Q&A #4: Fasting, Autophagy, & Fat Loss—Plus the Carnivore Diet

Hello, everyone. Okay, I'm going to go ahead and kick off this session. Before I, before I get started, so I just want you guys to know I went through all the questions. There, there certainly, as people were mentioning in the chat, That there's an echo. Hmm, let's see. Okay, is that better? No echo. Okay, perfect. That I went through all the questions and chose, you know, some questions that were at the bottom of the list even though they weren't upvoted because there is definitely a a bias for people that submit their questions early. Those questions, of course, get seen and upvoted. So I just want other people to know I did go through all the questions. And also, a lot of questions that were asked have— I've previously answered in other Crowdcasts or other podcasts.

But so those questions, I'm not gonna, you know, sort of beat a dead horse. So for example, there's a vaccine question that was upvoted. I went into great detail on vaccines the very first Crowdcast I did. So people can go back and check that Crowdcast out if they want to learn more about my thoughts on the vaccines. I did kind of make some categories where, like, for example, diet, aging, blood tests, etc., you know, where people had, you know, some similar questions. So I'm just going to go ahead and get started, and then also be taking some questions. on the chat here live, so I'll be checking those as well as I'm speaking.

I'm gonna get started with some of the more easy, the more not in-depth answers, because sometimes I tend to ramble on about some of the diet-related stuff, so I'll get to that in a little bit, but I'm gonna answer some of the other ones first. So, So the first category is aging blood test tracking devices. Regarding overall health and performance, what in your opinion are the most important biomarkers in a blood test that we should ask or pay attention to? So I personally, I really like True Health Diagnostics. They have a few panels that I really like. For example, they have a cardiovascular panel and their cardiovascular panel looks at traditional lipids, it looks at lipoproteins, It looks at a variety of inflammatory markers and peptides and other biomarkers of myocardial stress.

And there's multiple markers for each category. For example, traditional lipids are looking at things like LDL cholesterol, LDL particle number, your ApoA-1, ApoB, LDL particle size, omega-3 and omega-6 fatty acids. And then there's a variety of inflammatory biomarkers, high-sensitive C-reactive protein, myeloperoxidase, the fibrinogen, F2-isoprostanes, all those things, and then there's some other biomarkers for myocardial stress. So that's called the Cardiovascular Panel, and you can either go through, use True Health Diagnostics, or you can just look at the Cardiovascular Panel, and they list all the biomarkers measured, and you can request those biomarkers through your favorite testing service.

The other panel that I really like is the Diabetes Panel from True Health Diagnostics, And the diabetes panel measures things like glucose control, insulin resistance, and then your beta cell function. And again, there's a variety of biomarkers for each category, your glucose, HbA1c, fructosamine, your estimated average glucose, ferritin, leptin, free fatty acids, insulin, proinsulin, the C-peptide. So all those biomarkers I really like. And that's again the diabetes panel from True Health Diagnostics. You can also again just look at the— look at the biomarkers and see if there's, you know, some other, whatever your testing service that you usually use, you can just request those biomarkers as well.

So those are my 2 really favorite biomarkers to look at for long-term health and also just, you know, performance. The other few biomarkers that I like would be looking at thyroid You know, and that's something that, you know, doing a full thyroid panel, you know, once every couple of years or something would be, you know, sufficient. There's also a hormone panel for people that are more interested in a variety of hormones. It's also pretty good as well. So take a look at True Health Diagnostics and just kinda click through some of their tests that they have and look at some of the biomarkers there 'cause they're really good ones. Okay, so the next question in this category is from Peter, and Peter is asking about IGF-1 and what the sweet spot for IGF-1 is.

So IGF-1, you know, I've talked about in great detail, it's an important growth hormone, of course. It has a variety of important factors for, you know, muscle growth, muscle repair, brain and neuron function, the growth of neurons, neurons, maintaining neuron— maintaining the function of neurons as well. But it also is a growth factor that can potentially allow damaged cells to grow. And so if you look at a variety of mortality curves, there's always like a U-shaped curve where people in the very— that have the very lowest levels of IGF-1 have a higher mortality risk, and people that have the highest levels of IGF-1 have a higher mortality risk.

There's some sort of sweet spot that that people fall within that range and they have a lower overall mortality risk, including cancer mortality, cardiovascular mortality, which are our 2 main causes of death in the United States and also even worldwide. So it seems as though the really, the sweet spot range tends to be around 90 to 115 nanograms per milliliter. So, you know, I think that seems to be the real sweet spot in terms of lower all-cause mortality. In terms of how frequent and how often you should measure, I really, I really have no idea. I mean, if you're experimenting with different diets and things like that, probably you wanna measure it, have a baseline, and then measure it with each experimental condition.

Or if you're experimenting with any sort of exercise, you know, high intensity versus, you know, aerobic versus strength training, and if you're kind of interested in whether or not that's affecting your systemic IGF-1 levels, that also, would be a reason to measure it. Otherwise, measuring it something like once a year also would be sufficient. People are— so Charles is asking how you interpret your lipid panel results. Are relative numbers more important, and at what point do absolute numbers matter? Really good question.

I think that these lipid panels are, a variety of ways to interpret them, and obviously, like, looking at multiple, multiple biomarkers of not only lipid metabolism, but also looking at the glucose metabolism biomarkers I mentioned, all those things are really important to get the big picture understanding. So at a certain point, you do definitely wanna look at your own, you wanna consider things like your family history for cardiovascular disease. It also sometimes helps to have some genetic data to know, for example, if you're ApoE4 positive or you have one allele of ApoE4, that may explain why you have higher circulating LDL levels. And so you can sort of modulate your diet to lower some of the LDL by decreasing saturated fat, increasing poly and monounsaturated fat, things like that.

LDL particle number, ApoB, Those things are also really important, triglycerides. So, you know, again, cholesterol is one of those things that there's also a U-shaped curve and, you know, people that have really high LDL cholesterol can be at a higher risk for a variety of cardiovascular-related diseases, but also people with really low cholesterol are also at a higher risk and also they're at a higher risk for things like Parkinson's disease. So again, it's really— You know, there's a sweet spot for the cholesterol, and looking at a variety of biomarkers together in combination's really good.

Go back and listen to the podcast I did with Dr. Ronald Krauss, 'cause he talks about a lot of those biomarkers and how looking at them in combination's really important to sort of interpret your data. So another question in this category has to do with an Oura Ring, which is— actually, I'm wearing one. I do have an Oura Ring. It's a sensor that lays on your finger and can— it measures heart rate, heart rate variability, and also movement. And so together, combining that data together through some you know, algorithm. Uh, it sort of helps interpret, you know, your sleep, helps you sleep, track your sleep and the different stages of your sleep and also the duration.

Now, I recently, uh, spoke with Dr. Matthew Walker and asked him a little bit about what his thoughts are on the Oura Ring and how accurate it is, because obviously to really measure stages of sleep, you have to measure brainwave activity. And this ring on my finger is far from measuring any brainwave activity going on in my brain. So he says that if you compare it to what, like, the gold standard, which would be a polysomnography, that there's about a 60% variability in being able to accurately measure the stage of sleep that you're in. He says what is really accurate is it can measure the duration of your sleep, which is pretty accurate. So whether or not you're sleeping spending 20% in REM versus, you know, 18% in deep sleep.

Um, it's, it's not really accurate, although I do find it useful, and I do find that it does seem to correlate somewhat with, with my sleep. So for example, deep sleep usually occurs early in the evening, uh, REM sleep, uh, early in the, in the, in the morning. So, you know, towards the end of your, your sleep cycle. And I do find that when I go to bed earlier, that I get more deep sleep, and that's consistent. And also when I have to— when I get woken up earlier, for example, my son wakes me up earlier than usual, then it sort of dips into my REM sleep, and that shows up in my data. So I really like the Ring. It kind of helps me keep track of, you know, how certain things that I'm doing and how they may affect my sleep.

Certainly, I think I like the fact that it helps give me a estimated bedtime as well. By the way, I'm not like— this is not like any— I'm not advertising the Oura Ring at all. I'm just— I personally like it. I do think that it's, it's not very accurate, but I do find it useful. So, and the Apple Watch is, is, according to Matt, it's just as, just as good as the Oura Ring. Some people find it a little more annoying to sleep with an Apple Watch, and you probably want to make sure it's in airplane mode so you're not transmitting Wi-Fi signal and stuff right next to your head.

So, but in terms of accuracy, according to Matt, who's like a sleep expert, he says pretty much all the sleep tracking devices are more or less equivalent in terms of their capabilities of tracking different stages of sleep and duration. So, so if you have an Apple Watch, then, you know, you can probably just use that as well. And the last question in this category, sorry, not the last question, second to last question. So Jim asks about telomeres. So telomeres are a biomarker for aging. If you have short telomeres in one cell type, then is it likely that you'll have short telomeres in all of your cells?

So to answer that question, the answer is no. So for example, if you're measuring your telomere length in your leukocytes, so in your white blood cells, that's not necessarily indicative of what your telomere length is in your stem cells in your liver, for example. There are a lot of different— your immune cells are responding to a lot of different environmental factors. There's lots of changes going on in immune cells, and oftentimes, you know, your immune cells are secreting a lot of very toxic, you know, reactive oxygen species, things like hypochlorite or hydrogen peroxide. And, you know, these things can, you know, cause a burst of damaging radicals that can affect telomere length transiently in your white blood cells specifically.

But that's not necessarily what's going on in, you know, all the cells in your body. Now, they can also correlate sometimes. So, I mean, you can have a person that just overall has chronic inflammation, unhealthy lifestyle, sedentary or smoking, things like that. And so you may find that it is a good proxy, but it's not necessarily. So it is definitely something to keep in mind. Michael asked about the headband measures that— the headband that measures brainwaves. No, he didn't comment on that. I didn't even know about those. I should have asked. That's a good question. But I can certainly shoot him an email and ask him about that.

All right, so then the last question in this category is from Nick, who asks, what do you think are the most important efficient protocols to adopt in order to prolong and expand your healthspan as we all age? That's, that's a very big, big question. I think some of the The really important and easy-to-adopt protocols, one would be time-restricted eating. I think that that's probably one of the easiest things people can start to implement in their life that will have a big impact on their overall health and the way they age. Regardless of what you're eating, time-restricted eating will benefit you.

Even if you're eating a standard American diet, if you eat the standard American diet within 9 hours versus ad libitum, you know, where you're just eating pretty much all day and before, you know, right before bed, restricting your time window to 9 hours and then fasting for 15 hours will have benefits on multiple levels. You're gonna, you know, be within the circadian rhythm of when your metabolism's optimal, you're most insulin sensitive, your fatty acid beta oxidation's occurring the best, and also you're gonna have a fasting window and you need that period of rest for your gut, And then you get all the benefits from fasts, a lot of benefits from fasting as well.

So I think that would probably be one of the easiest things for people to implement no matter what sort of diet they're eating. The other thing I do think that is beneficial is a prolonged fast, maybe depending on the person, but maybe once or twice a year. And I think that it's something I have not done yet because I sort of got into it right when I was, you know, about the time right before I was getting pregnant or wanted to get pregnant. So I wasn't going to experiment with fasting. And then I got pregnant and nursing and all that. So, you know, I do plan on doing a prolonged fast at some point when I'm completely done with nursing.

But the reason I think that it's important is because I think that it does— I think Dr. Valter Longo has quite nicely shown, certainly in preclinical, has preclinical evidence showing that there's this systemic rejuvenation that occurs when you go through a prolonged fast. And that has to do with basically lowering IGF-1 levels to a point where it, you know, it's kind of a stress response that activates stem cells. You end up getting not only autophagy, clearing away of damaged proteins and organelles and pieces of DNA and stuff within a cell, but you actually end up killing cells. So apoptosis occurs. And it seems as though a lot of times the cells that are dying tend to be cells that are dysfunctional or damaged in the first place, which is something that you want.

And at the same time, stem cells are being activated and you're then, you know, replenishing and replacing these dysfunctional damaged cells with new healthy young cells. And I think that's, you know, he's quite nicely shown that with organs literally shrinking and then regaining their mass during the refeeding stage. And I think that in humans, he, you know, he's kind of trying to show things like that happen. He has some early preliminary evidence that there are activation of stem cells occurring. He's working on more studies right now in humans. But it does seem as though probably a prolonged water fast may, may be the way to go.

And so I, so I tend to think that's something for, um, just resetting the body, resetting the, the, you know, a lot of rejuvenation systems in the body as well. So I think that that's something that people can practice and, uh, do, you know, once, once or even twice a year, uh, for, for healthspan. Um, the other thing would be, would be exercise. And I think that a mixture of high-intensity interval training and aerobic exercise and strength training is really important. They all— there's overlapping benefits, but they also have really, um, you know, they have really important benefits within that they each seem to have on their own.

Uh, so for example, aerobic exercise was shown to, to increase the— this hormone called FGF21, which is really important for metabolism, for making sure that you are burning fat lipids and, you know, your fatty acid oxidations ramped up, also burning glucose. So it plays a really important role in metabolism. High-intensity interval training has been shown to really dramatically boost mitochondrial biogenesis in people. Strength training has been shown to increase muscle mass, which is also important for aging. So I think those 3 things combined, and then I think sleep, optimizing your sleep is really, really important. And we'll talk a little bit more about that when we talk a little bit about Alzheimer's disease.

But I think that one of the really important things that sleep is important for is the brain, and particularly for staving off neurodegenerative diseases. It seems to be important for a lot of things like, I mean, just immune function, cancer, cardiovascular, all those things. But there's really, really, really, really robust data for the brain. And And for neurodegenerative diseases in particular, so I think those are some of the easiest things to optimize for: the TRE, you know, just basically not eating for you know three three to four or five days, you know once or twice a year, the sleep and the exercise, and then you know optimizing all the food and what you should eat and all that. That's a little more work. People have more more hard time doing that. It's also very important.

You know micronutrients are extremely important. I think that getting all them from your from your vegetables and eating, eating a variety of healthy foods is important. But that's— that wasn't the question. So that would be my, my, my advice. So Shell is asking, what amount of days is considered prolonged for a fast? So according to Valter, for humans, it, it seems to be 3 to 5 days of just a water-only fast. That would be considered a prolonged fast. And this is a question that that I will get into in terms of the intermittent fasting. Someone someone asks about that as well. I can just go ahead and go into that section since we're sort of naturally going there. All right, so so basically Alex asks what is a true intermittent fast?

And you know does black coffee or zero calorie sweetener break the fast? So, um, an intermittent fast, I mean, it's very confusing because if you look at the, the media and stuff and a lot of press releases, I mean, it's sort of all over the place. Everything, everything's almost referred to as an intermittent fast in a way. But, um, but, uh, technically in, in animal studies, even an intermittent fast can be anything that's more than 16 hours. Now for humans, um, I think that it's fair to call someone who is doing time-restricted eating for 8 hours and then fasting for 16, so like the 8:16, I think it's fair to say that is time-restricted eating.

It's important to distinguish that because eating within the time window and eating within the circadian rhythm also has benefits independent of the benefits from fasting for 16 hours. But I think that would be fair to also call that an intermittent fast when when someone's fasting for 16 hours. And certainly anything that's 24 hours and up to 48 hours would be an intermittent fast. And then once you get past 48 hours and you start to go into greater than 2 days, then you start to enter the prolonged fasting spectrum. And certainly 4 to 5 days is considered a prolonged fast.

So, The question about black coffee and zero-calorie sweeteners and things like that, I think there's— it's important to distinguish, you know, if you're talking about someone on a prolonged fast, you know, black coffee, zero-calorie sweeteners, you know, probably isn't gonna have much of an effect. When you're talking about someone who's every single day trying to do time-restricted eating, and let's say you're eating within a 10 or 11-hour window, So not super, super restricted, but you're still, you know, you're still restricting yourself to less than 12 hours.

If you're always count— if you're only counting when you start to eat, but let's say you, let's say you, you know, wake up and get your first cup of coffee at 6 AM, but you don't count your first— you don't eat your first bite of food until, let's say, um, 8, and you stop eating at, you know, 7. So you're, you're, you're saying you got this 11-hour eating window, but every you know, every day 2 hours earlier, you're having black coffee. So is there sort of a— are you activating some of the metabolism enzymes and sort of, you know, potentially shifting your circadian clock? Which there is evidence in both humans and animals that caffeine, independent of any, you know, cream or calories, you know, calories added, caffeine shifts the circadian clock. So it does affect circadian rhythm.

So there may be an effect. Is it super, super, super powerful or robust? We don't know. A lot of people seem to say that they're— at least if you're looking at weight loss as a measure, it doesn't affect their weight loss and that they can drink coffee and not count it. So, you know, whatever works for you. I wouldn't worry too much about it. I personally try to consume— when I'm doing time-restricted eating, I try to consume everything within that window. Aside from, you know, people that are taking medications and all that, just of course listen to your doctor and don't worry about that. But I do try to drink my coffee within that window, but I also don't drink black coffee. I like to have MCT powder in mine.

So I really think that, you know, it's kind of one of those not— people are asking that question, I think, 'cause I've talked about it with Dr. Satchin Panda before. And I think that, You know, it probably does have a small effect on circadian rhythm. And, and, you know, again, if you're constantly doing it every single day and then you're, you're drinking your coffee a couple of hours, maybe even 3 or 4 hours before, you know, you may, you may have some sort of an effect. Um, but when you're talking about a more prolonged type of fast, I, I think that's— it's probably, you know, not an issue. So Robin asks, how about protein intake? How many grams a day in terms of not wanting to activate too much mTOR, IGF-1?

Do you think it's worth doing protein restriction one day or having a minimal protein one day a week? I think that's a really good question and I really— there's a lot of factors that go into that because While you do activate mTOR and IGF-1 when you take in, particularly when you take in a lot of essential amino acids, branched-chain amino acids, you also, if you're doing a lot of exercise, you're causing those branched-chain amino acids, for example, to be taken up into muscle tissue. The IGF-1's going and crossing the blood-brain barrier, getting in the brain, going into the muscle, so you're basically activating these systems in tissues that you want them to be activated to, you know, to improve muscle repair and growth and also to help with neurogenesis in the brain.

So it's one of those things where earlier I talked about IGF-1 levels and the sweet spot and measuring them and the question was how frequent to measure. Well, that may be something you may wanna experiment with. Let's say you're wanting to know, you know, the protein intake if you wanna kind of minimize it to one day or let's say you're eating a lot of protein but you're working out really, you know, you're doing some really vigorous exercise, um, it would be wise to then also, you know, get your IGF-1 levels measured, you know, with and without doing the vigorous exercise but having the protein to see if that changes because then you'll know what really works for you.

Um, personally, I do think, you know, like I, I, I do like one meal a week where, where I'm restricting my protein, um, to, to a lower, to a level, lower level and that typically I try to do that on days where I'm not so active. So, okay, so back to the fasting, uh, questions. I'm gonna mispronounce this name, but, uh, Galicia Ray asks what, what the best food for refeeding after a fast is, um, after a prolonged fast. So, uh, I, I talked to Dr. Valter Longo about this in the recent podcast, round 2 podcast I did with him.

And I mentioned IGF-1 activation because he talks about how while the prolonged fast itself lowers IGF-1, and that's critical for causing apoptosis, for activating autophagy, for activating stem cells out of quiescence so they are activated and, you know, wake up, they— the IGF-1 needs to come back after the fast during the refeeding phase because that IGF-1 is really important, critical for the proliferation of the stem cells that were activated because of the low IGF-1. So IGF-1 then plays a very important role in activating and re— basically causing the stem cells to grow and proliferate and differentiate into other cell types, uh, for example, cells that make up the immune system.

So you definitely want IGF-1, and we know things that activate IGF-1 happen to be amino acids and essential amino acids, branched-chain amino acids. Those things are really good. So, um, you know, personally, like I said, I haven't experimented, but I've spoken with a lot of people that have experimented, and some people really like eating a small piece of salmon and some bone broth. Other people like to do something a little more liquid. They like to make a smoothie, and they also like to add some like whey protein to the smoothie for activating the IGF-1. It's also important for IGF-1 activation, insulin is also important because the insulin response allows IGF-1 to be more bioavailable.

When your insulin levels are really low, The IGF-1 is bound up by IGF-1 binding protein 1, and that basically binds and sequesters IGF-1 and prevents it from basically going and binding to the receptor where it then does its function. So that's kind of where the smoothie comes in because you can add some fruit to get a little bit of a glucose response in addition to the whey protein. So a lot— there are quite a few people I've spoken with that really like using that. Some people, for their stomachs and guts are a little more sensitive after not eating for 3, 4, or 5 days, and so they like to sort of ease in with some, with some bone broth and, um, you know, just maybe a little, little piece of, of salmon. Um, so really kind of figure out what works for you.

But, um, I think that, that, uh, that, that's what people seem to like, and also it makes sense from a scientific point of view. So Alexis asks how fasting affects human growth hormone versus IGF-1 and what their respective roles are in muscle mass. There's— there was a lot of people talking about the fact that a fast, intermittent fasting, and even more prolonged fasting actually While it decreases IGF-1, it activates human growth hormone. And this is true, and this has been shown in humans as well as animals. And the reason for that is because growth hormone is most responsive to— it's part of the stress response. So things that cause stress can activate growth hormone.

And that's also why exercise and also even using the sauna The sauna very robustly activates growth hormone because it's a stress on the body and it activates stress response pathways, and growth hormone is part of the stress response axis. And so growth hormone gets activated during periods of stress. Alternatively, IGF-1, while IGF-1 is usually downstream of growth hormone and growth hormone can subsequently activate IGF-1, It's not always, and IGF-1 is predominantly regulated by dietary intake and in particular amino acid intake.

So you you can while you're not taking in any food, you can lower that IGF-1 because the main thing that regulates that is is food intake, and at the same time because not eating is actually a stress on the body, at the same time you can actually activate growth hormone. So it's kind of a little tricky to wrap your brain around, but I think explaining it like that sort of helps just understanding the difference between the stress response and dietary regulation of these pathways. So Valter Longo mentioned that prolonged fasting, he's shown in animals, there's a shrinking of organs including muscle tissue, and then during the refeeding phase, these organs re-expand to their original size. Yeah. And including muscle.

And he said that actually looking at in human subjects that did not a prolonged fast, but they did a fasting-mimicking diet, they had a transient dip in their muscle mass. And then actually after refeeding, they regained their muscle mass and actually even had more lean muscle mass than where they were at baseline. So it is kind of interesting, you know, the question is what's causing— is it the shrinking and the re-expanding? Is there a combination of growth hormone also that's playing a role? And, you know, the answer is possibly all those things. But we do know that the fasting and the refeeding is important and that the muscle mass does seem to come back. The transient loss in muscle mass seems to come back. Yeah. Testing to come back.

So, so I think that's sort of Andrew Bennett's asking about my thoughts on fasting for athletic types and the muscle mass, and I think, I think that should, should somewhat answer the question. And also he's asking about type of exercise during a prolonged fast, and I would certainly be very cautious. I've spoken with people that People respond very differently. Some people, their blood glucose drops really low and their blood pressure drops really low when they don't eat. So that exercise to them, they just can't do it or they literally risk hypoglycemia and just like getting dizzy and low blood pressure, really low blood pressure.

So I think that doing things like measuring, getting a glucose meter, Precision Xtra is what I use, and measuring your fasting blood glucose levels every day and during the fast and seeing how it affects, you know, and it would help you sort of gauge, you know, just how you're feeling as well. You know, if you can, to what degree you can start to exercise. I've had people that also have talked about, told me how during a prolonged fast they did exercise and then that ramped up their appetite, whereas before, previous times they had done the prolonged fast and didn't exercise, they were They were just fine, didn't actually get really hungry. So I think that it's really important to just take it easy and listen to your body.

You probably don't wanna do really, really intense exercise while you're fasting. So that's something I just can't really give advice on because I think that everyone's different and really you just need to kind of, if you really, really wanna do something, you can kind of try it out yourself and see what works. Is it yoga? and a little bit of weightlifting, or is it just going for a nice walk? It's sort of up to you. Okay. Let's see. Another question related to fasting. Again, as I told you guys, I sort of categorized the questions into these categories. The next question is— oh, by the way, Dr. Jed Fahey is on this call. Is he still here? Because there is some sulforaphane questions, which would be so nice if he could chime in. If he is still here, I will, I will go to that section next.

So Jed, if you're still here listening, type something so I can see it. And I think I can actually invite you on the camera as well if you're willing to speak. Okay, so the next fasting question is from Stan, and Stan asks, for autophagy, what would be more beneficial, 2 48-hour fasts or 1 72-hour fast? And this will be done in a 2-week period. So something to keep in mind in terms of the autophagy Yeah. And I did sort of mention this, the autophagy and apoptosis is that there's a spectrum. So autophagy, which is really important for cleaning out what's inside of cells. You take a cell and you have a variety of pieces of DNA and you have just protein aggregates and pieces, just gunk. And autophagy can help get rid of that.

It also includes you know, getting rid of damaged organelles like mitochondria, where this is referred to as mitophagy. Um, that also is really important for clearing away damaged mitochondria. So typically, um, that, that pathway is activated before the apoptotic pathway. So when you, when you're getting into like a 24 or 48-hour fast, you're, you're, you're dipping into autophagy As you start to get into more of a stress, so you get into the 48-hour mark and on to a prolonged fast, you start to get apoptosis where the stress becomes— the dose of the stress response is higher. And so you're now activating apoptosis pathways, which essentially take those cells that have all the damage and they just kill the cell. It's like, the cell isn't worth it. It's gonna— you know, I'm gonna kill it.

So cell dies. And at the same time, you're getting that activation of the stem cells. So I would say that the stronger the stress, the better to some degree. I mean, you obviously don't want to like— you're not— you don't want to like have a really, really strong, strong stress response, but that's, that's not happening from something a little more like a 48-hour fast or 96 or even, you know, 4 or 5-day fast. I think that probably the best thing would be, uh, if you do, if you do the 2 48-hour fasts, you're, you're getting, um, twice, you know, you're getting the twice the amount of autophagy and some of the apoptosis benefits. If you're doing the 72-hour fast, then you're going to really push into the apoptosis benefits.

But Stan says he's already doing a 96-hour prolonged fast, in which case you would get the apoptosis benefits. So probably 2 48-hour fasts would be would be my inclination, but no evidence on that. So completely just, you know, what would Rhonda do? All right, Evan asks, and this is very relevant to the question I just answered, could you talk about the relative effectiveness of different methods for stimulating autophagy, mitophagy, including things like water fasts, intermittent fasting, exercise, polyphenols? Yeah.

So I would say data shows, if you look at animal data, it shows that the strongest inducers of both autophagy and mitophagy are water, so basically not eating, so water fasts, and that would be probably more translatable to humans at like the 48-hour mark, but you probably also get some before, it's just, you know, This is all like kind of hypothetical stuff we're talking about. Exercise is probably also one of the strongest inducers of autophagy and also mitophagy, and that's been shown. There's been animal evidence and also some human studies looking at some biomarkers of autophagy after exercise in muscle tissue. It seems pretty limited. A lot of the autophagy studies in humans are limited to muscle biopsies.

So, whether or not exercise is inducing a widespread autophagy like fasting is, it's sort of unclear. Um, certainly you're working your muscles the hardest, and so it makes sense that that would have the most robust response. And, you know, at the same time, because you're working your muscles harder, you're then putting more energetic demand. So your energetic demand goes up, which means you're Your metabolism's increased because your your body is trying to utilize you know energy in order to to keep up with with the work that you're doing. So in that case, it's kind of mimicking a fast in a way because you're you're basically getting rid of the getting you're you're using up substrates, right?

So I think that the exercise exercise and the the fasting and exercise are the strongest inducers, and then the polyphenols, like for example some polyphenols in in coffee and also tea have been shown to mildly induce autophagy. And this can all be found, as Dan mentions in the chat, in the Guido Kroemer podcast. Uh, actually, I think it's pronounced Kramer, but, um, that podcast talks all about that stuff. Um, talks about the fasting and exercise and, and so, and the polyphenols and autophagy. All right. Um, Alexis asks how fasting affects the gut microbiome, and she, you know, goes on and on about how I've talked about wanting to ask scientists about this before and if there's any updates.

And so there's actually been 2 animal studies that have very recently— actually, this both happened this year— have, have looked at the effects of intermittent fasting, and, and this is in animals. So an intermittent fast, you know, if you're talking about a 24-hour fast in a mouse, certainly, you know, would be something more equivalent to, you know, a multi-day, like 3-day, you know, fast in a human because their metabolism is so incredibly fast. That— so fasting has been shown to increase, interestingly enough, increased diversity of gut bacteria and increased the production of short-chain fatty acids.

which it's presumed that's how diversity is increasing because presumably some of the ketone bodies may be getting crossing over to the gut and then fueling the growth of a variety of different commensal bacteria species. So I think it's very interesting that it seems as though fasting is positively— it seems to be positively affecting the gut microbiome, and there's also other biomarkers looked at the same time. So simultaneously, it's reducing inflammation and increasing mitochondria in adipose tissue. So these things are all— it's not only changing the microbiome, but it's also changing other biomarkers of health in a positive direction. So Proteus says, so the body may be actively feeding the gut flora. The mechanism isn't really clear.

It seems as though there's an increase in production and things like lactate and butyrate. Presumably, that's what's happening, but it's really unclear how exactly it's happening, but it is something that is happening. There is an increase in short-chain fatty acids. So, you know, it's a very interesting— I agree, it's certainly interesting. So, all right, I'm gonna move on because I have a lot to cover. So I think I'm gonna go into Dan, was Jed here? Is Jed still here? I can do the sulforaphane real quick because there's only a couple of questions on that. So Proteus asks— Jed said he's here. I'm not exactly sure. I have to— he has to— Trying to find his All right. I would like to add Jed. Dang it, I'm trying to find his. Let's see. Ah, here we go. Jed Fahey, invite on screen.

Can I invite you on screen, Jed? I'm not sure if you have everything set up. I'm gonna go ahead and invite you and see if it works. If not, you can just chat. So the first question on sulforaphane is by Proteus, and he asks, broccoli sprouts still the best way to get sulforaphane? How do you maximize the production in sprouts? Freeze them? Do you have to steep them? Both? Let them sit after blending to allow my rosinase time to react with the glucoraphanin. So I would say that personally, I, I was freezing my sprouts after, so I stopped steeping them. That whole protocol I definitely stopped doing.

I started growing my sprouts and doing only like a 3-day harvest because some of Jed's data showed that that earlier harvest had a higher concentration of glucoraphanin, presumably because the plants were younger, and it seems as though younger plants have more glucoraphanin. And then I was freezing them and then using the frozen sprouts. Now, for whatever reason, After— all right, so Jed should be able to do the, um, the video. I just invited him on screen. For whatever reason, this, this freezing the sprouts appeared to, um, give me stomach problems and Dan stomach problems. And we did test it multiple times, and for whatever reason, it just kept doing it. And then we started just Uh-huh.

And then I started putting the sprouts in the fridge after 3 days and just using the sprouts fresh, and it stopped the issue. So I don't know what exactly was going on, whether or not the freezing of the sprouts concentrated the sulforaphane and that was giving me stomach issues, or if there was something that was contaminating them from harvest to the freezing or within the freezer or just opening and closing the freezer door or whatever. I have no idea. All I know is that when I stopped freezing the sprouts, it fixed the issue. So I stopped eating frozen sprouts. Maybe Jed can explain. For some reason, the video is not connecting even though I invited him. And then in terms of letting them sit after blending, I certainly do.

wait a few minutes to allow the myrosinase to act, you know, become active and react with the glucoraphanin. On a similar note, Scott asks if freezing the sprouts decreases the epithelial-specific protein activity enough to maximize the formation of sulforaphane instead of sulforaphane nitrile. And that would be something that I would turn to Jed To answer, okay. So personally, I think that like broccoli sprouts are the the best way to get the sulforaphane. They're certainly the most cost-effective way, and I think they're the most concentrated comparing comparing to the supplements that are available available in the United States, of which there's really only one that I think is. is worth it, like Avocall, um, and which I have been taking, by the way.

So I've, I've recently been, been taking Avocall, um, because it's just— I've been so busy with being a new mom and everything else that I'm doing, uh, that it's just, uh, it's been easier for me to just take the supplement. Um, interestingly, I— so I take about 4 pills a day, and that There's around— I've talked to some of the manufacturers to get the actual concentration of glucoraphanin and then potentially sulforaphane in each pill, and it turns out there's really only about 3 or 4 mgs per pill, a little bit lower than I originally thought. So I'm taking 4 pills a day of the Avmacol, and I really like it. So that's another way to get, potentially get the sulforaphane.

But I do think broccoli sprouts are the way to go if you, if you, you know, and I will go back to doing that, to sprouting for sure. So steeping at 70 degrees Celsius for 10 minutes is not necessary. And that, that was something that, that was based on some data from another lab and Basically, I spoke with Dr. Fahey about whether or not it was necessary to steep the sprouts at 70 degrees, and he seemed to think that his data suggested no, that was not necessary. It's an extra step that's a little bit more of a hassle than anything else. So, and you potentially risk even botching things up because myrosinase is heat sensitive. So it's definitely simpler to not have to do that.

All right, I'm gonna move on to— I will get to diet eventually, like I mentioned, that's definitely one of the major topics. Let's talk about Alzheimer's disease. And if Jed, if Jed Fahey ever does connect, then he can answer some of those questions in more depth. So Alexis asks, what are your thoughts on Dr. Dale Bredesen's Alzheimer's Protocol? And it's really sort of fitting that she asked this question because I just interviewed Dale Bredesen a couple weeks ago. Went up to Berkeley and I had an interview with Dr. Matthew Walker and Dr. Dale Bredesen.

And so we talked all about his Alzheimer's protocol in that podcast, and he's got a really specific protocol, and he basically categorizes Alzheimer's disease into these 3 main cat— well, he's got actually, he goes into much more than 3 categories in the podcast, but I'm gonna simplify it to 3 categories, which he also has simplified it to 3 categories in publications. So he's got the inflammatory phenotype, which basically basically people have high biomarkers of high inflammatory biomarkers in addition to biomarkers for insulin, basically more of a metabolic syndrome, insulin resistance, high blood glucose. And a lot of people with the inflammatory subtype of Alzheimer's disease also tend to have an APOE4 allele.

Then there's the non-inflammatory type where basically have everything They may have everything, all the metabolic problems and insulin resistance, but they don't seem to have inflammatory biomarkers that are very prominent, and they may or may not be APOE4. So while APOE4 is overrepresented in the inflammatory subtype, it's not necessarily overrepresented in the non-inflammatory subtype, but it still can be present. And then there's the third type of Alzheimer's disease, which is seems to be its own sort of subtype. And it's people that get this, they have very different phenotype than most other people with other types of Alzheimer's disease where they tend to have some— exposed to some sort of toxin or something, they tend to be really zinc deficient.

And instead of losing their short-term memory, which is they're basically amnesiac, which is what a lot of people with Alzheimer's get, their short-term memory goes, these people tend to lose long-term important functions like how to process, like do math, or even actually even how to speak in some cases. So it's a very distinct type of subtype of Alzheimer's disease. But I will just say one last thing. He's got these inflammatory and metabolic biomarkers that he looks at and they're very specific. So he talks about, for example, he wants to improve people's diet and inflammatory status based on on having a fasting— wants their fasting insulin to be less than 7.

He wants their HbA1c to be less than 5.5. Um, he wants, you know, their inflammatory biomarkers like high-sensitivity C-reactive protein to be less than 1. He wants their albumin to globulin ratio, which is— can also be a marker for inflammation. He wants that to be less than 1.5. Um, he also looks at homocysteine and has a very specific requirement for homocysteine. Uh-huh. What does he want there? He wants their homocysteine to be— I can't find that, but he has a marker on it. He talks about it in the podcast. So he has this, he basically has all these really specific requirements and it seems to really work in at least with his patients that he's worked with. So I think that it's really interesting and I think that overall the protocol is a good thing.

He talks about doing time-restricted eating and intermittent fasting He talks about taking fish oil and probiotics and exercise and optimizing sleep. So all those things are really important. So I would say that I'm pretty much on board with that. You know, like I said, the podcast is coming so you can learn more about that soon. Looks like Jed's still working here. All right. The next question is, um, the next 2 questions are about the glymphatic system. And so the glymphatic system, so, so Sven asks, what are different strategies that we can do to stimulate the glymphatic system for optimal brain health? And which phases of sleep are important for the glymphatic system, which is important for clearing away amyloid amyloid plaques.

So during sleep, the brain actually squirts cerebral spinal fluid into the brain spaces in between neurons, extracellular space, and it basically clears out dead cell— you know, debris, dead cellular debris, clears out protein aggregates, it clears out amyloid beta plaques. It's literally like a cleaning system that squirts and washes everything and then cleans it out of the brain. Mm-hmm. And this actually happens during deep sleep. So the glymphatic system is activated 10 to 20-fold during deep sleep. The slow— when your slow brainwave activity is occurring in deep sleep, usually happens in the early part of the sleep cycle. So deep sleep also happens to be the sleep cycle that decreases with age. And so of course, Alzheimer's incidence also increases with age.

There's probably some connection there. So things that can improve deep sleep, I mean, it's a big question. And it seems as though in some studies, exercise, and particularly intense exercise, has been shown to improve deep sleep. improved, meaning you spend a longer time in deep sleep. So, um, which is really interesting because exercise itself has actually, in animal studies, been shown to activate the glymphatic system. And this was actually new to me. I was doing some research a few weeks ago on the, on the topic and found that, that study. And so I was really excited to see that exercise itself actually Um, to a much less degree, but it makes sense. I mean, you're, you know, you're— the lymphatic system and all those things are being activated with exercise.

So, so exercise— sleep is the main way and exercise is the second way. And it just turns out that exercise also seems to activate the stage of sleep, which also activates the lymphatic system. So it's kind of a win-win situation with exercise, um, for sure. And then Georgianne asks about other things that can potentially activate the, the glymphatic system, like inversion yoga and potentially the sleeping position, um, pillow. And I, I just don't really have anything to add there because there's just not a lot of data, or data at all, to, to really speak to that. But, um, certainly there's more people now investigating the glymphatic system and what activates it, so I'm hopeful that things will We'll start to learn more and more about other things that can activate the glymphatic system.

Okay. What are your suggestions for the best measures to prevent dementia in people who are ApoE3/ApoE4 carriers? So I will just mention again the podcast that I did just recently recorded with Dr. Dale Bredesen. all about that. We talk about APOE3, APOE4 carriers, best, the best modulatable risk factors that are important that can lower Alzheimer's risk for APOE4 carriers. And in a nutshell, it really seems to be, it really seems to be exercise and sleep. Optimizing for exercise and sleep are 2 of the key ones. I'm actually just changing. Okay, there we go. I'm inviting Jed again. So, so exercise and sleep are the main ones, and then avoiding alcohol consumption. Avoiding most mostly avoiding alcohol consumption. Okay, sorry, I'm I'm going to remove the the invitation to Jed.

I think that he's it's been frustrating enough, and so in terms I actually just. Just got a paper accepted for publication. I just pending a few revisions by the reviewers, which I just resubmitted, and the paper is all about a particular lifestyle intervention that ApoE4 carriers can do. As soon as that paper is 100% accepted and has a publication date, then I can feel more comfortable to talk about that. But right now, I'm still kind of keeping it. keeping it under wraps. So I will be announcing that and I will do a Patreon post on that as well. But really, some of the main things for ApoE4 carriers is actually sleep is one of the main ones because there's really 2 main ways the brain can clear amyloid plaques out.

One is through the glymphatic system, that's one of the main ways, and the other way is through an ApoE-mediated mechanism. Turns out ApoE4, so you make ApoE in the liver and it has to do with cholesterol transport and lipoproteins. and all that, but you also make it in the brain. There's 2 pools of ApoE, and the ApoE made in the brain plays a very important role in clearing away amyloid plaques through this whole mechanism where it binds to the plaque and like basically just pulls it out and clears it out. But turns out that ApoE4 binds to amyloid like 20-fold less efficient than ApoE3. So ApoE4 carriers almost exclusively rely on the glymphatic system to clear away sleep— I mean, to clear away amyloid plaques. Now, almost exclusively but not necessarily.

So people that only have one allele still have one. If they have an APOE3, they still have one good. So you're still not quite as bad as someone who is APOE4, APOE4, so has 2 alleles. People that have 2 alleles, I mean, they're just not clearing amyloid plaques from their brain via the ApoE mechanism. They're 100% relying on the glymphatic system. People with one allele still, um, have— don't have as much clearance as people that have ApoE3/ApoE3 in terms of clearing the amyloplex via that mechanism. But we have this other mechanism, the glymphatic system, which is completely active during sleep. It seems like exercise also activates it to a certain degree, and exercise also seems to improve the deep sleep, which is the stage that it's active in.

So that, that's, those are, and also there's been studies showing that people with APOE4 that routinely exercise and get good sleep have a complete normal Alzheimer's disease risk, just like people who don't have an APOE4 allele. So that research, and then the research on the sleep and the glymphatic system and the mechanism of amyloid clearance, all those things are what sort of make me say that really 2 real main, main, main things are exercise and sleep. And then there, of course, there's other, you know, important lifestyle factors like eating a healthy diet and not eating a lot of refined sugars and things like that, keeping inflammation at bay and all that. So Jed said— so Dan says— oh, Dan's talking to Jed. Okay. Let's see if there's any other questions.

Are you familiar with any research regarding Parkinson's and fasting? I am not so familiar with Parkinson's and fasting. There have been a couple of very small, very, very small— I mean, we're talking like 7 or 8 patients with Parkinson's disease where ketogenic diet was implemented and there seemed to be improvement. However, you know, there's, there's just, it was very subjective and there's no, you can't eliminate placebo effect. And, but there does seem to be some promise. Also, there's, there seems to be some evidence that, that ketone bodies themselves may be beneficial for Parkinson's disease, which, you know, which again would hint at maybe fasting and, and/or even possibly a ketogenic diet.

I am going to be looking into Parkinson's disease, and I'm trying— actually, I just emailed the Parkinson's disease researcher yesterday trying to do an interview, trying to get a podcast interview with an expert looking at— interestingly enough, low cholesterol dramatically increases Parkinson's disease risk, and statin use increases Parkinson's disease risk. So I'm trying to sort of dive into some of that research with one of the experts, and I hope that works out. I'm glad people are asking Dr. Fahey questions over here in the chat. It makes it easier. Frederico asks, Dr. Jed and Rhonda, is there any way to notice if Advocaat is quote unquote working, providing sulforaphane effectively to my body?

I mean, I know there's, you know, you can measure metabolites, but I don't think that's something that's done outside of a research setting, you know, so perhaps you can monitor other biomarkers of inflammation, oxidative stress, so inflammation should go down presumably. Okay, let's see, I've got an hour left, so I'm gonna get through this probiotic question and then I'm going to probably start getting into the diet. Okay. I got some supplement questions too. Okay. So there was a recent study that— so Stanley talks about a recent study that showed probiotic— supplementation with probiotics can cause brain fog. Yeah. That was a very disturbing study for me.

So I took a look at the study, quite complicated, and I'm actually gonna reach out probably to the authors and ask them some questions. But in a nutshell, the brain fog, the probiotic use and brain fog was limited to people that had small intestinal bacterial overgrowth. You're supposed to actually have most of your your bacteria in your gut are supposed to be limited to the colon, so the very distal end of the large colon. Small intestine is where your carbohydrates and proteins and fats are metabolized and absorbed. Fiber, on the other hand, is not meta is not absorbed in the small intestine, and it and it goes makes its way all the way through the large intestine, where if it's a fermentable type of of fiber, it will then be, um, it will then be used by, by the microbiome in your gut.

If it's non-fermentable, then it just basically makes its way into your feces and it kind of just helped move things, move things along. So the, the— sometimes you'll have bacteria that get into the small intestine, and this oftentimes are— these are more of a pathogenic type of bacteria, bacteria that contain little flagella and swim up, and a variety of You know, there's so many different things that can potentially lead to that. But once they're— once you have the small intestinal bacterial overgrowth, then you start to have bacteria then that can start to eat sugar because that's where glucose and stuff is absorbed. And so then you start to like, you know, it sort of becomes this problem that spirals out of control.

Well, it turns out that taking probiotics you know, some of the probiotics there are that, that you're taking in can produce short-chain fatty acids that are then utilized by the bacteria in the small intestine. And this can basically— there's some sort of something happening that can affect the brain. And, or at least, I mean, the brain fog is a very subjective measure, but regardless, it seems to be limited to people with small bacterial, small intestinal bacterial overgrowth. And again, I'm I think I'm going to reach out to the authors of the study and sort of ask some questions about that as well. Okay, um, I'm gonna quickly talk about some of these. Um, oh, I forgot one question about fasting had to do with supplements. That was from Dana.

She asked what herbs, supplements can, can you be take— can you take them at bedtime or breakfast? Um, or medications and things like that. Obviously take any medication that your doctor is telling you to take at the time they tell you to take it. Herbs and supplements, for the most part, I wouldn't worry too much about them, you know, breaking your fast. I mean, you know, certainly if you can take them within your eating window, that's better, but I wouldn't, like, I wouldn't sweat bullets about that. Okay, supplements quickly. What's my process for choosing a supplement brand?

Honestly, my process right now is I've basically spoken to other researchers like Dr. Jed Fahey that I, that have verified at least some brands of supplements, but I also use services like ConsumerLab, Labdoor, and the International Fish Oil Standards Program. And I basically just look at a variety of those sites and kind of figure out what doesn't rank well or what, you know, ranks well in combination with some of the brands that I know seem to be pretty reliable and I use that. In terms of fish oil, and there was someone that asked, actually Will asked about fish oil because he had mercury poisoning and has a very, is very sensitive to it. There's, you can look on the International Fish Oil Standards Program page.

If you click on product reports, you can type in a brand of fish oil a very specific brand of fish oil, and a variety of different measures are looked at, and they give you data for mercury, for, you know, other things like phthalates, um, um, and then, you know, they give you the total oxidation numbers. And so you can actually look and see, you know, sometimes you'll have some fish oils that have the low— have lower mercury but a little bit of a higher total oxidation. Um, some will have a lower total oxidation but a little bit higher mercury, and some will have low of everything. Um, and so you can basically, uh, go through the Fish— International Fish Oil Standards Program products page and find a fish oil supplement that suits your needs. Um, and, and that would be my suggestion.

I'm personally, uh, taking a fish oil supplement from a friend that makes it in Norway, um, and he's kind of convinced me that his, his stuff is really pure and he's got a total oxidation of less than 5, which is pretty exceptional. His brand is what I'm taking. It's called Norwegian Pure 3. I really like it. I've been taking it now since the end of 2016. Um, so that's kind of my, my thing on, on the supplements. Uh, on a similar note, Shufet asks, do you see any reason why we should not drink mushroom coffees or take supplements like chaga or lion's mane on a daily basis, or should we use them sparingly? I think there's really interesting data on things like lion's mane some early clinical evidence showing an increased nerve growth factor in the brain.

Also, it seems to improve cognitive function in elderly individuals in randomized controlled trials. However, a concern of mine with mushrooms is that they're really— they really are good at absorbing metals, and depending on where the mushrooms are grown, you know, there's a potential for heavy metal contamination. As well as potentially even other, other things. They're, they're very— they're good absorbing metals and ions and things like that. So I'm— I stopped taking— I was for a while drinking lion's mane, um, not the coffee but the, the tea, and I just kind of got paranoid and decided that until I can like have a lab test showing me that the product's pure, I'm just gonna hold off for now. But again, I have no evidence of that.

So it very well may be fine, or maybe someone can reach out to the companies making these products and ask them to show them their data. In fact, that's something I may do in the future. Lastly on this supplement, Kevin asks, is too much of a good thing when it comes to plant polyphenols? Plant polyphenols can activate the hormetic stress response pathway, much like exercise or fasting can, heat stress. So is it like, should you be getting these polyphenols from plants or can you take supplements? Or is there like a threshold? And I would say, honestly, my biggest concern with taking a lot of the supplements with polyphenols and things again has to do with the fact that a lot of supplements are just unfortunately full of crap.

So, so you're really taking a risk, particularly the studies have shown, there's been published studies showing that particularly like a lot of these herbal and polyphenol marketed supplements are bogus and you're essentially getting clover leaf and, you know, God knows what else. So, so that's kind of my biggest concern. Now you may find a more— a brand that's more— a little more vetted like Thorne. And, um, you know, like they have some— they have nicotinamide riboside, for example. Um, but, but, you know, so typically I, I like to get my, my polyphenols from, from the foods because then you're also getting a variety of them and you're getting a lot of the prebiotics and stuff as well and fermentable fiber. And, um, so I always think that's best.

Um, and then the last supplement-related question has to do with Chris, and Chris asks about what I think about the recent controversy about fish oil supplements having little or no effect on cardiovascular disease. Um, and do we know if there's any benefits to fish oil and what the safest way, you know, to get them is? And I think again, the, the International Fish Oil Standards Program products report page for fish oil supplements because there are a lot of fishy fish oil supplements that are high in oxidation, high in, you know, phthalates or mercury. But to speak to the meta-analysis of the randomized controlled trials, I will just say this.

Unfortunately, most of those limited number of randomized controlled trials that were analyzed in the meta-analysis were people that already previously had a heart attack and were taking either statins or aspirin or actually blood— other blood pressure lowering medication. And those individuals taking that medication, taking fish oil supplement on top of the medication had little or no effect. So I don't think it's fair to say that taking a fish oil supplement has no effect on cardiovascular disease risk because You're talking about a very, very particular participant population there, and, you know, someone that's already had a heart attack and is already taking some other statin or blood pressure or aspirin, you know, medication.

It doesn't speak to people that are— have not had a heart attack, are not on those medications, and are taking fish oil. So we don't really know the answer to that question with respect to cardiovascular disease. But I think the strongest evidence has to do with the effects of fish oil on brain function. A lot of new studies that have come out that I've actually even recently been sharing on social media having to do with fish oil supplements, in particular DHA, and the effects on behavior, cognitive function in children, and also the effects on cognitive function and memory and learning in elderly. So I think that I'm pretty convinced by, by the, the evidence that omega-3 is good for the brain. And so for that reason, I actually do take fish oil supplement.

All right, um, I've got about 40 minutes, so I do need to get into the diet stuff and But quickly, I'll just run through just a couple more questions I have on, um, the sauna. Ash asks, is there a way to mimic the effects of sauna use with— without regular exercise, without regular access to the sauna? I would say that there's now increasing evidence being published, uh, and also from speaking with sauna researchers, that hot bath, hot yoga, steam shower, things that are also causing heat stress that are activating the same stress response pathways, uh, likely have similar effects. Personally, um, I've been taking hot baths because I have not recently had any regular access to a sauna, uh, and it's just also really hard being a new mom and everything time-wise.

So I've been doing the hot baths, and, and, um, I do feel when I, when I submerge all, all from my shoulders down and I keep my, my, my legs and, and keep my, my feet and hands submerged I do feel, I do feel like I'm activating, getting a very similar activated heat response as when I sit in a hot sauna. And then Anita asks, in terms of the brain, we were just talking about brain fish oil. She asks, how do you lower the negative effects of menstrual cycle on mood and emotion? Are there supplements or foods that could help with this?

And I would say that one of the things that's known is that, you know, when when you're basically going into menstruation, your estrogen levels, when your estrogen levels drop during the luteal phase, estrogen actually activates the gene tryptophan hydroxylase 2 in the brain that converts tryptophan into serotonin. It activates it very, very powerfully, like 9 or 10-fold. And so when you take away estrogen, that enzyme decreases in activity. And so tryptophan isn't readily getting converted into serotonin in the brain. And so that can affect mood quite, quite acutely. And one of the probably most powerful ways to boost serotonin in the brain is actually exercise. So exercise is one way.

And then the other, the other way, and this is a publication of mine, happens to be through vitamin D and omega-3. Both they affect the— the vitamin D affects the same enzyme, 5-hydroxylase 2, as estrogen does. And, and, um, omega-3, actually there's 2 ways it actually— the EPA affects the release of serotonin from presynaptic neurons, and DHA affects the serotonin receptor function. So, um, and again, in animal studies it's been shown to improve serotonin functioning in the brain, omega-3 has. So that may be one way that also it's affecting mood as well. So that would be my, um, my suggestion. Andrew asks about air quality. He lives in Canada and has bad air quality, uh, asks about air filters and water filters.

I basically, um, I, I use a HEPA filter, uh, right now I'm using one that was a little bit, a little bit cheaper from Honeywell, but I actually plan on getting a more, um, like industrial type of HEPA filter. There's just too much data now coming out showing that air, air pollution is linked, you know, to chronic inflammation, just low-level grade inflammation regardless of diet and lifestyle. Uh, it's been linked to stroke disease risk, um, cardiovascular disease risk, Alzheimer's disease, and just all sorts of cancer, of course asthma and all that stuff. It's pretty, uh, more into— more, um, intuitive. So, so that's sort of my— and then Berkey filter is what I use for water. I'm gonna move on to the diet section now.

Let me just check the chat to see if there's any more questions because Um, um, let's see. I'm gonna— okay, so I'm gonna go on to the, to the diet. Section. Okay, so Alexander asks, I would love to get your thoughts on mechanisms of fat loss in the context of diet and different macro intakes like high carb, low fat, low carb, more high fat, what the most effective diet for— from a fat loss perspective is. Is it, for example, some say it's about calories in, out, others say it's more nuanced. So, and this is all in the context of fat loss because obviously there's lots of different factors, you know, health-related factors that one can consider. But so I would say that generally speaking, what the best diet is can absolutely vary from person to person. And that's been shown in studies.

It's been shown, various studies have looked at you know, glycemic responses to various types of foods and shown huge variation depending on a person's genetic makeup and also microbiome status. And so I think that, you know, you can, you can take an individual and that individual may, may actually be a lot more sensitive to eating a high-fat diet. And when they eat a high-fat diet, it can actually boost their free fatty acid levels, boost their blood glucose levels. They're not, they're not having— they're actually having higher blood glucose levels in response to fat. It can cause more inflammation, and the inflammation can then affect the weight loss. Inflammation directly does affect the ability to lose weight. I've seen that now in multiple clinical trials I've been a part of.

There's published studies on it as well where you can actually have a person that in all other respects should be losing weight, but they don't. And the one thing that seems to predict whether or not they're going to lose that weight is their inflammatory status. So, um, you know, so there's a lot of different factors that can play a role in, you know, whether or not someone loses weight based on a certain diet. So I think the best thing to do is see what works best for you. You know, I mean, I've, I've talked to people that have tried every single diet and nothing works for them. The only thing that helps them lose weight is actually not eating. They just have to stop eating, you know, do a prolonged fast and do multiple prolonged fasts.

And, you know, that's certainly— there's something to be said for that in terms of weight loss. And some, and some, something may be resetting. They may be resetting their hormones, their leptin, their insulin. All that stuff may, may need a reset. For things to kind of get more into balance, you know. And then once things are reset, then you can start to try to eat a diet that works, works best for you. You know, a ketogenic diet or even, even a low-carb, high-fat diet does not work for everyone.

It definitely seems to work for, for a lot of people, but, you know, I've spoke with a lot of people that it doesn't work for and have have people have told me about measuring a variety of biomarkers like their LDL particle number, small dense LDL particle number, and also triglycerides and inflammatory biomarkers go up. So the thing is, is that when inflammation goes up, you actually start to produce something called malonyl-CoA because it's important to make VLDL, which also goes up. And the problem with malonyl-CoA is that it is an inhibitor of something called the carnitine palmitoyltransferase transporter. And that transporter, also called CPT, is the transporter in which fatty acids get into the mitochondria so they can actually be used for energy.

If that transporter is inhibited, fatty acids can't be burned or used for energy. And so what ends up happening is that fatty acids get stored in adipose tissue. As fat, and so, or or the worst that you you can actually have them stored as visceral fat. But so the the point is that the malonyl-CoA levels increasing is what what causes that, and inflammation raises malonyl-CoA. The other thing that raises malonyl-CoA is constant fat intake. Like so if you're you're taking in more fat than you can burn off. Which would actually in this case have to do with calories in, calories out in a way.

Because if you're eating so much fat but you're not— your energetic demands aren't high enough to keep utilizing the fat, then the fatty acid, the malonyl-CoA that's being produced, builds up and starts to inhibit the transporter. And therefore you can't— there's no more fatty acids that are getting transported into the mitochondria. And so you end up storing fatty acids instead of using them, and you use glucose instead. So that's the other issue, and that's something that that can happen in animal studies.

Animals that are given a ketogenic diet, particularly ones that are given fed ad libitum, and and there's a lot of there's a lot of evidence that showing ketogenic diets can be obesogenic in mice and rodents, and that data has now sort of been teased out by people like Eric Verdin and others at UC Davis. That have shown if you limit animals, you know, the time that animals are eating the high-fat diet, so if you just put them on a time-restricted diet in a way or cyclic cycle them, they don't eat as much fat and they end up actually not only losing weight, more weight, that becomes beneficial in a lot of other respects. So, Sorry, I'm going to just get in. I'll come back to a question I just read by Ryan.

But the point is that, my point is that there is lots of nuance and that lots of nuance is buried in mechanism studies that are mostly from animals. And if you look at clinical studies, you will see mixed results. And maybe some of the animal studies, mechanistic studies can shed some light onto that. But obviously that's still, you know, combining the clinical data with the prospective data with the animal data is important because you need the big picture. So I would say that it certainly seems to be a lot more nuanced and it depends a lot on a person's genetics. You know, some people, they're a lot more sensitive to a high saturated fat diet and with a high saturated fat intake, people actually have elevated blood glucose and elevated blood pressure and triglycerides and of course LDL.

And so, um, and, and those things can lead to inflammation, can cause people then to start retaining more of the fatty acids in adipose tissue like I mentioned. So there's lots of, lots of things to consider. Um, and so for that reason, I think that— I think both diets can be good, and I think But, but I will say for someone, I'm talking about fat loss here, completely different perspective. If I'm talking about longevity, if I'm talking about longevity, really keeping the insulin response down and also keeping IGF-1 down to a certain degree, I think are, are important for longevity. I'm actually going to experiment, and I talked a little bit about this with Dr. Dale Bredesen.

Um, in the podcast I recorded a couple weeks ago, I'm gonna experiment with a ketogenic-like diet that is more, um, the fats are coming from plant sources and, and, and salmon. So avocado, macadamia nuts, olive, olive oil, lots and lots of olive oil and salmon. Um, and the reason for that is because I do have an ApoE4 allele, and I find that I do, I do better when I don't have a really, really high saturated fat intake in terms of my lipid, my LDL particle number. So, so I'm going to be experimenting with that. I do think that getting, getting a variety of vegetables is important and also some fruits as well. So that's something that can even be cycled maybe. Um, I mean, the vegetables I, I definitely want to have on a daily, daily basis.

And so I'm going to experiment whether or not I can get some of the benefits of, you know, I don't necessarily have to be in ketosis either. I think, you know, doing, doing time-restricted eating every day, you know, fasting for 16 hours, 15 or 16 hours a day, I am getting some ketosis benefits. Maybe once in a while then doing the prolonged fast Yeah. But really what I want to optimize for is just minimizing a really high blood glucose response. And the reason for that is because that pathway, when it's activated, inhibits a very important longevity pathway called FOXO. And I'm actually going to have a podcast, an audio podcast where I just am talking myself to myself and to you for, uh, for a little while about, about FOXO.

So I'll be talking all about that, um, in upcoming podcasts as well. But so that's something I'm experimenting with. So basically, um, I definitely think it's more nuanced, and I certainly think that to some degree calories in, calories out also can matter, but it's not always the case. So it seems to be a lot more nuanced in the context of fat loss, and I think that One thing that does seem to be consistent is inflammation and inflammatory status. And I think that that seems to be important for a person's ability to lose weight. And, and regardless on whether— regardless if they're on a low-fat, high-carb, low-fat, or a low-carb, high-fat diet, if their inflammation is high, the fat won't come off. And that, and that's something that is consistent.

So I do think that, that resolving the inflammation, that needs to be done. And, and the only way to do that is to try a variety of different things and continually measure that, you know, a variety of inflammatory biomarkers to see what is effective. And again, I think time-restricted eating and fasting sometimes often will reset that. In fact, and doing a prolonged fast may really help reset the inflammatory status as well. So, um, Henry asks, how close is your diet to Longo's longevity diet? I would say that I'm— I personally am not like a— like eating, you know, animal protein like every meal. I usually eat— I limit my, my animal protein usually. I'm getting I'm getting meat for for dinner, and that meat typically most of the time ends up being sockeye salmon, wild sockeye salmon.

But I also do eat some fowl, so I'll eat some you know chicken. I tend to try to get chickens that are pasture raised. Also, I'll eat you know pasture raised grass fed. Steak, you know, occasionally as well. But I also try to like correlate that with my exercise activity as well. You know, so the more I'm active, the more comfortable I feel eating, you know, more meat. So so personally, but but Walter's diet is really heavily on the vegetarian side, which is a little bit of meat. And I would say that I certainly eat a lot more than what is suggested in Valter's book.

But that's just because I think, um, if you just look at the epidemiological studies— and I've talked about this before, so I'm not going to go on about this— I think that, um, that, that the exercise, you know, exercise activity and a variety of other health status biomarkers really seem to be important for determining whether or not a person is at a higher risk for mortality or cancer-related mortality from eating animal protein. And that's, that's been published even by Valter, actually. He's shown that people that eat a lot of meat, um, do have a higher all-cause mortality and a higher cancer-related mortality, but only the people that are sedentary, obese, smokers, or consume a lot of alcohol.

People that eat a lot of meat and don't have any of those unhealthy biomarkers have the same cancer mortality risk and all-cause mortality risk as people that don't eat meat. So, um, so I think there's just— there's a lot of other confounding factors in a lot of this, a lot of observational and prospective studies that need to be looked at. That— so, so that's, that's, you know, um, one of the reasons why I don't really worry too much about eating, eating some meat. Plus it's important to you know, and maintain muscle mass and all that. Um, let's see. Oh, okay. Yeah, so this one's a big one. Um, let's— so my thoughts on the carnivore diet. Um, and I'm gonna, I'm gonna kind of just briefly speak on this, uh, because it is something I plan on speaking about hopefully.

Well, I can do more research on it and then speak about it More in depth, but I don't. I'm not a fan of this type of diet, diet of just eating only meat. I think most people probably would already, if they had to guess, would guess that I would say that. You know, there's it's just it's certainly not something that it's just you know you just just getting meat you know and not not getting the diverse important micronutrients that are present in in a variety of plants. and nuts and seeds and all that stuff is, in my opinion, just, it's kind of weird. I do think that there are, you know, there are people reporting certain benefits and I think those benefits are probably real. And, but can they, can probably be explained by doing a very restricted diet.

And I think that, for example, if you look at Dr. Satchin Panda's recent Cell Metabolism paper, he published a study showing in animals, if you treat the animals with antibiotics and wipe out their microbiome, it improves their insulin sensitivity and lowers their blood glucose levels, which are 2 biomarkers that you would— if you just looked at those in isolation, you'd say that's improved health status right there. Yeah. However, it doesn't mean that prophylactic antibiotic use is healthy. It just means that there are certain species in the microbiome, clearly, that are regulating blood glucose levels and, in turn, insulin sensitivity.

And I think that it is certainly known that the microbiome composition, and that's that's also something that's known is that microbiome composition also determines someone's glucose response to food. So if you're doing a really restricted diet, like for example, only meat, where you're not really eating fermentable fibers and likely affecting the microbiome, you may find that you're temporarily, transiently improving some some markers of health status. In a very similar study, antibiotic use was used in an animal model of multiple sclerosis, an autoimmune disorder, and gut microbiome has been linked to autoimmunity in multiple studies and particularly into multiple sclerosis.

Well, turns out when you eliminated the microbiome through antibiotic— actually a certain species, they seem to pinpoint it down to But again, using antibiotic treatment improved multiple sclerosis symptoms, and they showed this was because it eliminated a certain strain of bacteria that's able to migrate into the small intestine. I was talking about this earlier, and that strain that migrates into the small intestine has been shown to then metastasize to other organs and affects global immune function. Well, antibiotic use was able to eradicate that. Again, that doesn't mean that's healthy to do prophylactic antibiotic use.

It just means that there's an interesting interaction between the microbiome and the immune system, which we already knew, and that modulating the microbiome and changing it can affect immune function and autoimmune function. So finding a way to modulate it in a good way would be ideal and not, you know, prophylactically giving someone antibiotic— antibiotics, which are also harmful long-term. So I basically, I think, you know, these are things to consider. And, um, um, of course there's a lot of other things as well. People that are only eating a very restricted diet like that actually tend to end up eating a more calorically restricted diet in some cases. So there's just a lot of things.

The micronutrients, there's certain micronutrients that are really abundant in plants like folate and magnesium. Really important folate, you need to make new DNA and it's an epigenetic, it's used as an epigenetic precursor to change a variety of gene expression. Magnesium is a very important cofactor for basically to make and utilize energy, ATP, you need magnesium. But it's also important for DNA repair enzymes and a variety of other enzymes in the brain. Um, you know, you can to some degree get some of these micronutrients if you already eat organ meat, but most people on a carnivore diet are not eating organ meat every day. And honestly, you know, there's a lot of long-term biomarkers like looking at DNA damage, things that, that aren't accurately measured by consumer tests currently.

And so there's just no way to know, you know, what this sort of diet long-term is going to do to someone. Personally, I think that a lot of benefits can be had by doing something like even a ketogenic diet, which is a lot more studied and also not as restrictive. It allows you to get— you're getting some, some vegetables, you're getting some protein, and you're getting some fats. Uh, you know, so you're, you're at least you're getting a more balanced diet. And also, um, even just doing a prolonged fast, it's been shown to improve autoimmune systems. It's been shown to improve multiple sclerosis symptoms in humans. Valter's research has shown that. So I think there's ways to get some of the benefits that people are reporting anecdotally from a carnivore diet.

By the way, anecdotal data, most often it's interesting Um, but is confounded by so many other factors. Most people change many factors at once, and you also have people that are going from a standard American diet to then restricting themselves to meat only. And well, well, that means they're cutting out all the processed refined carbs, so what if they were to just do that? I mean, you know, so there's just so much to consider. I do think that there's enough public interest that a clinical study is warranted. I think that should be studied in a controlled setting with data that's peer-reviewed and published. But we don't have that data right now. And so it's really, you're kind of just going off of anecdotal data. So, okay.

There was a question that, oh, I think Ryan mentioned the fish oil supplement that I use is not on that site yet, the International Fish Oil Standards site. And, uh, they're basically kind of limited to Norway right now. And I, I know that he's, um, trying to, you know, expand his market. And I think once that happens, um, and I'll ask him about the International Fish Oil Standards, um, if he's gonna, you know, get on, get into that as well. As I'm sure it costs money, um, to do. Okay, uh, next question. You are very clear about the benefits of eating a lot of fruits and vegetables and recognize the concerns about IGF-1 mTOR activation. Cholesterol and saturated fat. Where do you think plant docs like Greger and Barnard get their research wrong?

Why not recommend a totally whole food, whole foods plant-based diet? Okay, um, so I do think that people like McGregor, um, they don't— they look at a lot, they rely heavily on the, these prospective studies and these epidemiological studies. I just mentioned the biggest one to date, and Vulture was part of that research showing that people that eat animal meat do not— that do not— that are not obese, that do exercise, that don't smoke, that don't drink excessive alcohol have the same cancer mortality and all-cause mortality risk as plant eaters or people that don't eat animal meat. So I think that relying too much on prospective studies is, uh, dangerous because there are so many other confounding factors.

Randomized controlled trials looking at, you know, people that are eating even, you know, eating a high protein diet. I mean, I just recently, I think yesterday, shared a study. People were eating a really high protein diet for 2 weeks, high protein, high fat, low carb, and they had an improvement in a variety of health, health factors. Again, You know, you need to look more long-term. 2 weeks is not enough, but there are other studies that have looked more at like a month and have shown improvements in biomarkers as well. I think also knowing mechanism like IGF-1, the main problem with IGF-1 activation is cancer risk.

And if you can use that IGF-1 in a good way, again, there's, there's a U-shaped curve if you look at, at mortality risk, cardiovascular disease risk, mortality, uh, cancer mortality risk, um, for IGF-1 levels. So it's not just you want, you know, you don't just want low, low IGF-1 all the time, but you want to be within the sweet spot. And that's because IGF-1 does play an important role in muscle maintaining muscle mass and also in brain function as well. IGF-1 is critical for the ability of brain-derived neurotrophic factor to cause neurogenesis, to cause the, you know, neurons to become stem cells, to be neuronal stem cells, to get active and produce new neurons, you know. So without IGF-1, BDNF can't do its job properly.

So that's an important function, particularly because, you know, we start to lose brain volume as we age and the potential for neurodegenerative diseases as well. So I do, I do think that understanding mechanism and understanding how other lifestyle factors can modulate the mechanism, like for example, you know, allowing IGF-1 to go into the brain and to the muscle as opposed to someone who's just sedentary all the time and IGF-1 systemically in the circulation and just going around to all this, you know, tissues and then activate, you know, allowing potentially damaged cells to grow when they otherwise wouldn't. So I think that understanding all those mechanisms is really important, and that's not something I've seen.

I'm not familiar with Barnyard, but at least McGregor, I haven't seen him talk about. And I have also seen McGregor rely really heavily on in vitro data sometimes, which is very, very odd. Because dumping, for example, a compound, um, I think even he's talked about sulforaphane, dumping it on cells in culture and showing that there's DNA damage can be caused is very different when we know that something like sulforaphane is, um, a hormetic inducer, which means there is a dose-response curve that dictates you know, whether or not something's going to activate stress response pathways like the NRF2 pathway versus whether or not it's just going to be stress.

Very difficult for someone who's consuming a cruciferous vegetable or, you know, or a glucoraphanin supplement to have such a high dose that they're going beyond NRF2 activation into actual causing cellular stress and DNA damage. I'm not sure I've seen any evidence that that can even occur orally taking something. So I would— so I'm just a little cautious with people that are using in vitro data to come to a conclusion. Okay. Shell is asking, yes, I'm going to get to lectins. Thank you. Is the physiologic insulin resistance ketogenic diet causes damaging? Does baseline glucose eventually go up as a result of keto diet? So that's something that again seems to vary from person to person depending on their genetic snips they have and also microbiome makeup.

And really the only way to know that, a good way you could, you could basically test that is get a glucose monitor, something like I use Precision Xtra. There's other ones out there and measure your fasting blood glucose levels, um, you know, at baseline. And then after, you know, after X amount of days on a ketogenic diet, You know, to see to see how that affects. So Dr. Jed Fahey is now posting here important things about prostafane, which is a supplement from France. He's just ordered it and is going to be testing it. Great, great to hear. Um, let's see. Yes, you have to poke your finger with the Precision Xtra, but it really doesn't hurt. It's very easy. The lectins— I need to get to the lectins real quick too. So let me just quickly go to the lectin.

Should have been in my diet section for some reason. Okay, Creon asks, is there evidence to back Gundry's claim that lectins are a major source of inflammation? So this whole topic of anti-nutrients that really has gained a lot of popularity and lectins are basically everywhere and they're just, they're in all sorts of foods. They're just found everywhere in nature. For the most part, they are mostly destroyed by heating them with high heat. But the connection between lectins destroying the gut barrier has been dramatically blown out of proportion. And in fact, without any substantive evidence, because the evidence of the inflammatory effects of lectins is 100% in vitro.

I have yet to see any in vivo studies feeding animals foods with lectins and showing that there's an inflammatory response caused or it causes gut permeability. Certainly no evidence in humans, let alone, you know, if there's no evidence in animals, there certainly hasn't been any evidence in humans. So this is largely coming from in vitro, again, evidence where people are dumping lectins on usually immune cells, but I believe maybe even gut epithelial cells have been used. And so that's where this is all coming from, which is a big leap of faith in my opinion, particularly because lectins are found in a lot of very good foods that are, you know, Good, good for you and, and have important micronutrients and important fermentable fibers.

Now there is something to be said for someone that may have small intestinal bacterial overgrowth or may have, um, IBS, IBD, colitis, some sort of gut issue. Um, they may be a little more sensitive to certain foods. that it may not even be the lectins, it may be more of a FODMAP thing. So I would, I would say that I think that there is definitely no animal or clinical evidence to substantiate Gundry's claim on lectins. There is biochemical in vitro evidence that shows that lectins can induce inflammatory responses. And that's that's about it. Food combining, Federico asks about my thoughts on food combining. Are there is there any evidence that you should not eat certain foods together? Excuse me.

I would say that not eating saturated fat with refined carbohydrates is really important, but in that case you should just not eat refined carbohydrates. Um, but so that combination is definitely very, very bad. Um, but interestingly, there, there, there was recently a study that was published in Cell Metabolism that showed combining carbohydrates with fats, um, not necessarily refined, but just carbohydrates with fats can activate the brain reward circuitry, um, very powerfully and can lead to craving more craving foods and actually to overeating. It's very interesting.

Um, but, uh, you know, what that all means and whether or not you should avoid eating carbohydrates with fats is, I mean, that's like another, I, you really can't answer that question based off of that data, but I thought the data was interesting. Um, the study, the same study also did show that, you know, fiber slows metabolism. So if, if the carbohydrates did have more fiber, that response wasn't quite as, um, robust. So, um, but it is, it is kind of interesting. But I would say that most, for the most part, I'm not super, super concerned about that, uh, with the exception of foods that are rich in polyphenols like blueberries, for example, combining that with dairy, um, or even some of the, the polyphenols that are found in, um, coffee or tea.

Dairy has something, has a protein in it that is able to, I think it's called salivary protein A, bind to the polyphenols and basically inhibit them, sequester them, and inhibit them from, from being biologically bioavailable. So I had at one point I was using half-and-half in my coffee. I had switched to this combination of MCT powder and coconut powder, and then I do a little bit of Ceylon cinnamon and some, a little bit of stevia, and it's a really good combination. But it doesn't have those proteins, so I'm hoping that the polyphenols in the coffee are bioavailable. But there's really no evidence to show To show what I'm doing affects bioavailability. All right, I've got about five minutes. Caleb asked recently posted a study some cancers can utilize ketones as fuel.

Basically, just wanting to know if mild carbohydrate diet to prevent ketosis is better. You know, so basically, I would say that we just we don't really know. The evidence on on the certain cancers that may use acetoacetate, potentially beta hydroxybutyrate, but I think there's more evidence that acetoacetate is being used. And just to keep in mind, acetoacetate, most of the time in humans that are in ketosis, beta-hydroxybutyrate is the major circulating ketone, as opposed to, I think, mice, the acetoacetate is higher. Something interesting to look into, particularly when we're translating mouse studies to human studies.

But I would say that the ketosis from fasting Like Walter has shown, that actually can be beneficial, particularly when combined with conventional treatments like chemo or radiation, because it actually sensitizes cancer cells to death more. We just don't have enough data to know, to really know the best, you know, best diet to eat or which cancers are using ketones or not. And then lastly, Pat asks about people having a PPAR alpha or APOE gene. Um, I talked about this a lot in the very last Crowdcast I did, so make sure you check that out. And, and I basically, um, talk about, you know, having a lower saturated fat and higher poly and monounsaturated fat intake.

That, that's been shown, at least in human studies, to, um, have you know, benefits on lipid biomarkers, on glucose metabolism, and also on weight loss. So, um, lastly, I just want to mention for anyone, I've got a bunch of t-shirts here. See all those envelopes behind me? These are all t-shirts, DNA Damage Sucks t-shirts. If any of you are dollar pledgers, you can click the link on the bottom here that says that you like this so much you want to upgrade your pledge. Um, upgrade your pledge to $5 and we will send you a shirt. But make sure you email me [email protected] or even just message me on— actually message me on Patreon, either way, and let me know your address. So for all you dollar pledgers that want a t-shirt, um, we'll send you one.

Feels overwhelming to figure out how to eat based on these reports. I think the the best really the best thing a person can do honestly is is just you know do do a panel of of lipid biomarkers and triglycerides and and and measure your your blood glucose and insulin sensitivity and and a couple of inflammatory biomarkers and and you'll really have an idea if the diet you're doing is detrimental or not to your health. Um, I think as I mentioned in the beginning, time-restricted eating, doing the exercise, these things play a really big role in, in your, your longevity and healthspan. So in addition to, you know, really avoiding the refined processed crap is probably one of the best things too, just cutting all that out. And like, like if it's not a whole food, don't eat it.

Like if it's Yeah. The refined sugar, all that stuff. It's just not nutrient-dense. After all that, looking at the high-fat, low-carb, that stuff, you can tweak a little bit. And I think that the real important thing is to cut out the refined stuff and to exercise and not be sedentary and to definitely optimize your sleep. And doing the time-restricted eating. The time-restricted eating is really important. And I think those things you'll find, you'll start to move, you'll start to modulate your markers of health status in a positive direction.