 you start to realize that it's the combination of all of these different functions that needs to be there in order for your body's handling of nutrient loads to be done in the most kind of effective way possible. The hack is GLP1. Yes, GLP1. It's all the craze now, right? It's an incretin hormone. So that's a fancy way of saying it's a gut hormone that helps your body deal with the nutrient load that your body takes in. And one of the primary ways it does that is it promotes insulin secretion. So this is super important because then it enables your body to get rid of the sugar from the bloodstream and move it to where it's needed, which is to power up yourselves. And so this is something, this hormone is something that we would normally produce and should normally produce. And are there, and we now know that this hormone among other things is used for weight loss. It was not the original intention of synthesizing this hormone. And I live in the LA area, and I think every human being seems to be on this drug for mostly bad reasons. But vanity would be the number one. A lot of people who use this drug notice that one of the major side effects is they are not hungry. Period. And sometimes they are still not hungry. They even walk around nauseated and that apparently is a good thing. So why is what we produce maybe better than these pharmacologic solutions? Yeah, I mean, I guess I would just separate entirely, right? Like a pharmacological solution, you should use it if you've got pharmacological reasons for that. So definitely kind of using it outside of that is not really a good idea because the levels of concentrations and so on that those are intended for are just a different scale. And what we're talking about here kind of your body's natural production of it is more about getting your system more into natural balance and having your system's appropriate response when you eat a meal. So it's more akin to the benefits of having a well-balanced meal with the right nutrients, right? That aspect of it is kind of well understood by people, but the microbiome aspect is kind of works hand in hand. So you can have the well-balanced nutritious meal, but if your microbiome isn't predisposed to handle it appropriately, you're not going to be optimal on that front. You're not going to be balanced. But yeah, GLP-1, the natural levels of it, it helps as I said on insulin secretion, but also to your point on satiety. So, you know, and for the natural levels, it just will help you get comfortable more quickly so you don't, you know, ingest more than you need, right? And another area that it helps with is actually on slowing down gastric emptying. And what that means is that as opposed to having all of the contents of your stomach kind of, you know, dumped into the rest of your system all in one shot, which results in these high spikes, it does it in a more metered way. And so if all of that is working as intended, then your meals will not be kind of this rocky affair, kind of roller coaster. It will end up being much more, much smoother, resulting in kind of better, better energy and not having the lows or the highs. So, we, you know, we talked about ecomensia a lot and how that particular bug is, to me, it's always been the Holy Grail. It's one of the, I think, cornerstone species of health. And I've been, you know, fascinated with it and butyrate production and promoting butyrate producing species. How is this different? Are they tied together or you got to have both? Why did you guys say, hey, GLP one and something else we should be looking? Yeah, that's a really great question. And this actually ties, I think, with what the theme for our discussion today, which is the way that these systems work together. So, GLP one is the signaling done by your cells. But then, you know, acromensia and these butyrate producers, as we talked about last time, as your listeners probably know about, they produce these very helpful postbiotics, things like the short chain fatty acids like butyrate. But we'll talk about other things as well. And what they do is that they help your cells function better. So butyrate, for example, is an energy source for the cells in your gut lining. And then they then, in turn, signal your cells to do their signaling. So the two systems kind of work hand in hand. So it's not kind of one or the other, but rather the two things together lead to the optimal outcomes. You know, again, the advertisements have been aimed at diabetics. So a lot of these pharmaceutical drugs were aimed at diabetics. And the side effects were noted. Our listeners who are not a diabetic or who aren't pre-diabetic, why would that be of interest to you and me to, you know, have better insulin control, have less brain veins, etc. Yeah, exactly. I mean, so this is why it's important to think about this kind of more as the natural system and how it's intended. And, you know, every meal can end up being, you know, kind of a much sharper, almost joyride versus a smoother transition, right? And if your meals are well balanced and if your microbiome is tuned up, then you'll kind of avoid, I mean, my analogy is you don't want to be on, you know, kind of the jolting seesaw, right, where you crash at the bottom and you like come up off your seat at the top. You want things to be kind of, this time and range is something that people talk about, especially those who use continuous glucose monitors and things like that. So you don't want to be very often either too low or too high, but in the band as often as possible. And if you do that, that helps your overall health. Basically, shocks to the system are just not good overall and they don't put you in a good space. Where's the research now on acromoxia, for example, in facility? Yeah, so that's been one of the areas that was really interesting. A couple years ago, there was this paper that came out in Nature Microbiology from a Korean lab that delved into acromance's role with the signaling with your body's GLP1. So they had a preclinical model and they showed that in that model, acromance was protective of minimizing weight gain and reducing the sugar spikes. And they delved in even more than that and actually showed that there's a specific protein that viable metabolic the active acromance it produces and they termed it P9. And that this P9 in turn interacted with the specialized cells in your gut, these L cells and induced them to produce GLP1. These cells are the ones that are the gatekeepers for GLP1 production. And so that was very exciting and we here pendulum reproduced, you know, their in vitro model and demonstrated that in this model of L cells that we when we put in the acromance of postbiotics from our strain under manufacturing conditions, we were also able to replicate that. So that was super exciting. So I think there is a direct link now with acromance on helping to maintain kind of your healthy response to food intake. You know, we talked about before, you have a product called glucose control that combines multiple strains, including acromance and in vitro. And you had shown in a clinical study that this is actually lower in hemoglobinacy. Have there been any people measured in a clinical study, not a preclinical study, GLP1 levels in humans on acromance? Are you doing that? That's something that's definitely in the works because obviously that's sort of the holy grail. It's one thing to have things in vitro model or even in a preclinical animal model, but it's obviously a different thing to be able to see it directly in people. One of the ways that you can get at it is through, you know, measuring, as we said, kind of with CGM, response to sugar spike. So that's, you know, further down the line, it doesn't give you directly to the GLP1 like how was it done? But it's helpful at least to tell us kind of where to dig. But that's definitely something we want to follow up with. All right, so now I got everybody interested, oh gee, I want more GLP1. Let's talk about, are there other ways to increase our GLP1? Yeah, so it turns out there is another approach which, you know, turned out from that as we dug into our clinical study and looked at kind of all of the postbiotic stuff that was produced there that could be helpful, we realized that there was this secondary bile acid, UDCA, or so the oxycholic acid that was higher in the group that responded the most metabolically, so the ones that had the drop in A1C and the lower sugar spikes. And this was very interesting. We hadn't considered that angle, that kind of bile acid approach. But then we looked into the literature and it turns out that in fact, you know, 10 years ago people had been seeing the effects of UDCA, and there they did measure in humans the increase in GLP1 upon taking UDCA, as well as, of course, the overall metabolic benefits. Interestingly enough, I've been recommending TUDCA, which to a lot of my patients, based on Chinese medicine, Chinese medicine believed, and they were obviously right, that bear bile was a real health time. And interestingly, bears to this day in Japan and China are hunting for their gallbladder. And they care less about the rest of the bear, but they want the bear bile and the gallbladder, and it gets large amounts of money. And you go, where the heck did that come from? And it turns out UDCA, your soul, is bear. And this is where all this came from. So I think it's amazing that all of this stuff that's been known for thousands of years, actually, we can now put a clinical measurement on go. Oh, that's how that works. Yeah, no, absolutely. I mean, I think this has been the exciting area of the microbiome, explaining a number of things that we hadn't understood before, and then revealing new paths for us. And the bile acid side of it is, yet again, this kind of two systems working together. You create the primary bile acid, but it's your microbiome that creates the secondary version. So again, if you have one and not the other, you're not going to be in the spot that you need to be. My new book will be coming out in January called Gut Check. And a lot of the purpose of the book in one of the chapters is it takes two. And the part that the microbiome play is, as you know, and I know, we're, every day we learn some important interaction that we would have never imagined was as complex an ecosystem that none of us would guess. So microbiome project. And again, it's, but the Chinese knew them two centuries ago. So there's a study right now to use the OLED, looking at, because role in metabolic syndrome in elderly patients, right? Yeah. So I think, I believe you're referring to the one where there was about 90 geriatric patients that were being studied. Yeah. Yeah. And they were studying it for liver disease. So non-alcoholic fatty liver disease. And it had been known for a bit of time that UDCA helps on that front. And so they were measuring liver enzymes and using ultrasound. And they did find that in fact, UDCA helped on that front. But then they were pleasantly surprised to find out that it also helped on glycemic control and insulin sensitivity. So that, you know, kind of started people thinking that UDCA might have, you know, more than just liver health benefits. And in fact, maybe I'll even mention, because there was a, in that same year, there was a much smaller kind of pilot study of about seven people that was in healthy volunteers. And this is the one that I was referring to earlier that where they gave UDCA and then they measured GLP1 to show that, in fact, one of the ways that it was working is by increasing GLP1 levels. And that in conjunction, it also resulted in lower glucose spikes. So it was a small study, but it was sort of like got to the mechanism. Let me back up for people who don't know. We have an epidemic of fatty liver disease in this country. We sometimes call it NASH, non-alcoholic fatty liver disease. And there's also a beautiful study that I have referenced. You can give fruit toast to rats and give them fatty liver disease really easily, folks. And you've also, there's also a study that shows that reverses that fatty liver disease in rats, right? That's right. That's right. And actually it's, in some senses, quite similar to that study I was referred to with acrimacia that was done, that preclinical study. So, right, they induced this metabolic syndrome in the rats through giving them a fruit toast. And then with UDCA, showed that it helped with insulin resistance and reduced oxidative stress. And it also dropped uric acid. That's right. So, I mean, I think you're seeing kind of a lot of these benefits from these postbiotics. And it's sort of, you start to realize that it's a combination of all of these different functions that needs to be there in order for your body's handling of nutrient loads to be done in the most kind of effective way possible. I'm going to pause there for a second because you and I throw around the word postbiotic like, you know, cocktail party discussion. If you've read my books, you know what postbiotics are, but if you're just joining us, it's confusing. Most people now know probiotics, so-called friendly bacteria, and acrimacia is a probiotic. Then people are beginning to understand prebiotics, which most people categorize as fiber. But if you listen to me and even pendulum, you know that one of the exciting findings is polyphenols are actually prebiotics that our gut microbiome just thinks is delicious. So what? Well, your probiotics eat the prebiotics, and they then produce postbiotics, which are the active compounds that simplistically comes from the digestion of prebiotics by probiotics. Sorry to be so confusing. I think if we had to do it all over again, we would have never used these terms, but we're stuck with it. So postbiotics are where the action gets done. And for instance, short chain fatty acids are postbiotics, gasotransmitters, when you fart, believe it or not, those are postbiotic signaling homologous. Sorry to do that, but we can go down nerdville, but we got to keep everybody. So postbiotics are really important. Absolutely. I know. And definitions are super important, and otherwise everybody gets lost in the woods. Yeah, exactly right. Postbiotics are really important. And as you're pointing out, it's about kind of building the right ecosystem. So the prebiotics, it kind of gets the right substrates, gets the right nutrients there, builds it, you know, gives you the right kind of plants that you want, right, the probiotics, and then they give you the fruits and vegetables that are helpful for your body, that are actually the business end, as I like to say, that kind of moves the needle on your health. All right. So what does all this mean for our listeners? How do they get their UDCA levels up and get their GLP1 levels up? Yeah. So actually, one of our best-selling products, metabolic daily, has all of these key strains. So it's a formulation that consists of five strains. It includes sacramentia, but it also includes three butyrate producers. And then it rounds it out with epiphydo that helps kind of break down a number of these complex substrates. So it's got kind of the full gamut that's able to tackle the problem from a number of different angles. So it's intended to help with this, you know, natural balancing for metabolic effectiveness. And folks, I take metabolic daily. I'm not afraid to tell you that. Again, in gut chef, one of the things that I think is really important for us all to realize is you have to have, it's almost like an assembly line. And one bacteria species has to be able to make a byproduct of its eating something. That a second bacteria species needs to complete its job. And in fact, there is a chain of bacteria species. And we may have, well, we now know that there are bacteria, there are five chains down the line. And if you don't have the first four bacteria, that guy can't produce the post biotic that we really want. So it's people like pendulum who have said, okay, you know, epiphyrancy is great. It's really important. It's a keystone species. But it's a facilitator because it's giving these other guys the things that you really want, like butyrate. And believe me, butyrate is you really want it. So and I think this is great. And I congratulate you guys for, you know, combining these is what is good science. You just didn't dump. Here's, here's 20 different strains and there's a lot of them. And we have no idea what they do. But here they are. And then we should swallow. No, exactly. I mean, it was in some senses kind of following the footsteps of what normally would be kind of the development of a pharma thing where you think through the functions that you really need. You know, what are those key ingredients and put those all together and test it all the way through. But yeah, no, to your point, it's important that you think about it in that ecosystem way in general, because otherwise it's hard sometimes to get some of these results that require, you know, a number of things to be layered in at the same time. There's a lot of talk, even in research circles, when I write about this in the new book, dead bacteria do tell tales. Dead bacteria have utility. On the other hand, live bacteria have potentially and probably more utility. And can you help us through that? Why don't I just take a bunch of dead stuff? There are some papers that suggest that dead bacteria do some pretty cool things. And I think they do. And you probably do too. But why living? Why did you guys work so hard to get the living bacteria? Yeah. And I totally agree. I mean, I think that there is science around some of the things that are, for example, just directly in the cell walls of the strains that can be helpful. And in some cases, because of the ease of it, it can be, you know, maybe you can pack more in. But you miss some of the what's produced that actually requires it to be metabolically active. So the reason why we kind of went down the much harder road is that we understood that there's going to be a whole slew of things that these strains needed to produce on the spot. And that part of the magic, if you will, is that they're in the right place, responding to the environment and producing things in the right ratios. And that's crucial, right? And I think we talked about a little bit the last time that, you know, some people even say, like, well, why don't you just give butyrate? You know that butyrate is good. Just give butyrate. And it's not that simple because butyrate is just not going to make it to the right spot, right? It's sort of throwing cash on the highway. Like everything can use it. And it's not going to be in the in the spot that it needs to to do the signaling and that's needed. So it's along those lines. I mean, one of them, as I always use, is like, the strain is like a really smart robot, right, that is in the right spot and interacting appropriately and responding to the environment. And that's very difficult to replicate by just kind of launching something over the fence and just hoping it happens to land in the right spot at the right concentration and does the right thing. And then there's just the general ecosystem argument. So beyond what the strains themselves produce, they kind of create the environment as you're pointing out for other strains that you want to grow to kind of flourish as well. So it's sort of like you create a nice lovely garden and then suddenly you have hummingbirds. Like, you know, you wouldn't that wouldn't have happened if you only kind of had like one or two ingredients out there. You need kind of the full system to be there to get some of the broader benefits. Yeah, we talked about acrimoncia and your other products. Why would you go for metabolic daily versus one of your acrimoncia products? Does somebody need both? One better for somebody? You know, why'd you come up with this problem? Yeah, yeah. That's a great question. And when do we get all the time? So as we touched on, metabolic daily has a broader set of strains. So it really tackles the metabolic question from a number of angles, right? So it's got the butyrate producers, it's got butyricum that produces that bear bile that we just talked about. And it has acrimoncia as well. So it produces the P9 and is a keystone strain. So kind of in conjunction, all of them work together really well for metabolic related issues and kind of keeping you on that time and range type of thing balanced. Acrimoncia, on the other hand, is very concentrated on acrimoncia. So it's for those that want to really supercharge and replenish that keystone strain. And it is an important strain. So it is one of the ones that helps on a number of fronts, but specifically for gut health, right? It helps with the lining, right? It's one of the few strains that's allowed by your body to be directly in the lining. And studies have shown that it helps increase the thickness of that and helps kind of the barrier integrity of your gut. So if that's what you're shooting for, then I would go for acrimoncia directly. I guess you just answered my question. If you can only afford one, you got a preference? As I said, it depends on what you're going for. I mean, I myself go for the broader set because I feel like I'm in good shape now on acrimoncia and I just need kind of a maintenance dose of it and I need some of the other strains to kind of round it out. Since you brought that up, I get that question all the time. Okay, I took acrimoncia for three months every day and I bet you I got plenty down there. And why should I even bother taking any more? I have seated my gut. What say you? That's a really great question. And we actually studied this directly. So in our clinical study, we had a washout period where we stopped giving any of the strains for a month. So the intervention period was three months, a day lay, and then a washout of a month. And it turned out that only one in five or less had any any strain remaining after the one month. Now it's important to note that we did not give any advice to change diet or to change your habit because this was part of the study. It was like to see the effect of the formulation. But this is the sort of thing that has to be done kind of in concert. So if you want engraftment and these strains to take, it is an ecosystem type of question. And you may need to always give a little bit of dosing in there for a while to support it, right? Or to combine it with supporting it with some of these prebiotics and the right kind of nutrition balance. Correct me if I'm wrong, but there aren't any foods that contain acrimonium. Yeah, not in any sort of significant quantity. So in fact, generally, as you pointed out, it's polyphenols that people have used to help, basically to help flourish the remnants of acrimonium that you might have. And if people have read my books and even in the upcoming book, super old people who are thriving have a much more generous population of acrimonium than, well, most people. And that's, I think, one of the reasons we probably ought to be interested in having acrimoncia around. Yeah, I think there was a very distinguished colleague of mine who recently had a video out about all the foods where you can get acrimoncia. I just actually cringe because there aren't any, sorry about that, but that's okay. Are there any other probiotic strains, friendly bacteria that support the production of GLP1 that you guys are looking at? Well, I mean, one of the reasons why we got into butyrate producers were that they were correlated with its sort of general metabolic health. And it was thought that maybe they could themselves induce GLP1. That part, I think, is still a little bit up for debate as to whether they do it directly because it may be that they do it indirectly through kind of synergy with strains like acrimoncia because acrimoncia and butyrate producers actually work kind of in concert exchanging molecules and so on. And then there's, as we said, maybe subsets of butyrate producers like butyricum that have this other quality, like the secondary bile acid. So they may have fallen under the umbrella of, well, butyrate producers help on this front, but it may be kind of a more specialized subset of those. So we're on the lookout for other ones. Right now it's mainly the UDCA route and acrimoncia. Yeah, you guys are always doing something interesting. So you're about to launch an Omega-3 booster. What are you? How do you boost Omega-3? Did you fill us in? Yeah, absolutely. So it's actually, if it falls in the footsteps of the success of the polyphenol booster. And so where polyphenols have been shown to help boost acrimoncia levels, Omega-3 has been shown to boost levels of butyrate producers. So kind of both of those boosters would work in concert with our strain products, right? And you can kind of bring them in together or maybe as initiating it or afterwards, right? So you can do kind of different combinations and they can help kind of work together with the strains. I think this is very important for people to understand. And I use the example in my home spring's office about probiotics and I call them basically grass seed. And I say, okay, I'm going to sell you this from grass seed. And you come back two months later and you say, you stole me bad grass seed. And I say, why? They said, well, you know, what'd you do with it? Well, you know, I took it out in the desert and put it in the sand. And I said, yeah, and did you water it? No, you didn't tell me to. Did you fertilize it? No, you didn't tell me to. And I go, well, wait a minute, what did you expect? And I think, you guys and me and lots of people are beginning to realize that, yeah, it's great to swallow some grass seed probiotics, but you got to give them what they want to eat. And you got to fertilize them. Or they're not going to grow. Is that just a naive way to explain that? No, that's a that's a perfect way to explain it. I mean, I think that's exactly right. And I think that's such a great analogy, because I think it will hit home with people and they realize like, oh, it's just it's not enough to just take these strains out of context. You've got to also water them. You've got to take care of them. You've got to bring other things along for the ride. You know, bring their friends along for the ride as well. So other other strains that kind of work in concert with them as well as these prebiotics are super crucial. Yeah, and your omega three point is actually very well taken because there's plenty of literature that shows omega three fats enhance the integrity of the gut wall. There's beautiful literature on short chain omega three fat alpha linolenic acid and actually preventing lipopolysaccharide incursion across the gut wall. And yet what we're probably going to find out is, well, these guys weren't doing it themselves. It was facilitating these species of gut bacteria, which are then making more mucus or making butyrate. And it wasn't the omega three that was the actual thing. It was what these bacteria needed from them to do their job. I think that's exactly that's exactly right. It's basically this this overall network, you know, and a good deal of the benefits come about from these indirect effects where they help to grow the right set of strains that can do these functions and can interact then with your cells in the right way. We've talked a lot about GOP one and it is obviously a hot topic. Are you are you developing with what you know now a GOP one product or? Yes, I mean, that that is definitely something that we're looking into. And just like in the discussion we just had, it you wouldn't be surprised that it will contain acrimacia and it will contain butyricum for the bear bile. And it's also going to contain inulin, right? So the fiber as well as rounding it out with a Bifido again to your point of that assembly line. I should really like that analogy. And so actually I'd want to like reach out to your listeners and say for those of you who may be interested to please reach out to us at pendulumlife.com because we're thinking of you know having a study to see its effects on cravings and other outcomes as one of the ways to learn to learn more about it. That'd be great. Yeah. All right. You heard it here first. I have a whole section in my new book about the effect on emotions from the microbiome and specifically depression and anxiety. Can you give us fewer thoughts on where are we with the you know the microbiome gut brain connection particularly in terms of depression? Yeah, no it's actually I think one of the most exciting fields in the microbiome right the gut brain connection. And you know I think it's still early days so I think there's still a lot to be done there but now I think there isn't any doubt. I mean you know a few years ago it might have been considered a little crazy to say that you know the connection goes two ways, right? And that your gut is able to actually influence your mood and you know it can have an effect on anxiety and depression but now it's you know it's widely accepted and in fact the question now is really understanding the mechanisms and understanding how to harness that knowledge and create you know intervention and things that can help on that front. So I think it's a very exciting moment for this for this specific field in the microbiome. Yeah I mean it's even got I mean it's got an entire you know term now psychobiotics and I mean there's divisions devoted to this now. I wish they hadn't chosen psychobiotic because it sounds kind of psycho but I think we're stuck with that term now too so or and it doesn't mean psychedelics either but but no I think you know Daniel Amen was now you know basically said I think we should really stop talking about mental health as a brain issue and we really ought to be you know talking about gut health and its deep connection to what our psyche is doing. No absolutely and you know out of fear of getting you know too philosophical but you know as I've gotten more and more into this field you really do recognize what you said which is the centrality of the gut and when you think about it it makes a lot of sense because for an organism the key thing is energy conversion right life is converting energy into being able to do all of the kind of life activities so it has to be kind of the thing in some sense running the show like if things go wrong there there isn't anything else that's going to happen so interestingly you know the brain and such is maybe an accessory organ. You know I for years now call this thing up here to the second brain and the real brain is down here and you know I've written about I think because of the incredible genome of the microbiome vastly more genes in our microbiome and they're constantly mutating they're constantly changing they're constantly getting new information from viruses and they're doing this you know consummated so I think we basically you know uploaded most of our processing power to this supercomputer that happens to live in our gut and that supercomputer sorry folks kind of controls everything that's going to happen sorry but apocrates knew this 2,500 years ago that's right that's a great quote now obviously speaking of the gut if he called it a green life force energy that wanted people to have perfect health and he didn't know what that was but I think snakes in your work and others were beginning to realize that this green life force energy maybe we should have called brown life force energy but yeah it's it's this it's this most important you know tropical rainforest organism whatever we're going to call it that is this life force energy no absolutely and actually I mean I actually find it beautiful that the description you know of us is really this super organism right we're we're not just the collection of human cells that's almost boring to think about it's really this interaction this deep interaction with all these other species that are all working in concert and it's an amazing network and it's a it's a complex thing that we're only now starting to you know piece little bits and pieces and as we do it I think we're beginning to realize you know a lot of benefits because not accounting for that was you know keep keeping us in the dark on on some really crucial functions yeah really you know up until 2006 we know these guys existed and in the sequencing you know I mean it's better and better we're getting you know deeper and deeper into the sequences from groups and species and families no that's exactly right because it basically was the advent of sequencing and the availability of it that enabled us to to see this kind of hidden universe good otherwise we were only left with the things that we could culture right which was never very good yeah yeah because a little bit of a catch 22 like how do you know what the conditions are to culture something they've never seen right yeah okay you have no idea what what substrates that might need what conditions it would be and I liken it to kind of deep sea travel like you know the the the type of organisms that live in that environment are just very different than anything that you see everywhere else so the next episode of the dr gunnery podcast is waiting for you now interestingly enough people who have some of the longest life expectancy the atchi aroles in southern Italy are small fish eaters and chovy eaters