Joel Greene Podcast Part 2: How To Reshape Fat Cells, Enhance Repair During Sleep, Target Your "Circaseptan Rhythms", Build Young Muscle & Get Rid Of Old Muscle.

On this episode of the Ben Greenfield.

Fitness podcast, muscle growth young muscle and blood flow are one and the same. As blood flow decreases, as circulatory power decreases, muscle gets old. There's just a whole laundry list of checkboxes we want to do to make sure that we're adequately oxygenating during sleep, particularly in the brain. That's really where we gotta jump on it. So if we wanted to come at the very one thing we could do above exercise, above anything else, to ensure that we live a long time, that we're in maximal health, we would have to correct this problem because. Because what this problem touches on is.

Health, performance, nutrition, longevity, ancestral living, biohacking, and much more. My name is Ben Greenfield. Welcome to the show. All right, it is time, high time for part two with Joel Green. I hope you guys liked the last episode with Joel. And of course you can go to BenGreenfieldFitness.com and just do a search for Joel Green to grab that episode with Joel. I would highly recommend you listen to part one if you didn't, because it will lay a lot of groundwork for what you are about to hear. Although I've kind of recorded these podcasts with Joel such that you could listen to them in any order and still get a ton of benefit based on this. It's a really big explanation and folks may want to rewind and listen again. But essentially, long story short is that we need to fix this issue by ensuring that we refill fat stores so that mechanical stress is relieved. And then we also need to reshape that extracellular matrix so that we don't get this type of stiff collagenous fibers that can drive more of these so called red team, these inflammatory populations in the fat. So that being said, what would be the strategy to refill the fat and reshape the extracellular matrix? If it's one strategy or if it's multiple strategies, I'm sure people are going to be very curious about how to do this.

Yeah. So just adding a sort of little clarification to that. The body's got two options to fix the problem of fat loss. One is to refill the fat cells. We don't want to do that. That's not the one we want, but it's the one that is most likely. The other is to reshape the ecm. Okay, now reshaping the ECM is enormously energy intensive. It takes a lot of energy, a lot of resources to do it because for the most part, fat cells are relying on Warburg metabolism. To do it, they're not pulling things into the TCA cycle. So it takes a ton of energy. And during active fat loss, very often the energy needed to reshape the ECM isn't there. So what this gets us to is at the end of a fat loss phase, there's a pretty big list of new checkboxes that nobody's ever talked about that we need. So we went through one of them, which is ticking off fibroblast growth. Can't get that one out. FGF 21, that's okay.

The abbreviation works fine.

There you go. Yeah. So we want to tick off FGF21. So we want to make sure that we do that along with that. What we want to do is we want to do a post fat loss biome intervention. Okay. Meaning there is a very large connection to the post fat loss gut biometric and the likelihood of weight regain. So at the very end of the fat loss period, it's a very good time for a lot of the protocols that we've been talking about just to kind of get in there and set the dials towards the lean phenotype. Because what you're going to find at the end of a fat loss period, particularly on the type of diet you've been using, particularly if you were leaning more towards a keto diet, you're going to find that a lot of the substrate in the gut needed for some of the healthier bacteria gets depleted. And so there's a whole school of research about this. So you want to definitely do a post fat loss biome intervention. That's one of the things that we want to look at. And then there's just a host of other things that we want to do in that period. And you really have a window of time, it's roughly somewhere between four to eight weeks at the conclusion of a fat loss period. And the interesting thing is that, and there's a lot of new research on this, it shows that the maintenance phase, entirely different sets of genes get activated that promote weight gain post fat loss. And so what we want to do is we want to get in and we want to be able to just kind of tick down the list and knock these out. So, for example, we would want to look at fatty acid binding protein 4 matrix melanoprotease 11. You know, there's a bunch of very specific things that we'd want to do. And so in this, it gets into immunology. And at the end of a fat loss period, for example, it's a great time for NIACIN that's when you'd want to do pure straight. Makes me flushed and uncomfortable. Niacin. So in your fat mass again, there's that very special receptor, GDP109, that is shared with butyrate in the gut. Well, it turns out that in your fat mass that this is intrinsically linked to weight regain. And so niacin at the end of a fat loss period is something that. That's when you'd want to use that for, you know, kind of every day for about two, three weeks. And we can just keep going down the list and just checking boxes here. But it brings into this notion that there is a corrective period post fat loss that we need to do. It's just like the analogy I use in the book is it's like a knee injury. If you injured your knee, you do rehab on the knee for, you know, six to eight weeks post injury, and you have to do the same thing with your fat.

Right. And I would say just from my own personal experience, the idea of resetting leptin with a high amount of prote protein at breakfast and even eschewing a long intermittent fast for a period of time, if you are leptin insensitive is one really good trick. And then also, and I don't know if you're with me on this, but really paying attention to your collagen intake and getting a lot of really good bioavailable collagen, whether it's collagen fibers or some of these gelatin powders, things like that in the diet seem to really help as well.

Yeah, 100% agree on both those. In fact, sorry, I got into ranting without bringing up leptin. So one of the most crucial things at the end of a fat loss period are these leptin interventions. And you'll see them in the book. But basically, long story short, there's really good research about massive breakfasts periodically at the end of a fat loss period. Massive amount of carbs, massive amount of protein, some fats, but it's the calories, sheer size of the meal. So you're getting, you know, 10001500 calories in. And what this does is we're short circuiting the leptin spike, or leptin deficiency loop. We're driving leptin up at the very end of a fat loss period, which is normally not what happens. And this helps to mitigate that particular aspect of it. And then, yeah, 100% on the collagens and, you know, glycine collagens, all that Stuff Very, very useful.

Yeah. And then one other thing related to the inflammation component. I was pleased to see you get into this in the book, and that's shutting down some of these inflammatory signals that visceral fat in particular can produce. And, you know, one thing that we already discussed, the high amounts of glycine with something like that pre be Jell O seems to reduce visceral fat pretty significantly and reduce some of the oxidative stress that that can produce. But then the other one is molecular hydrogen, and you actually get into the fact that you, like me, have met Tyler LeBaron, who runs the Molecular Hydrogen foundation, and that hydrogen can actually enhance one of the key molecules that suppresses intramuscular fat, which can contribute to some of these issues that we were talking about. So, I mean, throwing in, like, I do a big mason glass jar full of hydrogen water in the morning and in evening, and I think that's a. That's a pretty good strategy as well.

Yeah, I do, too. I. I do the hydrogen. Yeah. 100 lockstep with you in this. I feel like we've been running down parallel paths apart all these years, but, yeah, the molecular hydrogen. First of all, about Tyler. Good grief, man. I met Tyler, like, back in 2015. And, you know, I've met a lot of empty suits in this business. I met guys that, you know, like. Like, should know everything, and they don't really know nearly what they should. And again, I just always see myself as a consumer. Like, you know, I'm just a consumer. And I want, you know, I want. I want to believe in you. I want to believe you're this thing. And I've been disappointed more often than not.

Right.

But, man, I'll tell you what. Tyler and I got into it at this trade show, and holy cow. Like, I mean, that guy knows this stuff.

Yeah. Super, super smart. I have an interview with him, too, and I'll link to that in the show notes for you guys if you go to BenGreenfulFitness.com Joel Green, the number two. I've done a few podcasts on hydrogen, and I'll link those in the show notes. But, yeah, I mean, like, you know, you detail this in the book quite a bit. But I think, long story short, because I want to give us a chance to talk a little bit about sleep and a little bit about anti aging, two other areas that you dive into in the book. But, you know, it turns out that when it comes to fat loss in particular, mitigating some of the inflammatory effects that occur from Cycling fat loss. You gotta have a few of these ducks lined up in a row, like resetting leptin, like paying attention to some of this mechanical remodeling and collagen intake, molecular hydrogen to shut down some of the inflammation. Cold thermogenesis, within reason. And then some of some of these. These timing parameters in terms of the protein and the prebiotic fibers, or the fibers in particular, pre and post, these, these larger meals. You know, it's just this whole system that once you implement, doesn't involve you spending, you know, an hour to get ready to say, like, have a slice of cheesecake, but instead incorporates these. These natural habits that you're weaving in. So again, the book gets into a lot of this in even more detail. But I'm hoping to give people, whether or not they get the book, some really solid takeaways here. And so that all being said, let's turn to sleep. It's no secret that I'm a huge fan of breathwork. I'll do 4, 7, 8 breathwork prior to sleep. Sometimes I'll do carbon dioxide retention protocols and box breathing and things like that in the sauna, followed by a quick cold shower or cold soak prior to sleep. But get into one particular molecule that I find fascinating in the book. Hypoxic inducible factor or Hypoxia inducible factor HIF1. Explain what HIF1 is and how that relates to sleep. Like, why should people care about HIF1 and breathwork, particularly in relation to sleep?

Well, so let's think about something here. When you look at the machine that is your body, energy production and life are one and the same. Meaning that if energy production stopped in your body, you'd be dead right now. Like, within five seconds, you'd be dead. Okay? If your body wasn't producing energy, you cannot differentiate the production of energy from life itself. In order to make energy, you need two things. You need substrate, meaning you need a fuel source. So you need glucose, you need ketones, you know, you need a fuel source, and then you need oxygen. Okay, now think about something. Your body has several redundant backup mechanisms if it doesn't have substrate. Okay, so like, if you don't have food, then, well, you can deplete liver glycogen, you can deplete muscle glycogen. Then you've got your body fat. Then, you know, if you're done with all that, then you can recycle spare parts from your cells. You got all kinds of backup mechanisms. Okay, what are the backup mechanisms? If you don't get oxygen. Well, there's just really kind of one, and it's hypoxia inducible factor and hypoxia inducible factor. Again, I built my book around two concepts central to immunity, which are macrophages and HIF1. And there's. When you start to look at this, you cannot define how the body works apart from these things. You can't. So what hypoxia inducible factor is, it is a. Think of it as like a tension switch. So what it does is it's a tensioning mechanism. It's kind of like the coupling between a train, two cars and a train that allows some give and some take. And so when there's no oxygen available, you need a mechanism to allow your body to survive in the presence of no oxygen. That's HIF1. It's the backup mechanism when there's no oxygen. And the way that it works is it basically turns off oxfos, turns off the TCA cycle. Okay? So the mitochondria need all kinds of oxygen and basically shuts that down, lets the cells in question use Warburg metabolism temporarily and all's good. It's great. Now the thing with hypoxia inducible factor is normally that it dissipates, it's ubiquinated very quickly within the cytosol within the cell. But there is a condition called hypoxia and there's different types of hypoxia. The one we need to concern ourselves with is called cyclic hypoxia. And what we see with cyclic hypoxia is that it tends to happen during sleep a lot for most people. Okay.

And we're talking about elements of hypoxia during sleep. Even if you haven't been diagnosed with say a full blown sleep breathing related disorder, a lot of people are having these hypoxic excursions during sleep.

Yeah. And when we say hypoxia, we just mean that the cells in your body, whether in certain tissues, particularly the brain or you know, certain organs, are not getting quite enough oxygen. Okay. Now this is not necessarily an abnormal thing. We all get, you know, lack of oxygen and this mechanism is in place. But here's the thing, here's the reason we can't ignore this. And really it's a game changer. What you have to understand is that Warburg metabolism, meaning using just glycolysis, has a unique chemical signature wherever it's found. Okay. What we see is that when cells go into this, they tend to consume lots of glucose and they tend to Output lots of free radicals and lots of nitric oxide, okay? Now, in particular, immune cells do really well. Some of them do well in a low oxygen environment. In particular, the M1 or the red Team macrophages, the inflammatory guys, they do well. But the problem is when you get too many of them, what happens is you're getting this chemical signature that profiles 100% identical to cancer. In fact, there's no difference. In fact, I left a chapter out of my book on this. I called it DEFCON 1, the chemical signature of death. So what you find is that if we're going to talk core health, core immunity, core aging, you can't get away from the presence of oxygen and oxygen being properly disseminated in your cells. Because what happens is when cells begin to suffer chronic hypoxia, there's a very interesting thing happens. And this happens during sleep. And essentially what happens is normally inside your cell, hypoxia, inducible factor, it just gets broken down, it gets ubiquinated and we get rid of it, okay? But what happens is when you're suffering hypoxia, there is this daisy chain of enzymes, prolohydroxylase, Von Hippel protein, all this stuff that touches on the MTOR pathway, the growth pathway, okay? Cellular growth. And what it does is as within the cell, the cell gets oxygenated and then deoxygenated. Well, just think of two dials. One is the dial controlling oxygenation and deoxygenation, and the other is the level of HIF1 in the cell. And they both start bumping up and down and bumping up and down. But what happens is HIF1 starts going up and up and up because it doesn't know where to sit. And then eventually what it does is it stabilizes in the cell, okay? So it sits there permanently, and then it goes into the nucleus and it activates all these oncogenic genes. Most of them nothing good, okay? And the reason this is all so important is the place it tends to most happen is sleep. And so if we wanted to come at the very one thing we could do above exercise, above anything else, to ensure that we live a long time, that we're in maximal health, we would have to correct this problem. Because what this problem touches on is basically substrate metabolism of immune cells. And substrate metabolism of immune cells changes the way we think about metabolism. The old paradigm, metabolism is just, you know, my metabolism, I just, you know, I got a good metabolism, I eat, blah, blah. In an immune centric paradigm, you've got to think about the metabolism of immune cells. Because when the TCA cycle gets shut off, you get activation of all these lipogenic genes, genes that store fat, genes that activate all these other things like reactive oxygen species and do all these other things that affect the entire body and recruit immune cells into this inflammatory storm. So sleep is the place where we need to begin to knock this out. And so that's why it's so important.

Okay, so in a nutshell, this HIF one is a way that basically it's a protein, it's going to accumulate in periods of pseudo hypoxia, which would in particular happen during sleep. It would do things like enhance aging or accelerate aging, up regulate inflammation and result in a host of side effects that would dictate that high levels of HIF1 protein are going to be something that's not only disruptive to sleep, but disruptive to longevity in general. And that all being said, how would we actually down regulate this HIF1 protein? Like Boots on the streets. What are some practical ways that we could clear HIF1 from tissue, for example, or activate HIF1 when it needs to be activated.

Let me give you the high level and then we'll just break down three or four methods. So high level is you need to learn how to steer macrophages. Okay. And it's a kind of a core concept in the book, but long story short, you need to learn how to steer populations of immune cells, macrophages, from the inflammatory to the anti inflammatory. And the way you do that is tissue by tissue. And the protocols are unique to each tissue. That being said, here's just some specific stuff that we can do. So one of the ways that we can spin down hypoxia inducible factor is with niacin and zinc. And so by taking these two things at bedtime, it's going to spin them down a little bit. Okay. We can add into that a protocol after doing that where we use exogenous ketones, which is going to actually spin HIF back up a little bit. But it's not a bad thing, It's a good thing. It's kind of a compensatory mechanism. Niacin clears HIF1 from different types of tissues. Another way that we can do this, and I talk about this kind of at length in the book, is during a fast, we want to A fast, B, take omega 3s, C take niacin, take all those three together now on their own, all three of these things will help clear excess HIF1. But together during a fast, it may Be extremely useful for that particular, for that particular aspect of clearing excess HIF1. HIF1 is not all bad. It's fantastic post workout. You want to make more of it.

When you're working out, which, which is why things like nasal breathing, for example, during a workout would be a good idea. Or avoiding hyperventilation during a workout would be a good idea, you know, based on the teachings of guys like Anders olson or Patrick McCown. And. And you want some elements of carbon dioxide retention and hypoxia during exercise to drive up HIF1. But then you'd want to drive it down or back down, particularly when you're. When you're getting close to something like a sleep cycle.

Yeah, really, sleep is the first thing we want to go after. And so there's just a whole laundry list of checkboxes we want to do to make sure that we're adequately oxygenating during sleep and preventing the accumulation of HIF1 during sleep, particularly in the brain. That's really where we gotta really jump on it.

Yeah. Another thing that you say happens during sleep is something, I don't think there's kind of two terms you use in the book that not many people are going to be familiar with that I want to also unpack. One is pexophagy and one is circa septum rhythms. So you say something called pexophagy occurs during sleep. That. And if it's good, how would we actually accelerate that or maximize it during sleep?

So pexophagy is selective autophagy of the peroxisomes. Okay. And peroxisomes are these little organelles within cells that do a number of things. The two primary things they do is they break down the long chain fats, the omega fats, and they also maintain basically hydrogen peroxide balance within the cell. And there's an emerging body of research and I would say a paradigm shift that is underway, and it's shifting us from this idea that the mitochondria are everything, you know, in terms of longevity and aging and energy production, to probably a more accurate approach that the mitochondria are co equals with the peroxisomes. In terms of all the things I spoke of, they're like the twin pedals of a bike that they, their operation is so intrinsically linked and the way that they make energy and the way that they keep the cell healthy and the way they keep us young is so intrinsically link linked that we can't separate them. And so it turns out that peroxisomes working the way they should, has a whole heck of a lot to do with not dying and being healthy and aging well. And what happens with age is that the membrane of the peroxisomes begins to stiffen up and these key proteins, pex proteins, don't pass back and forth readily between the peruxisome membrane in the internal area in the peroxisome. And so when that happens, you get an imbalance of free radicals in the cell, you get an imbalance of hydrogen peroxide in the cell. And this leads to this daisy chain of cascading effects that essentially just kills the cell and kills you. So keeping peroxisomes healthy by the induction of pexophagy, meaning we want to clear peroxisomes, is something that really hasn't been looked at. And you know, it may just be as important as mitochondrial biogenesis. In fact, I believe that it is. We're going to wait and see, you know, as emerging research comes about. But there's a small body of very good thought on this and it makes a lot of sense when you dive into it.

So that's pexophagy. Basically what we're trying to do is steer peroxisomes via basically forcing them to go into pexophagy, which is almost like an autophagy based mechanism that is targeting these inflammation producing peroxisomes or essentially making new peroxisomes or clearing out old ones. And we want to do that while we're asleep. And so what would be the actual strategies we would use pre sleep to amplify that so called housekeeping effect.

There's a couple of ways that we can look at initiating this. It seems to be that, and this is super, super cutting edge, but it seems to be that food patterns may be the best way to do this. So the thing about peroxisomes is that we need them to burn long chain fats. Okay, that's what they're needed for. And peroxisome proliferation, PGC1alpha and all these sort of longevity kind of terms are kind of at the forefront of youth and anti aging and all this stuff, you know, getting peroxisomes to proliferate and activating the, you know, very specific receptors and all that stuff. Well, so what it looks like is that periods of fat feeding, particularly giving the body omega 3 fats initially so that the peroxisomes need to spin up, we need to make more peroxisomes to handle the omega 3 fats and then slamming after a couple days into stearic acid into omega 9 okay. And then at the end of maybe four or five days, slamming into a high carbohydrate meal may just be the thing that induces peroxisome proliferation. And in particular, if we can do this around bedtime, then it may just be the case that this is what drives pexophagy. And it kind of makes sense if you look at it. So there's some good research here that shows that after prolonged fat feeding, you know, the job of the peroxisomes is to break down fats. If you slam a big carbohydrate load into the body, you force pexophagy on cells. And so these feeding patterns and understanding sort of the timing and all that may be kind of the go to maneuver.

Okay, so you talk about, for example, magnifying butyrate production while you're sleeping at night by loading the gut with resistant starch not at dinner, but at. But at lunch as one way to enhance bexophagy. So consuming resistant starches with lunch appears to have this effect. And then you're also probably. One of the other really big tips that you give in the book is to take some type of omega 3 oil and some type of berberine prior to bed to actually enhance the pixophagy even more during your night of sleep to make new peroxisomes and clear out old ones as you're sleeping.

Well, clarification, I think the way I have that in the book is the resistant starch and all that stuff is to drive butyrate production while you're sleeping, to drive bifidobacteria. The whole pexophagy thing is kind of another module, like kind of something you want to throw in maybe once a month, which would be over a period of about four or five days, sustaining kind of high fat feeding from omega 3s, then switching to omega 9 stearic acid. And then finally at the end of that, having a day where you slam into carbohydrates, particularly, particularly like at bedtime, like a big carbohydrate meal, then. So what's going to happen is all of the things that we think of as like, you know, prolongevity, autophagy, all that's going to stop. And the things that. And then peroxisomes are no longer proliferating. In fact, we've got to clear them out. And so the cells now have a substrate, metabolically speaking, a very large imperative to get rid of, like the old dirty peroxisomes.

Yeah, yeah. And then. And then the other thing. And that may sound like a little bit more of an advanced protocol, but you lay it out really well in the book. Again, this is stuff that can be simplified and introduced as habits like, like, like brushing your teeth once you wrap your head around it. It just took, you know, I took a couple of weeks to read your book just because I had to really wrap my own head around everything you were talking about. Now I'm slowly implementing, but again, if you're, if you're listening and a little bit of that went over your head, also grab the book so, so that you're able to kind of systematize this. And for the, for the, for the part of the podcast you're listening to now, we're into part two now. So go to BenGreenfulFitness.com Joel Green 2 that's BenGreenfieldFitness.com Joel Green the number two and then part one. You'll find it at BenGreenfieldFitness.com joel green and in both cases, green is spelled with an E. One other thing I want to talk about related to sleep is this idea of circa septin rhythms. What's a circa septum rhythms? Because that's another thing that's really not a term that I've heard used very much until reading your book.

So it's an older area of research that has sort of gained new attention due to immunology. And there's a subset of immunology called chronoimmunology which is related to the timing of the administration of drugs. And what is bubbling up is this notion that certain days of the week are better for certain things. And that at least in the field of chronoimmunology that they can get 100% difference on the impact of the administration of a drug just by timing it to the correct day of week. And so it gets to this notion that is really fascinating that seven day rhythm is bound up into the biology of everything, whether it's a spider or a bacteria or a human, that these seven day rhythms seem to play out. And within humans it's kind of interesting. There's for example, sodium retention seems to work on a seven day rhythm that's independent of sodium intake. So I mean, that's crazy when you sort of think about that. Or another example would be like cortisol levels seem to work on a seven day rhythm peaking on Mondays, which is why people die on Mondays. Or with respect to cardiac rhythms, they seem to kind of reach their nadir on a Wednesday. And in the field of chrono immunology. There's this whole thing about heart attacks and happening on Wednesdays, you know, all this, all this stuff. Super fascinating. Yeah, yeah. In fact, in my veep system since 2009, we've kind of done this, which is this notion that to get beyond the macro calorie thing, it's the idea that unique days of the week have unique nutritional requirements. And it doesn't take like, you don't have to be a rocket science to kind of grab onto that. It's kind of like, think about it. Well, do you eat the same on Monday that you eat on Sunday? Right.

Because like Sunday for me is a super relaxing day and Monday is like super high stress. Go, go, go.

Yeah. And so when you start to go down this rabbit hole, we come up with this whole new thing and it's tailoring nutritional inputs to circuseptic rhythm. For example, Monday, Monday is like giant cortisol day. So there's good and there's bad to that. There's things that we can do that are, that are, you know, we can ameliorate cortisol production. What a lot of people tend to do. What I see a lot of, and, and I did these corporate wellness engagements for years and years where we didn't deal with fit populations, we dealt with employee populations and very large engagements, thousands of people. And what you see a lot of is people come into Monday and they really want to get on the plan and do great and they do pretty good till about 4 o' clock and then they come home and drink wine and eat carbs. The reason is they're stressed out of their mind and they need to blow some cortisol off and that's how they do that. So I mean this is just, we can do a whole show on this. But it's really fascinating looking at tailoring inputs to this kind of thing.

Yeah. And I would say, you know, if folks begin to look up circusceptin rhythms, you can find out which days that you're prone to specific issues such as the, you know, the cortisol to DHEA ratio being highest on Monday. So stress and depression are gonna peak on a Monday. Therefore Monday being higher in stress and you get into this in the book, might be a day to do things like prioritize a lot of flavanol and polyphenol rich foods early in the day to drive your vitamin B production to counteract stress later on in the day and then use something like an EPA oil in the evening to drive down stress induced cortisol at night. And it's just, it's fascinating to begin to look at the week rather than the day and actually adjust your nutrition intake based on which day you're on. I mean, we're getting into some, some kind of advanced and nitty gritty, almost like biohacking of one's weekly rhythm. But yeah, it's fascinating that we have the circadian biology and then also the circusptum biology. And I thought that was just a really, really interesting insight in your book.

There's also a seasonal biology and there's good research on this. So, you know, during the winter we tend to sleep more. We tend to have greater issues related to heart attack and all kinds of things during the winter. So there's daily rhythms, weekly and seasonal rhythms, and factoring all these things in there is kind of the next level.

Yeah. Yeah. Okay. So. So I know we're beginning to run up against time, but I would be remiss not to perhaps. And if your game maybe rapid fire a few questions regarding anti aging at you. And these would be things. You can keep your replies pretty brief if you would like. But I just want to, I want to ask you a few quick questions. So you say that, and this is kind of flies in the face of what a lot of other folks will say, you actually say that NAD supplementation may actually accelerate aging. That's going to surprise a lot of people. How would that actually be?

Quick answer. If you're younger, like 30s, don't worry about it. If you're older, take it very seriously. So basically, long story short, one of the things, perhaps the biggest thing driving aging is populations of immune cells and immune cell signals because they accelerate the inflammasome. Okay. And the thing to understand is that immune cells are cells. They're cells, they have the same energy requirements that cells have. And immune cells in particular express very specific types of receptors. They're called the C receptors. And you know, this is a whole thing that is like an endless rabbit hole of fascinating stuff. But long story short, there's a particular receptor on very specific types of immune cells that gobbles NAD. It's called CD38. And so if you are kind of in the inflammaging portion of life or you're dealing with kind of chronic inflammatory issues, there's a protocol, there's an order of operations, and research papers are starting to address it. Before you take nad, you want to spin down all of the inflammatory markers because if you don't, NAD feeds the immune cells it makes it worse.

Right. And this would be related to this whole concept of senescent cells. You know, there's these studies on things like quercetin and denacetib, I think is the pharmaceutical used to target senescent cells. And everybody who I've talked to in the anti aging field has said, well, you're going to need those senescent cells when you're young. And so in the same way, you wouldn't want to overdo NAD supplementation, one could argue that a very active, inflamed or person who's flying a lot on airplanes, exposed to a lot of emf, et cetera, could probably benefit from the DNA repair mechanisms induced by NAD in particular combined with sirtuins. But even then, more is not better. And this idea that as you age NAD would become more beneficial in the same way that as you age, some of these senolytic compound compounds would become more beneficial is a concept that makes just as much sense as the idea of consuming more, say protein digesting enzymes as you age, but your body changes as you age. And so that also made pretty good sense to me that NAD supplementation should be moderated early in life and then later in life especially, I would say probably post 50 years old based on some of the data I've seen. That's when you begin to start to target some of these senescent cells with things like higher dose quercetin or NAD supplement or something like that.

Yeah, very much so. I would offer. There's an order of operations. So, you know, you first want to spin down, you know, you first want to initiate senolysis, you first want to spin down inflammation, that's a whole topic, and then apply nad. You don't want to be like super inflamed and then begin taking nad. And even though you might see some improvement, you might say, I feel a little bit better, but there's a push pull to it. So again, it's not so much that nad, you know, good or bad, it's what, when and how.

Right now you explained fat loss and kind of the damage that occurs to the extracellular matrix when we're constantly remodeling these fat cells and doing weight loss, cycling and, you know, similar to that when it comes to muscle cells, there's this idea that working out, especially these, you know, really intensive bodybuilding style workouts or eccentric workouts like CrossFit workouts, for example, create these micro injuries that often can accumulate and result in what you call old muscle. And you've got this key idea in the book that one way to keep muscles young is to clear muscle damage. Do you have any targeted tips for. Based on where someone's at in life, how they should work out to maintain young muscle versus just building old inflamed adhesive muscle?

Boy, that's gosh. I'll do my best on this one. It's such a huge topic. I'll do my best to condense this.

Okay, just give us your key takeaways. Maybe even skipping a lot of the science behind it. Just get into some of the practical takeaways because some of the deep science is in the book. Of course.

Yeah. So the people that already know this are high level bodybuilders. They already know this. Like they all get what's called bodywork and they get some dude that goes in and finds those muscle adhesions and very painfully just gets them out. And so what you find happens is, and if you talk to people that do this, they stay pumped. They have young muscle, their muscles get pumped. It does the things it did when it was young. Conversely, if you're not doing that kind of thing, what you find is you can work out, but you can't get pump and all these other things. So the addition of very specific types of massage post workout at very specific periods, I would say about six hours post workout. And has to be very deep tissue. And it has to be in conjunction with a couple of other things that stimulate blood flow and blood circulation would be the first thing on the list. Muscle growth, young muscle and blood flow are one in the same. As blood flow decreases, as circulatory power decreases, muscle gets.

Yeah. And that's why I think one of the best things you can do. So I get a weekly two to three hour massage and then every morning 10 to 15 minutes on the foam roller. I've got Kelly Starrett's Becoming a Supple Leopard. Like a cookbook next to this wicker box that I have just full of all these different balls and rollers and toys. And I think, as you've alluded to, these adhesions are one of the big things that creep up, especially in very active people, along with the issue of the blood that you get into in the book, the young blood versus the old blood. But yeah, I mean, in a nutshell, taking care of the blood via specific use of some of the minerals and the vitamin C that you talk about while also engaging in. I think that this is the, this is thethe biggest thing is just regular use of deep tissue massage and foam rolling. And justjust getting just as comfortable with that as you are with working out is, I think, one of the best ways to maintain young muscle. And you definitely get into that in the book. Quickly. Explain when you say daisy cutter, because you've said that a few times during this interview, what do you mean when you say daisy cutter?

Oh, so the daisy cutter is just a diet protocol that I've been using for a number of years, and it's the most brutal thing you'll ever do in your life. And if you have gut issues, you have any kind of issues with fiber, gut, don't do it. It's only if you have a very solid gut. But basically, long story short is you want to flood the gut with massive amounts of very specific types of hemicellulose and cellulose, things found in green beans, things like that, for example. And a lot of it. And at the same time, a whole bunch of protein and no fat.

And how often do you do that?

Not very often. You burn fat like crazy on it and you force the body to make just a boatload of butyrate. So you'd want to do it in the evening leading into sleep. It works like crazy. It works really good. Makes your poop not smell, all these great things. It's super, super hard. Super hard. Because what you're doing is you're getting this big bolus of these fermenting fibers in the gut. You're not getting any fat, so there's no satiety. And then you're getting all this bifidobacteria production. It's great for fat loss. It's great to kind of retune the gut here and there, but it's very, very difficult to do. So it's kind of like here and there. You might want to throw it in there.

Okay.

Okay.

And then I promise this is going to be the last question I ask you. Then there's like a billion questions I could ask you. But I would be remiss not to bring this up because you talk about it in your book. And with you knowing this is the last question, you can take as deep a dive as you want. But ketosis and a ketogenic diet and your take on that, because you have a very unique take on it, and you are actually someone who warns people against this ketogenic diet, particularly based on this very special molecule called 4. So explain what 4HNE is and why, based on that, you would want to be careful with the ketogenic diet and what the proper approach for ketosis would be.

Yeah. So the main thing that in the book I offer with the ketogenic, first of all, I've used keto protocols for years. They're in my veep system. You know, they're extremely beneficial. They do, they're highly functional tool sets. I mean, it's kind of like the, it's kind of like the tool you take your oil off in your car. Like you have to have the thing. So they're very, very essential and they're very useful and they're very pro life extending in a lot of ways. The issue that we get into is overdoing it. Sustained long term, sort of keto diets. That's where I bring up the issue. So I don't have any issue doing them short term, couple months, six months, half a year. So here's the mechanism. One of the mechanisms by which keto diets work is that within the mitochondria they increase oxidative stress.

They increase oxidative stress.

They increase oxidative stress short term within the mitochondria. And then there's a hormetic response so that mitochondria upregulate production of glutathione and all these sort of like, you know, compensatory mechanisms. And so then what you see is that oxidative stress across the body goes down. Okay. And so you see this improvement in the parameters of oxidative stress. Okay. And again, I'm just mapping this with time and that's the real thing is when we make these statements like keto diets lower oxidative stress. My question is at what point in time? So what you'll see is this initial increase in oxidative stress due to fats being oxidized within the mitochondria. And then you see a counter effect sort of in the mid to long term and you see oxidative stress go down. But then over time, what begins to happen is the mechanism that's mediating the oxidation, oxidative stress is what's known as an electrophile. An electrophile is a highly, highly reactive molecule. Highly reactive. And the issue with this electrophile, it's called 4HNE, 4 hydroxy nonenal, is that it's happening within the mitochondria.

Same thing. By the way, 4HNE is producing massive amounts when you drink alcohol.

Yes, absolutely. It's why alcohol drinkers look, it's 4hne. But what you see long term within the mitochondria is you begin to run into the potential to damage a very special fat cardiolipin within the mitochondria. So as you're pushing fats down the TCA cycle, what you'll see is that damage to cardiolipin can begin to accumulate as levels of 4HNE accumulate within the mitochondria. Now, cardiolipin basically gives the mitochondria their ability to bend. And if the mitochondria can't bend, then they explode. So the issue that definitely is something to be aware of is that long term there's an uptick in 4HNE, and as you see 4HNE increase, then what you need to do is you need to look at the type of cell and the duration and the concentration of 4HNA. And it has different effects in different types of cells. So in cancer cells, in certain types of cancer cells, in small amounts, it kills them. Kills cancer cells. And that's why one of the mechanisms keto diets work in other types of cancer cells, it diffuses them to adjacent cells that don't have cancer and helps cancer spread. In non cancer cells, 4HNE in low amounts is beneficial, it helps lower oxidative stress. But in non cancer cells in higher amounts, over sustained duration, it can cause damage within the mitochondria. And there is now just beginning to emerge research, you know, and it's still in the animal stage, but showing that, you know, sort of these long term keto diets may be inducing damage within the mitochondria. And it just gets to this thing of like there's this belief that you have these, again, you have these polarized beliefs. You know, you have one belief that no, you know, ketone bodies are the body's rightful natural fuel source, you know, and the other side is no good. Glucose is essential. The truth is if you have too much of either one, you're going to get issues. If you have too much glucose, you're going to have problems. If you're just burning fat all the time, you're going to see issues with insulin sensitivity and all these other things. They need to be balanced out.

Yeah, One of the things you get into the book, for example, is 4H and E can switch on or switch off key protein that inhibits breast cancer. It can be implicated in gastric cancers and prostate cancer cancer. And so there are certain cancers in which you probably want to do your research before you say, okay, I have such and such a cancer and I'm going to switch to a ketogenic diet when in fact driving for H and E production may in fact drive the growth of that Cancer. And so again, you unpack this really elegantly in the book. But once again it points out the fact that the perfect diet in one scenario may not be the perfect diet in another scenario. And this idea of 4H&E and a ketogenic diet. I think anybody who's following a ketogenic diet needs to read this section of the book and really make sure you're very familiar with the mechanism of action via which this 4HNE works and that you're careful with sustained long term strict ketosis in particular. I personally am in a state of nutritional ketosis based on just physical activity and carbohydrate mitigation much of the time. But I cycle nearly every day. I mean, I'm eating 150 to 200 grams of carbohydrates every single night, night to cycle back into carbohydrate utilization, refill glycogen stores, give myself adequate glycans for joints, et cetera. And I find that model to be very sustainable. And as you really lay out quite well in the book, one of the worst things you would want to do if you're on a ketogenic diet that's already driving 4hne production is a drink alcohol in any appreciable amount or B eat fried food foods because both of Those are gonna drive 4H and E through the roof. So, you know, all the more if you're on a ketogenic diet, I think you call it, the stupidest thing you can do on a ketogenic diet is to drink alcohol and eat fried foods. So it'si think that'si mean. I'm not opposed to like a glass of organic wine with dinner. But yeah, I mean like binging on alcohol or having certain periods of time you're getting drunk or not being ruthlessly cognitive. Vegetable oil intake especially all the more so. So if you're on a ketogenic diet. Yeah, I mean that's bad news bears.

Yeah, I put that in there because like in the real world what you see a lot of is people who are like strict ketogenic diet people, you know, during the week and on the weekend they go party and it's, it's. Well, okay, look again, you know, like I can just hear the, I can hear the pro keto peeps just howling right now. Look, I'm very pro keto. Like short term, I think it's fantastic. It's highly functional. It's the long term sustained thing with keto that you need to think about. And in a practical sense, in the real world world. It's this whole thing of like you're gonna go out on the weekend, you're gonna drink and eat fried food, like all those things together. Not smart.

Yeah. Yep. Well, we, we kind of in two podcasts. The first, first part, you guys listening in@BenGreenfieldFitness.com Joel Green, Green with an E. And this second part at BenGreenfieldFitness.com Joel green, the number two like BenGreenfieldFitness.com joel green two we kind of scratched the surface surface of everything that's in the book, but I'm hoping we got some people thinking intelligently about a lot of these important things that we discussed. And the book, again, I haven't really said the title of it too much as I've been interviewing you, Joel, but it's called the Immunity Code. The Immunity Code, the New Paradigm for Real Health and Radical Anti Aging. I guarantee you get this book is going to blow your mind. There's a lot in here, but I think it's one of the more valuable books you can add to your library if you really want to hack your diet and your exercise protocol, your sleep protocol, your longevity protocol to the T. And so I can't recommend this book highly enough. We'll put links in the show notes for you to be able to get the book as well as to all the other resources and show notes that are going to be really comprehensive based around everything that Joel and I discussed. Joel, dude, thank you so much for writing this book and for laying all this out for us. I should probably give you a pee break at some point.

Point. Oh, thank. Thank you, man. This has been one of the funnest convos I think I've ever had. I mean, this, I don't get to nerd up like this very often and just you're one of the few guys I can do this with. So this has just been an absolute blast. Thank you for having me on.

Yeah, for sure, man. Well, we'll have to go for, for Farm Shop round number two, when I'm in la, I'll be, I'll be coming to LA this July. So I'll, I'll ping you and we'll make it happen. But in the meantime, folks, again, part one at BenGreenfulFitness.com Joel Green with an E. Part two BenGreenfieldFitness.com Joel Green, the number two. Thanks for listening in. And until next time, I'm Ben Greenfield along with Joel, the author of this new book, the Immunity Code. Signing out from BenGreenfieldFitness.com have an amazing week. Well, thanks for listening to today's show. You can grab all the show notes, the resources, pretty much everything that I mentioned over atBen Green infringfitness.com along with plenty of other goodies from me, including the highly helpful Ben Recommends page, which is a list of pretty much everything that I've ever recommended for hormones, sleep digestion, fat loss, performance, and plenty more. Please also know that all the links, all the promo codes that I mentioned during this and every episode help to make this podcast happen and to generate income that enables me to keep bringing you this content every single week. So when you listen in, be sure to use the links in the show notes. Use the promo codes that I generate because that helps to float this thing and keep it coming to you each and every week.