What's The Difference Between A HEALTHY Gut & A Gut "Missing" Key Beneficial Bacterial Strains? (& How To Fast-Track Your Gut Back To Balance) With Dr. Adam Perlman

My name is Ben Greenfield, and on this episode of the Ben Greenfield Life podcast, what GLP-1 really does is it gets released in response to a meal.

It goes to the pancreas, it tells the beta cells in the pancreas, make more insulin so your glucose doesn't go up too much. It goes to your stomach, it slows down your digestion to allow you to feel more full and actually digest your food, ideally absorb the nutrients. And then it travels up the vagus nerve to the brain and sort of triggers the shutoff valve telling you, okay, you're full, stop eating. GLP-1 is, is basically one of the signaling mechanisms, the hormones that tells your body to stop filling the tank up, so to speak, so it doesn't overflow.

Fitness, nutrition, biohacking, longevity, life optimization, spirituality, and a whole lot more. Welcome to the Ben Greenfield Life Show. Are you ready to hack your life? Let's do this.

Ben Greenfield: My guest today is Adam Perlman. He is known as an expert in integrative and functional medicine, and he's currently the chief medical officer at Pendulum Therapeutics, a company that might be familiar to any of you who heard my podcast with Colleen Cutcliffe or are aware of these new GLP-1 triggering bacteria or probiotic-type compounds that you you can consume. But, Adam, hopefully you don't mind if I call you Adam unless you like the formal. We can go Dr. Korman. I go put on my suit and tie and take off my tank top. You have a pretty impressive history. I mean, you're one of those guys I was reading your bio, you've been in health for a while.

Yeah. I mean, I've had a wonderful career. I mean, I'm board in internal medicine and You know, but I was interested in integrative medicine and functional medicine early in my career. Knew that's what I wanted to do. Had an amazing opportunity to start one of the earlier hospital-based integrative medicine programs way back in 1998 for healthcare system in New Jersey. And then when I went to Duke in 2011 to run Duke Integrative Medicine, eventually I oversaw the health and wellness portfolio for Duke. So Duke Integrative The diet center rolled up to me and then about a 2,700-member fitness center. That's when I really kind of got interested in gut health. I was already really interested in lifestyle medicine. I mean, a lot of this came out of a background in martial arts. That's probably a whole nother story.

Ben Greenfield: Yeah, that's interesting that you were at Duke in 2011, man. I did my practicum at Duke. I got my master's degree at University of Idaho in exercise phys, But, one of my buddies ran Coach K's sports performance lab down at Duke. So, I was down there, I think it was 2012. I was down there for about 6 months mostly at the biomechanics lab at Dr. Rafael Escamilla's biomechanics lab. But, I was all over university running around and walking down the quad. So, maybe we ran into each other. I don't know.

Ben Greenfield: We may have. I mean, Duke Integrative Medicine was on this separate campus just kind of across the street from the main campus. But beautiful building there and we had a fitness center. And again, I was way into all the lifestyle side of things. I know of that lab that you're referring to. I never collaborated with that individual.

It was a great time, man. That was back before we had the technology that could do a little bit better job. I don't know if you saw how they made Lord of the Rings with Gollum, how they put all the dots on him to track his movement in space. And you do the same thing with biomechanical analysis to analyze. I mean, In this case, the study we were doing was shoulder mechanics for the bench press, but it involved manual digitization of every movement point. So, I spent most of my time in that deep dark underground lab with a mouse and a clicker clicking on the joints of football players as the stick figure of them moved biomechanically through a dinosaur software program. So, that's my background.

Sounds like good times.

Good times. Yeah. Yeah. Yeah. Did you go anywhere after that before you came over to Pendulum?

Yeah, I mean, I actually— gosh, would be— well, last January was 5 years. I went to Mayo Clinic in Jacksonville, Florida to start their integrative functional medicine program. I was medical director for employee well-being, and that's where I met Colleen, met Pendulum. Mayo Ventures was an early investor in Pendulum. I got introduced to Colleen after I gave a few talks on gut health, the development of chronic diseases, really to do a type 2 diabetes for them on kind of our signature product, Pendulum Glucose Control. And got to know the product, got to know the team, got to know the science really deeply, was using the products in my practice, seeing it really help my patients with a number of conditions. And gosh, what is it now? Maybe 10, 11 months ago, the chief medical officer at the time decided to retire and I was pleased to— yeah, that was it, made the move.

Were you into taking probiotics or were you into the gut microbiome at all going through medical school or afterwards in your practice? Was that something— you mentioned you give your patients probiotics, but was that a real thrust of your practice like looking at the biome?

Yeah. I mean, definitely not in medical school. I mean, I did go to medical school knowing I was interested in, at the time, I mean, integrative medicine was just sort of an early term, but this idea of integrating things in from other healing traditions or things that might fall out of the technical mainstream medicine. I mean, a lot of it is what, you know, like you're doing. I mean, integrating saunas or infrared or whatever into your overall approach. And if you need a pill or you need a surgery, you know, that's something you consider as well. And I, you know, I was really interested in looking at the evidence for that and how do we integrate it effectively in an evidence-based way into helping people to not only address their health but really optimize their vitality.. And I would say it was probably maybe 2011, 2012, early in my tenure at Duke. I actually read— I got an advanced copy of this book by the Sonnenbergs. They run a microbiome lab.

Oh, yeah, they run a great lab.

Yeah, it's amazing. So that book was— I had a bit of an epiphany. I mean, just understanding, beginning to understand this connection to gut health, which I was already starting to train in functional medicine. So I was already getting into understanding the role of the gut and how profound it is and how it influences so many aspects of our health. But I would say after reading that book, whatever that was, 12 years ago or so, that's when I really began to focus down on the microbiome. So I would say more the interest was on the microbiome. Even at Pendulum, we don't really consider ourselves a probiotic company. We're a company that is interested in the science of the microbiome and its connection to human health. And well-being and longevity. And so that was really an exciting era for me. I began to not only focus on that science, but really integrate it into my clinical practice. And now with Pendulum, of course, I do things like this, but I also oversee a pretty robust research portfolio for the company on the clinical side, clinical research.

Yeah, I think the Sonnenbergs wasn't one of the pieces of research that came out of their lab, and I could be wrong, you might know, was the information that a lot of people who think that a gluten-free diet is helping their gut to feel better are in fact benefiting more from a low FODMAP approach from not consuming as many fermentable carbohydrates because of bacterial overgrowth. And, a lot of people who go low FODMAP see better resolution of symptoms than people who go just gluten-free or something like that. Am I remembering that correctly?

I sometimes mix up what came out of what labs, but I do know they have done work looking at diet and particularly looking at fermented foods and the impact that fermented foods have on the biodiversity of the microbiome, things like that. I mean, they've done phenomenal work. I mean, also it was this understanding of what happens to a woman when she gets pregnant and how there's shifts in the microbiome so that you absorb more calories from the foods that you eat. So you can support that growing baby, growing fetus. Actually, even another shift when women are beginning, if they give birth and they're lactating, breastfeeding. And I remember thinking, my goodness, how many women have I seen in my practice who one of the issues might have been telling me that they just couldn't get down to a healthy weight. They had maybe put weight on during their pregnancy, and no matter what they do with diet, they've just never been able to get back to that to that goal weight of theirs. And I began to wonder, you know, how many of those women had shifts in the microbiome that just never reverted back to sort of a healthy microbiome that releases GLP-1 and does all these things that we know ultimately helps you manage your metabolic health and live at a healthier weight.

Well, that's just silly. We all know calories in, calories out is what true physics is all about, and that something like, you know, gut bacterial diversity could in no way influence your utilization or absorption of calories or lack thereof. It is kind of funny though how much the microbiome plays a role. And of course, for any of you who are new listeners, it's a little tongue-in-cheek. But the interesting thing is I was talking with a guy named Joel Greene a couple of days ago. That podcast didn't come out yet. No, I should probably tell people the show notes for this podcast are going to be at BenGreenfieldLife.com/GLP1Podcast. BenGreenfieldLife.com/GLP, the number 1 podcast. And, what Joel was talking about was the idea of dietary diversity building the microbiome in such a manner that tolerance to certain food groups one might not have normally been able to otherwise tolerate improves. And, he went so deep as to show that, for example, Some of the polypeptides in dairy bind to iron and prevent potential hemochromatosis from meat consumption. Thus, myopically consuming only meat in the absence of dairy might not be a good idea. Or, we even talked about GLP-1 a little bit. Even certain sugars like a combination of honey and stevia might cause a little bit of a bump in GLP-1. But really, the main thrust of my conversation with him was about the importance of dietary diversity and kind of the sadness of the trend towards exclusive diets often driven by profit, by social media, by selling books, et cetera, right? The vegan diet or the carnivore diet or the paleo diet or extreme elimination diets that might work in some context for a healing protocol but aren't necessarily to be considered swallowed hook, line, and sinker as the ultimate human diet that we were all meant to eat from the dawn of time.

Yeah, I totally agree with that. I think, uh, and you made, made a number of really good points there. One is that there are a number of therapeutic diets, and certainly in my clinical practice, that's something that I do a great deal of work with. But those are temporary, you know, where you're trying to adjust and, and, and address— excuse me— you know, specific goals. And then overall, for most people, I mean, it's finding what works best for you, but it is really critical to have diversity in the diet. It's critical to have enough fiber in the diet, by and large, because most people don't. And you want to be feeding those, um, you know, those bacteria. So even when I'm recommending, of course, which I do all the time, you know, probiotics or the GLP-1 probiotic, you know, from Pendulum to my patients, um, I'm also recommending that they look at their diet, they look at the diversity of the foods that they're able to eat, you know, certainly their fiber intake. And, and then also it's sort of what you put in and what you don't put in. So, how much sugar, how much processed foods, ultra-processed foods, these things that have ultimately a negative impact on our gut microbiome and our health in general.

Ben Greenfield: Yeah, it was interesting because at one point, Akkermansia came up in that conversation and Joel basically said, well, you don't want to be just consuming massive amounts of Akkermansia willy-nilly because you need a proper Bifidobacterium to Akkermansia balance. And I brought up your guys' probiotic. I said, well, Pretty sure it's not just Akkermansia, the GLP-1, it's Akkermansia and what, Butyricum and Bifidobacterium, right? Those are three?

So the three are the Akkermansia muciniphila, the Clostridium butyricum that you mentioned, and then Bifidobacterium infantis. Those are the three. And yeah, I mean, happy to talk about that a little bit. I mean, again, this sort of was an interesting journey for the company. I mean, obviously Akkermansia was kind of our claim to fame, bringing that to the market, this anaerobic bacteria. But at the end of the day, these these 3 strains, really what we've been able to show is certainly through preclinical research, they really support the body's ability to naturally release GLP-1. And GLP-1, of course, you know, many of your listeners are probably familiar with it. Many people have heard of GLP-1, and many who haven't even heard of GLP-1 are actually injecting into themselves and don't even realize that that's what they're doing with some of these GLP-1 analog drugs. They just know that it's something that other people there, you know, are helping to and taking to lose weight or manage their diabetes. But in fact, those, you know, drugs are synthetic forms of GLP-1. And what GLP-1 really does is it gets released in response to a meal. Talk about that more in a minute. But it goes to the pancreas. It tells the beta cells in the pancreas, make more insulin so your glucose doesn't go up too much. It goes to your stomach. It slows down your digestion to allow you to feel more full and actually digest your food, ideally absorb the nutrients. And then it travels up the vagus nerve to the brain and sort of triggers the shutoff valve telling you, okay, you're full, stop eating. Almost like when you go to the gas station, let's say, if you're not driving an EV to go fill up the gas tank. I mean, it's amazing. You kind of put the gas tank in there, the lever in there, you click it on, you can sit and check your text messages or what have you., and then by magic, all of a sudden it clicks off.

I do, uh, I do jumping jacks.

Oh, there you go. You do jumping jacks, burpees, whatever you're doing. Yeah, you know, and then it just knows to click off. Well, you know, GLP-1 is, is basically one of the signaling mechanisms or hormones that tells, tells your body to, you know, stop, stop filling the tank up, so to speak, so it doesn't overflow. And again, these strains are really interesting. I mean, again, if you— I'm happy to go into some of the science here. You mentioned acromancia. And there's a number of ways that it stimulates GLP-1. Again, you eat a meal, bugs, the bugs in your gut, like Akkermansia in particular, eat that meal, particularly the fiber. And one of the things Akkermansia does is it makes this short-chain fatty acid called propionate that eventually gets converted to butyrate. And there are these receptors on these cells that line the gut called the L-cells. And, it's actually the Akkermansia making butyrate and then the butyrate binding to those receptors that then trigger the release of GLP-1.

Could I derail you for just a second? I'd love to continue that train of thought, but could you make a case therefore that if you have low Akkermansia levels, you might have low levels of butyrate in the gut? And, the reason I ask that is literally just yesterday I was looking over There's a gut test people can do for infants. And, one of my friends did one for their infant and I was looking over the results they sent over to me. And, the two things that were very low was acromancer was nonexistent and butyrate was pretty much rock bottom low. Are those two linked? Can you say that if acromancer is low, you might not be able to have as much butyrate in your gut?

They are linked and as well as the Clostridium butyricum. It's so funny you say that because I I literally saw a patient Tuesday, uh, who I used the same lab you're referring to, and he, he literally had no butyrate— excuse me, no Akkermansia on the test. And we do see that sometimes.

What about his butyrate? Was it— was his butyrate on the test?

The, the level, uh, was low, was diminished, wasn't zero, but it was diminished. And, and again, it's, it's not only Akkermansia, Clostridium butyricum, ergo the name, um, is, is a key player that makes butyrate as well. And butyrate is really important in the body. I mean, you can think of it as a signaling mechanism, again, binding to these receptors, but it's also a fuel for the cells that line the gut, the enterocytes. So, you know, often we're having cravings we can't manage, and, you know, we feel like we're trying to do all the right things, and we don't realize that just maybe it's not your fault, so to speak. There may be this imbalance in gut bacteria that's making it really hard for you to reach your goals, let's say, as it relates to you know, managing your cravings or living at a healthy weight. So it's a different way of thinking about health and well-being, sort of from the inside out.

Now, is the Bifidobacterium in there for the reasons that I mentioned earlier, that you want proper Akkermansia-Bifidobacterium balance, or is the strain of Bifidobacterium that you're using also some kind of an appetite suppressant?

Uh, it's, it's more the, the earlier, the first comment you made. I mean, the Bifidobacterium infantis, it's, it's what's called a primary fermenter, so it makes these postbiotics, in particular acetate and lactate. And they actually— it helps to keep a healthy ecosystem for the other bacteria. So, you know, this is a complex ecosystem. There's a lot of overlap of effort and bacteria supporting bacteria. And so these 3 strains, the Akkermansia, C. butyrate, and the Bifidobacterium infantis, they really work synergistically together to get the outcome that you're looking for, which in this case is enhanced release of GLP-1 and enhanced ability to manage cravings, appetite, feel fuller quicker, those kind of things.

Ben Greenfield: Okay. There's a lot of other stuff that makes you feel full besides GLP-1. When you have something bitter, the idea of whatever going to Italy and having a digestif or an aperitif or I'll often have some kind of very bitters-forward cocktail if I'm out at a restaurant or even use apple cider vinegar or some other homemade bitters type of compound or a shrub before dinner for activating things like polypeptide Y or CCK, things beyond GLP-1 that help with satiety. Is there any type of crossover between these bacteria that you're using to stimulate GLP-1 and other hunger or satiety-inducing mechanisms?

There is crossover. It's, it's more complex than what I just explained. Um, you know, there's— acromancy also releases this p9 protein. That p9 protein, and again, in addition to binding to a separate receptor, ICAM-2, on these L cells, and in and of itself stimulating the release of GLP-1— and again, we've shown this in preclinical studies— there's also effects on other cells, um, where you see this release of again, interleukin-6 and subsequently release of other hormones like some of the ones that you were mentioning that help control appetite. I think the key with the difference between maybe taking a bitter before a meal versus taking a probiotic, let's say in the morning or evening, is one is really an appetite suppressant you're taking prior to the meal to try to see if it can have a physiological effect. What we're doing with the probiotics, though, is you're taking them daily and trying to restore a healthy balance to the biological system. In this case, this microbiome, this ecosystem, which is really— many people refer to it now as sort of another essential organ. It's almost like another organ in the body that has many impacts on our health and well-being. And so you're trying to really restore that balance to that ecosystem so the body can function the way it's intended to function.

Yeah, it's kind of like weight training versus cold plunging, right? You could cold plunge for an acute increase in metabolic rate, or you could weight train to build muscle over time that becomes in and of itself something that stimulates your metabolism on a daily basis and keeps it up no matter what.

That's right. I mean, there's sort of like this feedback loop and overall the organism, in this case us, is healthier and functioning the way it's supposed to.

Now, of course, you mentioned the GLP-1 drugs. We got Ozempic and Wegovy and Mounjaro, and I forget the other one starts with a V, Vittoria or something like that. Anyways, yeah, Victoza, I think. There's, of course, a lot of people taking them and a lot of reported side effects. And, I think this might be something that's confusing with people, so I'd love to hear your take on it. Why wouldn't people see the same side effect, nausea, vomiting, pancreatitis, some of the issues people report, even muscle loss when taking those drugs versus taking something that like a probiotic blend that really powerfully activates GLP-1?

Yeah, sure. Great question. Again, let me be really clear. Our GLP-1 probiotic products are not a drug. They're not in that class. They're not intended to sort of replace the drugs. I mean, they are at the end of the day, a probiotic that are intended to restore a healthy balance to that ecosystem, that microbiome. They're probably about, you know, the drugs are probably about 100 times stronger. And to your point, depending on what literature you're reading, the drugs are that much stronger. You know, depending on what literature you're reading, you know, upwards of 50% or more people can experience certainly nausea, abdominal pain, you know, something like 1 in 10 get diarrhea. So those are the more common symptoms that people experience. And then you've already alluded to some of the more serious side effects. And that's not to say that these drugs don't have a role. They, they clearly do. I mean, for people that are struggling with metabolic health, they obviously are efficacious. I don't think they're a long-term solution. I think that's the biggest problem we're going to be seeing is, you know, what do people do long term? Clearly, when you're not taking a drug, when you're taking something like a probiotic that's intended to restore more of a natural balance, natural appropriate functioning to the body, and in this case, the gut, you know, you're not going to see the same level of side effects and serious adverse effects. And you didn't mention one that I would think you would mention, which is the potential loss of lean muscle mass too, which, you know, I think is a particularly concerning one for people. And certainly we have no evidence that that would happen with the probiotics.

Yeah, it is, man. I mean, yeah, I've talked about it before. I honestly think that it's kind of a simple fix on the same issue that we run into in chronic diseases overall. It's just people not eating enough protein or lifting weights. And, you know, totally, you can make it totally for that big an issue for just about any disease. But, but yeah, I think perhaps it is, um, more magnified with the use of a GLP-1. I don't think it's a mechanism of action like a, you know, say like a statin might affect muscle CoQ10 content. I think I think it's probably instead people are just eating way fewer calories and they're typically not lifting weights anyways. I'm trying to stereotype here, but if you're obese or overweight, it's less likely that you might have been a weightlifter. And so, those two factors put together, just fewer calories overall along with the absence of bearing weight just means that, yeah, you're going to lose muscle unless it's been your habit to eat enough protein and lift weights when you got on the GLP-1.

Yeah, totally hear that.

Totally. Yeah. Yeah. So, the thing with these GLP-1s, this is my last question about the drug component. I have no clue if you've looked into this at all, but I haven't heard somebody talking about it this morning. The idea of taking very, very small amounts of them almost like microdosing with the GLP-1 for other benefits. I think one I heard was lower blood pressure, better cardiovascular health. Have you come across any of that?

Well, I mean, what I understand from the literature is that certainly there seems to be benefits on cardiovascular health, a number of potential benefits beyond weight loss, let's say, with the drugs or managing of your diabetes, your insulin resistance. I actually haven't looked into the microdosing concept.

I have a bottle of semaglutide and a bottle of terazepetide up in my refrigerator right now. I haven't touched it, I haven't gone near it, but now I'm seeing all this information about microdosing, I've been thinking, "Huh, I should dig into this more and see if very trace amounts of these things might have some kind of pleiotropic effect that goes beyond weight loss or appetite satiation even at very, very, very low doses." But, I think it's interesting. I'll delve into that later. So anyways, I want to talk a little more about these bacteria because it's my understanding that they have to be in an anaerobic, an oxygen-free environment. Colleen and I talked about this, how the way that you make them at your facility is really complex because you have to keep them away from oxygen. But then, when I swallow them and they're in a capsule, isn't there oxygen that they're getting exposed to in my gut?

Actually, no, because they're put into— and this is something that the company had to figure out amongst a lot of challenges, including initially, how do you grow these in a way that you can kind of scale and make them available to the public, which they were available, let's say, in research labs, but really tricky to do. It took, I think, 3 years for Colleen and the rest of the team to figure that out and then be able to have a product. So I think, as Colleen had said to you on the podcast, I think we've had a product now for 2.5, 3 years. The company's been around for almost 11 years because they were figuring a lot of this stuff out to begin with. So for the question you asked, though, the probiotics are actually within a vegetable-based, acid-resistant, delayed-release capsule. So it makes it through the stomach acid, and then you really needed to get down into the large intestine where it then kind of gets released and and does its, does its thing.

Okay. So basically it's just, just don't break it open and put it in your smoothie or something like that.

Basically, yes. I mean, you know, people have done that. I've heard anecdotally, but that's not what we recommend. And, you know, you may be getting some of the bacteria down to where it needs to go, but you really want to try to take it within the capsule.

Yeah, it is important. I got a text this morning from a guy I'd done a consult with last week and he sent me a photograph Hopefully, I know he listens to the podcast, so I won't call him by name, but he sent me a photograph of all his supplements because I told him it was okay to put digestive enzymes in his protein smoothie. I told him you could actually make a case based on research that especially for older individuals with less digestive enzyme production, putting some enzymes into your smoothie can help with amino acid bioavailability of the protein. So then, he sends me a photo of this pile of supplements, all the capsules and tablets and everything he takes every day. He's like, "Can I just put all these in the blender?" in my smoothie. And I'm like, well, a lot of them are formulated to be time-released or bypass the acidic nature of the gut or not necessarily be pulverized and oxidized prior to consuming. So yeah, that is an important point. But that's pretty cool how you made it like that. And have you guys actually looked into or done formal research on what actually happens when you take them?

Yeah, so, uh, and, and this is an evolving story, of course. I mean, early on we did work looking at, um, in the lab, so preclinical work, looking at the ability of Akkermansia clostridium to actually lead to the release of GLP-1, lead to the release of this P9 protein that I mentioned earlier. Uh, we then went on and did a randomized clinical trial that looked at the one of our products, Pendulum Glucose Control, in patients with type 2 diabetes who are on metformin. We showed that there was a 33% reduction in glucose spikes. Hemoglobin A1C, one of the main labs I'm sure most of your listeners are familiar with that we use to measure glucose control, was actually reduced by 0.6, which is both statistically and was clinically significant. So that was really interesting. And then on the GLP-1 probiotic that we've been talking about, this 3-strain formulation, we actually did a consumer study, about 274 consumers, and we actually showed that after 6 weeks, 91% of the consumers had reduction in cravings. This data hasn't been fully analyzed. I think I can say this without getting in trouble. At 3 months, that went to actually 93%.. And it was kind of cool research. I hadn't done cravings research before. This particular questionnaire looked at 4 different areas like sweets, carbs and starches, fast foods, high fat foods. And we really showed that within every area there were significant reductions of cravings. And also kind of interesting, people that at baseline had higher cravings were really struggling with cravings. They saw the greatest reduction in cravings.

That's interesting. Now, was, was there a, uh, was there a control group that got the bottle that said, "We'll make you eat less," and it was just like, you know, a sugar pill?

Yeah, great question. Really important too, because, you know, whenever anyone is looking at, at these products and the science behind— not, not just our company, any company— it's really important to look at the science and understand what was studied and how it was studied. So in In the case that I just described, that was actually a consumer study. This product has only been out a short time, uh, since March. But we're actually now— this is again sort of half my role is doing this, you know, uh, providing and presenting the science, uh, to, to people like yourself and your listeners. But the other half, as I said earlier, is really to oversee this pretty extensive research portfolio. So one of the studies that we're just launching now is going to look in more depth at in a randomized, ultimately in a randomized controlled trial, the GLP-1 probiotic and some of the effects on the different things we've been talking about. So I'm really excited that that's launching now. It's going to launch any day. We're just waiting for final IRB approval.

Okay, got it. And back to the glucose control thing, those are interesting percentages you shared on the glucose and the hemoglobin A1C. Do you still have those in front of you?

That's from my memory, but go ahead.

Oh, from your memory. Very impressive. All right.

Still got a little bit of memory left.

On the glucose and the hemoglobin?

So, the glucose spikes, like area under the curve, 33% reduction. So, better glucose management overall. And then, hemoglobin A1c, 0.6 reduction. And this was 76 individuals and this was over 12 weeks, so 12-week study.

Okay, got it. And just so listeners know so we don't get confused here, Pendulum has more than just the GLP-1 probiotic that we're talking about. They have one called Glucose Control, which as the name implies is something you'd consume for blood sugar management. And, what I wanted to ask you was, and I know you got to be careful talking about drugs, but how does that compare, Adam, to something like metformin?

Well, again, in this study, many of the patients were actually on metformin.

Oh, and it still had that impact even they were on metformin.

Yeah, I mean, some people have suboptimal glucose control, so I don't want to directly compare that to metformin because again, I want to be clear, it's not a substitute for the drug in any way. It's a different class. It's not a substitute. But, you know, these are things, at least based on this study, that, you know, may be an important adjunct to people who are trying to limit, let's say, their reliance on the medications. Where I've used it in clinical practice is, you know, a lot of my patients want to try to avoid going on the medications if it's in the early stages of metabolic, you know, dysfunction or, you know, trying to wean off. Um, I had a patient right before I left Mayo Clinic that had been, you know, working hard on lifestyle, trying to get off of metformin, had lost a bunch of weight, was exercising, and, you know, had made progress but wasn't quite able to get over the finish line. And put her on PGC and, um, came back to see me 3 months later. And again, she was working with her other physician. I was more of a consultant in this case. And she was finally able to get off of the medication, which was the main goal she was trying to achieve and really improve her metabolic health. So, I see it in that way, certainly not as a replacement necessarily for the medications. Yeah.

Are you much of a self-experimenter? Have you ever slapped on a CGM and messed around with it yourself to see what happens?

Done it all. Maybe can't quite say I can keep up with you, but pretty close to most of the things you list. Some of them I haven't, but done the CGM and done a whole bunch of the different tests out there.

And so did you do the CGM and use the glucose control and notice anything?

To be honest, I didn't, because I did it a while back, and I think it was before I really had met the company. I mean, I did get some interesting insights, and I probably should go back and do it again because I really thought it was insightful. You look for something where you can make tweaks to your routine. I know that's what you're all about. And so, I haven't done that yet on myself, to be totally honest.

Ben Greenfield: Well, I've done a little bit of that. I can tell you they all seem to make an impact, weight training, walking, or cold plunging. Those all pre-meal or pre-Thanksgiving feast or night out in the town or whatever, those all make an impact. Drinking liquid ketones, that one's nuts. It's interesting because with that one, you can see a drop in blood glucose down into the 50s or 60s and often even if you aren't eating carbohydrates, still have a decent amount of energy. Those are very interesting. Of course, that's a whole different category. But then, yeah, I tried the glucose control. I tried berberine, specifically dihydroberberine, which probably as you know is another one that's kind of championed as good for glucose control. Bitter melon, and apple cider vinegar. It's like the shot of apple cider vinegar. And, I mean, a lot of people hear, "Well, do these things work?" I can tell you anecdotally for me, and one of my top genetic risks is for type 2 diabetes, which is why I look into this stuff and I'm very careful and I'm not wearing my CGM right now. I pulled it off 2 days ago because I had to get a massage and one of my triceps worked on. But, I mean, they do work anecdotally for me when we're talking about stuff like this. I'll see 5 to 10 lower for sugar when taking something like a glucose control or something that upregulates glucose transporters prior to a meal.

And sometimes there's overlap of sort of mechanism of action, but sometimes they're quite different. So, you mentioned berberine, it appears to have a similar mechanism to metformin, certainly affects on the microbiome, um, and on, you know, probably mitochondrial function, at least from what I've, I've read. There was actually an interesting review article about a year ago, uh, just, you know, just about a year ago on berberine. Bitter melon actually releases a chemical that is sort of similar to insulin. So again, a little bit different mechanism. Again, with, with, with our interest in the microbiome, it really goes back to trying to restore that healthy balance so that the— you're really getting the microbiome to work the way it's supposed to work. Work and release, in this case, let's say GLP-1, you know, in an effective way. And just so much that people do can have a negative impact on their microbiome, whether it's, you know, drinking or smoking or poor diet or various medications that they may have to take. But then things even beyond our control, stages of life, things like running in ultramarathons, traumatic brain injuries, all these things can have an impact on our microbiome. Circadian rhythms. And so, often without even knowing it, there can be imbalances and we want to try to address that at a root cause level.

Ben Greenfield: Yeah, yeah. And, I love that. It totally makes sense coming at things from the core of the problem. With the microbiome though, this is something I've always wondered about. And, it's kind of a tricky question too because obviously you're affiliated with the company and so I'm sure you have some amount of bias, but let's wave a magic wand and just say you're just a silent observer. What happens if I stop? What if I take it for a month? Would that just build up my Akkermansia and Bifidobacterium and the Butyricum to the extent to where I'm good, I've done the reboot, I don't need it anymore? Or, is this something that— because I know this is the case with some probiotics, you kind of got to keep feeding them through.

Yeah, no, that's, that's, uh, that's the golden question, to be honest with you. And the short answer to what is probably a very complicated answer ultimately, where we don't even have all of the facts yet, is that it really depends on the individual. So what I think the limited literature out there has shown, and we're actually trying to do— we're currently doing a study trying to look at when we see acromancia show up in stool, and we're using this new technology, and we're hoping to have results. Uh, gosh, that study should wrap up before the end of the year. So we, we— and then that's something we're hoping to get published. But, um, the reality is, I mean, just based on kind of looking at the literature out there, and, and is that some people seem to sort of colonize and can maintain, and, and others don't. And so, you know, it's hard to know, uh, but there are scenarios where maybe taking a statin drug, for example, where you really do need to take them, you stop the statin drug, your cholesterol is probably going to go back up. And I think for some people, you stop the probiotic, it's probably— particularly if you're not doing anything different with your diet or your lifestyle, you're probably going to return back kind of regression to the mean. You're going to return back to where you were. But there are also clearly in the literature examples of of individuals who for whatever reason are more able to maintain that colonization. And, I just don't think we have all the answers there.

Ben Greenfield: Is it one of those things where you kind of have to load with it for a little while? Sometimes when people start first taking creatine, they're a beast in the gym and they don't really notice much at all sometimes for 2 or 3 weeks unless they're doing— I don't recommend this because you get gut distress, some type of a more intensive 20-gram-a-day loading phase. But, is there kind of a point at which days, weeks, whatever where it really kicks in or do you feel the effects right away?

Well, so those were maybe two questions there. I mean, the first one is do you really need to load? I mean, the short answer from my perspective would be no. I think I would put the caveat that we really haven't studied that. We haven't looked at whether or not some sort of taking two pills for the first two weeks is going to make a difference. Certainly not what we recommend. It's not what the instructions say or the directions say. And I have no evidence that would suggest that that would make any difference, to be very honest with you.

And by the way, just to clarify, what I really meant was even just taking a normal dose, which might be 1 cap, I think, would you need to take even that just for a certain period of time before you started to feel the effects?

Right. So that's where I was going. I thought that was the second part of your question, which is how long will you feel the effects? And again, variable. Some people notice effects, you know, within a few days. What we recommend, just based on what we've seen, like for example, in the clinical trials, like in that study on the type 2 diabetics, is giving at least up to 90 days. I mean, most people are gonna see something, you know, within 4 to 6 weeks. But if you're not really feeling anything, you know, I usually recommend, and we recommend that people give it up to 90 days to see the effect. And again, that goes back to that variability in how our microbiome responds. To whatever it is we're doing to it. I mean, whatever that intervention is that we're putting into that ecosystem or that's influencing that ecosystem, different people respond differently.

Okay, got it. And then, one other question regarding usage, and that is the time of day. Is there a certain time of day that's best and also with or without food?

The best time of day is the time of day when you remember to take it. I mean, that's kind of part of the answer.

Kind of like exercise. It's like, exactly, I'm not supposed to exercise 3 hours before bedtime, so I'm not going to exercise. Well, I'm like, look, exercise, go take a cold shower after, you'll be fine.

Exactly. Just get it in. But so I think for most people, the easiest— most people just take it in the morning with breakfast. There's no reason why you couldn't take it with lunch or with dinner. In general, we recommend take it with a meal. It just helps with that whole process of getting through the stomach and down into the colon. If it's 8:00 at night, you already ate dinner and you're like, shoot, I forgot, just take it. That's fine. Again, there's no problem with doing that, but just in general, we advise that you take it with a meal. And there isn't any evidence I'm aware of that says taking it in the morning is better than the night. I think most people usually just kind of take it in the morning. I mean, actually, I don't because I don't usually eat breakfast first thing in the morning. So I usually take it with my first meal of the day, which for me is typically closer to around 11.

I'm one of those guys who forget stuff, so I've got it in my refrigerator. And because when I open up the refrigerator in the morning, uh, not to eat but to take the supplements that I have in the refrigerator, it's right there. So I just pop it in the morning when I get up.

Great. And you don't need to keep that product in the fridge. I mean, the Glucose Control you should keep refrigerated. You certainly want to keep it in a dark, you know, kind of cool area, but keeping it in the fridge is fine. I typically keep mine in the fridge also.

Yeah, yeah. I put it in there because I think at one point I saw recommended keeping cool kind of like you just said and I thought, "Well, my house does get kind of hot sometimes, so I'm just going to play it safe and put it in the fridge." But, the thing with these bacteria, of course, foods I know can, of course, as we were talking about earlier on, build dietary diversity and increase bacterial diversity in the gut. For these 3 strains, are they also found via certain dietary or lifestyle practices, or is the increase in them found in the gut via certain dietary or lifestyle practices?

If I'm understanding the question, there are certain things you can do, in particular things you can eat, that may influence your levels of, let's say, Akkermansia, for example. So fiber in general, but more specifically also polyphenols, have been shown specifically to increase levels of Akkermansia and can be beneficial. That's why we actually have a polyphenol product in addition to the probiotics. And it's actually from sources of polyphenols that we studied and were able to see were the most supportive to these particular strains.

That's interesting too, because so if I were traveling and had access to a lower diversity of polyphenol-rich foods, I could, for example, grab a bottle of the polyphenols and then the GLP-1 and the polyphenols would help to feed and cause the components of the GLP-1 to thrive in the gut.

That's correct. I mean, we do get the question, well, should I take two products? Can I do that? Again, not what I typically recommend. If you want to enhance, let's say, the efficacy of the product, really, certainly diet, of course, but it's really taking the polyphenol booster with whatever product you're taking, GLP-1 probiotic, whatever it may be. We also have something called Metabolic Daily, but again, that's that's a 5-strain formulation also. So whatever you're taking, the polyphenol product is probably the best option if you're trying to sort of boost the efficacy.

Okay, got it. What about butter? Butter is a form of butyrate. Would that kind of fill in some of the gaps for butyric acid?

There's one I'm not aware of. Again, I'm not sure, to be very honest with you. I haven't seen anything related to that. So I don't want to give an answer when I'd have to be guessing at it.

Yeah, yeah, that's right. And the Bifidobacterium infantis, do you know of dietary sources that might help out with that?

Again, fiber in particular, you know, is really important. That's one that you get inoculated with very early in life. Well, you get all these early in life anyways, but that Bifidobacterium infantis— and again, I'm an internal medicine doc, not a pediatrician, but certainly the pediatricians are, are particularly familiar with that. But it does have a role throughout life. And, you know, I think there, certainly a good high-fiber diet, again, a good high-polyphenol diet, kind of eating a rainbow, those sorts of things can be very important. And, you know, I think it's always important to emphasize not only what you could do, but maybe what you shouldn't do or what you could avoid. So it's also avoiding those things can have a negative impact on the microbiome. Like, as I've said earlier, I think, you know, a lot of sugar, high-sugar foods, a lot of ultra-processed foods, things like that.

Ben Greenfield: Yeah, yeah, that makes sense, of course. Now, the acromantia is interesting because I think it was a few years ago, there was a study that came out. I don't know, maybe it was out of Sonnenberg's lab. I don't know, but it was on athletes. And I believe you might know more about this than me. I believe they noted higher levels of acromantia in people who had elevated levels of athletic performance. Am I on the right track with that? Am I remembering that correctly?

Yeah, there's been a lot of interesting— and again, we want to be careful. These are associations. And it's funny that you've specifically called out athletes because that's a study that we are— another study. So I said we had a rich portfolio of studies, but that's another consumer study that we're about to launch. A couple of things with athletes. One is that, as you're probably familiar with, particularly long-distance athletes, there can be GI issues that develop.

Trust me, I know. I did Ironman for like 15 years. Right. So you know.

And part of what happens is the development of leaky gut. Now, what's interesting, because I didn't really go into this, maybe I digress just for a minute because we've talked a lot about Akkermansia, Clostridium butyricum, phytobacterium, and GLP-1. But with Akkermansia, there's another very important role, and that's really to help maintain the integrity of the gut lining. So when I say leaky gut or increased intestinal permeability can develop in you know, long-distance runners, these kind of things. What I really mean is that— and I think Colleen explained this on, on her podcast with you— she likes to talk about the lining of the gut being like, you know, the fence in her backyard. But basically, those boards line up and they should be tight, uh, so that things that shouldn't get through can't get through. And, you know, there's sort of a glue that holds them together, um, that along, you know, there's some proteins that hold them together, but there's also this what is called mucin. That's— let's consider it kind of like a shellac on the outside of that fence. And the mucin helps to keep the cells of the gut healthy, you know, just like it might help keep the wood of your fence healthy. But it also kind of acts like flypaper, and it kind of catches things that shouldn't get into your circulation, because when they get in, that causes an inflammatory immune reaction, what have you. And so it's really important to maintain a healthy mucin layer. Akkermansia muciniphila, or mucin-loving, what it does is it, as, as mucin begins to degrade, it sort of eats up like a Pac-Man that degraded mucin, and then it stimulates these other cells called goblet cells to, to make more fresh mucin. So it really helps to maintain that lining of the gut, which is so important. Again, when it isn't maintained, we do get— we develop, you know, leaky gut or this increased intestinal permeability. So really important role. So that may be, again, you know, to be studied, but that may be part of a mechanism through which it can help athletes, you know, is in terms of the gut health. You know, there are other associations. There are associations with less chance of, a lower chance of developing obesity when there's higher levels of akromancia. We see higher levels of akromancia in individuals that live the longest healthfully. So if you look at older individuals that are living healthy and you look at their microbiome, they tend to have higher levels of Akkermansia. It's a whole connection with longevity, which I think is really interesting.

There's a big connection between longevity and dietary diversity too, so that could be why.

Right. Where does that come through, right? I mean, more diverse the diet, probably better feeding of the microbiome and strains like Akkermansia, and and then by extension, you know, better metabolic health and other things that, that probably are driving longevity in the long run.

Yeah, that's— I actually did not know that about acromantia and leaky gut. I'd always known there are things like a colostrum, or there's a, there's an orally bioavailable peptide, I think it's called, uh, LVP, that, that connects similarly. Uh, but yeah, I did not know that about acromantia. That's super interesting. And of course, one of the things that was bandied about after that study on athletes was people were talking about fecal transplants from athletic populations into individuals who might want that similar biome. Have you ever looked into that whole world of fecal transplants?

Sure, certainly. I mean, to be honest, not as it relates to athletic performance. I haven't really looked at that per se. I mean, I think some of the early work that looked at And again, Pete, I'm gonna say his last, Turnbow's work, for example, that looked at twin studies where you have twin sisters in this case, so genetically identical. One happened to be overweight, the other was not. And they actually transplant the, they take a mouse who is thin or healthy weight, they transplant the microbiome from the overweight twin into that mouse, don't change the diet, the mouse gains weight. And as you might imagine, on the other twin who was normal weight, they actually transplant that into a mouse who was overweight. Again, don't change the diet, and that mouse goes back to a healthy weight. And then they actually transplant from mouse to mouse and see the switch. And so these are really amazing kind of studies. And part of what got me really interested, and I think got the founders of the company really interested, you know, 10, 15 15 years ago when these studies were coming out. Of course, for, you know, other indications within humans, we know fecal transplants can be really quite effective. I mean, and so it's a really interesting area of science that I think, you know, this whole area is really one of the next great frontiers of our under— as it relates to our understanding of human physiology and what it takes to really, you know, maintain human health and, and to truly thrive.

Yeah. And, speaking of fecal transplants, maybe I'm about to ask you the oddest question you've ever been asked on a podcast. I don't know. But, well, let me precurse it with this. The Akkermansia, the Bifidobacterium infantis, the L. reutericum, those—

Sibiu.

Sibiu, sorry. Those survive to the colon, to the large intestine?

In these capsules, right? In those capsules we talked about, they do, right?

Okay. And, they thrive in an anaerobic environment, which is what that area is. That is correct. So, there are a lot of people in the health world who pay good money for things like ozone enemas, which I would imagine is introducing a huge amount of oxygen into the colonic environment. Wouldn't that theoretically kind of nuke all this stuff?

I mean, I certainly have friends and have had patients that have used ozone therapy. You know, it's not something I've ever utilized in clinical practice, particularly practicing at places like Duke and Mayo Clinic.

Yeah, yeah, this is a total theoretical question. It just makes me think that when you talk about anaerobic environment, people are blowing oxygen up their butts, you know, is this sort of some sort of homeostasis reaction?

I mean, I, I don't know. I mean, but, um, you know, certainly anecdotally a lot of people seem to have benefited, but for me, you know, I'm still waiting for a little more evidence on that one, to tell you the truth.

Yeah. Well, I mean, I can tell you guilty as charged. I've done those ozone enemas before. I also do a quarterly stool analysis and I've never had bacterial imbalances. And obviously, the stool is coming right out the butt. But yeah, I don't know. I'm just curious about it talking about the anaerobic versus the aerobic environment. So, I guess that's another study you guys are going to have to do, Adam.

Well, I'll let you know so you can be first in line.

We'll sign you up. Yeah, yeah. Okay. So, I'm just curious, a guy like you knowing as much as you do, before we start recording, we're talking about how you use these headphones at the gym that allow you to do the switch to talk. So, if people start talking to you, the headphones automatically turn off when you start talking, which derailed our podcast but seems like a great idea for the gym. But, I'm curious, So, you're focused on health, you know a lot about the microbiome. I'm curious about how you eat. What's your diet look like?

Ben Greenfield: Oh, yeah, sure. I mean, first of all, I'm a huge workout guy. Again, I'm saying that to you, but for me, and I'm 57, almost 58, I'll be 50. And so, I've always been way into physical fitness. And, when I was younger, I was basically like a professional martial artist, not MMA guy, but I was teaching and training hours every day. And back then, I mean, we used to eat whatever we wanted and felt we could do that. And a lot of the guys I trained with ended up putting a bunch of weight on later because you start, you get older, you're teaching more than sometimes more than you're actually practicing and you end up putting weight on. But I always maintained my physical activity and then I really did start to get into nutrition. But I do try to find balance. So I'll play with certain things, but I'm not vegan. I usually try to use lean sources of animal protein. Primarily, I try to use fish as much as possible. I try to make vegetables the biggest thing on my plate. You know, I'm— I do some other things where I actually cold brew my own coffee and I cut the caffeine a little bit 'cause I'm a slow metabolizer. But I'm also a really strong proponent of you being an expert on you. I mean, if you go back to what you and I talked about a little while ago with all these different fad diets and different things, is, you know, life is about balance. That's what I mean. Again, you know, it's sort of like, I won't— how would I know that? Because I'll have pizza every now and then. And I just, in general, if that's what I'm eating every day, you know. And so I don't know if I use an 80/20 or maybe a little more like a 90/10, but by and large, that's what I try to do. And, and, uh, you know, lately this summer I've been hitting the protein a little harder. I've been supplementing, trying to build up a little more muscle mass. I'm staying in Massachusetts for the summer, and this, this is great gym that's like old old-school weightlifter gym. It's got some of the old-school equipment as well as the new stuff. So, I'll kind of just see how my body feels and just kind of listen to it. And, that's what I've been doing.

Ben Greenfield: Yeah, yeah, fantastic. Dr. Adam Perlman gaining mass in Massachusetts. The Pendulum probiotics, gosh, if you're listening and you were to pair the discussion that we've had just now with the one that I did with Colleen Cutcliffe about kind of a behind-the-scenes glimpse into how these things are made and more of the theory and science behind them along with these updates from Adam, there's a very strong case to be made for building up these bacteria in your gut. I've been using them since my interview with Colleen and I think that they work really well. So, go ahead, Adam.

Well, I was going to say, obviously, coming out of listening to this podcast, some of your listeners may want to try them. So, hopefully, they do because they work. I think we've set up a code with pendulumlife.com/Greenfield that provides like 20% off if for your first membership order, that kind of a thing. So again, I think it's pendulumlife.com/Greenfield.

You make my job easy. Geez, I'm horrible at remembering that stuff. I can't even remember that. All I do is I remember one URL, so I remember the show notes. Which in this case is BenGreenfieldLife.com/GLP1Podcast. I used to just riff off, "Hey, go here for this and go here for this and check out this link at PubMed.1235axyz." And now, I'm just like, "Just go to the shownotes. It's all in there." But yeah, 20%, it's pretty significant if you guys want to try it out. Give me your feedback. And also, if you go to the shownotes, you can ask your questions. Leave your comments. I'd love to read those. I'd love to hear from you guys. So, Dr. Adam Perlman, thanks so much for coming on the show, man.

Hey, I loved it. I really did. And, thanks for having me. It was great discussion.

Really enjoyed it. Awesome. Well, folks, until next time, I'm Ben Greenfield along with Dr. Adam Perlman from Pendulum signing out from BenGreenfieldLife.com. Have an incredible week.

Do you want free access to comprehensive shownotes, my weekly roundup, up newsletter, cutting-edge research and articles, top recommendations from me for everything that you need to hack your life and a whole lot more, check out BenGreenfieldLife.com. It's all there, BenGreenfieldLife.com.

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