– One thing I’ve noticed is that, you know, people often can’t control their cravings. They feel like they can’t control their hunger and they often feel guilty about it. And I guess I’d like to say, you know, you don’t need to feel guilty, because it may be the bugs in your gut.
– You’ve been a practicing clinician for over 25 years, and I suspect you’ve observed the benefits of Pendulum’s formulas in your own patients. Can you tell me about your experiences and why you wanted to become more involved with Pendulum?
– Sure, I’d be happy to. As you’ve just said, I’ve really been doing integrative and functional medicine for over 25 years, but within academic health centers. I was at Duke prior to going to Mayo Clinic and had the honor of running and developing their integrative and functional program. And as anyone who is familiar with functional medicine, certainly anyone who has read your newest book, and which I did and I loved, would agree that if you’re interested in looking at root cause of chronic disease, which I certainly am, you need to think about the gut. And so I developed a strong interest in the gut and the microbiome and the relationship to the development of chronic diseases. The quick story is that I gave a few lectures a couple of years ago, grand rounds at the medical center and a lecture at a Mayo Clinic nutrition conference on this connection between the gut, the microbiome and chronic disease. Our CEO, Colleen, who I know has been on your podcast, I think saw that. Interestingly, Mayo Clinic was so impressed with the science of Pendulum that Mayo Ventures was an early investor in the company. So I think through that, Colleen reached out to me at Mayo to see if I could do a study on their product on type 2 diabetes. And, you know, I was already familiar with the product because I was using it in my practice, I was getting good results, you know, always in addition to diet and lifestyle. But I was seeing improved metabolic health, patients better able to manage their cravings and hunger and live at a healthier weight. And so was familiar with the science, but in designing this clinical trial for the company really got a chance to dive deeply into the science and was really impressed, the commitment of the company itself to the science. And so when, six months ago or so now, when the chief medical officer decided to retire and the position became available, you know, I had really hadn’t been thinking about leaving Mayo, but this just seemed like such an amazing opportunity to be a part of a company that’s really having a profound impact on the health of individuals through this understanding of the science of the microbiome and how it influences so many aspects of our health.
– Quite a leap. You’re right, the company is very impressive, as you’ve learned, and I guess I’ve learned as well. Literally with each passing week, we understand the impact of the microbiome on almost everything that’s going to happen to us, in a good way and a bad way, that this is at least part of the future of precision medicine.
– Without a doubt, and really precision probiotics. I know you’re a fan, for example, of Akkermansia. I’m sure you’ve had interesting experiences with your patients in your clinical practice using some of these strains as well.
– Yeah, absolutely. And about 80% of my practice now is autoimmune patients who have, most of the ones who end up in my clinics have been everywhere and don’t particularly want to take transplant drugs for the rest of their lives. I don’t blame them as a transplant surgeon. That’s not a good idea unless you have a transplanted heart or kidney or liver. They want to try to get off of these drugs. And I’ve found that, you know, fortifying the gut wall, number one, and the mucus layer with Akkermansia, we can observe it in leaky gut tests on these folks. And I think the other thing I think we need to talk about, of course, is the whole ability of Akkermansia as a keystone species for promoting butyrate-producing bacteria, and happiness is something that I can observe in my practice. So it’s a good thing.
– It’s a very good thing, undoubtedly.
– So when I interviewed John Eid from Pendulum about, it’s been about six months ago on this program, we talked a lot about GLP-1. But for anyone who hasn’t seen that episode, the term GLP-1 probably starts sounding familiar for anyone who’s watched advertising and watched social media. I think it’s a great place to start. So what can you explain about this un-hunger hormone?
– Right, the un-hunger hormone. Well, even nowadays with all the electric vehicles out there, I’m sure pretty much all of your listeners, you, me, we’ve experienced filling our gas tank up at the gas station. And, you know, it’s amazing. You put the nozzle in, you click the little bottom bar there and it just fills up and it keeps going, and you can wash your windows or check your text messages and somehow that device is able to sense when the tank is getting full and it automatically shuts off the gas so that you don’t overfill your tank and have the gas go all over your car and of course all of that. And in many ways, GLP-1 is that sensor that turns off that fuel. So just kinda walking through it, we eat a meal and specific bacteria in our gut break down the foods, and particularly as it gets to the large intestine, we break down these fibers and polyphenols. And that is really a trigger, and I loved how you talked about in your book, is really the bacteria and all that they’re doing really being signaling things throughout the body, and that’s really the key concept. In this case, the bacteria, particularly Akkermansia and Clostridium butyricum, some of the strains that we’ve put into our products, they actually lead to increased levels of butyrate, and butyrate binds to these special cells in our gut called L cells that actually make GLP-1. There’s more to the mechanism. Akkermansia makes this P9 protein that also stimulates GLP-1. But suffice it to say that through the action of the bacteria on the food that we eat, GLP-1 gets stimulated, and then it does a number of things and very important things. It goes to the pancreas and tells the beta cells within the pancreas to release insulin, which we want to happen so that our blood sugar, our glucose doesn’t go too high. It slows down the movement of our gut, allows us to digest our food and in some ways help us to feel a little more full. And then very importantly, it also goes to our brain and tells us that we’re not hungry anymore, that we should feel full now, that it’s time to stop eating so that we don’t overfill that tank.
– One of the things, you and I have been in medicine long enough, I’ve been longer, way back when. I mean, we really used to think of the gut as this, you know, hollow tube and food and stuff went in and then magic happened and a few interesting enzymes got thrown in by the pancreas and the liver from bile, and we absorb sugars and proteins and fatty acids, and then whatever was left over kind of we pooped out as crap, and that was kind of the prevailing teaching. And we now know that it’s so much more complex, and I think thanks to the Human Microbiome Project, number one, that we even knew these species existed, which we didn’t know. And number two, that these single-cell organisms were capable of controlling behavior, whether it’s eating behavior, emotional behavior. So the mechanisms now are coming to the, like these keystone species, that without that there may not be these feedback mechanisms to stop us from eating, to regulate our eating, even control what sort of foods we’re looking for. And of course, that’s what “Gut Check” was all about.
– Right. Well, I mean, interestingly, I see maybe a little more diverse population, but having been, as I said earlier, at Duke and of course Mayo Clinic, people come to us there because they haven’t gotten answers from some of the other perhaps providers they’ve seen, and so typically see very complicated patients. But also do a lot of work around weight loss and have, historically, I oversaw administratively the Duke Diet Center when I was there. And one thing I’ve noticed is that, you know, people often can’t control their cravings. They feel like they can’t control their hunger, and they often feel guilty about it. And I guess I’d like to say, you know, you don’t need to feel guilty, because it may be the bugs in your gut and not your willpower or something else that really is on you. I think the good news is that, to your point now, is as the science has really advanced, as we begin to understand some of these bugs that were difficult to grow because they’re anaerobic, can’t be exposed to oxygen, we’re beginning to realize that they have a profound influence on our behavior, how we may be feeling emotionally, and of course, whether or not we’re feeling full, whether or not we’re having cravings for different types of food.
– I talk about it in “Gut Check.” I like the gut-centric theory of hunger. And as people hear about these particular pharmaceuticals that may impact this, I think it all comes back to this hormone GLP-1 is produced by the microbiome and/or the interaction of the microbiome with other cells in our gut. I think that potentially explains why some people seem to always be ravenously hungry and overeat, and other people seem to just go, “I’m not interested in that stuff.”
– Right. Well, I mean, you know, I guess that’s really the motivation behind the company developing this new GLP-1 Probiotic, which really has three very specific strains that have been shown really in preclinical studies to stimulate GLP-1. Have also been shown to reduce hunger, reduce cravings rather, and help people to live at a healthier weight.
– So tell me about these preclinical studies that really excited you and Pendulum and why is this so powerful?
– Well, I mean, I think we’ve talked a little bit just a moment ago about sort of what happens in the body. I think what Pendulum did basically was took a number of years to figure out how to grow these, again, difficult-to-grow anaerobic bacteria. That’s fine. But what they really did then was quite frankly spend millions of dollars to build a plant in the US where they could actually manufacture an anaerobic probiotic and make it available to the public. And so they, of course, did a bunch of science to show and back up whatever claims they wanted to be able to make, and in this case, we were able to show that, in particular, Akkermansia and even the other strains of probiotic that we use clearly can stimulate the release of GLP-1, in the case of Akkermansia also stimulate this P9 protein that I mentioned earlier. This is another mechanism through which these bacteria, in particular Akkermansia rather, stimulates the release of the GLP-1 protein. And that was done in preclinical work, and then the company took one of their signature products, Pendulum Glucose Control, and actually did a randomized control trial in people with type 2 diabetes to show that there was significant reductions in hemoglobin A1C, better management of glucose, and things of that nature. So the science was there, and then of course, with the new product, it was really refining that science around a product that really is targeting satiety, targeting cravings and with the goal of really helping people to maintain that healthier weight.
– I talk a lot about in “Gut Check” about why our appetite seems to be so out of control. Do you wanna kind of dive into a little bit of that about, so why would Akkermansia and butyricum and butyrate-producing species in stimulating GLP-1 have such a profound effect on our hunger? Or the suppression of our hunger maybe is a better way of putting it.
– It’s an excellent question. I think the answer is complicated. And of course, you may have been applying this earlier, I mean, the whole issue of hunger is more complicated than simply GLP-1, but GLP-1 is a key player in this whole process. And so I think if we think about that and we say, well, what actually influences GLP-1 levels and then by extension how hungry we may be feeling, there are a number of things. What we think about in clinical practice and what the individual maybe has the most control over is certainly the foods that they eat, actually how they may be feeling emotionally, because the stress we’re under and how we manage our thinking and that’s the stressors in our lives certainly can influence GLP-1. And then of course, as we’ve been talking about and your book goes into in great depth, you know, what’s the health of our microbiome and do we have the right good bugs, in this case Akkermansia, other butyrate producers, in the gut? Now, there are other things that may be a little less within our control, like our insulin resistance, our overall metabolic profile, our BMI in general, our gender. Obviously there’s something that, you know, physiologically we can’t necessarily influence and/or it’s difficult to influence. So I think it’s complicated, but what having products like the GLP-1 Probiotic do is they put more control back into the hands of the individual, and I think that’s what I’m so excited about.
– You know, all my books, I tell people, and I believe this profoundly, that for the most part, these things that are happening to us are not our fault. As we’re beginning to piece together why it’s not our fault, it’s, I think, actually very empowering. And this is one area where, you know, Pendulum ought to be really proud, that you are a supplement company that wants to impact something that’s not our fault, and it’s one area that’s really different. So you have a number of products and I’m a fan of all of your products and I use all of them in different ways. So Akkermansia is a keystone species. And again, for people who have not watched the other podcast, this company literally spent 10 years trying to figure out how to grow human Akkermansia muciniphila in a lab, in an anaerobic airless environment, ’cause exposure to oxygen would kill this bug, and spent 10 years trying to do it. And as you can imagine, that’s a lot of money. But it was really, I think, the dedication of the founder, Colleen, and her colleagues that just kept going with this. All right, so why not just swallow Akkermansia or why not take Glucose Control or why not take Metabolic Daily, which also does have some butyrate bugs, butyrate-forming bugs? Why GLP-1, your new formula?
– Great question. It really depends on what your goals are. And I think that’s really the way to look at these next-generation probiotics, is not simply, oh, maybe my gut is important, so I’ll just pick some probiotic off the shelf with God knows what’s in it and hope that I’ve got the right strain for me. But really saying to yourself, or as a clinician, a practicing clinician, what are my goals as an individual or what are my goals for my patient? So the way I think about it is when I have a patient who has clear signs of insulin resistance, type 2 diabetes, then I typically go with the Pendulum Glucose Control. That’s where we have the most evidence. When I have people with just more signs of metabolic dysfunction, they wanna do a better job of breaking down carbohydrates and sugars, I may use the Metabolic Daily product. Certainly if in my practice I’ve tested someone’s stool and they’re low in Akkermansia or I’m more worried about gut health and the lining of the gut itself, I may go with the Akkermansia product. Now, we didn’t really talk about this and I should mention it. You just said the full name there, Akkermansia muciniphila. which really means mucin-loving. And I don’t think I’ve mentioned yet that the other major role of Akkermansia muciniphila in the body is to eat up this mucin and help replenish it. So what is that? I mean, the lining of the gut, for your listeners that haven’t read your book yet, you know, is maybe like a fence, and there actually are nails that hold the boards of that fence together. I might consider those sort of the zonulin, occludins, and these proteins between the cells, you know, these enterocytes, the cells that line the gut. But there’s also maybe some glue or some sealant, let’s say, that helps to actually keep the wood healthy, and mucin helps to keep the cells of the gut healthy, but also acts sort of like fly paper, you know, also sort of catching things that shouldn’t get through and into the bloodstream. And that’s really the key with the integrity of the gut lining or the health of the gut lining, is that we wanna let in friend and keep out foe. And so one of the things that Akkermansia does is it really eats up the old mucin, sort of the old fly paper, and then it stimulates these cells called goblet cells to make more mucin, actually stimulates more goblet cells to multiply, but leads to sort of a refreshening of the mucin. So in that case, I might use Akkermansia alone. With the new product that actually is gonna be on the market by the time this podcast airs, and so I’ll mention this now that I know there’s a code for people, if they use Gundry when they go to order the product, they get 20% off of a new order, a first order on memberships. I wanna make sure to mention that. But for the new product, again, in preclinical studies, we’ve been able to show that the three components, these specific probiotics within that new product, do stimulate the release of GLP-1. And then in some consumer research that we’ve done, we’ve actually shown significant reductions in cravings. So we actually showed a 91% reduction in cravings. This was a consumer study done on 274 individuals. And when you look at cravings, they actually break it up into four different areas. And so we saw this sort of similar level of reduction within cravings for sugar, cravings for carbohydrates, craving for fats, and I love this, that this questionnaire does this, cravings for fast food, and this is a validated, you know, cravings, food questionnaire. And so in all of those areas we saw a significant reduction in cravings, and it’s exciting to be bringing this product to the market.
– That’s fantastic. So this is different and a different reason specifically for this new product than the other ones that might contain some of these same strains.
– It’s nuanced, right? In our practice, obviously there’s overlap, right? Because this is not cookie-cutter and people have needs and desires that overlap. But again, maybe a way I could explain it more clearly is, you know, that individual who is struggling to maintain a healthy weight, who is interested in managing their cravings and their hunger perhaps better, you know, the new GLP-1 Probiotic product is a great choice. In my practice, if I see someone who is trying to get off metformin through lifestyle and is having difficulty for their type 2 diabetes, as I’ve seen many times, I add in typically, you know, the Pendulum Glucose Control in that scenario. And as I’ve already walked through some of the different scenarios where I might recommend some of the different products. I mean, it’s not like it’s a mistake. It’s not like if you took Glucose Control you wouldn’t experience some of the same decreases in cravings and hunger. It’s just the GLP-1 Probiotic is really targeting that particular indication and desire for the consumer.
– In this clinical study, which is actually a lot of people, people noticed a change in seeking out fast food or enjoying fast food?
– Not enjoying, it was more the cravings. And again, I wanna be really clear here, this was a consumer study. We’re actually planning a more robust clinical trial at the moment. And the reason that I really want to emphasize that is that as you and I know, there’s a lot of misinformation out there on all kinds of natural products. And you know, I’ve spent almost 26 years, 25-plus years of my career practicing integrative functional medicine within academic institutions and really focused on where is the evidence, where is it not, and so I wanna be really clear about our evidence on our products. And although I think it’s really impressive, it was, you know, almost 275 people, this was consumer research, and it does warrant further research with more robust studies. However, you know, we’ve also seen this anecdotally with our other products as well as through clinical trials that, you know, this stuff really does work.
– No, you’re right. And again, just from my own practice, if I’ve got somebody with leaky gut, and quite frankly that’s almost 100% of the people who enter into my practice, then the first thing I reach for or try to convince my patients is buy one of the Pendulum products. And you’re right, this has to be combined with other dietary changes and lifestyle changes, but anything that we can do to help the patient out and get that mucus layer improved and get a barrier, you’re right, Adam, fly paper is a good way of describing it, getting a barrier reinforced, that the patient can’t do by themselves, quite frankly. In fact, let me say, I don’t do a lot of gut microbiome testing, because I come from the school that it’s a nice Polaroid snapshot of basically today, but that gut microbiome will change tomorrow depending on what you eat. But there are some keystone species and a lot of my patients who come bearing these tests, Akkermansia is frequently missing or really low. And interestingly enough, a lot of the short-chain fatty-acid-producing species are really low, which doesn’t surprise you and it doesn’t surprise me. And you really cannot eat, for most people, effectively to suddenly get these guys in abundance. Is is that a fair statement?
– I think it is a fair statement, and first let me say that I’m in your camp. I mean, I reference stool testing and finding low levels, but I don’t do a lot of stool testing in my practice. I will use it occasionally if I’m not getting the results that I would’ve expected to get through changing diet and through giving the right probiotics and the other aspects of lifestyle, but I don’t jump right to that either and I’m glad to hear you say that. I think the microbiome is a complex ecosystem and very individualized, right? And so some people respond a certain way to one intervention and others will have a very different response to that same intervention. And so I always start with improving someone’s diet. I have found that I do need to supplement with probiotics, but also I emphasize certain aspects of the diet. So are they getting enough fiber, you know, perhaps fermented foods? And certainly in the case of some of these butyrate producers, are they getting enough polyphenols in their diet through fruits, vegetables, coffee, tea, spices? And if they’re having difficulty to do that through diet, I mean, that’s why Pendulum actually has a polyphenol product, because we did see in our research that polyphenols really did help these bacteria, these probiotics to be more effective. And yes, some people have difficulty getting enough of that through their diet alone.
– Yeah, I chuckle when Pendulum came out with a polyphenol to help the probiotics, ’cause I’ve been saying that for 20-odd years now, but these guys go hand in hand, in tandem in producing the products we want. So when will this GLP-1 probiotic combo be coming out?
– Well, it’ll be out by the time of this podcast. So, you know, it’ll be coming out in mid-March, and I don’t believe this will be airing until April, if I understand correctly. So it’s available to whoever’s listening to this right now. Again, you know, obviously would encourage people to use the code Gundry and they’ll get this 20% discount, but we’re just really excited to be able to bring this product to the market.
– Maybe we didn’t mention it, but what’s the name of it?
– Oh, GLP Probiotic, GLP-1 Probiotic.
– Oh, okay.
– Yeah, yeah, I’m sorry.
– We’ve been dancing around it!
– You know, I was saying it like, you know, not realizing some of the listeners may not realize. That’s the name, it’s actually GLP-1 Probiotic.
– And that’ll be easy to remember, folks, ’cause you just have to turn on your TV every night and you’ll hear GLP-1 in one way or another, or on social media.
– Let me make this point too, right? I wanna be very clear. The GLP-1 Probiotic is not a drug. It’s not a replacement for these GLP-1 analogs. You know, it’s not intended to treat disease and those sorts of things. It’s intended to help restore a healthy balance to the microbiome and help the body to naturally release this GLP-1 hormone. That’s really the intention. And I would even, doing that in conjunction with diet and lifestyle, of course.
– That’s a very good point. This is a natural hormone that we produce, as you have so elegantly described how we come about producing it. You and I have spent our careers trying to get natural solutions to a clinical problem. And I like the fact that metformin is given away like water. And don’t get me wrong, metformin is an incredibly useful drug, but I actually like to spend my time weaning my patients off metformin rather than saying, “Well, we’ve got this fabulous drug to treat diabetes, let’s just use that and not worry about it.”
– Yeah, it’s such a gratifying way to practice medicine. I mean, literally one of the last patients before I left Mayo Clinic to come to Pendulum was a woman I was working with who was in her really kind of late 40s and had struggled with type 2 diabetes, but had really committed to lifestyle and came to me because, you know, despite having lost some weight and certainly made some progress, she was still on metformin, albeit a low dose, and wanted to get off the medication. And so we made some tweaks to diet, but I added in Pendulum Glucose Control in this case, of course. And right before I was leaving, she came back and was able to get off of metformin, which is just such a gratifying thing, and certainly for her of course, but as a clinician to be able to help our patients to reach these goals and to be able to do it without medication, when possible, of course, is just a wonderful thing.
– Don’t get either of us wrong, I will certainly use pharmaceutical medications when they are needed. Just like I tell my patients, well, if you break your leg, I’m gonna put a cast on it. But you’re not gonna wear a cast the rest of your life. You’re gonna heal your leg and we’ll take the cast off. And that’s how I approach these. You know, there are fabulous life-saving pharmaceutical drugs, but a lot of times we can intervene to fix the original problem that caused the need for that.
– Totally agree with you. I think the other side of it is sometimes we tend to have this default to, “Oh, just take a pill,” right? And yeah, the medicine is important, and again, I believe wholeheartedly, I write for medications when they’re required, but I also encourage, just like with the probiotics, even with the medications, you still make the appropriate lifestyle changes to support your body, to support your physiology, and your overall health and wellbeing.
– So as the chief medical officer of Pendulum Therapeutics, what are your visions for the future of probiotics and metabolic health and how does GLP-1 Probiotic fit into this vision?
– Yeah, great question. It’s funny you’re asking me that now, ’cause I was sort of sitting here having this little thought in my mind that, my goodness, this is fun. I really enjoyed doing this with you. It’s been such an honor. And I had this kind of quick thought like, well, let’s see, a year from now we could be talking about some totally different indication for these probiotics, and a year after that it could be a different indication and a year after that a different one, because we’re really realizing, again, this connection between the bacteria in our gut and pretty much every organ system, right? It’s hard now to imagine or come up with an organ system that isn’t influenced by the microbiome. And the future is to understand with more precision what particular strains of probiotic are most beneficial in what scenarios, you know, what goals is a patient trying to accomplish? And it’s everything from looking at autoimmune conditions. Obviously we know that certain bacteria are involved in the development of rheumatoid arthritis, for example, amongst other autoimmune conditions, to kidney stones, to autism, to potential role in cancer. And again, I’m not saying treating or curing, just saying in terms of the microbiome itself influencing these particular aspects of our health and our physiology. And so when I think about the future of the company, obviously our goal is to continue to develop and bring to market innovative next-generation probiotics to help people leverage this emerging science of the microbiome and how it influences people’s health. When I think about the GLP-1 Probiotic, you know, we’re very excited about the preclinical work that we’ve done. We’re very excited about the really robust results we got with this consumer study that we had accomplished. And I’m excited to take that to the next level in terms of deeper amounts of research, looking more at human physiology so that we can continue to contribute to the field, quite frankly. And help people to better manage their hunger and live at a healthy weight. I mean, that’s the end game, right? That’s what we’re really after.
– Correct, because clearly it’s out of control.
– Right, right.
– Thanks for watching, but don’t go anywhere. The next episode of “The Dr. Gundry Podcast” is waiting for you now. Even if it’s a diet drink, diet sports drink where it says zero calories or zero sugar, look at the label. If you see aspartame, sucralose, or acesulfame, run!
