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 igf-1 fasting mimicking diet the ketogenic diet for autoimmune diseases sensitivity of biomarkers of inflammation and autophagy aerobic 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 the top pudgy and apoptosis Reef.
Feeding 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 aliquot members only podcast for a full timeline with time codes for each topic and access to the entire episode head over to found my fitness.com forward slash aliquot. That's a li quot 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 it 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 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 lactobacilli bacteria, which are which are commonly used in probiotics as well. Those those have been shown to play a role in promoting T regulatory cell numbers through the production of short chain fatty acids.
Um, it also enriched other bacterial species like private Ella, 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 basically was facilitating microbiome growth as well. So I thought that was a really interesting.
Eating study because fasting itself has been shown to also affect autoimmunity through other mechanisms aside from the gut microbiome, which that study. I just cited really focused on but there have been other studies a lot. A lot of Studies have been done by dr. Valter Longo and colleagues that have found either fasting fasting mimicking diet or even a ketogenic diet has
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 just one week of the fasting mimicking diet or or six months on the ketogenic diet so much longer period to be on the ketogenic diet versus the week of the festive mimicking diet. They had an improvement in clinical measures for a variety of clinical measures for
Or for multiple sclerosis and then animal studies sort of confirmed that that the you know, there was a lot of a lot of effects on T regulatory cells and a variety of different effects on auto immune regulation from the fasting mimicking diet or also fasting. So other Studies have found that fasting itself can basically lead to two
Is preferentially preferentially lead to the death of dysfunctional cells and this seems to happen quite a bit in the immune system. So as a fast becomes more prolonged a topology starts to happen and at apogee is basically clearing out damage stuff within a cell but as the as the stressor becomes stronger if the entire cell is actually damaged enough
the cell will die by 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 hematopoietic system where the stem cells increase by six fold
This causes stem cells then to make brand new immune cells young brand new healthy immune cells and interestingly its vaulter has shown that they make naan they make they make functional immune cells. So you can clear out a non-functional immune cell that protect perhaps would be 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 igf-1 levels just plummeting going going way down and it's important to to realize the translation of animal studies like that to humans. There's a lot of factors to consider. So for example and mouse or rodent will lose 20% of their of their body weight after a 48-hour fast whereas a human will only
Is 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 igf 1 by 50 percent. Whereas it takes a human five days on a water on a you know of basically not eating anything to lower their igf-1 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 autoimmune disease like the multiple sclerosis when 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 hematopoietic Stem Cell Activation. Like I just mentioned with the animal studies, so I think that you know without without giving any sort of recommendation I
That you know, it would 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 with 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 will start to find things like a fasting mimicking diet low calorie diet or
Even just you know General fasting perhaps even ketogenic diets will start to be be used in had, you know, clinical setting. That's the hope. I'm going to there's a related question that 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 a top edgy a little bit. I know there's been there's been
quite a few fat questions one from Xavier and another from Jay I believe asking about
A few things one fasting duration required to activate a tapa gene in humans as well as biomarkers. And also what are called these calorie restriction memetics or sometimes they're referred to as fasting memetics like Resveratrol or spermidine during a fast to promote etapa G. So so let's start off, you know at apogee. I just mentioned what a topology is. It's basically, you know, the the clearing out of damage.
Organelles, like mitochondria or other other organelles inside of a cell or even damage even bits of you know pieces of DNA floating around or you know piece of 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 can activate a tapa G exercises one variety of plant polyphenols that are found in
Coffee and tea and also that are some of the other found in in fruits like the skins of blueberries and grapes or Resveratrol for example fasting is a definitely a major activator of a toffee G. There is very limited evidence looking at a table gene in humans. There's one study that I like to refer to from. Dr. Guido Cromer who I've interviewed on the podcast.
Few years ago. He is one of the world's experts on a tapa G 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 how what was the soonest time point at which you know, the biomarkers could be measured and that time point was found to be 24 hours in a human do
Water fast. That doesn't mean that a toffee gee isn't occurring when your 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 a tapa G 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 two types of sensitivity bio markers for inflammation. I mean see reactive protein High sensitivity C-reactive protein, you know, my my high-sensitivity C-reactive protein comes out as point one. 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 tend to think that that it's Hoffa G. 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 toffee to be occurring in those cells in order to detect it. So what if it's occurring in, you know, 50% of those cells that you know 12 hours, but but you can't detect that.
That because it's not enough cells for your for your for your measurement to detect right doesn't mean that a topology doesn't happen after 1/6 or after a 12-hour fast. It just means that you're not detecting it. So one of the major signals for a tapa G to happen is a decrease in what's called protein acetylation and and that biomarker that I'm referring to that was measured was protein acetylation on a lysine residues in
And so so basically that that was what was used to detect or topology and and it you know, it is a biomarker. There are other biomarkers that are used the conversion of you know atg 182. There's our sorry l31 l32 conversion or is another biomarker, but those are not really readily used in the clinical setting.
So those there's still a lot of development there in terms of the biomarker sensitivity.
the reason the protein is a relation is important to realize it's because that happens is sit Elation, you know is something that you know happens when you when you eat food you make acetyl Co a and you know, some of that is, you know, as little boys get gets used or converted and tab alized into basically acetyl groups that are that are you
Just in isolating 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 assimilation as well. One of those things is permitting and another one is Resveratrol. And so that sort of was the question from from a couple of individuals.
So we've talked quite a bit about Resveratrol Resveratrol indirectly decreases protein assimilation because it activates sirtuins a group of enzymes that are histone deacetylases. So essentially these enzymes are removing acetyl groups from proteins. So so that's basically mimicking what happens when you are not eating food, you're approaching installations going down. Well another way to do that is to activate sirtuins sirtuins then remove.
Move these these acetyl groups from from proteins as well. So Resveratrol has been shown to activate a tapa G in animal studies as well as in cultural studies as well. It's permitting directly lowers protein installation. And let's talk a little bit about spermatogenesis. Permitting is something it's a polyamine. It's it's found in very high concentrations in that toe, which is the fermented soybeans that are
Are commonly consumed in Asian countries particularly in Japan it basically inhibits protein installation and inhibit inhibits. Basically the direct transfer of acetyl groups to proteins. So whereas whereas sirtuins are are taking this little groups that have already been put on off its permitting stop prevents that whole process from even happening. So the steel groups don't even ever get put on
It's permitting has been shown in animal studies or in lower organisms studies of yeast and flies and also nematode worms to extend lifespan. It's extended lifespan in an audit opit topology dependent manner. So basically, you know, it's been shown to increase the lifespan of these lower organisms by increasing at apogee. It's been shown spermatid has been shown to to basically when you when you give dietary Sperma ting to
Two mouse strains that are short-lived so like accelerated aging Mouse strains, it can prolong their life span. There's been some studies looking at the brain concentration of spur mating in flies and that correlates with memory capacity. There's also been some studies and in mice that have the in age older animals that giving those older animals dietary spermatozoon can
Prove their their heart function. It actually has been shown to enhance a top G and specifically my Toph AG 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 its permitting and you know, so mitochondria are extremely important for heart function. The heart is is basically primarily using what's called beta oxidation as a
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 using mitochondria solely as a source of energy. So that's that's been shown in animal studies in mice and against permitting and Resveratrol both been shown to
To basically induce the topology 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 calorie restriction Medics as they're often referred to also the etapa G1 is a top is you start in the passing duration again, aerobic exercise and Hillary's mentioning or sorry Andrew. Bennett is mentioning in the chat about aerobic exercise being doing aerobics exercise fasted.
Can a deuce the top as you more easily than in a Fed set State? There's been many studies looking at a variety of adaptations that occurs specifically in mitochondria in response to exercise either in a Fetter 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 more of like a refined type of carbohydrate like like toast with jam on it and things like that.
Jay's asking in the chat. Are there any human studies widths permitting and etapa G. Not that I'm aware of yet again.
We really have blunt.
Blunt, you know tools with respect to measuring at apogee and humans and I really 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 a top Aegean humans and whether X Y or Z effects of topology without the actual tools to detect it, and there was also a related question with the with the top Gene fasting that had to do with fasting mimicking.
promoting a toffee G as well as a basically, you know doing doing the the water-only fast and you know again, I think that if we if we look at, you know, even igf-1 levels that go down, you know, it takes five days of a water fast to lower that by 50% you know, the the
24-hour fast that I referred to word. We're after 24 hours at apogee was detectable in humans. That was that was a 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.
you know, so I think that as more data comes out will start to have more of that translated into a clinical setting but until that happens, it's still it's still it's still difficult to to to translate this to a clinical setting and certainly getting the information out to Physicians also is another challenge which which hopefully that you know 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 podcast and the variety of episodes that we put out there.
And by the way, I guess also there have been some studies looking at a toffee G in long-term caloric people that are have been practicing caloric restriction long-term. So for about six years and there are increased markers of a topology found 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 diets even more than what a calorie restricted restriction diet would be but basically, you know, autophagy biomarkers have been measured in humans that happened practicing calorie restriction for for 6 years or longer.
With respect to exercise. There's quite a few questions in the chat about exercise increase in a tapa G and you know, what type of exercise is needed, you know, there's just really limited evidence in this in this field. A lot of studies were done by the late Beth Levine. She had done a variety of studies and animals looking at a tapa G, but I have yet to see to see really studies that have been done in humans looking at different types of exercise.
You know and how that can promote at apogee. So again, it's one of those things where we're sort of getting ahead of ourselves by making a statement like well Itachi does increase sorry exercise does increase the top edgy, but we just don't really know how much exercise how much etapa G is happening. What types of exercise are there some that are better than others. You know, that's the thing is is that exercise is a
A ball it's a type of metabolic stress like fasting, you know exercise you are you're basically putting yourself in you know, your your your blood glucose levels are going down your your your 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
Does it you know takes your blood glucose levels and plummets them and 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 a toffee G that we can use, you know that are proxies of you know, potentially some atop issues occurring and you know, I think I think you know blood glucose levels going down and
Atone going into ketosis could potentially be be one of those markers because protein is sit Elation 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 a toffee G because fatty acids can be used to make acetyl COA and while that is being done.
Done when you are in a fasted State your 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 Co a and more than acetyl groups that can be used to simulate proteins. So I'm not sure you could make the direct comparison of fasting versus ketogenic diet. For example,
Still taking in fat you're still taking in food because again one of the strong signals that's needed to activate a tapa G is a decrease in protein assimilation. 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 Co a and less acetyl groups going around. What do you think are the most important efficient protocols to adopt in order to prolong?
Ang and expand your health span as we all age. That's that's a very big question. I think some of the
thanks for listening to this preview of our special aliquot mashup episode featuring Clips covering some of the many health benefits associated with fasting including Associated mechanisms of Health and Longevity health benefits, and when and how to break a fast today's preview is the last of three free
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