Carnivore Diet, Raw Beans, Lectin Myths, Pre-Sleep Gelatin, Apple Peels & More - Q&A Episode With Joel Greene!

On this episode of the Ben Greenfield.

Fitness Podcast, Hyper expression of interferon gamma. When you have an autoimmune issue and that can directly modulate ikremansia populations.

Boy, talk about an industry that needs a revamp or rethink.

What's really true and always been really true is that both are essential. The real question is, which one comes first? And these are cancer promoters, which we've been under the baby talk idea that acidity is bad, alkalinity is good. It's total baby talk. Higher alkalinity in the colon will give.

You cancer help, performance, nutrition, longevity, ancestral living, biohacking, and much more. My name is Ben Greenfield. Welcome to the show. All right, this is a pretty special podcast episode for a couple of reasons. The first reason is that my son Taren is actually shadowing me at the office today. Say hello, Taren.

Hello.

Have you enjoyed your morning so far? Yeah, we've only been awake for, like.

An hour and a half.

What have you done so far this morning since you've woken?

We did the bio charger.

We made chocolate coffee, or not coffee, but chocolate tea.

And then we stretched and we did work for 20 minutes and used the big head.

The big head. The violet. Yeah, we did. Oh, I woke you up nice and early. We tucked away and we read our Bible. And then later on, we'll go upstairs and do our meditation and journaling. And we started the day doing what dad likes to do called eating the frog. Remember, eating the frog means doing the hard stuff first, doing the hardest thing first. So for me, it was working on an article. For you working on a speech. Working on a speech. Awesome. All right, so say hello to Taren, everyone. He's my sidekick today. And the other thing that I want to tell you is that today's podcast is actually with Joel Green. And Joel Green was one of my most popular podcast guests of all of 2020. He was on part one, which was about how to reboot the gut, eat cheesecake without gaining weight, amplify any fasting protocol, and maximize your fat loss. And then in part two, he talked about how to reshape fat cells, enhance repair during sleep, target what are called circuseptin rhythms, build young muscle and get rid of old muscle. And we got so many questions from both of those podcast episodes, we. Which I'll link to in the show notes for this episode, in case you missed those, that we have Joel on for a part three in which it's him solo answering all your questions, meaning that you guys left a lot of questions after both those shows in the comments section and Joel was kind enough to dig in and answer the biggest ones for you. So if you want the show notes for everything that you are about to hear in today's show, you can go to BenGreenfieldFitness.com Joel3 that's J O E L the number three BenGreenfieldFitness.com joel joel3 where do they go for the shownotes?

Taryn BenGreenfieldFitness.com JoeL3 Joel3 you got it. All right, these are the follow up questions to the first podcast that Ben and I did. And this first one has to do with Crohn's disease and Carnivore and it says my wife has Crohn's. She recently, as of six to eight months ago, stopped her infusion and has gone on a mostly plant based diet. I listened to the podcast on the Carnivore code and after listening to this podcast I'm curious your thoughts about combating and healing her gut with a carnivore approach. Ah, great question. Short answer, near term probably going to see a nice amelioration of symptoms. Long term probably not going to fix anything. Research suggests probably going to make things worse up to and including cancer risk. This question is right at the heart of two very important questions that the marketplace has just not answered. And the result is that literally millions of people are just totally confused. Let's wipe that out and fix this problem. The first question gets to what foods are essential? Like what are the foods you need to heal and seal the gut? And what you have in the marketplace is all this one dimensional baby talk back and forth about plants versus animals doesn't really get us anywhere. The next question is even more important and the marketplace hasn't even asked it yet. It hasn't even considered that there is an order of operations that is really the what, the when and the how. And in order to understand that, just think about a gasoline engine. You've got oil and you've got gas and they're both essential. But even more important than that is the order in which you put them in. You got to put the oil in first and then the gas and then you start the engine. If you put the gas in first, start the engine and then try and.

Put in the oil, you're going to.

Wreck the whole system.

You.

And with that simple analogy, it's very easy to see that the order of operations to the essential things is just as important and just as essential. So what I'm going to do here Real briefly is just summarize a seminar that I did for your kion coaches a few months back on the structure function of the gut. What the listener here is going to readily see is two things. You're going to see what's essential, what are the foods that are essential based on how the gut works. And then you're going to see that there's an order of operations, and it's going to explain a lot. So let's first think about this. There's some really good research with Crohn's, and what that research suggests is that if you have Crohn's, then a good solution is a diet that is high in both fish and fiber together, and that long term, you're going to get a nice healing for Crohn's disease. And conversely, at the other end of that, there's also a pretty good number of studies, about 20 or so that I can think of, that strongly suggest that if you have a diet that's high in meat or fats or both, and particularly omega 6 fats, that you're going to increase your susceptibility to Crohn's disease over the long term. Now, what's interesting is we hear these anecdotal reports, you hear these reports of people that went on a carnivore diet and their symptoms improved. And this, together with the plants, animals debate, just confuses the heck out of everybody because you don't know what to think. Is the research flawed? Are the reports just hype? So the way we solve this problem is we understand the structure function of how the gut works mechanistically. So let's start with the colon. And that's where most digestion takes place. And the colonocytes are the cells that line the colon. Their primary fuel is butyrate, the short chain fatty acid. And I'm going to. We're going to walk through how butyrate gets made. The critical thing to know is that there's a lot of different fermentation pathways to make butyrate. There's not just one, but what the available body of evidence most strongly supports is that there's an optimal pathway to make butyrate. And it's called sarcolytic fermentation. Sarcolytic is a really fancy word. You can throw it out at a dinner party. It just means fiber, just means that you're fermenting plant walls, plant cell walls. What you need to understand is that you get two things when you go that route. Sarcolytic fermentation gives you antioxidants and it gives you short chain fatty acids. And so when you have the right bacteria in place, you give them fiber. You're going to get optimal amounts of butyrate and moderate amounts of propionate and acetate. That's important because you can get too much. You can get too much acetate, it'll give you fatty liver. The second thing though is the antioxidants. And that' and the reason is this. The gut, and in particular the colon, exists in a state of extreme oxidative stress. And it's normal for the colon. And so because of that, you have all these immune centric adaptions. For example, macrophages in the colon are hyposensitive or they're adapted to ignore inflammatory signals like Interleukin1b. And what maintains this colonic homeostasis of extreme oxidation is antioxidants. So a really good question is what happens when you deprive the colon of antioxidants for extended periods? The answer is you will bleed down ascorbate levels in the colonic wall and you'll spin up inflammatory mediators like tumor necrosis factor alpha. And that is a disaster, because when you elevate tumor necrosis factor alpha in the gut, in the colon, you shut off or impair and turn off butyrate transport. And what that means is that the gut can't make use of butyrate. Now, Crohn's disease is characterized by a loss of butyrate producing species and a gain of methane producing species of bacteria. So that's really, really, really important. Now here's the thing. You can make butyrate from other pathways, like for example, you can make it out of amino acids or rather protein. But there's some really important differences. Now, when you use the sarcolytic pathway or fiber, you get two things. Antioxidants, you get short chain fatty acids. When you use amino acids to make butyrate, you get two things. You get short chain fatty acids and ammonia. And that may not sound like much, but over the long term, consequences are massive. Remember, when you deprive the colonic environment of antioxidants, long term you spin up tumor necrosis factor alpha and you get other problems. So without the ongoing antioxidants from phenols or fiber, you jeopardize the oxidative balance of the colon. And worse, you can get some really bad things from sustained production of ammonia. For example, you can get things like alkylated carbonyls, and these are cancer promoters, which, by the way, we've Been under the baby talk idea that acidity is bad, alkalinity is good, it's total baby talk. Higher alkalinity in the colon will give you cancer. I even had to correct a very prominent figure in this whole debate here on that fact. Additionally, the bacteria that make short chain fatty acids from protein and the pathways used may not be optimal. For example, when you make butyrate from fiber, there's a salvage pathway. And what it does is acetate gets salvaged back into acetoacetate, which gets converted back into butyrate. So you have optimal levels of butyrate. Well, that doesn't happen in some of the amino pathways, like the lysine pathway, for example. So you have some key differences. When you make long term butyrate from things other than fiber, you get a lack of antioxidants, you get ammonia, you get imbalances in the short chain fatty acids. And all those things can really add up over time. And at a high level, when we look at, well, what's essential? What's the optimal way to feed the colon? The answer is fiber. In plants, that's really the answer, mechanistically based on what is true. But that's not true when we look at the intestines. Yet a different story. In the intestines, amino acids rule the day. In the intestines, the enterocytes are the primary cells and their primary fuel source is not butyrate, it's glutamine. And glutamine works in conjunction with other aminos synergistically. So, for example, arginine and glutamine work really well together. And then you need tryptophan. In the picture, tryptophan is essential for things like secretory iga. You need glycine, you need the sulfur aminos. And what's your best source? What's your best source of amino acids? The answer is animal proteins. Those are by far the best source. So, answering the first question once and for all, putting this debate to bed, what's essential, plants or animals? The answer is both. And it's easy and readily apparent. Even with just a quick cursory glance, like we've just done here, what we can see is that the plants feed the lower gut, they feed the colon optimally, they help prevent cancer, they make butyrate optimally. The upper gut is really best fed by animal foods. What's really true, and always been really true, is that both are essential. But just like our oil and gas analogy, the real question is, which one comes first? Here's what the Science says there's very good research that shows that amino acids together with niacin, very healing on Crohn's. And in our last podcast we talked about this. That butyrate shares the niacin receptor GPR109A. And as a result, things like interleukin 10, which shuts and seals the gut, are affected dramatically. So the question would be if aminos and niacin together are healing on Crohn's, and it's a great first step, what's the best source of those? And the answer would be meat. Meat's our best source. It's high in both, high in aminos, high in niacin. And what this does is it explains something. It explains the anecdotal reports. Hey, I went on a corn of our diet and things got better. What's the mechanism? Amino acids and niacin, which meat is abundant in. Now question, does that solve the problem? Now remember, Crohn's is characterized by a loss of butyrate producing bacteria. And we see butyrate transports impaired by tumor necrosis factor alpha. So what's next? In our order of operations, we have to clear tumor necrosis factor alpha. Until we do that, we can't even get butyrate to work. So we have to spin down inflammation in the gut and clear TNF alpha.

And then what?

What's the next step? Well, research shows that the addition of very specific strains of bacteria, e.g. key strains of bifidobacteria, are extremely healing with Crohn's disease. And it explains a lot because in order to get butyrate production back, the butyrate producing species have been cleared out. We need starter dough to get them back. And through cross feeding reactions, these very specific strains will begin to add the butyrate producing species back. So notice something here, we are not yet at the place of using fiber, but fiber is essential. It's the best way to make butyrate. But what are we seeing here? We're seeing clearly an order of operations is just as important as the things that are essential. And we hear these reports that confirm that. You hear people with Crohn's and they go on a high fiber diet and they have problems. It's just like trying to put the gas in, start the engine and then.

Put in the oil.

It was the order of operations that explains everything. And then once we've gone through all these steps, we've added aminos and niacin back into the picture. We've cleared TNF alpha, We've replaced key strains of bacteria, jump started butyrate production. Finally now we get back to using fiber and we can jumpstart that with red phenols and human milk oligosaccharides. And then finally we can titrate in small amounts of fiber. And with this, we have just elevated the entire conversation for the ecosystem right out of the baby talk and into what is always and really was true. Both plants and animals are essential. And on top of that, there's clearly an order of operations based on what's mechanistically true in the gut. And if you have Crohn's, you have ibd. If you go to a really good practitioner, that's exactly what they're going to do. They're going to give you an order of operation.

Okay, next question.

Is there any correlation with mental health and what was stated in this protocol? That is, if someone is severely depressed or anxious or both, can implementing these strategies help? I would offer the answer as yes, but it's probably by a different pathway than what we've been led to believe. And what I mean by that is when you look at a lot of the research into the gut and depression, there's something interesting that stands out. And that is a lot of that research, or much of it is actually done with mice. And you can't really ask a mouse, hey, how you feeling?

Are you depressed?

So we have these sort of ways of interpreting mouse behavior by putting human words on it. And the thing that we actually measure in those studies is mobility and energetics. And when you actually look at the mechanisms involved, they are metabolic in nature. So the less mobile mice are depressed and the more mobile mice are not depressed. And the mechanism of action proposed really has a lot to do with the way that bacteria influence metabolic function. And that aligns very well with what I have personally noticed. Anecdotally speaking, what I have seen is that changes in the gut biome will give you a nice bump in energy, and it's an immediate proof of it. But they don't necessarily translate into immediately realizable massive differences in affect and mood and things like that. But what does seem to translate into that are reductions in body fat. And when we get these very significant reductions in body fat, what we see are these improvements in metabolism and bioenergetics. And I have noted those things do tend to correlate very well to affect and mood and cognition and ameliorating depression, which is interesting also because obesity one to one correlates with depression. And on an interesting note, I think Very soon here we're going to be able to directly measure these things. We'll be able to measure the effect of incursions on the gut biome into very specific parameters in humans. There is a very fascinating research project underway that I've been invited to participate on where I'm doing the dietary protocols for. And it's headed up by Dr. Ryan Darcy, who is a neuroscientist. He is a tenured professor at the University of British Columbia and Simon Fraser University. And essentially he has spearheaded a technology that essentially is a Fitbit for the brain or effectively like what the oura ring is to sleep. This is for the brain and it allows us to measure the impact of very specific inputs on different indices of cognitive performance. So things like mood, depression, affect, recall, all these things can now be mapped and measured based on very specific inputs. So we will be able to soon pass the mice mobility stage and be able to go and directly measure how things like changes in the gut biome can affect things like depression and mood and energy and all those things.

Okay, next question. At the moment I have a specific question about the signal amplification, page 78. Joel says to eat raw black beans. Do uncooked beans contain toxic lectins? Should they be soaked at least? There's no info about how one should actually do this safely. Okay, so yes, to clarify, you definitely want to do them cooked but cooled down. And it brings us to actually a very interesting topic, which is the notion that lectins are all bad and toxic, and that is simply not true. For example, chickpea lectin inhibits breast cancer. Banana lectin can slow the growth of liver cancers. Concanavulin legume. Lectin kills certain types of cancer cells in mice and it ameliorates diabetes in humans and even hiv. And in fact, human lectins are actually essential for immunity. So the old baby talk that lectins are all bad is something that needs a serious rethink. But definitely, yeah, with most of your beans, black beans, all that, you want them cooked but cooled down. The one exception is green beans. With green beans, the beans are not mature themselves and so you don't have the same issues. Next question. How much gelatin should you eat before bed or in the afternoon? I think you got two questions there, so let me do my best here. I tend to eat about 6 ounces or roughly about 100 grams. And I do it in the form of just five calorie jello. And then you're going to have different effects depending on when you take it at bedtime. What a lot of people will report is some nice improvements in body fat reduction. And the research tends to support that. So the glycine and the jello tends to sensitize adiponectin and helps improve insulin sensitivity and then having it in the day. I find it's a really good tool to ameliorate hunger if you're really dieting strictly. So that's how I would look at that. If an apple peel is the first way forward, my question is, how much apple peel should we aim for? 2 to 3 apples. Is red apple better than yellow ones? Yeah, this question comes up a lot. It's a good question. I lean towards the red apple due to the color pigments which are consistent with the red polyphenols and their known properties in terms of amounts. It's not an exact science. What we have are individual tolerances and those can vary pretty significantly from person to person. So the basic idea is start small and then titrate your dose up. And you have to do that really according to your tolerance. Now, a lot of it will depend on the strains of bacteria that you currently have in your gut. Some people don't have any bifidobacteria in their gut to start, although it's kind of rare. So the less you have to start, the smaller you have to start dose wise. And on top of that, if you have like a known apple peel allergy, obviously then you know this isn't something that you would want to do. Next question. I'm confused about whether we take the HMO powder dry or mix it with water or drink it, or make a smoothie with apple peels and the HMO powder. I tend to make a smoothie where I'll take the HMO powder, the apple peels and the phenols and I'll mix them all together in one with some whey protein and I'll do that as a shake. That's kind of the easy way that I like to do it. You can mix the HMO powder with whey protein. You can take it dry if you want it. It doesn't really have much in the way of flavor, so it's best to mix it with something at least the red phenols and that that tends to work. Next question. What about modified citrus pectin? Any thoughts on taking pectin powder like the kind used to make jellies in order to feed achromansia? Yeah, citrus pectin is amazing stuff. I would say it deserves an entire show in its own right. It's kind of similar to apple peels in that you have these huge polysaccharides that really don't absorb very well in the gut unless you heat them up. But in terms of feeding achromansia, that's kind of where the similarities end. It doesn't really do that, but it does do a number of things. Top of the list things like preventing cancer. And these are mainly due to sort of a unique ability that citrus pectin has to bind human lectins that are rate limiting steps that accelerate metastasis. Crazy question. Can you tape apple peels and pre digest them like sauerkraut? There's no crazy questions, just good questions. I would not do that, just me personally, because again, key idea of fermentation is what makes bacteria. So if you want to ferment them, then the action or the fermentation action that's going to make bacteria in the gut isn't really working for you. So my preference would be not to do that. But that's just me. Is there a clean baby formula or another supplement that you can recommend? Not that I know of. Baby formula is. Boy, talk about an industry that needs a revamp or rethink. Yeah, it's, you know, in many ways the infant formula stuff is at the leading edge of science. I mean you got some big dollars behind some of these things like hmo, but I mean it could just really use a rethink from a holistic organic level. It's just not there. So for hmo, there's a lot of products on the market now and more every day since Ben and I did the original podcast. I think the main thing with HMO is it just you're getting a pure source of it. And there's Also some new HMOs that are going to be coming on the market very shortly. There's another three or four that are making their way out, so I'll be announcing those as they hit. In 2013, he published the first article to the health and fitness community on the dangers of MCT oil supplementation. Can the dangers be clarified or a link provided to this article? Yep, absolutely. I did a bitly for it, so it's pretty easy. It's bit ly mct palmitic P A L M I T I C. That's bit ly mct palmitic. And that will take you right to it. It's dated October 12, 2013. But basically to sum up the article, it's that the derivatives of coconut oil, specifically palmitic acid and palmitate. There's some good evidence to show that they're invol insulin resistance. And the basic reason has to do palmitic acid down regulating gene expression of adiponectin. And on top of that, palmitic acid actually cleaves it in the serum. So yeah, there's also some links there to the supporting research and you can go check it out. Next question. I get what Joel is inferring. Watch your inflammation markers before taking NAD supplements. That's exactly the issue that Nuchito Time is trying to address. And there's a link here. What's your opinion? Yeah, I like what these guys are doing. You know, I didn't know about them before this question, but I took a look at it and what I can say after looking at it is this is, this is what I consider to be a legitimate, honest attempt to solve a problem. They're really looking at the structure function of how things actually work. And I think I've mentioned that so much of what we see in the industry is not based on how things actually work. And it's actually more true than not true. And so what they're doing here is trying to get their arms around how things actually work and provide a good solution for that. So yeah, I really like what they're doing here and I think that there's probably some different ways that they could go about it and I think over time they'll probably come out with some other cuts with a few other bites at the apple, so to speak. But this is cool. Next question. Do I do the two weeks of apple skins HMO phenol powder before I attempt any of the other modules or do I start the two day core eating right away? Do I do the daisy cutter protocol right away or wait until later and at what point do I add the other modules in? Okay, let's start with the first question here. Do I do the two weeks of apple skins HMO powder before I attempt the other modules? Yeah. So the way the book is structured is very much like a car coming into a tune up shop. There are things that you do if your car hasn't been tuned up in a while that are under the aegis of maintenance. They're not things you're going to do all the time, but they're things you're going to do periodically. So that was the reason in the gut what we see with most people is there's, you know, there's immune related, immune centric issues in the gut and that's the first thing we hit but the key to understand is that it's not something you do all the time. Like the HMO Apple peels Phenol protocol is something to do for about 15 to 20 days and then you go off it for a while and then you can bring it back in whenever you need to. Like I use it for a day or two. Like if I've, you know, eaten bad or once every, you know, three, four months, I'll do it. But it's like anything else, you know, you can, you can imbalance anything. So yes, that's a good place to start. Next question, do I start the two day core eating right away?

The answer, yes, absolutely.

You can start the two day core right away. Two day core pattern is really the main emphasis on the book. And you have to inventory the problems we actually really have to solve in the real world over time. So we have to solve, number one, the issue of declining bifidobacteria with age. We have to solve the problem of aging in general. We have to solve the problem of sleep disruption. We have to better the idea of being in autophagy all the time and disrupting leptin and disrupting sleep cycles from too much fasting. We have to deal with the real world circumstance most people live in, which is scarcity of time resources and time going to zero most of the time. And then we have to deal with how people really eat over time, which is ad libitum, and that they just tend to eat whatever the heck they want from time to time. So all of those ideas are built into the two day core pattern and it's meant really to solve those problems. And it's something you can start away. Next question, do I do the daisy cutter protocol right away or wait until later? So I would not do that up front. It's very brutal. The daisy cutter is something to do like kind of once. It's just kind of like a thing you do to prove to yourself how powerful retuning the gut is. And I've gotten a lot of feedback since Ben's original show. Most of it, 90% of it has been super positive. And people having these astounding results. You know, it's like anything else. There's no 100% solution. Nothing works for everybody. So, you know, there was a 10% just didn't work for. But it's a great protocol to get measurable effects. By retuning the gut, you'll see massive drops in body fat, your poop stops smelling, comes out real easy. And so it's kind of like something that you could do, I would say, like it's something at most to do once a year. At what point do I do the other modules? So most of the other modules in the book are things that you can intermittently throw in. And again, it's the tuning the car up analogy. Like, you know, once every three months, once every six months. So for example, there is an inflammation spin down in there. You probably want to do that twice a year. There is an addition to that where you can, you can do pexophagy. And you know, it's good to do once every three, four months. I do it once a month. And so the idea really with most of those is that they're intermittent. The main thing that's meant to be done like on a regular basis in the book is the two day core, the sleep protocols, the integrated interval, and those are like the foundation. And the other ones you can add in, as you see bit. Next question. When to do Joel's B vitamin protocol? Again, that's just sort of a test. It's something you can do when you, when you feel like you need energy or just to prove to yourself the power of the gut. And there definitely were a couple of protocols that I put in the gut that were tests. So one is on page 78 where it's just a test, you can make yourself hungry with food, and then later on it's a tool that you can use strategically, like if you need to amplify growth hormone at night. The B vitamin protocol, it's a test where you can prove the power of food. You can do it in one day and your energy skyrockets. And I've heard this over and over and over from people since the podcast who, yep, it works. And later on it could become a tool set for when you need energy. So hope that explains it. There's going to be a staging area coming out here early in Q1 that will have a little bit better step through of some of the protocols in the book. And one of the things I was up against in the book was trying to keep it under 400 pages. And it, it was very, very, very difficult to do.

So.

Next question. It's interesting that nad may increase inflammation. I did some googling and I see a study that Joel may be relying on. Below is a study with a finding. It potentially conflicts with the Nature article. In the below study, researchers found that nicotine and riboside, the NAD precursor, may reduce inflammation. The issue with this really gets to immune cell metabolism and it's really not that difficult to see. So when we look at the red team, or the inflammatory macrophages in particular, inflammatory macrophages in body fat, they depend in on NAD salvage for energy metabolism. And the mediator is lipopolysaccharide. So lipopolysaccharide can drive the upregulation of NAMT or nicotinamide phosphoribotransferase. Okay? This is the salvage enzyme that you need to make nad. And what happens is these inflammatory macrophages in body fat become dependent on it. So when you have inflamed fat and then you feed them nad, they multiply. Okay. And the key is body fat and the gut. So you have lipopolysaccharide translocates from the gut, and then you get macrophage tissue translocation, where macrophages from the gut find your fat along with lps. And then as we age, what happens is that your body fat basically becomes a reservoir for senescent cells. So you have macrophages in your fat that need nad. And when you have all of these things together, you have, like, a perfect storm for aging and cancer. And so then this brings us back to an order of operations. You have to do a number of things first in order to spin this down before bringing NAD into the picture. And once again, you just have to look at immune cell metabolism of macrophages.

And you can see that it's definitely.

A very real thing. Next question. What is your source of hmo? What brand and product? Yeah, me personally, I've just used baby formula for the longest time. So, you know, I grew up poor, and in a lot of ways, biohacking can be a very, you know, very, very, like, costly, costly endeavor. So one of the things that's always been very important for me is to find hacks or ways to make it very affordable. And I've been able to do just great on things like, you know, five calorie jello and baby formula. I'm using the pure stuff now just because I get it directly from the manufacturer. But, you know, I've used the baby formula. It's got the other junk in it that other people don't like, but, you know, it does serve its purpose.

All right, next series of questions are from Raja at Seed. And I guess I didn't know about them prior to this. They're a probiotic company. And Raja says that he wanted to. He said he wanted to share some notes about the research I cited with regard to the microbiome, prebiotics, and probiotics and said that it's at odds with our current understanding. And then he goes on to say that tight junction integrity is important to gut homeostasis more than pectin or polyphenols. L. Glutamine is the most potent regulator in the preservation of the gut barrier. The gut mucosa is the major site of glutamine metabolism, and glutamine is the preferred fuel for enterocytes and colonocytes. Wow, that's a big one. We'll get into that. We've interrogated tight junction protein expression pretty heavily and single strain as well as consortia. Okay, so he just. He goes on to basically say they make probiotics and that those probiotics are very effective at sealing the gut junction. This sounds like seminar talk.

I used to hear MDs 2014, 2015.

Come back from seminars, and they would kind of speak about glutamine in that way. There are couple of just profound mistakes in his assertions there. Easily, easily sort of refuted and easy.

For anybody to prove.

So let's break this down, okay? For our purposes, once again, the gut is the small intestine, large intestine, and the colon. Okay, now, similar to our look at Crohn's disease, when it comes to the colon, the primary cell or the cells of the colon are the colonocytes. And it turns out that butyrate, not glutamine, is the primary fuel source of the colonocytes. And that's really easy to see. In fact, you can verify it right now. All you got to do, go to Google, type in primary fuel source colonocytes. And if you just type that in, basically what you'll see is tons of research all saying exactly what I'm saying, that butyrate, not glutamine, is the primary fuel source of the colonocytes. And that skews a lot of those statements Raja made kind of, kind of into the marginal zone just for that, Just for that alone, because that's a big one. You really cannot afford to get that one wrong. Now, when it comes to the colonocytes, they can use multiple sources of fuel. They can use glucose, they can use glutamine. Butyrate is the primary fuel source. And so, as such, butyrate in the colon is far more important than glutamine at sealing the tight junctions. And that's also fairly easy to establish. Not that tough. Now, when it comes to the intestines, similar to when we looked at Crohn's disease, it's a different story. Their glutamine is the main fuel of the enterocytes. And so of the aminos, it is probably the most important one, or rather is the most important one. But the key point, and I stressed this when we looked at Crohn's, is that the most accurate way of characterizing the role of the intestines, the role of amino acids in the intestines, is to say that amino acids work synergistically together. And in fact, you can make a really good case that you can have abundant glutamine and be missing other aminos and then have all kinds of problems like leaky gut. So by itself, glutamine drives glutathione production in the gut, drives nuclear factor kappa beta along the PIK3 growth pathway. So what's interesting is arginine does the same thing, but it also drives nitric oxide. And that's why arginine and glutamine are better than just glutamine alone for the intestines. And then there is the case of tryptophan. And what's interesting is that when you look at IBD and tryptophan deficiency, there's an extremely high correlation. So you could have adequate glutamine but be deficient in tryptophan, and you're still going to have leaky gut. You're still going to have issues. Okay, so it is much more accurate to say that aminos in concert, in synergy wield vast power over gut junction integrity in the intestines. And that's probably a much more accurate way to characterize that. Now, in fact, this takes us to a very interesting place, which is, once you start to factor in tryptophan, you can make a very good case that it is not aminos at all or glutamine at all that wield the most power over the gut junctions, but instead key strains of pathogenic bacteria in concert working together with tryptophan. And Raja kind of makes that case himself by talking about their own probiotics that work to seal the gut. So you can. You can argue very well that it's.

Not aminos at all.

It's more bacteria in the gut that mediate gut junction integrity. Okay, Next he goes on to say, I like that you guys hit on butyrate and its role in host metabolism, especially when it's a metabolite of bacterial cross feeding. Basically, he goes on to talk about that they have a strain of bacteria that increases butyrate production to higher levels than the original baseline, and that they tested it after exposure to antibiotics and alcohol I would expect that. And yeah, that's fantastic. What's kind of interesting there is that in theory, just in theory, it'd be a good experiment on a single dose. You could probably get the same thing from just a single dose of vodka or single dose of alcohol. And the reason is that it gets converted into acetate. And then depending on the bacteria present in the gut, there's a strong possibility that you could get acetate salvage back into acetoacetate, back into butyrate. So in theory at least, you could increase butyrate production from a single dose of alcohol, which is kind of going to be something that would be fun to see if you could do. Now, chronic alcohol consumption, that's not true. You're going to decrease butyrate and elevate acetate and probably get fatty liver and a bunch of other stuff. But single dose, that would be a very interesting experiment. Next, Raja goes on to say, talk about Ekkermansia. He says, it's a cool bug. I know the scientist who put it on the map. But it's not so simple to associate its presence in lean people and mice models with health. So he says a big debate we had at the Keystone Conference was why it's there in lean people but elevated in the gut of patients with neurodegenerative disease. It has a lot of promise, but we need to be careful about associations. It's also present in Japanese women, but virtually non existent in Japanese men. So there's more to the story than focusing on a single bug as a marker for microbiota mediated metabolism. Okay, let's look at this first. Let's look at obesity. So that I know of. There's about at least a dozen studies with obesity and Akkermansia. And what they basically show is that with obesity you have low levels of Akkermansia. It correlates well to obesity. And that when you administer Akkermansia, whether it's dietary or whether it's supplemental, you get reductions in fat mass, improvements in insulin resistance, improvements in liver fatty acid metabolism. It restores the tight junction proteins in the gut and it rescues the inflammasome. So over and over, when you look at disorders of body fat, you find low achromansia and achromansia. Administration seems to drive these crazy radical improvements in body composition. It's also interesting to note that the study that Raja quotes is Japan studies. Since we're on the subject of Japan, there's actually some research on a Japanese herb called Campo. And what campo does is it improves Gut barrier function, and it basically spins down endotoxins and improves insulin resistance in obesity. And the way that it does it is, wait for it by driving Akkermansia. Okay, now here's the really, really interesting thing. So you could take the skepticism about Akkermansia as a analysis error, and here's why. Achremansia has a very special place in the immune system. And when we see hyperactivation of immune signals that can affect Akkermansia populations, it is entirely possible that it would be an equal mistake to not think that achremansia is exactly what it seems to be and that instead, we have failed to account for Akkermansia's role in the immune system. So a good example is you can get hyperexpression of interferon gamma when you have an autoimmune issue, and that can directly modulate Akkermansia population. So where I think we're on pretty good ground with Akkermansia is to say that it's the principal player in mucin foraging in the gut mucus layer, and that when you don't have it, it seems to correlate to metabolic dysfunction and that by increasing it, in most cases, it seems to restore metabolic health. I think that's probably on pretty good ground, and that characterization seems to be substantiated by the weight of evidence. There is an evolving understanding of how the immune system interacts with Akkermansia and affects Akkermansia populations. So it may well be in the case of autoimmune disease that autoimmune modulators like interferon gamma directly affect Achremansia in ways that we don't yet understand. That's entirely possible. But that being the case, that would not in any way take away from what Akkermansia indeed seems to possibly be. Okay, next, Roger goes on to say human evidence for polyphenols in stimulating Akkermansia hasn't been sufficient to date. And then he quotes a paper that I cited. He quotes the final paragraph, and basically what it says is that that in the last sentence, polyphenols have not been sufficiently analyzed in human subjects, and the evidence for its involvement increasing the abundance of Ekremansia has not been sufficient. So when you read research papers a lot at the very last paragraph, what you'll see a lot of are these kind of calls for more research on the subject. Okay? But if you read prior to usually that ending paragraph, what you'll find is direct evidence in the study that supports the very thing that they're asking for more research on. And that's exactly what we find here. So if you read the previous paragraph to that statement, it says this polyphenols derived from grapes act to increase the abundance of achremansia in the intestinal tract and as a result they have been shown to enhance intestinal barrier function. And then it goes on to say polyphenols derived from cranberries have also been reported to increase the abundance of achreomantsia as well as suppress obesity, insulin resistance and intestinal inflammation. And then it further goes on to say that Matsumoto, who is a scientist, obviously demonstrated that apple derived macromolecular procyanidins. Remember I talked about those in our first podcast. The very long chain procyanidins, highly polymerized procyanidins induce an increase in the abundance of intestinal achromansia. And then it says administration of macromolecular procyanidins suppress changes in inflammation in intestinal mucosa, weight gain and abnormalities in liver metabolism induced by high fat fat sucrose diet. So if you just read the body of the study, it does seem to very well support the idea that polyphenols can indeed increase akromansia. Let's see. Next, Joel talks about TNF alpha and intestinal inflammation blunting the protective effects of fiber. In general, I agree with the sentiment that carnivore and fiber elimination, that carnivore plus fiber elimination probably helps people that have upstream intestinal issues rather than being a net positive at the population level. A group at UCSD has shown that prebiotics blunt the effects of TNF alpha. Yeah, I would agree with that. In fact, this just gets back to what I talked about earlier order of operations, and it also gets to what I talked about in my book. So in my book, basically I'm against the sort of indiscriminate use of probiotics, using them as Chiclets OR M&MS. I think you do more harm than good. But as I said in my book, I think the future of probiotics is really in the hands of highly skilled practitioners who use selective strains for very specific outcomes. And I think that has a very, very bright, positive future. I think some miraculous things are going to be possible in that. So I'm not against probiotics, I'm against the misuse of them. I think that at this, at least with that statement, we're really on the same page. We're both in agreement that you can do some really amazing things selectively. With probiotics. And I think for practitioners, there are some really fantastic things on the horizon that will put tremendous power in their hands to heal very specific conditions through the use of probiotics.

So, yeah, I would agree with that.

And then Raja finishes by saying that he wanted to make sure the audience didn't take away too broad a message about probiotics than being bad. And I would agree with that too. So I would agree with you on that. And with that, I think that about wraps it up. So yeah, Ben, thank you so much for having me back. And it was a blast. And anytime you want to do it, just.

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