Ben Greenfield [00:00:00]: My name is Ben Greenfield, and on this episode of the Ben Greenfield Life Podcast.

Dr. Chris Rhodes [00:00:04]: When people fast for 36 hours, there's this unique set of metabolites that are elevated in the body that are really only elevated during a fast. And when we screened through those molecules, we were able to find that those were the ones that were really responsible for activating a lot of these cellular health and longevity benefits of a fasten. What's in Mimio are those four fasting metabolites that we identified have these synergistic effects. And what Mimio is basically doing is taking what the body naturally produces during a 36 hours fast and giving it back to people. So you can kind of recreate that state of fasting at a molecular level, stimulate activate these same beneficial cellular pathways that are associated with fasting to get the benefits of fasting without actually having to fast.

Ben Greenfield [00:00:56]: Fitness, nutrition, biohacking, longevity, life optimization, spirituality, and a whole lot more. Welcome to the Ben Greenfield life show. Are you ready to hack your life? Let's do this.

Ben Greenfield [00:01:21]: My guest on today's show is super duper smart when it comes to nutritional biochemistry. He has a PhD in nutritional biochemistry and also happens to be an expert on something nobody at all cares about these days, human fasting. I'm just kidding. It's obviously a pretty hot topic, especially that that age old question I always get, will this break a fast, bro? So anyways, and by the way, yes, putting 200 calories of creamer in your morning coffee will break it fast. But my guest on today's show may also have a little bit of a hack for that. I've been looking into his research and some of the formulations that he has gotten behind and helped to develop. And there's actually some really, really interesting so called bioactive metabolites that seem to be able to be mimicked by certain supplements that could mimic a fasting state. So my guest is Chris Rhodes.

Ben Greenfield [00:02:23]: And Chris has helped to found and is now the CEO of a company called Mimio Health, which is what's called a nutra technology company. And they create things that are designed to biomimic certain states in the body in addition to, or in particular, fasting. So if you want the juicy show notes for everything that Chris and I talk about today, you can go to bengreenfieldlife.com/Mimiopodcast. That's or Mimiopod. Sorry. M-i-m-i-o. Mimiopod.

Ben Greenfield [00:02:56]: M-i-m-i-o pod. So, Chris, I got to just jump right in and ask you the million dollar question here. What the heck is a biomimetic.

Dr. Chris Rhodes [00:03:07]: So a biomimetic is essentially kind of what it sounds like, right? It's something that's meant to mimic biology. So whether that's something like what we're doing, where we're trying to mimic these interesting regenerative states with a body or something like how speedos were designed from shark skin, or how certain wind turbine patterns are designed from those twirly blades of grass. That's the key thing about biomimicry, is that we're basically taking what nature has already designed, teasing it out, understanding it, and then using it in this new way so that we can kind of tap into these thousands of years of evolutionary knowledge and natural design in order to really skip forward in scientific advancement and create something that's useful for us that maybe nature didn't intend. I think that that's really, really powerful because I think of it as like a scientific cheat code almost. You know, like humans have been out playing around with science for hundreds of years, whereas nature and biology have been doing this constant trial and error for thousands and thousands and years. So why shouldn't we learn from everything that's happened in nature already and kind of use that as our jumping off point to develop things that can really have a big impact in human life?

Ben Greenfield [00:04:37]: So I know that some people, even though we're going to get into this idea of biomimicry when it comes to fasting, or right off the bat. So I'm just going to address this right away and ask you about it right off the bat. Going to push back and be like, well, Ben and Chris, there are so many spiritual benefits to fasting, or character building benefits to fasting, or, you know, or self-control enhancing benefits of fasting. Why would you just want to pop a pill that kind of drops you off at the top of Mount Everest rather than, you know, gaining all the character of the journey to the top.

Dr. Chris Rhodes [00:05:13]: Sure. Absolutely. I mean, there's definitely merit to that, right? Like, fasting in and of itself can be a very empowering experience, especially when you do it for the first time. I remember when I started getting into fasting, I was an immunology fellow at Stanford. You know, just started pouring through the research, really got interested in it. Started doing my own fasting, testing my blood at the same time, seeing what was actually happening in my body. And I remember the first time that I fasted, I thought I was going to die, right? Like I had never actually gone more than, I want to say, five or 6 hours without eating in my entire life. And I had been fed that message throughout my childhood and early adolescence, that if you don't eat every 3 hours, your body starts eating itself.

Ben Greenfield [00:05:59]: Right. It's kind of similar to my own initial, my own initial experiences with accidental fasting. Were you, I'd be out training for Ironman and run out of food. And so I just have to figure out how to ride my bike 60 miles without access to grocery stores and gas stations to get back.

Dr. Chris Rhodes [00:06:16]: See, that's a bit more intense than my experience. That's definitely more of a one-up story. I'm just like, I was sitting in my house trying to be like, how do I not eat for the next 30 hours?

Ben Greenfield [00:06:27]: Yeah, exactly. I wasn't intentionally turning myself into fat burning machine or enhancing my fat oxidation capabilities. I was just kind of doing it because I didn't plan well to have enough food on board.

Dr. Chris Rhodes [00:06:40]: I mean, the main thing that I really learned from that experience was that, you know, I had always been on that conveyor belt of, oh, if there's food around, like, you should eat it. You know, like, I'm not really hungry, but, you know, I know that I have to eat right. So I do. And so it was kind of like food had a bigger role in kind of controlling me than I had a role in controlling it. And fasting was the thing that really kind of helped break me through that. When you realize that you can go 24 hours, 36 hours, 60 hours, 72 hours without food, it really helps kind of empower you to be able to make better food choices in your daily life. Because if somebody brings pizza or cookies or whatever to the work break room, you don't have to be like, well, that's all that's available, and I have to eat. You can just be like, okay, I'm not going to eat that because I don't have to eat.

Dr. Chris Rhodes [00:07:33]: I can wait until there's something better that'll actually fuel me rather than weigh me down.

Ben Greenfield [00:07:39]: What's the longest that you fasted, Chris, in this, in this experimentation early on that you did with fasting as a grad student?

Dr. Chris Rhodes [00:07:45]: Yeah. So personally, the longest I fasted is 72 hours. And while I was doing that, I was also drawing my own blood every, you know, for the first 20 hours, it was every 2 hours, because I wanted to really track the fine gradation of when does the fasting process really start? When will we start to observe these changes? And then in the later stages, probably just once every six to 12 hours, depending on what time point it was. It was my first 72 hours fast, and I was poking myself with needles the whole time, but we learned a lot from it. And there were these really interesting things that happened to my cells, to my plasma during that 72 hours period. And we basically saw that you really transition into this fasting metabolism after around 20 to 24 hours. And then these functional effects, especially these anti-inflammatory ones, really started PEAking at around 36 hours and stayed elevated all the way up to 72 hours.

Ben Greenfield [00:08:50]: And when you say you saw patterns of a fasting metabolism, how would you define that a fasting metabolism?

Dr. Chris Rhodes [00:08:57]: Fasting metabolism is basically where you're gonna stop relying on exogenous energy stores, right? So whatever, whenever your last meal is, you're probably relying on the energy that's coming from that meal for around, you know, 4 to 6 hours after that. That's what in the nutrition world we call the postparandial response, or the post eating response is where you're basically in a fed state, right? You're focusing a lot on metabolism, nutrient breakdown, you know, harvesting energy from your last meal, turning it into energy stores. After that point, then your body's gonna like kind of start switching into like the early, early stages of what we would call like a fasting metabolism, which is we're gonna rely on the endogenous energy stores, the things that we already have in our body, and start breaking those down. And in the early stages, that's going to be all about glycogen breakdown. So breaking down the stored sugar in your body, and that's going to run basically until around that 20 to 24 hour mark. And that's when your body really starts to deplete its stored carbohydrates. And at that point, you get this shift from carbohydrate metabolism over to lipid metabolism, a fat breakdown, and then as a result of that, ketone body production and ketone body metabolism. And that's going to be the major signaling factor that tells your body, all right, now we are really in a fast, and we need to start shifting around holistic metabolism to kind of create these metabolic efficiencies that'll help us actually survive longer as we enter into the deeper stages of fasting.

Ben Greenfield [00:10:35]: Okay? So when I look at your research, particularly related to Mimio, you've got some pretty hefty and impressive claims about increase in lifespan in model organisms that you've tried out some of your biomimicking compounds on. What's going on beyond the fasting metabolism that you just described, that would result in increase in lifespan in correlation to fasting? Because it's nice to know, okay, I've initiated mechanisms from a fasting metabolism standpoint, which you've just explained, that would allow me to go for a long period of time without food, which could be useful for productivity reasons, weight loss reasons, etcetera. But what's going on when it comes to this lifespan increase?

Dr. Chris Rhodes [00:11:21]: Yeah, absolutely. So, fasting is one of the few ways and most reliable ways that we know of to extend lifespan in model organisms. And that's true from all the way down to single-celled yeast, up to C. elegans, little nematode worms, to mice, and higher organisms as well. And that's basically due to this really interesting conserved evolutionary mechanism that goes along with caloric restriction and fasting. If you think about what the body is doing in a typical fed state, it's basically getting an evolutionary signal that says, okay, cool, my environment is very good for procreation. If we have a kid right now, there's plenty of nutrients around, there's plenty of resources around. That means that this is a good time to actually raise a child.

Dr. Chris Rhodes [00:12:14]: So your biology kind of shifts over more towards like, let's focus on the next generation, let's focus on less, on maintaining the health of the current organism and focus on trying to actually get to the reproduction side of things so that we can have a kid continue the species when we have this great state of energy abundance. In a fasted state, you kind of flip that on its head. So when there isn't a lot of nutrients around, suddenly your body's getting an evolutionary signal that the surrounding environment would not be good for the next generation. Right? Like, there's not enough resources even to support you as an organism. So this would not be a great time to have a kid. So the way that your biology shifts that around is that, okay, now, instead of focusing on the next generation and their survival, I'm going to focus on this current generation and its survival. So things change around at a cellular level to really try to enhance your lifespan as much as possible, so that you can go and find a new environment that would actually be suitable for the next generation. So this turns on things like these metabolic efficiency processes, like making sure that we can maintain ourselves for the lowest amount of energy possible.

Dr. Chris Rhodes [00:13:31]: It turns on things like autophagy, where we're breaking down damaged and dysfunctional proteins and organelles into their constituent parts, so we can recycle them to create new and functional ones. It's going to be decreasing mitochondrial stress, and usually also increasing mitochondrial biogenesis. So we have better energy utilization and energy production without producing as much damage. It's going to increase a lot of these stress resistance genes and stress resistance response elements that help to keep a cell stable. Because at the end of the day, when you're fasting, your cells don't have enough energy if something goes wrong to produce a new cell. So they're going to be really, really focused on maintaining the health and survivability of the current cells that they have. Rather than, say, in a fed state where it's like, if something goes wrong, I'll just make a new cell, it's not a big deal. So that shift in cellular functionality to really focus on the survival of the current cells that you have is ultimately what leads to longevity, because that's ultimately what longevity is, right? It's just maintaining what you have for as long as possible.

Ben Greenfield [00:14:41]: That is a really interesting way to describe the benefits of fasting. I don't think I've heard it positioned in that manner before, meaning, hey, when I'm fasting, that's sending my body a message that I might not be able to achieve immortality through creation of offspring or life extension for my species through propagation of new life. Therefore, I'm going to initiate mechanisms for myself to survive as long as possible via enhanced cellular autophagy, recycling, cleanup, etcetera.

Dr. Chris Rhodes [00:15:15]: Yep, exactly. And I mean, it makes sense from an evolutionary perspective, right? If it's like metabolism and nutrients, sensing is just ingrained into the fabric of our DNA. It's one of the most important things that we do as a body, and it's one of the most crucial things that's going to determine how we function, right? Like, even back from the days of when we were single-celled organisms, we evolved to move around and gather nutrients just to keep ourselves alive and maintain those metabolic processes. And that has continued forward even to the higher states of organisms that we are now. We're very, very governed by our metabolic state and our nutritional wants and needs.

Ben Greenfield [00:16:00]: Now, the original, what you call the free radical theory of aging, which I think was kind of positioned as early as the sixties and has gone on with some variants since then, hypothesized that a downregulation of metabolic rate might be one of the reasons why fasting or calorie restriction could extend lifespan. In research I've seen since then, it seems that it's not necessarily a downregulation of metabolic rate that is the real clincher when it comes to fasting and calorie restriction, because in some species, and you probably know a lot more about this than I do. You don't necessarily see a downregulation. Sometimes there's an increase in metabolic rate and that instead, if you look at kind of like this newer, mitochondrial, free radical theory of aging concept, it's more an upregulation of cellular protective mechanisms, including an upregulation of, say, endogenous antioxidant production that is part of the life extension that you get from fasting or responsible part of life extension that you get from fasting. And it's not that your metabolic rate is decreasing. What do you think with fasting or calorie restriction? Is the whole, like, you live longer because your metabolic rate decreases a thing of the past, or is there still some reasonable aspects of that idea?

Dr. Chris Rhodes [00:17:28]: I think that there's definitely some reasonable aspects of that idea. Right. The major principle behind that being if your metabolic rate is lower, it means that ultimately you have lower energy requirements. Right. Which is, I think, ultimately going to be an adaptation to fasting or caloric restriction in the long term. And that's also going to send these metabolic signals to your cells, essentially, that's going to upregulate all of these other things, like autophagy and like the stress response elements and like the decrease in oxidative stress that's going to happen from the mitochondria and the anti-inflammatory effects that happen along with a fast. You know, it's all kind of connected together. I definitely wouldn't say that it's the only thing.

Dr. Chris Rhodes [00:18:15]: Right. I don't think there's ever going to be just like, oh, there's this one thing that fasting does, and that's the reason why all these things, like, happen and are so beneficial. It's always going to be very multifaceted. Right. Like, I just rattled off a list of at least, you know, five or six things that happen during a fast that are all really protective and beneficial for cellular longevity. So I think that, you know, there's, there's definitely just a lot of different ways that fasting is going to help you. And I'm not entirely sure if, you know, one is, like, the most protective or the most important versus the others. Yeah, that's, that's really what I would say, yeah.

Ben Greenfield [00:18:50]: The more research I see, just from my perspective, is that there's a lot less benefit of fasting that is derived from a slowing of the metabolic rate, a slowing of the heart rate, and a slowing of metabolism in general. And it's more the autophagy and even the stress induced kind of like, hormetic induced endogenous production of some of these metabolites, including, you know, superoxide dismutase and glutathione and some other cellular protective mechanisms that are more important than say, hey, my body's going into hibernation mode because I'm fasting. And that's at least more of what I've seen.

Dr. Chris Rhodes [00:19:29]: I mean, I would actually agree with that. I think that's actually a really good segue into kind of like what Mimio is doing, right? Like you have these bioactive metabolites that are produced during a fast that are these signaling molecules essentially that help tell your cells, like, okay, these are the pathways that we need to be activating in order to have this bioprogram of longevity that's activated during a fast. And that's kind of what we're trying to mimic. Right. These great beneficial signaling molecules that are typically only upregulated during a fast, we give them back to people as a supplement so that they can activate those same pathways on demand rather than having to go through the 36 hours fast that it takes to actually get them there.

Ben Greenfield [00:20:14]: Yeah, well, I want to talk about those, Chris, but I've still got a few other questions before we dig into that, because Mimio was pretty straightforward. I think we'll definitely be able to show people the different metabolites you guys have researched that you're able to put into the body to mimic a facet state. But first of all, back to my original question, which I'm guilty of derailing you from. So you didn't quite answer it yet, but I think I'm seeing where we could probably go with that question. Right? Like why skip out on fasting? And especially because you can get a lot of mental, spiritual, psychological benefits of restricting food, you know, having that willpower, etcetera. I think that you named one, right, potential downregulation of fertility with long term fasting, which you especially see, I think, more in women, but also in men, almost like a hypogoNADal response to calorie and food restriction that if done rePEAtedly, could cause some long term downregulation of the endocrine system and possibly, if excessively done, the thyroid. I think that's one reason that you may want to consider not excessively fasting or having tools to increase cellular autophagy beyond just fasting.

Ben Greenfield [00:21:34]: I think another one that just about anybody knows if they've experienced ozempic face and ozempic body is the problem with protein restriction and the muscle loss, the cachexia that can occur with excess fasting, which you can, and multiple studies have shown this with calorie restriction, but adequate protein and weight training, you can actually maintain and even build muscle in a fasted state. But it sounds to me like perhaps the answer to my question is there are some mental and spiritual benefits derived from fasting, and you can still get those from occasional fast. But if you don't want to fast excessively and want the benefits of fasting without the potential impact on fertility, muscle loss, etcetera, it might make sense to use a little bit of better living through science to mimic fasting without fasting, while still throwing in occasional periods of fasting. So you can kind of have your cake and eat it, too.

Dr. Chris Rhodes [00:22:32]: Yeah, that's exactly what I would say. Adding on to that, there's also just populations that could really benefit from the underlying cellular effects of fasting, but for whom fasting just isn't really safe. Right. You see this all the time with folks that are maybe 65 years and older, they don't have the luxury of being able to maybe lose some muscle or, or go for long periods of time without being like, you know, without having sufficient caloric intake. So, like, this is, this is great for, like, you know, the older folks who could really use those cellular regenerative benefits, but, you know, just can't actually do the fasting to get them there. Or like you mentioned, Ben, like, women who struggle with fasting because it is like a much different hormonal game than it is for men. You know, we've had plenty of folks who talk to us about why they use the product or why they like fasting, but can't really do it. And plenty of women, you know, have that cycle disruption that happens because they can't, you know, do the long term fast.

Dr. Chris Rhodes [00:23:31]: And the way that female biology works in terms of fasting is so different than what happens in, in men that the, like, the timings that we know of right now and the studies that have been done just don't really apply. And so having something that's, you know, a fasting enhancer like Mimio can be or a fasting support network for them or something that can just give them the benefits, but without actually having to do the fast can be really beneficial.

Ben Greenfield [00:23:58]: I think that one of the things that people are going to ask about that I'm actually very curious about, this might fall into the same category as maybe all the magic of fasting is in the downregulation of metabolic rate. You'll often hear people, and I've even said this in the past, claim that much of the benefits of fasting are not necessarily the compressed feeding window or the long periods of time without food, but instead the easier calorie restriction enabled via fasting. Meaning that if over a 24-hour period of time I eat, let's say a restricted calorie diet of 1500 calories and I do it without fasting, but instead just eating that much ad libitum over 24 hours and you achieve the same via fasting, let's say, only eating between 10:00 a.m. and 06:00 p.m. let's take an intermittent fasting scenario that the metabolic and life extension results would be relatively synonymous. If you compare the two, what do you think about that idea?

Dr. Chris Rhodes [00:24:56]: Yeah, that's a really interesting concept, and I would actually say it's the opposite based on what we see in the scientific research. So what's really interesting about caloric restriction, especially in a scientific setting, when they're doing like, like mouse studies and things like that, is that typically caloric restriction studies end up accidentally being intermittent fasting studies. Because how they run these studies is that they have the mice that are in their cages and they're feeding them a set amount every day, but they're usually not feeding them at intervals throughout the day. So you'll have the scientists come in and it's usually once per day they'll put in all the food at the level of caloric restriction that the mice are supposed to eat at one time. And then the mice, because they're super hungry, right, and they're on a caloric restricted diet, will basically go and eat all the food all at once and then they won't get fed again for another 24-hour period. So a lot of the studies that have been done on mice are, yes, caloric restriction studies, but also kind of accidentally intermittent fasting studies where they're getting this big bolus of food all at once and then not really eating for the rest of the period until they get fed again. There was this really great study back in 2021 out of the University of Wisconsin that basically looked at the difference between caloric restriction and fasting and found that lifespan extension effects were actually dependent upon fasting for a lot of what we typically associate with caloric restriction, and that there are some distinct benefits to caloric restriction and fasting that just like, don't really overlap with each other all that much, because fasting in and of itself is very different than just straight up consistent long term caloric restriction.

Ben Greenfield [00:26:52]: That's actually really interesting how much of a relic of the logistics of the study is part of the results or the quality of the study. Meaning if a lab research assistant is only going in and feeding the animals once per day based on their school schedule, when they can get in there, they're almost accidentally creating a fasting study instead of just a calorie restriction study.

Dr. Chris Rhodes [00:27:14]: It happens all the time. There's not a ton of protocol oversight when it comes to, okay, let's really try and tease out, is this caloric restriction or is this fasting? Which is why I love that 2021 study. And then there's also been previous studies that have looked at, you know, just fasting in and of itself as a longevity extension thing. And they've found that you can still get lifespan enhancement up to, you know, like 20, 30% with fasting, even in the absence of caloric restriction.

Ben Greenfield [00:27:44]: Oh, interesting. So, a calorie equivalent diet with one set of calories being consumed ad libitum over 24 hours, and the other set of calories being consumed over a compressed feeding window of, let's say, 6 hours or 8 hours, or I don't know what study you're referring to, you would actually see more benefits even with equivalent calories of that food being given in a compressed feeding window.

Dr. Chris Rhodes [00:28:10]: Yeah, absolutely. And that's because there are just certain obligate responses that a body has to go through during a time when there's no food around. Like we were talking about before. The real postprandial state in the body, that fed state that we think of lasts for around 4 to 6 hours. And then after that point is when you're gonna start getting into more of the fasting metabolism and relying on endogenous energy stores. And that's gonna shift cellular and whole body metabolism around more towards those cellular protective mechanisms. And that's going to be very distinct from, say, like a typical Western three meal a day kind of thing. Right? Where if you're eating at nine and then twelve and you have a snack at three and you have dinner at six, you never actually leave the postparandial state.

Dr. Chris Rhodes [00:29:01]: You're just always in kind of like this constant fed state, trying to get out of the resolution of whatever your last meal is, but you never really achieve it until that overnight fastenden when you sleep.

Ben Greenfield [00:29:12]: Yeah. I'm convinced that everything that you've just said applies very well to longevity and possibly even even health span. With my background in primarily metabolism, exercise science and physiology, fat loss and muscle gain, I would say it's the least important when it comes to fat loss. Meaning, I still think CICO calories in, calories out trumps everything when it comes to fat loss. And, you know, if you're wanting to lose, let's say, half a pound of fat a week, and I'm restricting calories by, say, 500 calories a day, I really don't care how you do that. Whether you fast or don't fast, as long as you're eating at that 500 calorie restriction each day, I don't think the fasting makes much of a difference. Besides, logistically, if you give yourself those fasting windows, it does make it a lot harder to overeat calories. If you can only eat your calories between 10:00 a.m. and 06:00 p.m.

Dr. Chris Rhodes [00:30:08]: Yeah, absolutely. And I mean, that's typically what you see in the clinical research as well. There's always those big headlines about how fasting doesn't work. And it's usually because, oh, we compared intermittent fasting and, like, on a 16:8 schedule to a calorie match, just like caloric restriction thing, and we didn't see any differences in weight loss. And that, to me, is like, a nutrition researcher is kind of like the biggest, well, duh, like, response that can possibly get. Because it's like, yeah, it's all about energetics, right? Like, if these people are consuming the same amount of calories and your end goal is just weight loss, then they're gonna lose the same amount of weight. Like, there's no, there's no way around that, right? Eating your calories in a smaller window is not going to, you know, increase your metabolic rate or something like that, to a point where you would get more weight loss benefit. It's all going to be like you said, Ben, like, calories in, calories out. That's just physics, right?

Ben Greenfield [00:31:04]: And then also the headline, intermittent fasting doesn't work. Doesn't work for what? You know, heart, health, longevity, weight loss, you always have to raise an eyebrow at that as well. So, with Mimio, what is in it and why?

Dr. Chris Rhodes [00:31:17]: So I think the best way to answer that is kind of to tell a little bit of the scientific story behind it. So this was what I was doing as part of my PhD at UC Davis, getting a PhD in nutritional biochemistry, basically studying what happens in the human body during a 36-hour fast. So we had 20 people come in, ten men, ten women, to avoid a gender bias. And we had them fast for 36 hours and did a before and after looking at their plasma and cellular functionalities. Basically, what we saw was that when people fast for 36 hours, there's this unique set of metabolites that are elevated in the body that are really only elevated during a fast. And when we screened through those molecules, we were able to find that those were the ones that were really responsible for activating a lot of these cellular health and longevity benefits of a fast. And we were able to identify this synergistic combination of four of those molecules, these fasting metabolites, that when we combine them together, could recreate a lot of those cellular health benefits that we were seeing. So we saw, you know, improvements in their anti-inflammatory state, their antioxidant cellular protective state, their cardio protective state, their like, their metabolic functionality.

Dr. Chris Rhodes [00:32:41]: We also saw that when we took these molecules and gave them to C. elegans in a lifespan extension experiment, we could extend their lifespan by 96% just through supplementation with these fasting mimetic metabolites. So what's in Mimio are those four fasting metabolites that we identified have these synergistic effects. And what Mimio is basically doing is taking what the body naturally produces during a 36-hour fast and giving it back to people. So you can kind of recreate that, that state of fasting at a molecular level, stimulate, activate these same beneficial cellular pathways that are associated with fasting to get the benefits of fasting without actually having to fast.

Ben Greenfield [00:33:29]: Okay, now this is interesting. I may have learned something here because I've been using Mimio. You guys were kind enough to send me a bottle so I could actually see if I liked it in the weeks leading up to this show. It's a very interesting formulation, by the way. I recently did a podcast on exercise mimetics, not calorie restriction mimetics, but I was kind of saving some of the information on that for this episode. Even though exercise mimetics are also very interesting, I think there is some crossover between the two. What I've learned here is my body produces endogenously these same metabolites that I am consuming exogenously with Mimio. It's not as though Mimio is causing me to produce different metabolites.

Ben Greenfield [00:34:10]: You're actually taking the same metabolites produced during fasting and putting those in a capsule, essentially.

Dr. Chris Rhodes [00:34:16]: Yep, exactly. And that's our whole biomimetic approach, right? We're just taking what your body does naturally and putting it in a pill so you can get those same benefits on demand.

Ben Greenfield [00:34:27]: What are the four compounds?

Dr. Chris Rhodes [00:34:29]: So the four compounds are nicotinamide, spermidine, palmitoylethanolamide, or PEA, and oleoylethanolamide, OEA.

Ben Greenfield [00:34:40]: The nicotinamide, the first one is that like. Is that like nicotinamide riboside? Like the NR you see a lot of people taking about?

Dr. Chris Rhodes [00:34:48]: It is kind of like nicotinamide riboside. So nicotinamide is basically the precursor molecule for both nicotinamide riboside, NMN and NAD in the body. So you can kind of think of it as like, you know, a broad spectrum NAD precursor. If you take nicotinamide, you're going to have increases in NMN, you're going to have increases in NR, you're going to have increases in NAD. And that's really important because NAD is essentially one of your body's primary nutrient sensing molecules. If you have a high amount of NAD+, that is essentially your cell's way of saying, I don't have a lot of energy and resources. So it kind of helps to stimulate these caloric restriction fasting like pathways from a holistic basis by upregulating the levels of NAD+, which then, you know, goes on to stimulate through the NAD cert pathway changes around your epigenetics, your transcriptome, all that fun stuff. And in our formulation, also really helps to potentiate the benefits of all the other ingredients because they're working together to basically recreate that, you know, holistic, quote unquote bioprogram of fasting.

Ben Greenfield [00:36:04]: Is it an issue if I'm already taking NAD or NR or NMD in terms of too much nicotinamide?

Dr. Chris Rhodes [00:36:11]: Yeah, it really depends on how much you're already taking. So what's in the Mimio formulation right now is 250 milligrams of nicotinamide, which is like a clinically validated dose. There have been plenty of clinical studies looking at nicotinamide concentrations up to 1 gram per day and showing good results on both cardiovascular metrics, but then also, interestingly, skin cancer metrics as well. So that would be the super high dose that if anybody's exceeding, I would probably be like, it's probably too much, but at that 250, if you're also taking another 250 of NR or another 250 of NAD, you should be okay, as long as you don't have any kind of genetic sensitivity to niacin, which some people do have.

Ben Greenfield [00:37:00]: Yeah, I would agree. I've seen the same thing about 1 gram being the ceiling for the potential law of diminishing returns with any type of NR, NMN, NAD, nicotinamide, niacinamide type of supplementation. So if you're at 250, that still leaves some space for people who might want to still be using their NAD or getting the occasional NAD IV. You mentioned palmitoylethanolamide, PEA, as a secondary component. That one is very interesting. I've been looking into that more and more. Recent study showed impressive improvement in brain derived neurotrophic factor and cognitive function with that one.

Ben Greenfield [00:37:34]: I saw another one, and this was just last month. Irritable bowel syndrome also responds very favorably to PEA. It's a very interesting molecule. I talked about it briefly when I interviewed Kyle from level up health, who packages up some really cool formulations, basically orally bioavailable peptides. We talked a little bit about PEA, but what's the main reason that you included it along with the other three?

Dr. Chris Rhodes [00:37:58]: Well, so, ironically, the main, like, you know, the reason why we include anything in this formulation is because, you know, when we looked at what happened in the body during a fast, we actually found that there were over 300 significantly elevated metabolites in circulation. And then we took that list and basically screened through all of those molecules, looking for ones that could recreate these beneficial effects of fasting, but also ones that had synergy with each other. So I like to say that we didn't actually design our formulation. Nature did. Right? Like, these things just happen to work really well together. And when we screened through them, that's what we saw. We were just following the data, so we didn't make, like, a conscious decision to necessarily include PEA.

Dr. Chris Rhodes [00:38:41]: We just went where the data told us. And this was a really powerful molecule that worked with all of these other molecules at the same time to recreate those fasting benefits. But I love PEA as a molecule. It's kind of become my favorite. We found that it had, you know, the best lifespan extension ability at the lowest concentrations. We were also the first to identify that PEA actually did have these lifespan extension capabilities. And one of the reasons that I love it so much is because it has all of these really interesting and far-reaching effects. I think of it kind of as like your body's natural rest and recovery molecule.

Dr. Chris Rhodes [00:39:18]: So it has these potent anti-inflammatory effects. It stimulates through the CB1, CB2 receptors. So it has, it's kind of like, almost like your body's natural CBD to a certain extent. It has these mood elevation effects, like you were talking about, the cognitive enhancement effects. It increases gut barrier integrity, which has those beneficial IBS effects, the cognitive enhancement effects. But also, really interestingly, it has these great effects on pain relief as well, like really good clinical evidence showing that it's great for relieving nerve pain and, like, diabetic neuropathy, things like that. So it's kind of like this one molecule that really packs a big punch, really helps just stimulate a lot of these regenerative systems in your body. It really helps to calm and inflammation, you know, it's a COX-1 and 2 inhibitor as well. So, like, I don't know, I think of it as kind of like a miracle molecule.

Ben Greenfield [00:40:16]: Yeah. Toss out your ibuprofen, replace it with that. Yeah. I think we'll see more and more about PEA in the literature, for sure. And I am seeing more and more about it already. The third one you said was spermidine.

Dr. Chris Rhodes [00:40:27]: Spermidine, yeah. And, of course, spermidine's, you know, really, really popular. It's best known for its ability to, you know, enhance the autophagy, and I think that's why it found its way into our formulation as well. You know, that's a big component of the benefits of fasting, getting that, you know, cellular regeneration, being able to break down these dysfunctional proteins and organelles, and particularly mitochondria. Because spermidine doesn't just enhance autophagy, it also enhances mitophagy. It has its own anti-inflammatory benefits, has its own lifespan extension benefits. So it's just like a great inclusion that really helps to round out the formula and again, create that larger system of fasting.

Ben Greenfield [00:41:09]: Yeah. Before we get to the fourth one, I'm just curious about this. This may have been placebo, but I seem to notice a suppression of hunger when I started popping the Mimio in the morning. I'm not quite sure if that was just in my head, but do you tend to see, along with the amplification of what the body would normally do during a fasting scenario, even if you're feeding some type of hunger suppression effect?

Dr. Chris Rhodes [00:41:31]: Yeah, actually. So that's, like, probably a great segue into the fourth molecule, which is oleoylethanolamide, which is actually involved in the gut brain axis and has a really great, like, clinical and experimental backing for suppression of appetite. So basically, what OEA is doing for you is helping to, you know, suppress appetite. It's a PPAR-alpha activator, so it's also, you know, promoting fat breakdown.

Ben Greenfield [00:41:57]: Right. So that could also fall into, like, the exercise mimetic category.

Dr. Chris Rhodes [00:42:01]: Yeah, yeah, absolutely. Yeah. I'm sure that there's a lot of overlap between fasting mimetics and exercise mimetics, because, you know, in the same way that fasting and caloric restriction are similar but different. You know, fasting and exercise are going to be similar but different.

Ben Greenfield [00:42:13]: Yeah. A lot of people are also interested in the field of so-called GDAs, glucose disposal agents to lower blood sugar. Right. Even though a lot of people think that's how GLP-1 one works, it's not really, it's more acting on appetite regulating hormones. But if you look at berberine or bitter melon or in some cases herbs like Ceylon cinnamon or apple cider vinegar, these can all increase the uptake of glucose into cells. Do you see any type of glucose disposal agent activity with the calorie restriction mimetic? And the main reason I ask, by the way, is kind of similar to NAD. A lot of people use these GDAs and I'm curious if they could combine the two or if they don't even need to.

Dr. Chris Rhodes [00:42:56]: Yeah, that's an interesting question. With the Mimio formulation, to my knowledge, we don't have any of the glucose disposal like activities outside of, you know, we are, you know, we're simulating more like fat metabolism. So you could potentially say that we're like a glycolysis inhibitor to a certain degree. You know, OEA and PEA are both PPAR activators. They both activate AMP kinase. So you have. And like, you know, NAD is doing its own, like, energy restriction thing. So you have a lot of cellular signaling that's happening, that's shifting things more away from the glucose metabolism, the glycolysis breakdown, and more towards fat oxidation and, you know, fat metabolism within cells.

Dr. Chris Rhodes [00:43:38]: So in that sense, like, yes, there could be some effects on, like, changing around glucose metabolism, but we're not going to be disposing of glucose in any kind of way. It's not, it's not the kind of formulation that's going to, you know, take the glucose and take it out of cells or like, prevent you from absorbing it or get it into cells faster. It's more that we're shifting these cellular metabolic pathways to favor fat metabolism over glucose metabolism.

Ben Greenfield [00:44:04]: Right. So if you're taking something like Mimio in the morning, you could still take a little berberine or something like that prior to a, a carbohydrate containing meal later on in the day and not see a lot of overlap.

Dr. Chris Rhodes [00:44:14]: Oh, yeah, exactly. I mean, and that's, that's the nice thing. Like, you know, berberine, it's known really well for its AMP kinase activation. OEA is as well. So I mean, like, if we, we actually like to say that you should take Mimio, like a half an hour before a meal. Because number one.

Ben Greenfield [00:44:28]: Oh, really?

Dr. Chris Rhodes [00:44:29]: Yeah. Where you'll get, like, your most appetite suppressing effects. And that's typically what we see from our customers. But then also it's really, really helpful for just helping to control some of these metabolic markers of glucose metabolism as well. So there's been an eight week study with OEA in prediabetes, basically showing that it can reduce fasting and postprandial glucose levels, insulin levels, HbA1c levels, CRP levels. So a lot of, you know, glucose control that's happening within that, that, I think is due to AMP kinase and PPAR activation.

Ben Greenfield [00:45:08]: Okay, interesting. And would there be any benefit to taking Mimio on a fasting day or when you're already fasting?

Dr. Chris Rhodes [00:45:14]: Yeah, I would say so, yeah. So we like to say that you can use it as a fasting mimetic or a fasting enhancer, you know, because it was designed to mimic what the body does during a 36-hour fast. Right. So if people are doing something like 16:8 or they're doing one meal a day.

Ben Greenfield [00:45:28]: Ah, okay. Okay, so 36 hours, meaning, like, if I'm doing an intermittent fast, but I'm only getting, let's say, the benefits of a 16-hour window, I can throw in the benefits of a 36-hour window if I'm using Mimio.

Dr. Chris Rhodes [00:45:41]: Yep, absolutely.

Ben Greenfield [00:45:42]: That's interesting.

Dr. Chris Rhodes [00:45:42]: And it helps to actually make the fast easier as well. Right. Because you get the appetite suppression from the OEA, you get the mood and cognitive enhancement from the PEA. You get these, you know, great underlying cellular health benefits that are coming from the spermidine and the NAD that you might not otherwise be experiencing during that 16:8 or OMAD style window. So, accelerating your benefits while also making the experience easier. That's great.

Ben Greenfield [00:46:09]: Okay, got it. Have you done any actual studies on all four of these together?

Dr. Chris Rhodes [00:46:14]: Yeah, yeah, we actually have. So after the discovery study, which was published in American Journal of Clinical Nutrition, our next step was basically to do a pilot clinical study. What we did for that was we had people come in, eat a standardized breakfast on its own alongside a placebo control, and then looked at their plasma functionalities and their cellular functionality just like we did in the previous study. Then we had those same people come back after a washout period, eat that same standardized breakfast. But then with supplementation with Mimio. And basically what we found was that when people ate the standardized breakfast alongside the placebo, there was this big loss in plasma functionality. So their plasma became more pro-inflammatory, less antioxidant less cardio protective. But when they ate that same meal, but with supplementation with Mimio, we were able to show that we could actually prevent all of that loss of function and then add gains of function on.

Dr. Chris Rhodes [00:47:13]: On top of that. That mimicked what we saw during fasting. So instead of being pro-inflammatory, their plasma became anti-inflammatory and antioxidant and cardioprotective. So not only preventing a lot of these negative impacts of eating, but also mimicking the beneficial effects of fasting, even during a meal.

Ben Greenfield [00:47:30]: Wow. And was this like a cinnabon or a breakfast burrito, or what did you choose?

Dr. Chris Rhodes [00:47:34]: It was actually two Larabars. So just like dates and cashews, essentially, yeah.

Ben Greenfield [00:47:40]: And the placebo, I'm assuming they were just. The placebo group was just taking the same colored capsules, but not with the Mimio ingredients.

Dr. Chris Rhodes [00:47:47]: Yeah, yeah, exactly. And actually, this was a, so this was a crossover study. So the same people that we used in the placebo were also the same people that we used, you know, for the Mimio, so that, you know, helps keep things consistent.

Ben Greenfield [00:47:58]: Yeah, yeah. Was that the primary study you guys did?

Dr. Chris Rhodes [00:48:01]: So that was our original pilot study that's about to be published. We're really excited about that. We also just recently, we recently did interventional case study alongside Mount Sinai, where we had someone go on Mimio for eight weeks and basically looked at their blood work and their biological age before and after. We were able to see some really, really interesting stuff. The big one is that we could actually reduce biological age by two-and-a-half years in just eight weeks of supplementation on Mimio, as well as improve a lot of cardiovascular markers like HDL, LDL ratio, cholesterol levels, triglycerides, and then a lot of metabolic things as well, including, you know, improving glucose levels, improving HBU and C levels, insulin levels. And then also really interesting, from that study, we found that we could enhance free testosterone levels by 50% in just those eight weeks.

Ben Greenfield [00:49:03]: That's interesting. And that kind of seems to fly in the face of what you'd expect with fasting in the discussion about downregulation and fertility. So these fasting metabolites don't necessarily have, like, a feedback loop into the endocrine system to downregulate hormone production, as you might expect.

Dr. Chris Rhodes [00:49:20]: Right. Yeah, it doesn't really seem that way. No. Yeah, from the data that we have.

Ben Greenfield [00:49:24]: Hey, so for those of you listening in, I'm going to link to Mimio. We do get a discount code on this stuff for my listeners. I will link to that in the show notes. If you go to bengreenfieldlife.com/Mimiopod, that's m-i-m-i-o. Pod, Pod. Chris, thanks so much, man. This is super fascinating.

Dr. Chris Rhodes [00:49:43]: Oh yeah, absolutely. And just like to clarify, m-i-m-i-o.

Ben Greenfield [00:49:47]: What did I say? Did I say e? I meant i. I need to take more PEA. All right, so m-i-m, bengreenfieldlife.com/Mimiopod is where the juicy show notes reside. And until next time, I'm Ben Greenfield along with Chris Rhodes, doctor Chris Rhodes of Mimio, signing out from bengreenfieldlife.com. Have an incredible week.

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