

plummets them. And that is something that, you know, this has been another question that I've seen submitted on several occasions. Are there sort of indirect markers of autophagy that we can use, you know, that are proxies of, you know, potentially, some atopausee is occurring. And, you know, I think, I think, you know, blood glucose levels going down and ketone, going into ketosis could potentially be, be one of those markers because protein acetylation, a decrease in protein acetylation requires a decrease in glucose intake, in food intake in general, also in fatty acids. So I'm not sure that a ketogenic diet is going to, induce autophagy because fatty acids can be used to make acetyl-CoA. And while that is being done

when you are in a fasted state, you're immobilizing fatty acids that are stored in adipose tissue, and those are going to be used as energy sources. If you're giving yourself more and more and more of that, you know, that's just more potential acetyl-CoA and more than acetyl groups that can be use to acetylate proteins. So I'm not sure you could make the direct comparison of fasting versus a ketogenic diet, for example, where you're still taking in fat, you're still taking in food. Because, again, one of the strong signals that's needed to activate autophagy is a decrease in protein acidulation.

And so that does happen when you are exercising because you are using your, you're using up energy. And so there's less acetyl-CoA and less acetyl groups going around. What do you think are the most important, efficient protocols to adopt in order to prolong and expand your health span as we all age? That's a very big, big question. I think some of the... Thanks for listening to this preview of our special Alawquot mashup episode featuring clips covering some of the many health benefits. associated with fasting, including associated mechanisms of health span and longevity, health benefits, and when and how to break a fast. Today's preview is the last of three free previews of the Alawquot that we're sharing on

our public podcast feed. We'll be regularly releasing more ALEquot episodes, much like the one you heard today on the Found My Fitness premium podcast feed. To learn more and subscribe to our private podcast feed, head over to foundmyfitness.com. forward slash aliquot and sign up to become a Found My Fitness premium member. That's Found My Fitness.com forward slash al-I-Q-U-O-T, Aliquot. Not only will you get complete access to our private podcast feed, delivering new episodes of the Aliquot, but you'll also get access to live monthly Q&A's with me, lifetime updates to

our genetic report, regular members-only emails, and more. Thank you so much for listening and stay tuned for more new content soon. Hey, one last thing, guys. I just want to make it clear these members' Q&A's that this content originated from are really meant to be a discussion of the science. It's definitely not meant to be diagnostic or as a treatment for any health condition. This podcast does not establish a client-patient relationship. So just keep that in mind.

Talk to you guys soon.