Rhonda Patrick — Fasting, Lowering Dementia Risk, Sauna for Longevity

16:8 fasting explained: not eating for 16 hours triggers autophagy and metabolic flexibility

Patrick walks through time-restricted eating -- 16 hours fasting, 8 hours eating -- and how it promotes autophagy and metabolic adaptation. They discuss how the fasting window can shift (noon-8pm or 2-10pm) and that training at harder intensities during the eating window enables metabolic flexibility.

"You've talked about, you mentioned the 16-8. So essentially you're talking about not eating food for a period of time. And that period of time, you know, can either be 16 hours, it can be 24 hours, it can be longer, in which case it would not be an intermittent fast, it would be more prolonged fast, which you also talked about. But with respect to the intermittent fasting, there are a few things that happen and there are a few reasons why people like to do intermittent fasting. First and foremost, I think most people like doing intermittent fasting is because they want to actually lose weight. And the weight that they want to lose is not necessarily their lean body mass. They actually want to lose their fat mass, right? So they want to lose fat. And that's a big reason why people do intermittent fasting. Well, it turns out that intermittent fasting is more of a tool for weight loss. And what I mean by that is that there have been multiple studies now that have looked at different types of intermittent fasting in sort of a community dwelling aspect where people are just kind of free to eat the way they're going to eat, but they're supposed to be practicing intermittent fasting. And what it's been discovered is that naturally people end up eating about 200 fewer calories per day when they're doing some form of intermittent fasting. So if they're eating all their food within an eight or 10 hour period, for example, usually they'll eat their food within a 10 hour period and then they'll fast for 14 hours. If they do that, they end up actually eating 200 fewer calories. And so they end up performing what's called caloric restriction, which we know can lead to weight loss. And so a lot of the weight loss actually comes from reducing calorie intake. But that doesn't necessarily mean that everything that's beneficial from intermittent fasting comes down to calories because it doesn't. But the weight loss definitely seems to come down to the calories because if you keep calories the same and then have people do intermittent fasting or not intermittent fasting, they won't lose the weight, but they will have a whole host of metabolic benefits. You mentioned glucose regulation improvements. I mean, you know, fasting glucose, postprandial glucose, HbA1c, which is a long-term marker of glucose regulation. They're, you know, lipids are more favorable. And then they have improvements in blood pressure, for example. That's another big one that people get with a more of a longer type of intermittent fasting. So they're fasting more like 18 hours and eating their food within like a six-hour window. That's another benefit. Now, you go even further, and I know this is something you're very interested in. So beyond metabolic benefits, and people want to get them, they want to get into what's called ketosis. So they want to be making ketones, these things that we're talking about earlier with respect to taking an exogenous ketone ester. Well, you make something naturally when you start to actually burn fat as energy, you start to make something called beta-hydroxybutyrate. But it takes about 12 hours or so. It depends on the person. It depends on how heavy of a carb diet they eat or how physically active they are. It can be a range, right? So if someone's doing a more ketogenic type of diet, they can actually deplete their liver glycogen quicker than 12 hours. It might even cut it down to like eight. If they're physically active on top of that, you might go down to like even six or something. So there's a big range here, right? But for a standard person on like a normal diet, they're going to take around 12 hours before they start to deplete their liver glycogen and then start to immobilize fatty acids from their adipose tissue and use that as energy. And when you start to do that, then you start to get into ketosis. Your body starts to then make beta-hydroxybutyrate, the major circulating ketone. Why do people want that in their system? Because it's not just a very energetically favorable source of energy. What I mean by that is that it takes less energy to use beta-hydroxybutyrate to make energy than it does to use glucose, for example. It takes more energy to actually use glucose. So it's more energetically favorable. It's a clean fuel. Yeah. Also, BHB, the beta-hydroxybutyrate, as I understand it, I mean, highly anti-inflammatory effects as well, right? Exactly. That was the next point I was going to make is that it's called a signaling molecule. So your body knows that it's in this stress mode. Okay. There's no food. It's food scarcity time, right? And this is something that it's evolutionarily tapped into our system, into our DNA, where times of food scarcity, when we're not eating, our body switches into ketosis, beta-hydroxybutyrates produce, and it signals to these other genes to basically make more of something beneficial. So it's been shown to reduce inflammation. It depresses something called the inflammasome, which causes inflammation. It's an HDAC inhibitor. So it's a histone deacetylase inhibitor. So it's globally affecting gene expression in such a way that it reduces genes that are involved in making oxidative stress. It actually activates brain-derived neurotrophic factor. That's the beneficial neurotrophic compound that's made in the brain. That exercise also activates as well. So it's doing all these beneficial things, right? And the other thing that it's doing is it's getting into the brain. It's being used as a very great source of energy. And so you have this sort of, you know, bypass for glucose where the glucose can then be shunted to be used to make glutathione, that very important antioxidant I talked about earlier that sulforaphane activates. Well, it turns out when you give your body ketones or your body's making ketones, your brain actually consumes a lot of that. There have been, you know, tracer studies that have looked at that. And what happens is because neurons are now using the beta-hydroxybutyrate as energy, glucose is no longer needed. And so that glucose that is there is then used to make NADPH, which is a precursor to make glutathione. And so it's called glucose sparing. You get this glucose sparing effect. And so that's another reason why people are interested in intermittent fasting. And then another main reason, and there's many others, I'm not going to like touch on everything, but the other main reason is it activates repair processes. And what I mean by repair processes is to be in repair mode, you have to be in more of a catabolic state. And we were talking about this earlier. People get so freaked out by the word catabolism. Oh, yeah. Last night when I was walking around New York City, we were talking about this, the catabolism. And I think even over the last few years, intermittent fasting has kind of gotten a bad rap because people now equate it with, oh, loss of muscle mass. I'm going to be catabolic. Well, in order to be in a repair mode, you actually do need to be in a catabolic sort of mode. These repair systems are so important for cleaning up all the garbage that's inside of our cells. And that can be things like protein aggregates. These are things that lead to aggregation, you know, like alpha-signuclein, which is involved in Parkinson's, amyloid beta aggregates, which is involved in Alzheimer's disease. It's not the cause. It's like the cause and the symptom. It's like both. It's involved in Alzheimer's disease. and then aggregates in our cardiovascular system that play a role in cardiovascular disease. But it also cleans out even damaged little, what are called organelles. And so mitochondria are organelle and our organelles get damaged. So you want to be able to repair that damage. And this process of autophagy is the process that does that. And there's lots of different types of autophagy. So if it's a mitochondria repairing damage to itself, it's mitophagy. But for all this stuff to be active, you have to be in that more catabolic state, which can be induced by not eating, can also be induced by like heavy endurance exercise as well. Okay. So talking about those sort of outcomes that people are interested in, those different endpoints that people are interested in achieving, I think something that you're specifically interested in is the metabolic effects of intermittent fasting as well as the repair processes like the autophagy. Yeah, for sure. And that's why I was asking because I don't really look as vain as the next person. I like looking less fat if I can, but it's not my main driver. It's mental acuity and hopefully staving off on some level things like neurodegenerative disease and even cancer possibly, which has been part of the reason I've done a lot of these extended water fasts, which is I realize there are a couple of hops here in terms of speculation, but it seems plausible that you might zap, you know, punch a couple of precancerous cells in the nuts by doing that. Not only does autophagy play a role in preventing Parkinson's disease, but also Alzheimer's disease as well. Again, this has been shown in many animal studies. We know that autophagy plays a role in clearing away the amyloid beta plaques that are involved in Alzheimer's disease. And yes, there are some people that have amyloid beta plaques that don't get Alzheimer's disease. They may be the more resilient non-APOE4 type of person. But we do know that many, many people do get Alzheimer's disease with amyloid plaques. And in fact, people that have, again, the SNPs in what's called the amyloid precursor protein, APP, that leads to amyloid beta plaque buildup, they get early onset Alzheimer's disease. So autophagy plays an important role in clearing away those plaques. And I will say what we don't have a lot of evidence on is like, what's the minimal effect of fasting dose to activate autophagy, right? God, I wish we had this. Right. I think what we do know in humans from like some of these old studies is that you do see some signal of autophagy activation after 24, 48 hours in humans. Now, does that mean that that is the only amount of time it takes to activate autophagy? No. So, most humans are probably doing, you know, anywhere between a 12 to 16 hour nightly fast, right? There's a period of time when we're not eating, and that is when we're sleeping a little bit before bed, right? Autophagy still happens in people. We just aren't measuring it because we don't have sensitive tools yet. And so it's not that I don't think a 16-hour fast doesn't act. I believe it does in humans. I believe there's some autophagy going on. It's probably not that much. But if you go into that 48-hour fast, then you're really starting to get more robust activation of autophagy. You mentioned sleep. And I've been trying to look at Alzheimer's from every possible angle and found literature looking at disruption of sleep architecture in patients with Alzheimer's disease and the possible application of Xyrem, I believe it is, which is another, it's a brand name in a bifurcated schedule for GHB, gamma hydroxybutyrate, which you have to be very careful with. It's a party drug. People die of it because it suppresses respiration. The person who bought my apartment in San Francisco died of a GHB overdose. But it actually is a tremendously interesting compound for increasing, I think it's deep wave sleep specifically, which does what? It helps the cleanup crew, right? To do its work and to actually take out the garbage cellularly. And so if I could wave a magic wand, I would have my relatives on something like Xyrem, might actually be a different type of sleep medication, like the Nora class. Nora might be Dora. I would also look at, and this is something obviously not suitable for most elderly people, but potentially lower dose psilocybin or psilocin. And there are, there is some actually very interesting, I don't want to call them speculative, hypothetical applications of that to Alzheimer's disease, which you can find on PubMed. And like the, from a mechanistic perspective, they're, they're super, super interesting. So I just want to double click on the sleep because that is such a critical component, whether you're fasting or not, to try to ensure that your sleep architecture is not hyper disrupted, which can be the case with lots of different types of sleep medications that you might take. And if you have really bad insomnia, it's like, okay, you can do all these other things, but boy, oh boy, it would make a lot of sense to try to fix sleep whenever possible. Great. I mean, yeah, so true. This low-wave sleep does activate the glimplatic system, which is cleaning out the amyloid beta aggregates as well. And the last thing I kind of want to mention is you were talking about the intermittent fasting and more prolonged fasting and the muscle mass loss or lean body mass, which people equate with muscle mass, which it's not. There's a lot of things going on. So the thing is when people are doing intermittent fasting, I mentioned they eat fewer calories, which means they're eating less meals. They're eating fewer meals. They're not eating as many meals. And so what ends up happening is people lower their protein intake. And that's an important signal for maintaining muscle mass and certainly growing muscle mass as well. So it increases muscle protein synthesis, which is important. If people are engaged in resistance training and doing intermittent fasting, they're not losing muscle mass. And in fact, they can even gain muscle mass a little bit, not much, but they can gain it too. So I think the key here is that if you're doing an intermittent type of fast, like a 16-8, where you're fasting for 16 hours, that's really not a long, long fast. There's not a lot of concern with losing muscle mass if you're, you know, resistance training. Now, a more prolonged type of fast, you're talking about 14 days, that's a long fast. And definitely, you're going to be losing some muscle mass no matter what. Now, how much you lose depends on how, I guess, if you can resistance train lightly while you're fasting, that would be huge because you would be then activating muscle protein synthesis through another signal, which is not protein, it's mechanical force, right? So that, I think, would be really important for preventing the loss of a lot of muscle mass. But what is interesting is that you do lose lean body mass, a lot of it, when you are doing a prolonged fast like that. And looking at the old literature and some of the literature that's been done, a lot of water, up to 10 pounds of water rate, which is crazy. You lose that, and your organs shrink. And this is something that's been also shown in animal studies and also by Dr. Walter Longo many years ago. He's shown in animal studies, prolonged type of fasting actually causes organs to shrink because a lot of the damaged cells, not only is autophagy getting activated and you're cleaning out damage within a cell, but cells that are so damaged that autophagy can't even fix them, they actually undergo death, cell death. And so you end up getting a lot of cells that die. And then what happens is during the refeeding phase, and this is key, the refeeding phase is the growth phase. And this is when you regrow organs. It's when your muscle mass comes back. You can go back, get your muscle mass gains back. And so having that refeeding phase is really important and getting the right nutrients like protein, for example, is key for that refeeding phase. But you also lose fat during that fast and you're losing visceral fat. And you had brought this up last night when we were talking and I did some reading on it because it was like, oh, it made perfect sense. Because your organs are shrinking, you're losing a lot of cells in your organs. You're also losing some of the visceral fat that surrounds the organs, right? I can get misclassified. Exactly. It gets misclassified as lean body mass. And so you look at this lean body mass and all you think about is muscle. Well, it turns out muscle is a small part of that. There's a lot of other stuff that's going into that lean body mass. So yeah, it's a pretty big undertaking, a 14-day fast. but i'll say this and this kind of like goes into what you mentioned about the fasting mimicking diet and perhaps even adding you know cream we can talk about that as well i do think i mean the fasting mimicking diet and perhaps even adding cream. We can talk about that as well. I do think, I mean, the fasting mimicking diet, you're not going to get the same amount of autophagy that you would get if you did a five day fast, water fast, because it's just impossible. You're getting some protein, you're getting some amino acids that's activating mTOR that shuts down autophagy. You're getting energy, ATP. There's a ratio called the ATP to AMP ratio, which you want it to be low to activate something called AMP kinase for autophagy to happen. And so when you're eating heavy cream or eating whatever, fill in the blank, any type of calories, you're changing that ratio. And so that AMP kinase is not getting activated as robustly. Now, the amount of inactivation of those pathways, which then will inactivate autophagy, depends on how much you're feeding, right? How many calories that you're eating, how much of that is amino acids. Specifically leucine, right? In the case of Longo, like really trying to minimize leucine as an activator of mTOR and so on. Yes, exactly. Yeah. So I think for the cream, if you're trying to do 16-8, if someone is trying to do 16-8 on a daily basis, and it's a non-negotiable for having an earlier feeding window because social, just everything compliance-wise isn't going to work, and you have to do it later, which means you have to wake up and still be fasting in the morning, right? Then you either like have to love black coffee, learn to love it, or try maybe MCT powder, MCT oil, because then you're not getting the amino acids in there to activate the mTOR, but you can do like a small, maybe like a tablespoon of it. And so you'll maybe just get a little bit of depression of autophagy, but not much. That would be my recommendation. Just a quick thanks to one of our sponsors and we'll be right back to the show. As many of you know, for the last few years, I've been sleeping on a midnight luxe mattress from today's sponsor, Helix Sleep. 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I also want to clarify for folks listening just to really make it specific. When I have had, I just like saying dirty fasting, I didn't realize that was an expression. I just think it feels fun, like a dirty martini. So dirty fasting is kind of cheating in this way. But when I do that, which is not all the time, I usually have black coffee or tea or something like that, but it is heavy cream, which is almost entirely fat. It is not creamer that you would just pull off the shelf. It is not half and half. It is heavy cream, which just from a macronutrient perspective is very, very, very different. And you can really overdo it on the calories also. So it's just like liquid fat effectively. But the MCT powder is a good idea. I tell you what, let's, if you're open to it, let's shift gears a little bit. I will just say, I wish somebody, nobody's going to do this, but would somehow get the ethics board, IRB, et cetera, to approve long-term human studies again in fasting, that would be great. Because you used to be allowed to do it. There are case studies of people who literally fasted for 300 plus days. I mean, like fat, what is it? 9,000 calories per pound. Like there's like, you can do a lot with that fat. So we'll see if I do 14 days. If I can do 14 days and then I might just go to 30, but then the refeeding gets really tricky. Yeah. I think people are concerned with gallstones. So when you don't eat for a long period of time, then you're not stimulating the gallbladder and the gallstone risk increases, which is what I think is the big concern with the long, long fasts. But I mean, if you're doing something like that once a year, I don't know if it's that big of a deal. Yeah. I mean, that's why I was doing a seven-day fast once a year for a long time. And then I took a break for a few years and I did a seven-day water fast and it was so incredibly unpleasant. And I had orthostatic hypotension where I'd stand up and I felt like I was going to fall over and my vision started to get funny and I was like, you know what, maybe this isn't for me. But I think it's because my machinery just wasn't developed for that. Having seen really stark differences in my mental acuity and sustained focus with the intermittent fasting. I'm like, okay, I feel like doing intermittent fasting, which part of my reason behaviorally, my interest in that also is that getting people to change their diet is fucking hard, meaning their diet composition, the food they eat. So if you can just say, hey, look, keep eating, whatever you want, same thing, but you have to fit it within this window, it's an interesting option B that might work for people who otherwise aren't going to follow a paleo diet or whatever. But if you do the IF, and then what I've done is like, all right, do the IF, maybe if you have some grains or in my case, legumes and stuff, okay, fine. And then shift to a mostly ketogenic diet for a period of time. Then I feel like you're pretty well teed up for a longer water-only fast. Maybe you supplement with electrolytes. This gets into all sorts of controversial territory. But if you're okay with it, let's talk about training for a minute because, and I'll force a really awkward segue maybe, which is one thing I noticed is that my ability to do zone two training, let's just for simplicity's sake, say that for people that's, you're on a stationary bike or a bike stationary is just easier to keep keep consistent. And you're cycling for 60 minutes at a wattage and a speed that leads you to the point where you could have a conversation with someone on the phone in short, full sentences, but you don't really want to, right? That's like the talk test. Intermittent fasting plus ketosis really helps by zone too. And then this leads into the question of just training in general. So I have to click on this. What type of exercise reduces heart aging by 20 years? Do you want to start there or do you want to start with VO2 max? We can start with VO2 max maybe because they're kind of leading to each other. And people might be going, what is VO2 max? It's essentially a cardiorespiratory fitness. It's calculated by VO2 max, which is essentially the maximum amount of oxygen you can take up during maximal exercise. And what's so fascinating about that is it's a really important predictor of longevity. So there have now been enough studies that have come out looking at cardiorespiratory fitness in the sense of VO2 max and how people with a higher cardiorespiratory fitness have a five-year increased life expectancy compared to people with a low cardiorespiratory fitness. In fact, if you have a low cardiorespiratory fitness and you go anywhere above that, like from low to low normal, it's associated with a two-year increased life expectancy. and people with a low cardiorespiratory fitness, and you go anywhere above that, like from low to low normal, it's associated with a two-year increased life expectancy. And people with a low cardiorespiratory fitness actually have higher all-cause mortality that's comparable or worse than people with known diseases like type 2 diabetes or cardiovascular disease or smokers, for example. So in other words, being sedentary is a disease and we need to think about it as a disease. And we should be trying to train to improve our VO2 max. And that is something that should be in our minds. And I say this because like just having this conversation that you and I are having right now, it takes about 11 milliliters of oxygen per minute per kilogram body weight just to have this conversation. Now just sit still and just breathe, it takes about 11 milliliters of oxygen per minute per kilogram body weight just to have this conversation. Now, just sit still and just breathe. It takes about three milliliters of oxygen per minute per kilogram body weight. And that's important because as we're aging, we're sort of heading towards this cliff of VO2 max. Our VO2 max goes down as we age just naturally. Even if you're training and doing everything, it goes down. And once you get to that cliff, everything becomes a maximal effort. Like talking, you're out of breath. Carrying groceries to your car from the store, you're just out of breath. Everything is a maximal effort and you don't want to be there. So you want to start from a higher up point so that when you're going down, that cliff is much further away. And that's where the training comes in because you want to find a training program that's going to improve that Thank you. so that when you're going down, that cliff is much further away. And that's where the training comes in because you want to sort of, you want to find a training program that's going to improve that cardiorespiratory fitness. And that's where you talked about zone two training. And that's the kind of what I would call moderate intensity exercise. So you're able to sort of the talk test, I like the talk test because heart rate is so dependent on the person's fitness level. But let's just say on average, generally people are, they're not at like 75 or 80% max heart rate. They're kind of below that on average. Now, some people may actually be above that, but the talk test is great because you can have a conversation, you're breathy, you don't want to have a conversation, but you can. So so. We know that people that are doing that moderate intensity type of training, if they do the standard guidelines of physical activity, which are about two and a half hours a week of moderate intensity physical activity, people that do that for two months, 40% of those people still can't improve their VO2 max. Yeah, yeah. Just different gears. Well, unless they actually add in high intensity interval training and that's where i kind of get into this i think people should be doing vigorous intensity exercise that's the type of exercise where you're unable to talk right so you you can't have a conversation because you're going you're going harder your heart rate is about 80 85 you know it's above 80 max rate. That type of exercise has been shown to improve VO2 max, especially if you're doing sort of what's called high-intensity interval training. As you know, you've talked about this a lot as well. You're doing sort of these intervals of going more vigorous intensity exercise, and then you have recovery periods where your heart rate goes down. So there's been a variety of different protocols out there that have been shown to improve the VO2 max if you do them. Generally speaking, what's happening is you're putting a stronger stress on your cardiovascular system, so on your muscular system, even on your brain. So the adaptations are greater. One of those adaptations is increasing your stroke volume. So being able to like basically transport oxygen to tissues faster."

190F sauna for brain health: Patrick uses sauna to get lactate and prevent neurodegeneration

Patrick targets 190F for sauna use, motivated by preventing neurodegenerative disease. Hot tubs show comparable effects on blood pressure regulation. She also uses 20g of exogenous ketones before early morning talks for a caffeine-free brain boost.

"And I'm giving a talk early in the morning, which is like 6 a.m. my time. I got to be like on my game. So I take the 20 grams and I kid you not, it's like you get this brain boost, but without I love you not, it's like you get this brain boost, but without like the caffeine, it's hard to explain. Yeah, without the creepy crawly ants on your skin. Right, without that like jittery thing. And even that, sometimes the caffeine isn't enough. Like if you're really jet lagged, especially if you're going across time zones. Well, also for me, it's like I'm a caffeine fast metabolizer. If I have a cup of coffee, I'm on fire for 25 minutes and then I'm sleepy. I think some of that is actually a glucose response, but that's a whole separate thing. Like I, I using glucometer when I was doing all my ketogenic experiments and so on, I'm like, wow, if I have too much coffee, there is a huge, which is not that surprising, spike in glucose and then a very predictable subsequent drop-off. So it doesn't end up being net-net that helpful for me unless I'm doing a 20-minute sprint on something, which is probably never. So the creatine is super interesting to me. Let me ask some very specific, maybe mundane questions, but I think they're practical, which is when the subjects were taking 20 or 25 grams, was that in one sitting? Was that in multiple divided doses? When you take it, is it in powder form? Is it little sachets that you can take with you on travel days? Is it encapsulated? What does it actually look like? With respect to all the studies, I don't remember if they were in one sitting. A lot of studies are. If they do like a 20 gram, it will be in one sitting. What I do is different. I do five gram doses. So creatine monohydrate is the form I take. It's the absolute true. It's the gold standard. Yeah. There's a lot of other marketing out there that talks about other types of creatine, but that's really the gold standard. And I had Dr. Darren Kando on my podcast. He's a creatine researcher at the University of Regina in Canada. And we talked all about this and he really convinced me creatine monohydrate is the way to go. I asked him about every type of of, you know, creatine under the sun, but the way I take it is in five gram doses. And so I do five grams first thing in the morning, and then I'll do my workout. And then I do another five grams about 11 AM. And that's my 10 grams that I get when I'm traveling. I do have these sachets that again, Thorn makes, by the way, no affiliation. I mean, there's like probably a million other, you know, I like Thorne because they're creatine is NSF certified. And so it's, it's free of contaminants. Like I really like that. So again, find your own favorite brand, but I like this brand and I like, they have sachets, which are five gram sachets. And so I will have my 10 grams for the day. Or again, if I'm traveling for work-related purposes, I will take 15 to 20 grams depending on how much I need. In that case, I will do two 10-gram doses. For me, I can tolerate that. I don't have any GI problems with it. Yeah, I was going to bring that up. Yeah, some people do. I think doing the five-gram doses is pretty easy on the gut. Most people don't have a big problem with the five grams. It's when they go above that. Right. So I'll say a few things. The NSF certified is a pretty simple cheat code just to use as a filtering mechanism for a lot of supplements. And it is shocking how inconsistent supplement contents are. I mean, I've looked at lab reviews of like 20 off-the-shelf melatonin products, and it ranges from zero melatonin up to like 20x the label amount. It's just bananas. So I use Momentus Creatine, but it's passing the same hurdle. And I will say good news, you can reduce the likelihood of cognitive deficit from sleep deprivation. Bad news is you could increase the likelihood of disaster pants if you have 20 grams at one sitting. And I will say, maybe from personal experience, maybe I'm just talking about somebody else, but if you really want to increase the likelihood of disaster pants, then you can do a bunch of caffeine, double espresso, or black coffee with MCT powder, and then have your creatine around the same time. That would be asking. You're going to want to pack some Pampers in your travel kit if you do that. So yeah, just be aware of the GI stuff. But I'm excited to up my intake because the science that you cited in the study or studies in your newsletter seemed really compelling. And it's also one of those supplements where it's like, okay, look, I assume this is on the grass list, like the generally recognized as safe. It seems very well tolerated over decades and decades of research, assuming you don't have some, who knows, right? Like really outstanding kidney dysfunction or something maybe. So why not in a sense? It's also relatively inexpensive compared to a lot of things. Let me ask you, just because this has been on my mind, with the sulforaphane, I mangled the pronunciation a bit, sulforaphane. You take that better on an empty stomach, better with food. This has become an issue when I'm doing the intermittent fasting sometimes, right? Especially if there's something like the A-Reds too, which I'm taking for the eye health, which is supposed to be twice a day. And I'm like, oh, it's part of the reason why I've been doing like the quote unquote dirty fasting with a little bit of fat in the form of that heavy cream in coffee was to try to take supplements earlier in the day that are benefited from some type of fat in terms of absorption. So sulforaphane, does it matter? I think if you can take it fasted, that's great. Some people find it kind of as hard on their stomach. And so they like to take it with food. And that's really the only reason to take it with food is because they get like upset stomach. Like it's like, you know, GI problem. So that would be, again, the only really real reason that you would have to really take it with food."