Q&A #2: Protein After 65, Saturated Fat & Longevity—Plus Whole Grains

Hello, everyone. Great. Can someone in the chat let me know if you guys can hear me all right? Awesome. All right. So, go ahead and get started with the most upvoted question. We have 2 hours, so. I can, I can, you know, there's some, some questions I think I can go a little more in depth and require a little more in depth, but I'm going to try to get through as many as I possibly can this time. So, and then of course I'll be looking at the chat so that you guys, you know, can post questions live while I'm explaining an answer if another question comes up, and I'll try to, try to hit some of those as well. And please let me know if like anything changes with my sound or anything like that. So, um, the first and most upvoted question has to do with the, um, the vegan diets.

And the question states, and this is from Henry Reed, says, hi Ronda, the plant-based community has become increasingly more aggressive over the past few years due to popular documentaries and YouTube channels. They bring up good points about the environmental hazards of animal agriculture, but on the nutrition side of things, they present convincing evidence that meat, dairy, and eggs can in fact cause long-term negative health outcomes. How much of this science is legitimate and how much is fearmongering? So to start off with that, it's definitely— I've got one second. I've got this like new chapter going. Oops. This is a really, really important question that I am continually asking myself.

I probably, I would say like every 2 to 3 years, go through this like stage where I freak out and go, okay, should I be vegan? Should I be vegetarian? Am I getting things right? You know, because I definitely am trying to eat the healthiest I can, the best diet that I can, you know, to to have the best health outcomes for myself. So this is certainly something that I am particularly interested in as well. I will say that some people are saying a blank screen and no sound. Yeah, okay. I will say that nutrition science is extremely complicated and notoriously a murky field.

Because a lot of the studies rely on observational data, which means that these are studies that are looking at associations between people that eat certain diets and relying on a variety of ways like dietary recall to see what people have been eating, and then looking at that person's long-term health status, whether or not they're dying of cardiovascular disease or cancer or some other type of age-related disease. So a lot of correlative data there that is hard to really tease out whether or not something is causal.

And for that reason, it's really, really important in nutrition science to not only look at these what are called prospective studies, or, you know, these epidemiological studies which are associative, and look at, for example, people that are vegetarian or people that are omnivores and what their, you know, what percentage of people are dying of cardiovascular disease or cancer earlier in life. In addition to looking at that data, it's really, really important to look at and understand mechanisms. And oftentimes for that, we have to go to animal studies. It's important to look at clinical trials where instead of looking at health outcomes, usually there is a biomarker that's looked at and biomarkers that are associated with negative or positive outcomes are looked at.

So with clinical trials, you can actually, in a controlled setting, give a person a certain diet and then for a certain amount of time and then measure various biomarkers. So it's important to look at that data. And it's also important to understand the interactions between various types of foods. And this is where, you know, the epidemiological, the prospective studies can be very confusing because, for example, if you're looking at the effects of saturated fat on heart disease, Well, you also have to take into account the effects of refined sugar in combination with saturated fat and how that affects heart disease. So these different systems are interacting, and that's also important.

So you have to look at the totality of the data to really get a good snapshot and idea of what is happening in the body and what is healthy and not healthy. And then in addition to that, there's genetics, and that's also something to consider. to consider. So I would say that— are most people having a problem with the screen? Yes. Okay. I'm seeing a lot of chat questions here that are not related to what I'm talking about, but related to not being able to actually hear or see me. So All right, so with that said, I will tell you my outlook on what I have looked at in terms of all those pieces of data. So first and foremost are the prospective studies where we're looking at people that eat a vegetarian or a vegan type of diet or people that eat meat and various types of health outcomes.

I would say that more often than not, It's been shown that people that eat a vegetarian or vegan diet have a decreased risk of all-cause mortality as well as cancer mortality, and particularly cancer mortality. So that's, and that's something that you really can't ignore. Now you will find some studies showing that, you know, no, vegetarians do not have a lower risk compared to omnivores or meat eaters. But I would say by and large, Majority of the data shows that there is a reduced all-cause mortality, and there is reduced cancer-related mortality with vegetarians and vegans compared to meat eaters. And so I would say that well, you know, there are what's going on there? You know, is is are there other factors that are that are playing a role?

And one of the largest studies that have been done so far, meaning the largest population sample of people. Looked at, again, all-cause mortality, cancer-related mortality, and vegetarian versus meat-eating diets and found that only people that ate meat and had another unhealthy lifestyle factor, just one unhealthy lifestyle factor present, including being obese or overweight, sedentary, so not being physically active, smoking, or excessive alcohol drinking, Those were the 4 unhealthy lifestyle factors that were included. If they had just one of those unhealthy lifestyle factors and they ate meat, they were at a higher risk of all-cause mortality and cancer-related mortality compared to vegetarians that had one of those unhealthy lifestyle factors but did not eat meat.

Now, meat eaters that had none of those unhealthy lifestyle factors, meaning they were not obese or overweight, they were physically active, they did not smoke, and they did not obsessively, sorry, excessively drink alcohol, they did not have an elevated risk for cancer-related mortality or all-cause mortality compared to the vegetarians. So what that says to me is clearly there are interactions between other lifestyle factors, other foods that are being eaten, whether or not you're physically active and your risk for earlier death if you eat meat. And if we look at some of the mechanistic data and also animal studies, as well as some clinical trials, what we do know is that the cancer-related mortality seems to be one of the highest risk factors for people that eat meat.

And that's largely due to the IGF-1 mTOR axis. And IGF-1 is, It's activated with essential amino acids, which are more abundantly found in meat versus plants. So IGF-1 gets active, and what IGF-1 does is it allows a cell that otherwise has some sort of mutations it's acquired or other sorts of damage, damaged proteins, damaged mitochondria, Whatever the damage is inside the cell, the damage that can lead eventually to a cancer cell, those cells usually die. Your body knows to get rid of them. However, when IGF-1 is around, it overrides that whole system, and so IGF-1 is this powerful growth signal that doesn't allow the cell to die.

So the cancer cells really like it because they kind of can override this protective mechanism that we have hardwired in our genes that detect when cellular damage occurs and they kill the cell. So the IGF-1 is one of the main mechanisms and we know that from many, many different animal studies. For example, if you take animals and you inject them with human tumor cells and then you feed them a high protein diet and then either restricted protein or a high protein diet, the tumors will rapidly grow and kill the animals in the high protein that were given the high-protein diet. We know from humans that have elevated IGF-1, they're at a higher risk for cancer.

We know from humans that have a genetic polymorphism that makes them make more IGF-1, they have increased cancer incidence, and we know from humans that have a polymorphism that have less IGF-1, they actually have decreased cancer incidence. So we look, we know looking at all these studies, mechanistically, the prospective studies, the epidemiological studies, the genetic data, and then if we look at clinical studies where people are put on protein-restricted diets, their IGF-1 goes down, which IGF-1 again is a biomarker for increased cancer incidence.

So with that whole data in totality, I would say that if you're going to eat meat, you better make sure that you're not a couch potato, that you're not a smoker, that you're not excessively drinking alcohol, and that you're either not obese or overweight or trying to lose that weight if you are. I mean, there's obviously ways you can lose weight and fat while eating meat. So I would say That, that, that's kind of my answer. I personally do eat meat and I eat vegetables. I eat meat and vegetables. I'm an omnivore. I don't eat all the processed sugars and refined sugars and refined carbohydrates and all that stuff. So that's kind of a nutshell, I think in a nutshell, what, what the science says. Now, you know, some scientists really think you should limit your protein intake for longevity.

And, you know, there's this— to a certain point that may be true, but also data has showed that when you're over the age of 65, actually protein intake is inversely correlated with all-cause mortality— sorry, directly correlated with all-cause mortality. So the lower the protein intake, if you're over the age of 65, the higher risk you have of dying earlier. And that largely has to do with the fact of people are more frail and they're losing muscle mass. And that can increase the risk of things like falling, which can take a person out. So there's this age-related factor as well as when you become older than 65, obviously you do need to make sure that you're increasing your protein intake. And that's been shown in studies as well.

So I think, yeah, and the main, thing, the main, you know, take-home here, I think, is that, you know, eating excessive amounts of protein, you should definitely make sure you're physically active if you're, if you're doing that. You want to make sure that IGF-1 is going into your muscle and going into your brain, which is where we actually want IGF-1. IGF-1 is not all bad. You know, IGF-1 is a really important growth factor that helps muscles grow. It helps repair damaged muscles. It actually crosses the blood-brain barrier and gets into the brain, helps neurons grow, and this has been shown in animal studies and also it's been shown in clinical human studies that exercise causes IGF-1 to go be taken up into muscle.

So I think again, if you go back to that large prospective study looking at vegetarians and meat eaters and all-cause mortality, the ones that didn't have any of those unhealthy lifestyle factors, meaning they were physically active, did not have an increased risk of cardiovascular disease and cancer. So I really do think that that's really important to consider the whole package and the whole diet and lifestyle. And really that's what the data is showing us is that that is important, irrespective of the benefits of micronutrients and prebiotic and fiber and all that, just talking about meat consumption itself, is it harmful? I think the answer is it can be if you have a terrible diet and you're obese and you don't act, you're not active.

I mean, you need to make sure that the amino acids and proteins that you're generating and the IGF-1 that you're generating is being used. It's going to a good use and it's not just sitting around in your plasma and going to organs and allowing all your cells damaged or not to keep keep growing and growing and not die when they're supposed to die. Cells have a certain lifespan and when that lifespan's over, they die and they're replaced with new cells. Well, what happens when you keep accumulating trash is that it piles up and eventually it's gonna do some damage and that's kind of what happens as you age and decades go on. Well, these damaged cells that don't die 'cause there's all this IGF-1 constantly being around, they eventually are gonna form a tumor.

And then the tumor is going to grow fast if you keep, you know, adding the IGF-1. So I do think that that's sort of my take on the vegetarian diet. Now, you know, there's the whole cardiovascular disease risk and that kind of— there's kind of a blurred line between, well, eating meat and then the saturated fat, you know, that, you know, increases the risk of cardiovascular disease. Well, we're going to get into that in a minute, but just addressing that protein part, I think the protein part really, the dangers of it come down to too much protein with not physical, no physical activity and being overweight, obese, having other unhealthy lifestyle factors that are causing a lot of damage like eating refined carbohydrates, which lead to inflammation and cause damage and also smoking, which obviously causes damage.

So I'd say for smokers, there may be some evidence, there may be an argument for smokers to actually cut down on their meat intake. Honestly, the best thing they could do is just stop smoking. That would take care of it. But obviously that's not easy for people to do. So I think that's really, the important take-home when it comes to that. You know, now the question is how much protein per meal, and I'm not sure that Mercola and Perlmutter have actually— do have real evidence to suggest 20 grams of protein per meal, you know, keeps IGF-1 down. In fact, it all depends on what your total— what percentage of protein makes up your total caloric intake.

So we know that if you're eating, for example, if you eat really low protein intake, so like 10% or less of your caloric intake comes from protein, then your IGF-1 will be really low. But 20 grams of protein per meal, I don't really know if we have evidence whether or not that keeps it low or not and I'm not sure where that— is coming from, but I will say that in addition to amino acids from protein, essential amino acids from protein, meaning actually from animal protein, there is a component of energy intake and sugar that regulates IGF-1 as well, and that is because insulin causes the proteins that bind IGF-1 and keep it from becoming active Yeah. Insulin actually lowers those proteins.

So basically, in the absence of something that's gonna cause an insulin response, like a refined sugar, for example, you'll have higher levels of what's called insulin-binding proteins. The insulin— the IGF-1-binding proteins will bind to the IGF-1 and keep it from actually becoming active. So there is sort of this balance between making sure your protein intake isn't too much and making sure if your protein intake is high, you wanna make sure you're very physically active so that IGF-1 is going to your muscles and going to your brain. So I'm not saying you always have to keep your protein intake low. I'm saying if you take your— if you eat your protein, make sure you're physically active.

Like it's important, but also the sugar as well because the sugar can regulate the availability of the IGF-1. So I think both of those factors are really important when we're talking about the function of IGF-1 as well. So someone's asking if insulin is low, protein is not as much of a problem. No, that's not actually the case. It's not, it's, you know, eating, having a lot of IGF-1, even in the absence of an insulin, having a lot of protein that activates IGF-1, even in the presence of the insulin-binding proteins doesn't necessarily mean that's gonna take care of the problem. It just means it's not gonna be as bad. So the IGF-1 does, it's still active even with those proteins around that bind it 'cause they're not binding 100% of it.

So there is, it's definitely something, I think it would be better, and that's where people on a low-carb, diet, you know, obviously do better because they're not— they're, they're keeping their insulin response low as well. Um, but, but yeah, so I mean, I wouldn't conflate that with, oh, you can just eat as much protein as you want as long as you, uh, don't have insulin. That's, that's actually not the case as well. It's just, it's something— it's kind of like a— it's kind of like a titrating the effect kind of thing. Um, you know, so, so I think that's just That's my take from as far as I've looked in the literature. And that's kind of why I still eat meat.

I would say that looking at some of these comments on the question, people are interested in other things as well, like TMAO, heterocyclic amines, and a lot of heme iron from meat. So I will say that TMAO is something that really comes down to the type of gut bacteria that you have. That's, and that's been shown. So people, you know, basically if your gut microbiome sucks, you may have a higher risk of making TMAO, which can, you know, which can cause damage as well. I'm not so much of an expert on that topic as I am on IGF-1 because I've just, I've done research on IGF-1 myself and I've done a lot of reading about it. But I do know that the gut microbiome plays an important role with TMAO.

And so for me, I obviously am eating, you know, with the gut microbiome, the most important thing for gut health is actually making sure you're getting a diverse array of prebiotic fibers. And that's found in a variety of plants. It's found in vegetables. It's found in fruits. It's found in seeds. Seeds, you know, nuts, legumes, mushrooms, oats. They have a variety of different types of prebiotic fibers, which feed different species of bacteria in your gut. And what happens when you don't eat that prebiotic fiber is your gut bacteria start to eat what's called mucin. And mucin is the lining that makes up the gut barrier. That breaks down the gut barrier. And literally, it's one of the number one cause of— I mean, breaking down the gut barrier, people are so concerned about gluten.

Well, actually, the most important and most robust thing that breaks down the gut barrier is actually lack of prebiotic fiber. And that's been shown. I mean, that's been shown in multiple studies. That's, it's, you know, it's consensus, scientific consensus that that's one of the main things that break down the gut microbiome. And also leads to wiping out diversity of the gut microbiome as well. So I kind of went off on a tangent there, but so the TMAO, of course, I— that's, you know, obviously why I, I like to really consider eating a variety of different, you know, vegetables and seeds and nuts and things for my, for my gut microbiome as well. And In terms of like the heme, the heme iron, you know, it's a topic.

It's an interesting topic that I I don't know that we have enough data out there yet. I do know that there does seem to be a dose-dependent effect. For example, in terms of at least for cardiovascular disease risk, I know that Ron Krauss's data has shown, for example. People that eat red meat, which has iron that's the most bioavailable, like they're eating it for every single meal. So they're eating it 3 or more times a day in combination with saturated fat. Something about that combination, whatever it is, increases the amount of small dense LDL particle numbers, which is something that absolutely will increase cardiovascular risk. I'll get to that in a few minutes. He doesn't know why that is. I've emailed him and asked him.

He said that they're actually currently doing a clinical trial to try to test the hypothesis of whether or not it is the actual too much iron overload that's happening, but it's not really known. And that may also come down to genetics because there are lots of genes that are regulating how iron is transported and used in your cells. So that's really a big open question. I would say, Most people aren't eating red meat for 3 or 4 meals a day in combination with saturated fat. So, you know, it may just be a really small, you know, subset of people that are doing that that are maybe at a high risk. And, and we don't even know for sure. This is all like early preliminary data that really needs to be teased out.

And so, you know, for that reason, I— it's something I'm aware of, but I, you know, I have in the back of my mind, but I don't really talk about because I don't feel like We understand enough about what's going on, you know, whether or not really is a risk or not. But it is certain certainly something to keep in mind. And then the heterocyclic amines, which are formed when you cook meat at really really really high temperatures. We have enzymes in our body that detoxify those in like the the NAT2 enzyme, for example. Some people do have polymorphisms that put her at a higher put them at a higher risk for. For producing these heterocyclic amines, which by the way, get converted into nitrosamines and things that are known to be carcinogens. And that's kind of like their risk.

I'd say most people are not at risk for that because we have beautiful detoxification enzymes in our body that take care of that. For the most part, people aren't at risk, but there are certain genes and genetic polymorphisms. In fact, if you run your— if you have 23andMe data and you run it through my genetic tool, All of you guys should be able to do that for free endlessly. It'll tell you whether or not you are at risk for that certain polymorphism, but it's not the majority of the population, so it's not something that's a super big risk factor. But I do think vegans like to talk about it because it's just, you know, potential ammo for why people should be vegan.

I think really the biggest argument has to do with the IGF-1 cancer risk, and I think the The way around that really is you just, you know, for people that are eating more of a paleo-like diet, for people that are physically active, you know, it's really not a problem because the IGF-1 that you're using gets taken up into your muscle and into your brain. And also the IGF-1 isn't as big of a problem if you don't have as many damaged cells around and if you're not having so much insulin around. So there's lots of other factors to consider, but hopefully— that makes sense to people. We're going to talk about ketogenic diets and saturated fat in a minute, but hopefully that was good enough. I don't want to spend too much time.

I actually am going to go— so the next upvoted question has to do with a high-fat meal, and it has to do with gene polymorphisms involved in the way your body processes fat, particularly saturated fat. But there's another related question that was also really upvoted, and that question was, um, my— okay, that my take on saturated fat— fats and the fact that there's conflicting evidence out there regarding, um, you know, risk for cardiovascular disease. So I'm going to talk about that question first and then get into the genetic polymorphisms because I think it naturally follows that. I don't want to just start diving into the gene polymorphisms.

So this is a topic that I have really done a lot of reading about, and I've talked to, and I'm friends and colleagues with people in the field that are looking at the effects of saturated, Ron Krauss being one, the effects of saturated fat on heart disease. And so from all of my reading, I have come to the conclusion of for myself is that saturated fat doesn't in and of itself necessarily cause heart disease. But on a population level, and that's on an individual level, on a population level, the association between saturated fat and heart disease may be something that's real, and I'll explain the reason for that. And I think that's why associations like the American Heart Association make the recommendations that they do.

So saturated fat, the reason that it's considered to be associated with heart disease is because it increases what's called low-density lipoproteins, LDL. And LDL is a known risk factor for a variety of of negative heart outcomes, mainly coronary heart disease or atherosclerosis, myocardial infarctions, and things like that. So it is associated with those negative outcomes, but not always. And the reason for that may be, and this is new science that's been coming out over the past, I'd say, 10 to 15 years, Maybe because the LDL itself isn't necessarily what's bad, but it's a byproduct of the LDL, the small dense LDL. So LDL is transporting a variety of fatty acids and cholesterol and other things to various tissues, and it's phospholipids and things like that.

And that's a very important function because every cell in your body needs fatty acids and cholesterol and phospholipids. Every time you damage a cell, you need to replace that, repair that damage with fatty acids and cholesterol and phospholipids, but also every time you make a new cell. So when you have a cell die and it's replaced with a new one, guess what? That new cell needs cholesterol, fatty acids, and phospholipids to make new cells. So LDL serves an extremely important function. However, that LDL also You know, it serves its function, and then after it serves its function, it's it's you know it's got a certain lifespan itself. It gets recycled. It gets recycled. So basically, you know, the LDL is made by the liver.

It goes does its thing, goes transports these fatty acids and phospholipids and cholesterol to tissues, and then it goes back to the liver and it's recycled. You know, and recycling is a very important process. I mean, imagine if you were you know just if your house is like a vessel as a vessel like your like your body is, and you never left your house, and had plastic and you just kept making more and more plastic bottles to drink water out of, but you never recycled them, eventually the plastic bottles is going to like overfill the house and clog everything up and it's going to be a problem. So recycling it and just using this, you know, it's an important process, you know, to make sure that things aren't gumming up the system. So the recycling process is very important.

Well, what happens is that the LDL, and when I say the LDL, it's usually called large buoyant LDL, large buoyant LDL can undergo inflammatory transformations, which cause it to become smaller and more dense. And so the LDL particle gets cleaved, and now you have a smaller particle of LDL. And what ends up happening is that smaller particle of LDL has a certain recognition site on it that becomes obscured called ApoB. ApoB is what helps— it helps the LDL particle get recycled back to the liver. So you can think about APOB kind of like a key, and you know if you don't have the key you can't unlock a door, right?

So when that key is lost, the the small dense LDL particle can't go back to the liver, so the door is shut for you know to get back into the liver, and so it stays in the vascular system. It stays in the arteries, and then as it's in the arteries longer, it undergoes more inflammatory transformations, which then attract more immune cells, which then increase the production of pro-inflammatory cytokines. And then you start to get immune cells, you get things like endotoxin, which are binding to the LDL, and your immune cells thinking it's bacteria, and they start to try to eat it. And so you get the formation of an atherosclerotic plaque, which ultimately stems from inflammatory processes. But you can see how LDL does play a role in that.

And so if you look at the small dense LDL, particle number, that actually is what more tightly correlates to cardiovascular disease. And so, you know, having large buoyant LDL in and of itself isn't necessarily bad. And I think that's why you can find some studies that show LDL doesn't necessarily correlate with atherosclerosis, because maybe people that have the LDL have more of the large buoyant variety and not the small dense variety. And, you know, so the small dense variety is when it really becomes dangerous because that's what sticks around the bloodstream indefinitely. You just— it's there and it can't go away, and it undergoes more inflammatory processes. And over decades, I mean, it's just— it's really bad for the vascular system.

So I would say that that is something really, really important to consider when it comes to saturated fat, LDL, and heart disease. Now, What causes small dense LDL particles to form? Well, we know from a variety of different studies that it's actually refined sugar, that particularly refined sugar causes small dense LDL particles to form, and that's been shown in prospective studies and it's been shown in clinical trials. So for example, people that have been given a 20-ounce soda for 3 weeks increase their small dense particle small dense LDL particle number from baseline. So this, you know, the soda, which is basically refined sugar, is doing that. So, and you know, that's, like I said, that's been something that's been shown in clinical studies.

It's been shown in prospective studies and also in animal studies. There's a lot of evidence showing that small dense LDL particles are what's the most dangerous. So what happens when you look at people that are eating saturated fat, and eating, and you're just looking at the saturated fat and heart disease risk. Well, those people that are eating saturated fat most likely are also eating cookies and candy and soda and, you know, the standard American diet. And so you're having this data being obscured by the refined sugar.

And we know that when people, and this was recently in this American Heart Association put out this like huge review article that broke down all this evidence showing that people, when people replace their saturated fat with complex carbohydrates, it lowers heart disease risk. When they replace their saturated fat with polyunsaturated fat, it lowers their heart disease risk. When they replace it with refined carbohydrates, it does not lower their heart disease risk. So the saturated fat, basically the refined carbohydrates are in combination with saturated fat seem to be what's really dangerous. Not something that the American Heart Association has directly addressed yet.

And oftentimes it takes a couple of decades before— of data before something gets addressed, before policy changes occur, I guess. But I think that it's really important to realize that on a population level, if someone's eating refined sugar and saturated fat, if they decrease their saturated fat intake, They'll probably lower their heart disease risk on a population level. But guess what? If they reduce their refined sugar intake, they're probably going to reduce their heart disease risk. In fact, that's also been shown that that does happen. So, you know, the question becomes, well, should we be focusing on saturated fat or should we be focusing on refined sugar? I think refined sugar is a key player in heart disease risk.

And that's something that really, it's, it, it, it, Science is starting to shift towards that, and I think that it will continue to over the next decade. So that's in a really sort of thousand-mile-high nutshell of my assessment of the saturated fat and cardiovascular disease and whether or not it's really, really something to worry about. Now, that's not the only thing to consider. So your lifestyle is really important, particularly refined sugar intake, but also genetics is really important because people, so before the industrialized civilization, people were really, the food they ate, they were beholden to where they lived. So geographically where they lived determined the kind of foods they would eat based on climate and things like that.

And so the theory is that a lot of these, variations in our genes that we see, because a lot of them are really related to nutrition, happen as adaptations that allow us to live better in that region so that we could process the food that was available in that region better. And so for that reason, we have a variety of different variations in genes that are involved in processing saturated fat, amino acids, carbohydrates, insulin response, micronutrients, you know, all sorts of things that are related to nutrition. People absorb, transport, all these things are different in various people. And so that's kind of the theory at least. We still have yet to prove that that's really why we have such strong gene variation in all these genes related to nutrition.

But the reality is that they exist and we need to acknowledge that they exist. So there are a variety of polymorphisms that are associated with the way our body processes fat. And saturated fat. One of those polymorphisms is in the FTO gene, and there's a few different ones in the FTO gene, and the other ones are in the PPAR alpha and gamma genes. And so these genes are involved in the uptake of and transport of fatty acids and whether or not fatty acids are gonna be stored into adipocytes or used by the liver for energy, so they're involved in transporting the fatty acids to cells. They're involved in all these processes that involve fatty acids. There's also the ApoE, which is involved in cholesterol as well.

But the point is that the ones that are involved in the fatty acid transport and utilization, uptake, oxidation, people have polymorphisms that don't allow them to do that, to do all these processes as well. And so what ends up happening is you'll end up having more free fatty acids floating around in the bloodstream and also, you know, in cells. And so what ends up happening is that, for example, it can increase your risk for type 2 diabetes. It can also affect your blood glucose response. And that's because free fatty acids antagonize the insulin receptor and prevent insulin from doing its function.

So when you have a lot of free fatty acids around, even though you have an insulin response, insulin can't bind to the receptor, and therefore it's as if you weren't having an insulin response. And so what ends up happening is your blood glucose levels stay really high. And this is, we know this from data, for example, from the Weizmann Institute, which published a study in 2015 in Cell Metabolism, showing that over 800 people that wore a continuous glucose monitor, which measures blood glucose levels every 5 minutes, those people were given diets. This was a controlled trial. They were given diets that were high in complex fiber, complex carbohydrates. They were given like bananas. They were given refined carbohydrates like white bread, and they were given fat.

And their blood glucose responses were measured. And what was found is that the whole idea of glycemic index was kind of, brought into question because people, a lot of people had a high glucose response in response to fat, which is kind of counterintuitive. You think, well, there's no glucose there, you shouldn't be having an insulin response. Well, that's not the case. People were having an insulin response. In some cases, they were having a really high one. And also some people's blood sugars were even more elevated in response to that, even though they were having an insulin response, again, coming down to the free fatty acids being around. So genetic data was accumulated from these people and also microbiome samples were accumulated.

And what was found was that the genetics and microbiome was really, really important in dictating whether or not this person was gonna have a negative response to fat or a high glucose response to fat versus carbohydrates. So again, just sort of highlighting the importance of the interactions between these genes and other factors. nutrition as well. I'm just typing that in. So, and this, so the question is then how do you know if you have these, how do you basically, what should you do on an individual level? Well, for one, if you're gonna adopt a diet that's really, really high in saturated fat, or if you're doing a ketogenic diet, you should definitely do a full lipid panel, measure triglycerides, small dense LDL, measure inflammatory biomarkers and things like that.

True Health Diagnostics is a great one. You can also do things, something like WellnessFX or Life Extension. But I would definitely, actually, I don't think WellnessFX measures lipid particle size. They might now, I don't know, you'd have to ask. But you definitely wanna make sure you're measuring the size of the LDL particles. So Kevin Patrick says that they do actually measure it. That's good. I'm glad to hear. So then back to the genetics. Okay. Well, you— so to answer that question, what do you do? I think you need to— you definitely should measure the biomarkers and you can also measure your genetics. So if you do a 23andMe test, for example, you can use services like Promethease, which kind of gives you everything in the kitchen sink, you know, so it's lots and lots of data.

You can look for those genes or you can use my genetic tool, which identifies all the saturated fat-related polymorphisms that I could find so far that 23andMe is testing for, including the APOE. APOE is a genetic polymorphism that affects the LDL biology, so it actually You know, people with, for example, ApoE4, they don't recycle their large buoyant LDL very well. And so they have an increased chance of having that LDL large buoyant undergo inflammatory transformations that convert them into small dense LDL particles. It's not necessarily going to happen, but they have a higher chance of that happening because their LDL is circulating longer than someone without the ApoE4. Polymorphism. So that is actually coming. I've got a whole report I just did, and that will be uploaded this week.

So if you've run your genetic data through my tool, make sure you run it again next week, or actually the week after, because this week is when it's going to go live. And also, I'm adding a lot more genes to that in the next month. So make sure you continually check back because it's like a work in progress. In terms of, you know, I'm adding a lot of really cool nutrition-related ones and also longevity-related ones. But I also wanted to address the coconut oil. So someone asked about, you know, the saturated fat in animal versus coconut oil. You know, well, the whole— with the studies with coconut oil, at least the 8 studies that were in this American Heart Association review, all of them were looking at LDL LDL as an endpoint.

So they weren't looking at heart disease risk in people that eat coconut oil. They're looking at increased LDL particle number. And coconut oil has got a ton of saturated fat. And so it's not surprising that it does increase LDL particle number. So what does that mean? Does that mean that you should not eat coconut oil? Not necessarily. It just means that it's also another source of saturated fat if you are a person with ApoE4. So for example, I personally used to cook with coconut oil. I have one allele of ApoE4, which makes my LDL number higher than my husband's, even though we eat the exact same diet, because he just has— he has zero ApoE4 alleles. So, um, I, I actually cut out coconut oil from my diet.

I stopped cooking with it and shifted to avocado oil, which is monounsaturated fat, and my LDL particle number dropped by like 20 points. You know, so, and it's not like I think coconut— I think there's some benefits to coconut oil. I don't think it's necessarily bad, but it is something to consider if you are— if you do have a genetic, you know, factor that's increasing your chance for having a high LDL particle size or for having a lot of free fatty acids, you know, then you might want to consider, do you really need to cook with coconut oil or can you cook with avocado oil? You know, so I choose to get my saturated fat from the whole foods that I'm eating as opposed to just some oil that I'm cooking with 'cause I feel like that's not really, I don't need to like cook with saturated fat.

I'm not on a ketogenic diet or anything either. So that's kind of sort of my take on that. And so Val says, even if you don't eat sugar, you can still lower risk by replacing saturated fat with complex carbs and polyunsaturated fat. I would say that in the studies that were— that have been done looking at replacing saturated fat with either poly or monounsaturated fat or complex carbohydrates, refined sugar was not taken into account. So it's actually not known. Whether or not— I would say that state— you can't really make that statement if you don't eat sugar, because in those studies, people were likely still eating sugar. That wasn't, that wasn't something that was looked at.

So it was just like, okay, if you just replace the saturated fat, not even the, the dietary sugar intake of those people was not even accounted for. So I would say that, um, you're— that's a hypothesis that needs to be tested, uh, Val, but I'm not sure that we, uh, have any evidence that actually suggests that is that's the case yet. So then let's see, someone's talking about arachidonic acid increasing inflammation with, with Beyond saturated fat and heart disease, there is no way around arachidonic acid increasing inflammation.

All right, let me address this real quick because, um, it's some— somewhere, somehow in the literature, this proliferated for a while, and I actually fell victim to it until I submitted a paper for peer review when I got basically crucified by, by, um, by the reviewers. The omega-6 omega-3 ratio and how omega-6 is so, so unhealthy There is really, you know, there's really not a lot of evidence showing that omega-6 is causing inflammation, systemic inflammation in people. In fact, the biggest, biggest cause of inflammation in people is poor gut health. The gut is the major, major source of inflammation in the body.

Now, vegetable oils and those things can be inflammatory and are bad for sure, but the biggest prob— the biggest source of inflammation in the body is actually the gut because The gut is what is— has the largest source of— it has the largest number of immune cells and the largest number of bacteria. And basically, when the gut barrier is compromised, the immune cells recognize the bacteria and think it's something that's gonna kill the host, 'cause usually that's what bacteria does. Your immune cells don't think and go, oh, that's the microbiome. That's supposed to be there. No, all they do is go, oh my God, bacteria. I gotta kill it. Kill, kill, kill. And so they end up firing all these pro-inflammatory cytokines and it just causes havoc.

And what ends up happening is pieces of bacterial cell membranes, which is called endotoxin or lipopolysaccharide, get into your bloodstream and that raises even more havoc because again, all the immune cells in your bloodstream are like, oh my God, bacteria is here. I'm going to die from sepsis. I got to kill this thing. And so your immune cells get all active inside your vascular system and you get this chronic inflammatory process occurring. That's the major source of inflammation stemming from the gut. The arachidonic acid, I mean, by the way, your cells need arachidonic acid. They need a lot of it, actually even more. I was surprised to find this, even more arachidonic acid in cell membranes than DHA, the omega-3.

So, you know, it's, I think there's a valid point when it comes to like the vegetable oils and oxidizing them and, you know, when they're Heat it up because polyunsaturated fat is very prone to oxidation, and consuming that and that being inflammatory because it absolutely is, and that's been shown in studies as well. But I think that people are missing the point when it comes to inflammation. What they really should be focusing on is is gut health when it comes to inflammation because that's really the major driver of systemic inflammation in the body is the gut. So. This— so someone's saying, um, they have the SNPs I mentioned but also follows a keto diet. Um, outside of cholesterol issues, is there any reason to be cautious with that?

My organic acid test showed I'm hugely elevated markers related to ATP energy production. Well, I would say that, you know, for someone with those SNPs that are following a ketogenic diet You should look at your triglycerides. Triglycerides are really important because those are the free fatty acids that are floating around, and that can also affect your insulin response and your blood glucose levels. But you can also measure your fasting blood glucose. You can measure your glycated hemoglobin, your HbA1c, which is a marker of long-term blood glucose levels. Make sure that looks good. And the small dense LDL particle number, you know, and I think that measuring those biomarkers all are really important.

In addition, looking at you know certain micronutrients as well, magnesium, you know you want to make sure you're you're getting enough folate, magnesium, things like that when you're when you're on a restrictive diet. I also really really like the Genova Diagnostics full metabolism test because they're they're measuring a variety of different. You know, endpoints to look at how your body's metabolizing not only fat but carbohydrates and also amino acids and micronutrients and, you know, looks at deficiencies and things like that. Um, you know, so, so for— and also inflammatory biomarkers are really important. So for someone with those SNPs that's on a ketogenic diet, doing that whole panel, looking at that whole panel, and if everything looks good, then that's data, you know.

So it's probably— you shouldn't be concerned. But if you start to notice that things don't look good, then you may reconsider whether or not a ketogenic diet is really for you or not. Okay, so I think that covers the saturated fat cardiovascular disease and the saturated fat polymorphism front. I think based on some of these, some of the live questions, I think I've, I think I hit on some of those. And for those that are really interested in the, in the actual genes, again, just, just run your genetic data through the, through My Report, even if you don't have them. If you click on the less notable section, I list the genes. So you'll see, like, you'll see which ones are involved in, in, in fat metabolism. Um, and, uh, okay, so I think that's it for the saturated fat.

The, the name of the test is— it's, it's the Genova Diagnostics, and it's just the metabolism test. If you just Google that, you'll find it. Um, all right, so the next upvoted question has to do with, uh, let's see, it was, I think, my— the water. Um, Yeah, what to do for drinking water, basically. And, you know, so personally, I choose not to drink water out of— as much as I can, except when I'm traveling— plastic water bottles, because I don't want, you know, the BPA and BPS and all the other stuff that's in plastics to leach into my water. That particularly was a concern when I was pregnant because the developing fetus is much more sensitive to those chemicals.

Our liver does inactivate a large amount of BPA, but before it becomes inactivated, it actually can cross over the placenta and really have a negative effect on developing embryos. So that's something that I really paid attention to during pregnancy. But generally speaking, I just don't want it in my system at all because it is an endocrine disruptor and it has been associated with negative health effects, at least in large doses. So I actually use a Berkey filter and it's really easy because it's just like, it sits on my counter and I put the water in and it filters out fluoride. It filters out a bunch of other crap and also it doesn't have the plastic. So the, the thing is, is that I guess people are concerned about the minerals also getting filtered out.

And there are like some mineral drops you can buy to add to your water. I bought them, but I never actually use it, um, because I eat— I get such a— like, I have new— a lot of my, my minerals is coming from greens and plants, um, and, and fish and stuff. I'm getting trace elements and all that. So So I don't actually, um, add those back into my, to my water. Um, I think I, I stopped doing that during pregnancy because I was concerned about the, the mineral oil itself was being, was held in, it was contained in a plastic container and I was extremely averse to anything plastic during my pregnancy. So I just kind of haven't revisited that ever since, uh, having my baby. Um, So let's see, I'm gonna go down. Yeah. Okay. Um, the next question that was most upvoted was plastic.

Um, Yeah, so basically, you know, plastics is being found in all these like deep sea creatures and stuff, and it really is a concern. And, you know, the question is like, should you not— should you stop eating fish because of that? And, you know, I don't have a really good answer. I'll tell you the data that I do know of and the decisions that I've personally chose to make, whether or not they're the best decisions. I don't know, but so far it's the data that I have available, and it's what I've used to make decisions for my own my own self, basically. So there's there was a study in 2015 published that was showing pregnant women that consumed fish actually there was better neuro neurocognitive outcomes. In their babies compared to women that didn't.

And that the fish, the omega-3 fatty acid content in the fish itself outweighed any of the negative risks of other toxic compounds, heavy metals, phthalates, and things like that that are present also in the fish. So the bottom line of the publication was that the pregnant women for a while were recommended against eating during pregnancy because of like mercury and things like that, but it ended up actually harming, doing more harm than good because they stopped eating the omega-3 and they weren't supplementing. And so the developing fetus wasn't getting as much of the omega-3 fatty acids, which is extremely important during brain development.

And the reason I go to that study is because fetuses, developing fetuses are even more sensitive to all these disruptive chemicals, to heavy metals and all that. And yet they were protected from that with the with the fish, the whole fish because of the omega three fatty acids. So I I basically take that as okay well obviously you know there's you're you're you're doing more more good by eating the fish. Now I choose to eat fish that has a really low mercury content per you know so basically like. You know, if you look at, you look at a variety of species of fish, certain fish have a low mercury content and other ones have higher ones. The ones with the lowest mercury content happen to be the ones that also have the highest omega-3, like wild Atlantic salmon.

Wild Alaskan salmon is one of the highest omega-3, has one of the most highest omega-3 content, but also the lowest mercury. So there's only 2 micrograms of mercury per 4 ounces of fish compared to that to swordfish, which has 50 micrograms of mercury. per 4 ounces. So sorry, 100, I think it's 150. Tuna has something like 40 micrograms. So I actually don't eat tuna. So I, so that's kind of my, my, my take on the fish. In addition to that, you can sweat out heavy metals, you can sweat out BPA, you can sweat out phthalates, you can sweat out a lot of these components that are in plastic. And what that means is you need to exercise and/or use the sauna because this stuff does get excreted, you know, through sweat. It also gets excreted through urine.

Other compounds like the beta-mercaptans in garlic have been shown to bind, for example, mercury and carry them out through the urine. So they help kind of basically get rid of some of these heavy metals like mercury in your system. So, um, so that's, that's basically, uh, why I, um, still eat fish. And Val's asked me why not just take algae-derived omega-3. Well, the reason is because the algae-derived omega-3 doesn't have high enough concentrations that I want personally. In addition, I'm trying to get the, um, the phospholipids that are also in The fish phospholipid, the omega-3 in phospholipid form is really, really a great source for the brain, particularly developing brain. It gets taken up 10 times better in the developing brain.

And also it's been shown to get taken up better in the adult brain. So that's kind of another reason why I like consuming the omega-3 in fish form. Also, there's a variety of other good things in fish. You know, there's the zinc and the selenium, iodine, a lot of micronutrients and minerals. And then there's astaxanthin as well, which has benefits of its own. So that's kind of why I actually, and I supplement with fish oil in addition to eating fish. So I'm kind of hardcore like that. Okay, so the next upvoted question has to do with the, the NAD-increasing supplement called Elysium, which contains nicotinamide riboside and pterostilbene in it. And, um, uh, the— so I did address this question somewhat last time.

Um, I did talk about, you know, some of this, some of the preclinical studies that have shown, for example, nicotinamide riboside can reverse mitochondrial aging. It has all these positive benefits on various— the way various tissues age, and also it improves physical performance in older mice, cognitive function. So I've talked about that's all preclinical evidence, meaning animal studies. We don't know how much of that actually will translate to human studies. This recent study that was released used in— it was clinical study that was released, looked at a dose response of the Elysium supplement, which contains both nicotinamide riboside and pterostilbene at a lower dose and a higher dose, and found that it did increase NAD levels in human plasma in a dose-dependent manner.

And it also lowered blood pressure However, it also increased LDL cholesterol, and that largely probably is due to pterostilbene. So there have been randomized controlled clinical trials looking at just pterostilbene and the effects on blood pressure and also on LDL cholesterol, and pterostilbene, for whatever reason, has been shown to increase LDL, significantly increase LDL levels in people. And And I don't exactly know why. So it's possible that the reason for the LDL increase in the Elysium supplement is as a consequence of the pterostilbene and not the nicotinamide riboside. However, I don't know for certain. There are other supplements out there that use nicotinamide riboside. For example, Thorne has a couple.

Thorne has one that has resveratrol mixed in with it and it has one that has does not have resveratrol and it's just nicotinamide riboside. Life Extension also has one as well. So, and I think that those are, Thorne's a very, very, Thorne is my go-to brand actually. It's a very reliable supplement brand. Life Extension's pretty much pretty okay as well. And I'll take that sometimes as well. In terms of the cancer incidence, so I looked into that a little bit and I found no evidence that taking, nicotinamide riboside actually decreased age-related diseases and increased lifespan in animal studies and preclinical studies. The cancer connection I think people are confusing has to do with the fact that cancer cells increase a pathway that recycles NAD+ called the salvage pathway.

It's a way that our body— so there's a couple of ways that we make NAD+ in our body, and we make it— it's actually made Um, you know, from, from B vitamin, vitamin B3, but also levels really, really increase in a fasted state. So they, they increase in between meals and they increase when you're, you know, overnight fasting or you do any type of fasting. NAD levels dramatically rise. Another way of increasing NAD levels is through this pathway called the salvage pathway, which basically recycles the NAD. That pathway is increased in cancer cells, and so because of that association, I think people on the internet kind of have associated NAD with cancer, and it's just it's not the case. Cancer cells upregulate everything; they upregulate anything that's good for you.

They you know they increase they increase pathways involved in lipid beta oxidation, you know in in using folate. You know, you know, all sorts of energy metabolism pathways. You know, everything is haywire in cancer cells. Now, that doesn't mean that a source of NAD through something like nicotinamide riboside is going to like cause cancer. So it's just, it's kind of confusing. Hopefully that makes sense to people that it's just a pathway that is known to increase NAD is upregulated in cancer cells. So, so that's, that's something that needs to be sort of clarified, I think, hopefully on the internet somewhere. And in fact, I did just do a podcast with— well, I'll be releasing it sometime in the next 10 days with the president of the Buck Institute for Research on Aging, Dr. Eric Verdin.

We talked a lot about ketogenic diets because there— because he just published a preclinical study looking at the effect of ketogenic diet on lifespan in animals. But also we talked a lot about NAD+ because he's doing a lot of research on NAD+ as well. So we do talk about that and we talk about the salvage pathway. In fact, the salvage pathway decreases with the aging process and it's thought that's one of the reasons why NAD+ levels drop during aging is because the salvage pathway goes down. So the fact that cancer cells kind of like find a way to to, to increase that isn't surprising because they, they pretty much do that with like everything. Um, anything that can— that's good for a cell, uh, the cancer cells can somehow take advantage of it and turn it into something bad.

So, um, let's see. Is tarot still being— is it dangerous? I don't, I don't, I don't No, honestly, I don't know. I think there's also a lot of— there's at least preclinical studies showing it improves cognitive function and learning and memory in animals. You know, again, it lowers blood pressure and yet increases LDL. Like, blood pressure is another, you know, biomarker that's a risk factor for cardiovascular disease. So it's kind of weird in my mind. I can't really understand how it's improving one risk factor for cardiovascular disease But like making another one worse, I don't quite understand it. You know, we talked about LDL doesn't necessarily you know it's not necessarily a bad thing, and the degree that it that raised it is really really really tiny.

It's significant, meaning it you know it's significant, but it's still like a tiny percentage. And in fact, it's not even something that you would you compare like saturated fat increases LDL like much more robustly than something like terastilbene. So I'm not I'm not sure that it's dangerous. It's just something to keep in mind for people that are really. Really, really concerned about their LDL. Um, you know, um, okay, so another upvoted question. Um, oh, the timing of it. That's an open question. So like the question is when, you know, how often or when do you take, do you take this nicotinamide riboside? And like the answer is, you know, we don't know. You know, a lot of this evidence is preclinical.

We know a lot of the positive evidence on aging is preclinical on mitochondrial function. It's in animal studies. And so we don't know how much of that and how will translate to humans and how robust it will be in humans if it does translate. Like that's yet to be determined. You know, the question is, well, do you time it? Do you take your nicotinamide riboside when you're fasting to like even more robustly increase your NAD, or do you want to take it when you're not fasting so that like during those periods when your NADH levels are higher, you can also increase your NAD a little bit more? Because, you know, it's an open question that we don't really know the answer to.

And, you know, honestly, the NAD, one of the things about NAD is it's required to— your mitochondria need it to make energy. Like without NAD, you can't make energy. Like it's from— it doesn't matter if you're eating fat or carbohydrate or amino acids, it doesn't matter. You can't make it without— you need NAD. But the other problem is, is that NAD is used to repair damage, particularly DNA damage. And it's constantly happening inside of our cells. And inflammation and those things are a constant source of causing that damage. And also inflammation causes immune cells to use a lot of energy because they have to be activated. So it's like this inflammation and DNA damage enzymes that, for example, PARP is an enzyme that requires NAD to repair damage.

It's one of the most, it's like the sort of go-to DNA repair enzyme that's constantly being activated. Well, it sucks NAD. I mean, it just uses up NAD. And so what ends up happening is, you know, if you were trying to repair that damage, that your NAD becomes limiting and then your mitochondria suffer. Or if your mitochondria are using, you know, the DNA damage is suffering because you're not getting all that NAD, it's not being used to repair the damage because the mitochondria are using it to make energy, you know. So basically either way, it's a lose-lose situation for some, for a person.

So the fact that there may be a way to boost your NAD levels other than fasting, 'cause fasting does it, exercise does it as well, that's kind of a cool thing in the aging field because it's like, oh, well, maybe you'll be able to, you know, improve the way you age by improving mitochondrial health and improving, you know, basically lowering the amount of damage that occurs inside of your cells, which will then, of course, have a positive effect on aging, which has been shown to some degree in preclinical studies. But we just— there's not enough evidence to really make, I think, a strong statement that, oh, we should be supplementing with it, and it is absolutely gonna have the same effect as it has in animal studies.

We don't know, and we certainly don't know what kind of dosing to do as well. So that's basically my take on that. I see Debbie Shapiro asking, do fish oil supplements have phospholipids? No, they don't. Fish oil supplements have, well, majority of them have omega-3s in triglyceride form. Sorry, majority of them have them in ethyl ester form, which is the worst form you could have it in. The good ones out there have it in triglyceride form. So for example, Norwegian Pure 3, which is what I take, has it in triglyceride form. Also Nordic Naturals, which is what I used to take, has it in triglyceride form. Phospholipid form would be krill oil or eating salmon roe or fish roe in general.

The roe of fish, which are the eggs, also known as caviar, they're about 60 to 70% of the omega-3 fatty acids that are in fish eggs are contained in phospholipids. Whereas Maybe up to 5% is in fish, and fish oil doesn't have any. So that's one of the reasons why I obsessively ate a lot of salmon roe during pregnancy, because developing brain takes up the omega-3 in phospholipid form 10 times better. And there's studies showing that consuming omega-3 in phospholipid form increases the phospholipid omega-3 that circulates in the bloodstream. So that's one of the reasons why I continually even still eat salmon roe. I get my roe from Vital Choice. Vital Choice. They have wild Alaskan salmon roe that you can buy in bulk.

And I put it— if you look, follow me on Instagram, you can see how I prepare it. I usually eat it on top of an avocado with some lemon and like maybe some Tabasco sauce or something sometimes. But, you know, other people choose to put them on whole wheat crackers or something. I generally don't eat those, those kind of crackers. But, but salmon roe is really good. Oh, highly recommend. Thank you. I will check out this takustore.com. I've got it open in my link now. Thank you. All right, so let's see the next question. Okay, that was the terosilvane one. Okay, so the next question is from George. Um, I'm gonna butcher the last name. I won't, I won't attempt. Uh, so George asks, hi, can any other method replace sauna and have the same effects?

on all-cause mortality reduction for like hot baths or long steam showers. Basically, can they— can you use any form of heat stress in lieu of a sauna? So to answer that question, at least in terms of the all-cause mortality, cardiovascular-related mortality, dementia, those studies were performed in Finland. People were using traditional saunas. There was a dose-dependent effect. You know, people that were sitting in a 179-degree Fahrenheit sauna for 20 minutes or more you know, had a 50-degree, you know, 50% lower cardiovascular disease risk if they did it 4 to 7 times a week, 60% lower Alzheimer's risk if they did it 4 to 7 times a week.

Um, you know, whether or not that same, same risk will— I mean, same lowered risk will occur with a hot bath or a steam shower, we don't know for certain. But I will say that, um, there is evidence that some of the same pathways, for example, looking at like the endocrine response to us sauna versus a hot bath. They've been similar. Also, I recently interviewed a professor who did a clinical double-blind— not a double-blind, a blind— no, it was double-blind. It was double-blind controlled trial looking at heat stress on depression. And he did something that was very similar to what a sauna would be, but he had to like do that, make this whole device in order to have like a placebo effect.

And I'll be releasing that, that podcast, um, uh, coming soon after this next one that I release on the, on the Buck Institute guy. But, um, he, he seemed to think, and I asked him this question, I said, do you think that hot baths, steam showers, um, even hot yoga can, uh, have a similar effect as the sauna? And he seemed to say yes, he does. And I tend to agree with him. I think the heat stress is what's the most important thing In his study, he showed the important thing was elevating the body temperature up. I think it was like 1 degree Fahrenheit. And he says that you can do that through a variety of different modalities of heat stress, including even hot yoga.

So I think that, you know, for me, what I typically use right now, I'm taking hot baths because I don't— first of all, I'm still breastfeeding. And so I'm not really doing the sauna like I would like. Plus, Plus I don't have access to a sauna like I used to since I had moved 2 years ago. So it's been about 2 years since I haven't really routinely been using the sauna. I didn't use it throughout pregnancy for sure. But I'm going to be slowly getting back into the sauna again soon once I'm done breastfeeding. But I do use hot baths at home. And what I do typically is I wait for my heart rate to elevate. And of course I have my Apple Watch, which can actually quantitate that for me. But you don't need a device.

I mean, if you have a Fitbit or something, I mean, you can just tell when your heart's racing. That's one sign. And then also I do sweat, but it's kind of hard to tell because this, you know, the steam as well. But additionally, just feeling really uncomfortable, like that feeling like you're hot. And I mean, that's another, another way I know that I'm getting the heat stress. So, um, uh, so that's the So that's sort of the answer, I think, to that question is I think it's very likely that they will have similar effects. Again, we don't have empirical data showing that a hot bath reduces cardiovascular mortality, but that's just because that sort of stuff's not being studied really.

All right, the next question I think I sort of tried to address, but I'll do it just briefly a little bit better is how can This is from Andrew. How can I best interpret and actionize the data I get back from 23andMe? And well, the answer to that is I really do like Promethease just because they give you lots and lots and lots of data. Now, unfortunately, they don't really tell you how to actionize on that data. It's just they give you a bunch of data and you kind of have to figure out what to do with it. So, you know, in one respect, it's kind of like, well, I get all this data, but I don't know what to do. But I just, I like getting the data.

The genetic tool that I am continually developing is probably what I would recommend because, well, I trust myself and, you know, I try to be as comprehensive as possible when looking at the data and trying to figure out how to actionize on some of these gene polymorphisms. I haven't been working, I hadn't worked on it for a while because of a couple of academic publications that I've I've finally, and now like in the process of have, you know, got submitted and, you know, so I'm done writing and all that. And all this other stuff I was working on, the podcast and all that obviously takes a lot of time, but I'm now getting back into the genetic tool. And so I'll be adding, like I said, I just did the ApoE report. I have FOXO3 that's gonna be coming soon, MTHFR.

All those are gonna be coming in the next, I would say like, month and a half, 2 months, you know, those, those will all be coming into the report and I will just continue to work on it. Um, I'd like to also eventually, um, uh, work with another geneticist, uh, science scientist that I can, um, trust and find, uh, find a good scientist to help, to help, uh, tease out some of this genetic data because, um, it'd be really, really nice to have a geneticist since That takes— it takes a lot of time for me to figure out all these genome-wide associations and what's actually statistically significant, what doesn't, you know, how much of a— what magnitude the effects are. And it's really hard. You know, it's, you know, it's a lot of data to go through.

And, you know, so I definitely am looking forward to getting some help with that. There are some other companies that do offer those services. I've seen a couple of them. And I've seen flaws, meaning like outright wrong data being said, or not data, but wrong advice that's being misinterpreted from data. And this is being done by people that are not scientists. I assume just kind of sloppy. They're trying to kind of just get it done and have a lot of data there. So I would be very cautious about making too many actionables from those sorts of services.

In addition, on the tool that I am developing, what I try to say, and I think this is extremely important, is that it's one thing to have this genetic data and to understand and look at these polymorphisms that you have, but you really need to measure biomarkers because sometimes they really don't make a big difference. And, and so there's no point in getting really scared about something, um, until you measure a biomarker, until you measure and quantify an endpoint. Um, then, then it's like, well, for example, you may have some genes that, um, put you at a high risk for vitamin D deficiency because you don't convert, um, you don't convert vitamin D3 into 25-hydroxy vitamin D very well, which is the major circulating form of vitamin D. That gets converted into the steroid hormone.

Well, you may have that polymorphism, but guess what? Your vitamin D levels may be just fine because of other polymorphisms or because you're, you know, getting enough sun and you're supplementing and all that, you know. So unless you measure your vitamin D levels, if you see that risk factor, I wouldn't freak out until you measure your vitamin D levels. The same goes for the fat-related polymorphisms. You may have all these polymorphisms, But you know what? There's so many other polymorphisms that we may not even have identified, and maybe you know these genetic servicing companies aren't testing for that we don't know exist that cancel out and you know negate whatever bad effect the polymorphism you may have you know has.

And so, unless you measure your you know triglycerides and your your your you know fasting blood glucose, your your glycated hemoglobin, and your small dense LDL, and all these other other bio markers, you're not going to know whether or not you should even worry about those genes. So I think that one thing to keep in mind with these genetic tools is that they're just another tool in the tool kit of someone who's trying to optimize their health and try to get as healthy as they possibly can. It's not the only tool. I mean, we've got all these different blood tests available that we can do and we should be doing.

We should be doing them often, frequently, because it's our bodies and the only way we're gonna know what we're doing to our bodies, whether or not it's good for us, is by measuring something, quantifying it. You can listen to any scientist, you can listen to any guru, you can read any blog article you want. Ultimately, at the end of the day though, it's up to you to take your health into your own hands and really the best way you could do that is by measuring some some biomarkers and endpoints because what works for some people doesn't work for everyone. They're really, and I would say that there's not a one-size-fits-all diet.

However, we do know that some things are universally bad and, you know, so avoiding those things are obviously good, but So Jim Dekas is asking, how about a comprehensive biomarker list with suggestions to improve unhealthy levels? Great idea. Yeah, you know, I think maybe I should try to somehow incorporate that into— that's a good idea. You just gave me an idea, Jim. Thank you. I think that's something that I'll try to maybe put together a report on that. Also, I will, I will let you guys in on a little insider. I'm taking a 3-week— it's not really a vacation, but I'm heading to my in-laws in Tennessee who are going to help me babysit, which is going to give me more time to work. One of the things I'm going to be working on is a book and a book proposal.

I've got a lot of information, really just needs to be put together, and I think that That's one of the things that will be— there'll be a chapter in the book on that, on the biomarkers, what to measure and how to improve them, generally speaking, how to improve them. So yeah, I think that's a good idea. And it's certainly something that I could at least, at the very least, give to my patrons and my supporters beforehand, you know, like a report or something. So let's see. Thank you for clarifying relative risks. Yeah. Yeah. Again, like I said, I have this genetic tool and the reason I'm doing it and working on it is because I'm very interested in the field of nutrigenomics, extremely interested. We're really just sort of starting to scratch the surface of this field.

We don't know much, but I'm super interested in it. And so I'm trying to stay on top of the literature and keep as up to date as I can with it. However, you have to be really cautious about— because it's become a really popular topic and a lot of companies have kind of come up with ways of telling you how to eat according to your genes and all this. to a certain degree, that you need to take caution with that because really, really, really, we don't know enough about the magnitude of these genetic polymorphisms and we don't know all of them and all these things are working in concert together and there's only so much information you can gain from it.

If you're not measuring any sort of biomarkers along with it, I would say that it's, I would say the biomarkers are the king and the genetics tool, the genetic data would be the queen. Like, it's like you need to do the biomarkers first. That's, that's really what's going to tell you what's going on. And then once you get that data, if it's bad, you know, looking to the genes kind of helps give clarity. And that's what I've had a lot of people say to me. Um, but that's definitely something to keep in mind. All right. Um, the next question has to do with oats. And so this question is from Triptodan, and he says, can you please discuss oats and why they are still recommended as a healthy breakfast food?

Have studies not shown that they can be problematic due to their protein structure, avenin being very similar to gluten, thereby contributing to leaky gut thyroid issues? Is there anti-nutrient concern? And also, he wants to know whether or not the prebiotic fiber, which is very abundantly found in oats called beta-glucans, whether or not wild mushrooms, which also has beta-glucans, can suffice as an alternative. A very, very complicated question, so I'll try to not spend too much time answering this. I will say, first of all, With the gluten, the, the effect of gluten on the gut has a lot to do with zonulin, which is a protein that's released and that can quickly open up the tight junctions that your gut cells form.

And the tight junctions are what keep the barrier together and keep your immune cells separate from your bacteria in your gut. When those tight junctions open up, it's almost kind of like a a little hole being poked in a way in your— into your gut barrier and allows your immune cells to come in contact with your bacteria. Again, inflammation happens because your immune cells freak out. Oh my God, bacteria! This happens very, very, very transiently in people without celiac disease, meaning it opens, boom, and it closes within a matter of minutes, really, really quickly. People with celiac, it's open and it stays open, and they get all sorts of, you know, inflammatory issues. With that said, personally, I think I'd rather not have it open at all, but it's not always that harmful.

And what I mean by that is if we look at data, so for example, if we look at the prospective data that I was talking about, which is, you know, looking at— it's their associations, and so you really can never look at causation. But there have been studies, for example, like one involving like 11,000 women that took in close to 5 grams a day of fiber from whole grains. And whole grains can include oats, and— but they also can include things that have gluten in them. And what was found is that for every 5 grams of fiber that was eaten per 2,000 calories a day, there was like close to a 20% reduction in all-cause mortality. So you'd think that if something was really, really bad for you, there wouldn't be a reduction in all-cause mortality.

And it's thought largely that that's due to the fiber content because fiber is so beneficial for your gut microbiome and, um, and can, you know, negate any, any negative effects of, you know, the, the gluten that the gluten may have. Additionally, there's another study in about 8,000 women looking at people that had type 2 diabetes. The women that had type 2 diabetes, they basically had like anywhere between a 15 to 30% lower all-cause mortality the more grains, whole grains they ate. Again, associative study. And there was another study that actually looked at biomarkers of inflammation.

So they looked at C-reactive protein, they looked at fibrinogen, and others, and they looked at people that ate either refined grains or whole grains, and they found people that had whole grains had lower markers of inflammatory biomarkers. If it was so inflammatory and bad for you, you'd think they would have higher markers of inflammatory biomarkers. Now, whole grains can include oats, quinoa, brown rice, things that do not have gluten in them, but they also can include more, you know, bread with some gluten as well. But, um, so, so that data always— I go back to that data and I always think, well, geez, if it was so bad, you know, why is— why are we seeing this reduction in all-cause mortality and all that? So, um, so there's that.

Uh, I still choose to not eat a lot of— I mean, I, I'll eat quinoa and I actually do, um, eat oats Uh, and I, you know, I, I react well to them. You know, I don't have a huge, huge insulin response. Um, I tend to like them with some nuts or some berries in them. Um, I'll, I'll eat them, you know, maybe 1 or 2 times a week. Um, so I don't eat them like every day. Um, and I do eat them specifically, you know, specifically because I want to get the, the beta-glucans and the fiber. Um, but I don't eat refined, refined grains. I don't eat, you know, breads and stuff like that. I certainly don't eat any of those things. So I don't know. It's one of those things where it's like, well, if it was so bad, why is it reducing all-cause mortality?

Well, then the question is, well, what if they didn't eat any of those whole grains and they didn't eat any refined grains and they just had a paleo diet? Maybe their inflammation would be low as well. And in fact, that's probably the case. Would it be better? I don't know. I really don't know. Maybe it all depends on what you're giving your gut microbiome. You know, people that are eating a variety of nuts and seeds and a variety of vegetables and actually fruits, fruit skins have a really diverse array of prebiotic fiber. Maybe that, you know, that's all you need. That's typically the kind of diet I eat. I actually don't eat a lot of the oats are the exception, oats and quinoa, but I don't even eat that a lot. I just once in a while, you know, I have it.

Once in a while I eat quinoa, put it in a salad, and you know, like I'll have oats maybe once a week. You know, it depends on the week. So, and I've actually just started eating them a little more recently than I used to, mostly because I'm so dang busy with having being a new mom and stuff, and then also working. You know, but so, you know, I don't know the best answer. I just I'm looking at the data that we have, and I do think. With mushrooms, I've often wondered the same thing. Can wild mushrooms, you know, be an alternative source of the beta glucans? Probably so, but I'm always concerned about the heavy metals. You know, mushrooms, they are— they sop up heavy metals. They're like— they like— they're like a sink for them.

So I'm always concerned about the source of mushrooms and, you know, where they were grown and how much heavy metals are in them. I'm particularly, you know, very cautious now. I don't eat them because I'm breastfeeding and, you know, I wanna make sure that I'm not getting heavy metals, you know, in my breast milk. So that's, you know, that's kind of my take on it. And I really don't have the best answer. I think that you can be extremely healthy without eating whole grains as long as you're not eating refined grains as well. And I think that you can also have a diverse, gut microbiome without eating whole grains as well. I think there's a lot of other fermentable fibers and other foods that you can eat, and, you know, you don't have to eat whole grains.

So do I— but do I necessarily think that they're like, like really, really, really, really bad for you? Uh, it depends on the type. I mean, I think that the processed grains found in, uh, bread are, are a little different than, for example, oats. And of course they don't have gluten, so there's that. And again, I personally try to avoid zonulin response as much as possible, even though I don't have celiac disease. I don't particularly like my tight junctions opening up for any amount of time. I think that if you can minimize that the best you can, it's probably better. People are asking about fruit sugar. So the sugar in fruit is not is completely metabolized differently than refined sugar. It's slow. The problem is with the refined sugar is that it's a big, huge bolus of it for your gut.

So first of all, it's irritating on the gut. Second of all, it goes to the liver and it's overwhelming. It's too much at once. And so what ends up happening is you end up having triglycerides being made and storing them as fat and fatty liver and all that stuff. ends up happening. I'm completely like not going into detail on this because it'll take me way too long. I only have 30 minutes left or 25 minutes left. Um, but the, the way you metabolize, uh, fructose and glucose in fruit is extremely different. It's much, much slower. Um, you're getting the, the fruits have a, are actually one of the best source of prebiotic fibers. I was surprised to find that out.

I thought vegetables were, vegetables have a lot of fiber, but they actually have a lot of lignans and cellulose, which are non-fermentable fiber, which is still good. It serves the purpose of moving stuff through your gut. I mean, you want to clean out your gut, but it's not fermented by the microbiome, the bacteria in the distal portion of your gut. And of course, that's extremely important. We're learning so much about the microbiome now and the importance of it. So my top 5 favorite fruits are— I'm a big fan of berries. I like the blueberries, raspberries, strawberries, I like kiwi. I like dragon fruit. Um, I think those are, those are the ones that I'm eating the most, um, right now. I also like apples, um, for the pectin. So, so I think those are like my top 5 or 6, uh, fruits.

Also, I, I tend to, you know, not eat the ones that are super, super high in sugar like grapes. Um, so, um, so, you know, J.A., can you restate your question about something you can miss? Are you talking about in response, in respect to the gut microbiome? Um, so, uh, okay, where was I going with this? Yeah, gut. Uh, so that basically— I know that's kind of— I just went on tangent there, but, um, I think that, um, you know, the whole grains and the oats and all that, you know, I think that, um, it's, it's, it's less clear how bad they are, uh, particularly with like oats and things that don't have gluten in them because of the positive effect on the microbiome.

But you know what, some people don't respond well to it and some people may have a higher blood glucose response based on certain gene polymorphisms. And, you know, so it's maybe not for everyone. And again, you know, I think you can get a lot of the beneficial Prebiotics in other foods that don't include oats or grains in general. So, so yeah, fruits are a really good. There's there are different polyphenols and prebiotics and you know nutrients that are found in fruits and vegetables. And I personally, there's a lot of various polyphenols that are found in fruits that I like, that I personally like. And so I do, I do, I do like to eat berries and I do like to, you know, eat the kiwis and dragon fruit and things like that.

But, you know, I think vegetables are probably the most important, really important micronutrient dense. And also they do have a lot of these plant hormetic compounds, you know, these compounds that actually are natural insecticides or fungicides that are made by the plant to ward off insects but end up having really positive and beneficial effects in humans through the hormetic response, which is very similar to what fasting does and exercise and heat stress and things like that. Okay, yes, there'll definitely be a chapter on gut health. So the next question is, how useful is the full genome sequence or microbiome sequence? Are they both too early to be very actionable? I would say they're, yes, they're very early, too early to be actionable.

I, you know, previously I've used uBiome to sequence my microbiome. I've done it a few times actually. There's a new one I've been aware of called Viome, which I took a cursory look at and they looked pretty decent as well. We're just, we're really just now starting to get more and more data about how the microbiome changes our glucose response and our insulin response and things like that. So, but again, I think that you nailed it in the question, or is it too early to be actionable? And I think the answer is yes, full genome sequence included. I think that it's really cool that these techniques are becoming available, but I'm not sure how actionable they are yet, you know, and if they're really worth, worth the money.

Okay, so the next question is about MCT oil and coconut oil and exogenous ketones and comparing them. So this is from Christopher. And he's asking to compare those things. And someone did kind of a really great answer here, so I won't spend too much time on it. But, you know, basically, if your endpoint is to go into ketosis based on your blood levels of the major circulating ketone body, beta-hydroxybutyrate, Your best bet would be to fast ketogenic diet or take exogenous ketones. Coconut oil has a modest amount of of capric acid and caprylic acid, which are the the eight and ten chain medium chain triglycerides, and it has a abundant medium chain triglyceride.

It has this lauric acid, which is twelve, and And, and so those can be converted into ketone bodies, but you have to understand they're not— just because you ingest them doesn't necessarily mean they're going to be converted into ketone bodies. They'll be used as energy, but in order for you to convert them into ketone bodies, you have to, like, you have to limit your carbohydrate intake. You know, you have to be more on something like a ketogenic diet. And taking those because your body's not going to convert, um, is not going to start going into ketosis, you know, in the presence of carbohydrates, uh, or significant amount of carbohydrates. So, um, so it's not like you can just, you know, take your MCT oil and that's gonna like kick you into ketosis.

It's not, um, that you, you know, so, so maybe if you are in addition to that you are on a ketogenic diet and some of the fats you are consuming are are made of these medium, medium-chain triglycerides, that would be easier for you to convert them into ketone bodies. But it doesn't necessarily mean that you're going to. Exogenous ketones, on the other hand, is a way of immediately kicking your body into ketosis even in the presence of carbohydrates. Now, I have done this. I recently experimented with the new product that's going to be out on the market in February, or at least so they say, Human HVMM— HVMN. I tried their exogenous beta-hydroxybutyrate ketone ester.

I did it after eating a bowl of oatmeal with raspberries in them, and it took me from— my blood levels of beta-hydroxybutyrate were 0.1 millimolar, and it shot me up to 4.5 millimolar in 60 minutes. So I went, I mean, 4.5 millimolar is what you would expect for someone who's been on like a 3 to 4 day fast. So it really did take me into like a pretty significant ketotic state. And, but of course that's not going to last. I mean, you're going to use up the ketone bodies as energy and I was doing endurance exercise. So I was really using them as energy. So 1 hour after I did it, I did a 1 hour cycling class, and after that hour, I measured my ketone levels again and I dropped down to 1.8 millimolar.

So I had used up a majority of the exogenous beta-hydroxybutyrate that I had just consumed within that hour. Now, if I hadn't gone cycling, the question is, would I have had higher levels of beta-hydroxybutyrate an hour later? Probably so. I did do another round of the beta-hydroxybutyrate I had 3 rounds. I gave one to a friend to try, but the second time I did it was during an interview. And so I didn't— I couldn't like measure my ketone levels while I was interviewing. So I didn't actually get to measure that. But I did notice an energy boost in that as well. So I hope that makes sense in terms of the difference. I think that's pretty straightforward. The question is, question here from Tim about consuming vegetables raw to get the full benefits of prebiotic fibers.

I do not know, you know, I really haven't looked, um, to see whether or not heat— as far as I know, it doesn't disrupt the prebiotic fibers, uh, as far as I know. So I— and it's not something that I really like studied in depth. So I would say that you're probably getting them even from the cooked vegetables, but I'm not certain on that. So good question. Next question is from Val and has to do with fasting and whether or not, what the effect of fasting has on the gut microbiome. And, you know, because I mentioned when you don't feed your microbiome the fermentable fiber, which is also known as prebiotic. Prebiotics are synonymous with fermentable fiber, which unfortunately has been synonymous with soluble fiber, which is— we're sort of phasing out from the soluble, insoluble fiber.

Soluble fiber is what's thought to be the fermentable fiber, but now it's being called fermentable fiber because soluble fiber is not always fermentable. So Anyways, the point is is that when you're fasting, you're obviously not eating anything. So the question becomes then what happens to your gut microbiome? And the answer is like we we don't know. I was I was supposed to have a round two podcast with Dr. Valter Longo last Wednesday Tuesday or Wednesday I don't remember. But the LA fires stopped me because I was driving from San Diego to LA and the 405 was like closed, and so we had to reschedule for mid-January. But that's one of the things, questions I'm going to ask him. Excuse me. So, you know, the question is like, do we end up having a lot of species of bacteria that are dying?

And so And so you kind of free up residential space in your, on, in your mucin, and that will then allow you to like repopulate with good bacteria. Does it, you know, so the question is like, what is it doing to your gut? And what I particularly want to know is because we know that fasting increases beta-hydroxybutyrate levels and we know that butyrate is, is a short-chain fatty acid. So beta-hydroxybutyrate differs from butyrate in that it has a hydroxy group on it, one of the carbons, and so it's got an alcohol group and an oxygen and a hydrogen atom. I don't know how much that changes the function of, for example, butyrate, but we do know that butyrate is produced by a variety of beneficial commensal bacteria in the gut and it's used to fuel your gut epithelial cells.

So it's actually the predominant source of energy that your gut epithelial cells will use, butyrate, as energy. It's anti— it has a lot of benefits, basically. It's modulating the immune system and all this stuff. So basically, I'm going to ask Valter about that and see if he'll be interested in looking into that because I'm curious whether or not the beta-hydroxybutyrate you generate during ketosis can make its way to the gut and can basically feed the gut, feed not only the microbiome that's in there, but also the gut cells and whether or not that's been looked at or he would be interested in looking at that because I think that's very interesting. So Alexis here comments, Alexis Espinoza comments on this question.

Can you explain some of the lost benefits when doing a fasting mimicking diet versus water fasting? And I think someone else asked additionally to explain the ketosis versus that fasting. I'll quickly explain that because, because I think it's, it's, it's an important thing to understand. And by the way, Bill, yes, I'm going to. That was one of the things I was going to ask Walter was the refeeding. Um, advice, um, because he, by the way, has a book coming out January 2nd. I've already, um, I got a pre-cop— a pre, um, pre-released copy of that, so I've already read the book, but that will be coming out in January. And he does, he does talk about some advice in, in, in that book on refeeding, but I have some questions about it, and so I'm gonna, um, question him about that. For sure.

So the differences between the fasting mimicking diet and the water fast, one of the main differences is that when you're on the water, 5-day water fast, there is a very robust induction of apoptosis, which means cells are dying and predominantly it's damaged cells that are dying. And this causes stem cells to get activated and to replenish those cells that were killed or died with new cells. So it's essentially, autophagy is cleaning out damaged things within a cell, so damaged mitochondria, damaged enzymes, pieces of DNA, pieces of protein aggregates, all the trash and gunk. Autophagy cleans that out and autophagy can be activated earlier than apoptosis. Once you get into a strong stressor, there's like a threshold.

And this is something Valter and I will talk about in the upcoming podcast. That's something that I will discuss with him. But I did talk about this with Dr. Guido Kroemer, the autophagy expert. If you haven't watched that podcast, go to the episode page, check it out. You can click on the timeline and find the point where we talk about this if you don't want to watch the whole hour-long video, um, and there's also a summary, but the timeline will show it. Um, um, basically there's a threshold when you start to fast for a longer period of time, you start to shift into apoptosis and cells start dying.

And so, um, the fasting-mimicking diet, uh, at least Valter has shown, um, there is— he's shown preclinical data that does— you do, you do get some of that And a very preliminary clinical trial he did showed there may be some stem cell activation happening. But the question is, how robust is that? Like, how, you know, you're still getting, you know, some food, you know, so how much of that apoptosis is occurring? And that's the question. And maybe Valter will answer that for us. Maybe he doesn't know. He probably doesn't know, but maybe he does. We'll see. But that would be one of the main differences between between the water fast and the fasting mimicking diet.

Also, to some degree, you are you know with the water fast, you got to make sure you're gonna you you definitely want to make sure you're taking some minerals and salt and things like that. You know to to prevent you know headaches and all that. But but The ketogenic diet, that, that doesn't happen with the ketogenic diet. You're not getting that massive apoptosis. You're not getting that autophagy, massive autophagy, massive apoptosis happening. Lots of other, you know, metabolic benefits that are similar with ketogenic diet and fasting, but, but that's not happening. And that is something that I will discuss with Valter as well in the upcoming podcast because I think that's something that people are interested in learning about.

And the coffee thing, with respect to the coffee, Dr. Satchin Panda and I did discuss that. And again, go to the episode page I have on FoundMyFitness and check it out. There's a transcript available for that one. So you could even go click on this transcript and search, do a search for coffee and find out where I asked him about that question. You know, he basically gives a really good answer. It's not a black and white yes or no answer, which I know people are wanting. But basically what he's saying is there's two aspects to time-restricted eating. There's the eating within the circadian rhythm aspect, and then there's the whole fasting when you're not eating because you are not eating, you're fasting. There's that aspect. Now, for someone that is doing a prolonged fast, coffee is okay.

Black coffee is okay. You know, that's kind of what Valter has has in his, um, with his fast. And, uh, in generally speaking, because time-restricted eating, you're trying to eat all your food within the circadian rhythm, you know, when your metabolite metabolism is optimal. When you're doing a prolonged fast, you're not eating at all. So like that whole circadian component is not something you're considering. You're fasting. So the, the black coffee, um, isn't as much of an issue, uh, with that, if that makes sense. But I will make sure to mention that with Valter again. But check out Dr. Satchin Panda, and Dan is linking to the episode pages in the chat. So Chris Dunham is asking, is apoptosis necessarily a good thing? Not necessarily.

It's a good thing when we're talking about killing off damaged cells, and that it seems so So stress, whether that's stress of fasting, whether that's stress from exercise, whether it's heat stress or stress from taking a hormetic PLAC compound like sulforaphane, stress will cause, you know, normal cells to activate stress response pathways, which are largely anti-inflammatory, antioxidant, stem cell proliferate— proliferation, Autophagy activating pathways. These things will all get activated in the presence of stress. When you have a damaged cell, like a cell with a lot of mutations or a bunch of aggregates or something that's dysfunctional, those pathways, the stress doesn't, isn't acting the same way that it does on normal healthy cells. Those pathways don't get activated.

The stress, in fact, it doesn't know what to do. It can't counter that stress. So it ends up killing it. And in fact, that's one of the main mechanisms by which chemotherapeutic drugs and radiation, ionizing radiations kill cancer cells is because those are toxic compounds. They're given in large, large doses, but they kill cancer cells because cancer cells, they can't, the stress basically tips them over to death. So Valter talks a lot about this differential stress resistance in the first podcast we did. If you go to the episode page and again, click on the timeline and just do a search for differential stress resistance, you'll find it.

Click on that part of the podcast and listen to it because basically the beautiful thing is, and he's shown this in clinical trials in humans, he's done a couple of clinical trials in humans with water fast only, 72-hour water fasts in cancer patients. That were undergoing standard of care treatment. So I think they were undergoing radiation therapy, if I remember correctly. And they did a water fast 72 hours before the radiation. And what he found was that the fasting was tolerable for the most part. It was a little hard for people to do, but it was tolerable. There weren't any negative side effects.

And what it did, what it was, reduce the negative side effects of the radiation because their the differential stress resistance from the fasting caused the cancer cells to become more sensitive to the radiation, and it caused the normal healthy cells to upregulate or increase all these pathways that help them deal with stress. And so they were able to deal with the radiation better, and so they didn't end up getting this myelotoxicity, which is a side effect of radiation. So So that— so now apoptosis can occur in stem cells, and you don't want your stem cells to die of apoptosis because your stem cells are what are replacing all the other cells in your body. And so that could lead to the aging process, and that usually happens when your stem cells accumulate too much damage.

And it's a way of protecting your stem cell from acquiring a mutation which will allow it to become a cancer stem cell, which is like the worst possible thing that could happen. So, um, so you end up dying. And, and I talk about this with, um, Dr. Judy Campisi, um, that episode with Dr. Judy Campisi. So you can click on that episode and click on the timeline and search apoptosis. We talk about this as well if you want to learn more about that. Um, so let's see the next— the PQQ question. It's a supplement that I am taking. It's something I'm taking 20 milligrams by Life Extension because 20 milligrams is what's been shown in clinical trials to improve cognitive function.

And it's also, it's also been shown to improve— that dose has been shown to decrease markers of inflammation and increase markers of mitochondrial function in humans. And so it's also something that's found naturally in foods. Um, it basically, since I'm like speed talking to quickly, um, get through this, it's, it's really good for mitochondria without getting into all the details. It's really, um, heavily concentrated in breast milk, meaning it's something that our body's already, uh, wanting to give to, to babies. So I'm, I'm actually taking 20 milligrams a day of it. Um, so, uh, that's why I'm taking it. Uh, in terms of saying Dave Asprey says PQQ is inactivated in the stomach and that's why he combines it with CoQ10. I have not seen evidence of that.

And so, in fact, you know, I'm not sure where he's getting that from. So I would, I would, I would be skeptical of that because in those human studies I'm talking about, the 20 milligrams of PQQ was not taken with CoQ10, and it absolutely had positive effects on a variety of different biomarkers and outcomes. So I'm not sure where he's getting that from. Um, So I've got like 1 minute before this, this thing's gonna end. Or do I? Let's see. Yeah, um, let's see any other live questions I can, can answer. Uh, what's the significance? What's the significance you break your fast? Um, prolonged fast, 3 days, is it more just rather? Okay, so the question about what you break your fast with—the reason there's there's a few things to consider.

One is obviously you know you haven't eaten for a number of days, so your gut can be very sensitive to like you know whole foods and stuff like that. But it can be sensitive to fatty foods as well. So you really have to like your own. You'll have to figure that out for yourself. But Particularly what I'm interested in is talking about IGF-1 because he's in his preclinical studies, he mentioned that activating IGF-1 after the fast was really important for the stem cells to keep proliferating and growing and making new cells and making new stem cells. So I wanted to ask him, you know, that would imply that it would be important to actually eat essential amino acids or even, you know, meat or maybe salmon or something like that after the fast. because you want that IGF-1. And so that's kind of something I wanted to talk to him about.