Probiotics For Diabetes with Dr. Colleen Cutliffe: Rational Wellness Podcast 228

Dr. Colleen Cutcliffe speaks about a new Probiotic that helps to manage Diabetes with Dr. Ben Weitz.

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Podcast Highlights

0:30  Akkermansia mucinophila is a new probiotic on the market. Because it is an anaerobic bacteria, it is very difficult to manufacture it, since it needs to be produced in an oxygen free condition. If even a single molecule of oxygen is present in the manufacturing process, the whole batch of Akkermansia dies.  Pendulum Therapeutics managed to solve this problem by creating an oxygen-free manufacturing process.  They are offering a product that contains Akkermansia and several other probiotics and a prebiotic in a product called Pendulum Glucose Control, which has been shown to reduce blood sugar spikes and hemoglobin A1C in a clinical trial.  Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation

8:57  Akkermancia has been well studied and has been shown to be beneficial for helping with inflammation, immune response, obesity, metabolic syndrome all the way through type-2 diabetes, and leaky gut.  It lives in the mucin layer in your gut and it helps to regulate that mucin layer and make sure it’s the right thickness so that all the small molecules being generated in your gut are staying where they’re supposed to be and that they can get access to the receptors that they need to bind to in the gut lining for the downstream signaling pathways to be operating properly. The challenge is to grow Akkermansia in an oxygen free process but make sure that you provide all the ingredients needed for this strain or probiotic to grow and thrive while not being attached to a mucin layer.  And you have to create a product that’s stable at room temperature so that you can sell the product and it needs to be functional in your gut as well.

16:50  Pendulum Glucose Control includes strains of probiotics that produce butyrate, including Akkermancia, as well as a prebiotic. It was reasoned that if you could increase butyrate production, you could help people improve their LGLP-1 response and their insulin/glucose control.  A placebo-controlled double-blinded randomized trial found that people who were taking Pendulum Glucose Control versus placebo had a Hemoglobin A1C lowering of 0.6% and a lowering of blood glucose spikes by 34%.

18:16  GLP agonists are drugs prescribed for diabetes patients and they are being looked at as potential longevity promoters. Butyrate production is upstream of GLP-1, so stimulating butyrate production can promote the release of GLP-1 agonists.

21:42  Non-alcoholic Fatty Liver (NAFLD) is a major health problem today and it is related to dysregulated glucose control and their study did show that Pendulum Glucose Control reduced the ALT and AST enzymes that indicate improved liver health.

22:14  The effect of Akkermansia probiotics on the gut. Nine out of ten people who took their product reported improved gut symptoms, though there has been no trial specifically on that.  Akkermansia may improve the health of the gut by improving the mucin layer, which is the gut lining.



Colleen Cutcliffe, PhD is a CoFounder and the CEO of Pendulum Therapeutics, which developed Pendulum Glucose Control, which is the first and only probiotic that lowers blood sugar spikes and hemoglobin A1C in a clinical trial.  Pendulum Glucose Control is a probiotic and prebiotic product that contains Akkermansia Mucinophila along with several other strains and inulin from chicory. You can get more information about Pendulum Glucose Control by going to PendulumLife.com and if you use the code WEITZ20 you will receive 20% off your first order.

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.


Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

Hello, Rational Wellness Podcasters. Today, our topic is about a new probiotic on the market for the first time known as Akkermansia muciniphila. Thanks to Pendulum Therapeutics. And we will be having a discussion with Colleen Cutcliffe, PhD and co-founder and CEO of Pendulum Therapeutics. Akkermansia muciniphila has been discussed as one of the more important bacteria that exists in the microbiome of the gut. But it has so far not been available to the public.

Akkermansia muciniphila is a bacteria that grows primarily in the mucous lining of the large intestine. And it plays a critical role in maintaining this mucous layer and in supporting a healthy gut lining and preventing leaky gut. Akkermansia reduces gut inflammation. And patients with Crohn’s and ulcerative colitis tend to have lower levels. Akkermansia is also one of the primary butyrate producers. And this strain of bacteria improves insulin sensitivity and may reduce diabetes risk. It may play a role in reducing obesity. And it may also improve the response of patients with lung or kidney cancer who receive immunotherapy.  The reason Akkermansia has not been available on the market so far is that it is an anaerobic bacteria. So, it can only live and be produced in conditions where there is no oxygen. This makes it very complicated and expensive to manufacture. If even a single molecule of oxygen is present in the manufacturing process, the whole batch of Akkermansia dies.  Pendulum Therapeutics managed to solve this problem by creating an oxygen-free manufacturing process.

Colleen Cutcliffe, PhD, is co-founder and CEO of Pendulum Therapeutics which developed Pendulum Glucose Control which is the first and only probiotic that lowers blood sugar spikes and hemoglobin A1C in a clinical trial. Pendulum Glucose Control is a probiotic and prebiotic product that contains Akkermansia muciniphila along with several other strains and inulin from chicory Colleen, thank you so much for joining us today.

Colleen:               Thanks so much for having me, Dr. Weitz. I feel like that whole intro, that’s it. You got the whole story. I don’t know if I can shed any new insights here.

Dr. Weitz:            The only scary thing is every time I say Akkermansia muciniphila, if you say muciniphilia, it sounds like some deviant sexual thing.

Colleen:               I’ll tell you the trick in our company. We just call it A [muke 00:03:19] just to solve all that.

Dr. Weitz:            There you go. Perhaps, you can tell us a bit about your professional journey and how you came to start Pendulum Therapeutics.

Colleen:               Sure. My background is in pretty hardcore science research. So, I have a PhD in biochemistry and molecular biology from Johns Hopkins. I did a postdoc at Northwestern’s Children’s Hospital. And then, I moved out to the Bay Area where I worked for a pharmaceutical company. We were developing drugs for Parkinson’s disease. And then, I moved to a company called Pacific Biosciences which was building a DNA sequencing instrument. And it was an early stage startup company, went through rapid growth and went public.  And on the other side of that IPO, I started Pendulum with two co-founders. All three of us worked at Pac Bio together. We’re all three very technical. I’m a biochemist. Jim is a biostatistician. John is a biophysicist. And, really, the three of us, what we saw in the technology space was that even though things like probiotics and yogurts have been on the shelves for decades, it’s been the same kind of set of ingredients that have been mixed and matched in all these different products.  There hasn’t really been any new invention until the microbiome science has really started to emerge over the last decade. And the reason that the microbiome can even be a science is because DNA sequencing technologies have enabled us to really understand what are the microbes, what are their functions, what are they doing.

And so, we were coming from a DNA sequencing instrument company and realized that we had all the tools and technologies to be able to take microbiome samples and to develop kind of these microbiome maps of people, and think of it like a systems biology problem where you have all these different pathways in your microbiome. How are they connected to each other? How are they connected to our body? And then, I’ll just share that not only was there sort of a technical expertise. But as I started to learn more about the microbiome, I realized there was sort of a personal connection for me which was around my older daughter.  So, my daughter was born almost two months premature. And when you have a baby that’s born that early, you kind of get to hold them for a few seconds. And then, she was taken away to intensive care where she spent the first month of her life actually hooked up to all these machines and monitors and receiving multiple doses of antibiotics.

And there happened to be a study that came out right when we were thinking about this company where they looked at 12,000 children and found that babies under six months of age were systematically on antibiotics were also systematically more prone to obesity and type-2 diabetes as they grew older and became teenagers. And so, I realized, “Oh, my gosh. We could create novel products that could help millions of people including my own daughter,” and that the microbiome is this really unique opportunity where if you develop products with the scientific and clinical method, you can create products that have the efficacy of a drug but the safety of a probiotic. And that was sort of the origin story and mission of the company.

Dr. Weitz:            Yeah. I think it’s interesting. There’s kind of been these two trends in some of the research that we’ve been discussing on the microbiome and probiotics. And one sort of argument is that probiotics, in general, have a beneficial effect. There’s certain categories. And it really doesn’t matter which strain you have. And the other the other way of looking at things is that each strain is very different, can have specific properties. And it’s very important that we stop just looking at research on probiotics.  In fact, I recall talking to Dr. Pimentel when we were talking about research on SIBO. And he kept saying, “Look, you can’t tell me that this is a valid scientific argument to say that probiotics are beneficial. You’ve got these studies. They’re all using different probiotics, different strains. And you’re blending it all together. Imagine if we took a bunch of different drugs and said drugs are beneficial. It doesn’t work that way. You’ve got to get more specific about this.”  And so, I think that some of the research that you’re doing and that’s being done on some of these species like Akkermansia are super important because I think we are starting to see that particular strains have particular properties and these are not just captured by taking broad spectrum probiotics.

Colleen:               You’re absolutely right. And I think we’re just starting to get a more sophisticated understanding of these different strains and their functions, and what impact they have. So, I’m sure you get asked a lot from patients, “What vitamins should I take? And what’s going to be helpful for me?” And you don’t say, “Just take vitamins.” You know specific vitamins for specific issues. And I think we’re just starting to get there with probiotics.

Dr. Weitz:            Right. Now, you mentioned the fact that we’re having stool tests that use DNA. And one of the important things is that a bacteria like Akkermansia would not be picked up by stool tests that cultured bacteria.

Colleen:               Absolutely right because if your stool test is culturing based, then, it requires you to be able to grow these trains. And that’s been a fundamental problem in why the field hasn’t been able to make as much progress as we would like. It turns out that where all the business is happening in the large intestines there, it’s anaerobic. There’s no oxygen there. So, they don’t grow in the presence of oxygen.  So, if you kind of try to culture them in a non-anaerobic environment, you’re going to lose kind of all the meaty guys. They’re not going to be able to grow there. So, it’s got to be a sequencing-based approach or a metabolic-based approach in order to be able to capture these key strains.

Dr. Weitz:            So, let’s talk a little bit about Akkermansia and exactly what it takes to manufacture it.

Colleen:               Oh, man. It’s a diva. So, Akkermansia has been quite well studied internationally and has emerged as important for many of the things that you mentioned, inflammation, immune response, obesity, metabolic syndrome all the way through type-2 diabetes, and this leaky gut concept where it’s just really important that you have the right gut lining. It’s even been implicated in gut brain issues.  And the finding has been that in all of these different disease states, people appear to be low or missing Akkermansia whereas healthy people have a vast abundance of it. And the underlying mechanism is that it is actually living in your mucin layer and helping to regulate that mucin layer so that it’s just the right thickness, so that all the small molecules being generated in your gut are staying where they’re supposed to be and that they can get access to the receptors that they need to bind to in the gut lining for the downstream signaling pathways to be operating properly.  So, to grow Akkermansia, you kind of have to take all those conditions into consideration because that’s its home. That’s where it likes to live and thrive. And then, we live and thrive out here where there’s oxygen. And we’re not attached to a mucin layer, and we’re trying to grow at scale.

And so, really the challenge has been how do you create an end-to-end anaerobic process where you don’t let any oxygen in. How do you give the ingredients needed for this strain to be able to grow and thrive even though you’re not putting it right up in a mucin layer? And then, also, there’s a temperature sensitivity to it. And so, how do you try to get it to be room temperature stable so that you can actually sell the product?  And the most important thing is it’s got to have viability at the end of this entire process. And so, we actually have three different assays that we use to measure viability. Not just is the strain alive, but is it able to produce butyrate? Is it functional at the end of all of this manhandling? And that’s really key because Pendulum Glucose Control is delivering on a promise of reducing A1C and blood glucose spikes. And so, it’s not just the strains are in there. It’s not just a CFU count. It’s are they going to function in your gut?

Dr. Weitz:            Now, there has been a paradox in all the data related to probiotics. And the paradox is the following, is that we can test the microbiome. We can see which species are low and high or absent, et cetera. We can take specific species. But pretty much, all the data has shown that none of the probiotics we take become permanent residents. They’re just temporary visitors. But yet we know they have these beneficial effects.

Colleen:               Yes, absolutely. Actually, it’s sort of interesting because in our study that was published in BMJ, we did a washout period where people didn’t take the formulation. And then, we looked at whether the strains were still there. And this has been reported for other probiotics. For the vast majority of people, they were gone. But a small percentage around 15 to 20% of people, they still had the strains in their microbiome. And so, of course, the million-dollar question is why? What is it about them that enable them to keep the strains?  And the hypothesis that we’re testing and many others are testing is that there’s something about your microbiome ecosystem. And it is an ecosystem. So, you have to know that there’s a bunch of other things in there that have to grow alongside it. Everybody’s microbiome ecosystem is either going to enable new strains to colonize or not. So, I like to think of it like a garden. You’ve already got a garden that’s got all these plants and flowers growing it. And you’re trying to introduce a new plant.  Some gardens are not going to allow that plant to flourish. And some gardens are. So, what are the kind of things that you can do to your garden to help these new strains flourish? You can change your diet and provide the prebiotics that are really going to help these strains grow. So, higher fiber diets tend to really enable Akkermansia to grow, high polyphenols and things like that.  But, generally speaking, it’s kind of hard to account for all the factors that lead you to have the microbiome that you have. Your microbiome gets depleted over time through things like just aging, stress, circadian rhythm. Every time you go to a place where you have to change your days and nights, for women, menstrual cycles and menopause, these all cause you to become depleted. Well, you can’t really do anything about those things. So, you’re-

Dr. Weitz:            Not to mention all the antibiotics and pesticides sprayed on food, and herbicides, and all these things that kill bacteria in our gut.

Colleen:               Absolutely. So, then to ask this plant to thrive in a garden that you’re constantly spraying with things that are going to kill it, it’s pretty hard to do.


Dr. Weitz:            We’ve been having a great discussion. But I’d like to interrupt this discussion for just a minute to tell you about a new nutrition product that is very exciting. We all know that there’s a lot more to health than just healthy eating. And there’s a lot more to nutrition than just calories. Having a healthy microbiome is also a key to better overall health. And diet can significantly impact our microbiome. Over time, people with type-2 diabetes tend to lose some of the gut bacteria that helps digest fiber and manage our blood glucose levels.  A new probiotic, Pendulum Glucose Control is the first probiotic that can help rebuild your microbiome and help you to manage your blood glucose and your A1C levels. Take control of your glucose levels today. Visit pendulumlife.com. That’s P-E-N-D-U-L-U-M-L-I-F-E.com to find out more. And use the promo code Weitz 20. That’s my last name, W-E-I-T-Z 20, for 20% off your first order. Once again, that’s P-E-N-D-U-L-U-M-L-I-F-E..com. Promo code Weitz 20. And now, back to the discussion.


Dr. Weitz:            Let me ask you a quick clinical question. I don’t know if you know any answer for this. But as we were talking about the mucin layer, and we’ll get right back to Akkermansia. Besides Akkermansia, do you know of nutritional products that can help enhance the mucous layer of the gut?

Colleen:               I don’t know that there have been really kind of validated clinical trials around that.  And I would say also that the gut lining is a hard thing to measure without actually taking a biopsy of somebody’s gut lining.  But I think that some of the studies have really pointed to anything that really helps is actually pretty much tied to Akkermansia.  Anything that helps Akkermansia grow does tend to have these clinical outcomes of improved GI, improved digestion, and things like that.  And so, on that front, things with polyphenols, so, grapes, cranberries, things like that, they tend to help boost the Akkermansia growth in the lining as well as things that feed the butyrate producers, so, inulin, anything with inulin and Jerusalem artichokes. You can actually buy inulin by itself. Those things also help.

Dr. Weitz:            Well, that’s good. What about mucilaginous herbs and or L-glutamine?  Can they be beneficial?

Colleen:               Oh, man. Now, you’re getting into territory that I don’t know.

Dr. Weitz:            Okay. No, I know. That’s clinical stuff. But I know since you’ve been digging into all this stuff. Okay. So, let’s move on. So, let’s talk about some of the therapeutic benefits of Akkermansia and, in particular, your Pendulum Glucose Control product which contains more than just Akkermansia.

Colleen:               Yes. So, our hypothesis around the consortia that’s in Pendulum Glucose Control is that if you could increase butyrate production, the metabolism of fiber into butyrate, and you could increase this mucin regulation, that you would help people improve their GLP-1 response, and then ultimately their insulin glucose response. And that was based on mostly correlative studies where we found that people with diabetes and pre-diabetes and obesity were lower in these particular functions.  And so, we basically identified strains that could produce butyrate. It’s a multi-step biochemical reaction to metabolize fiber to butyrate. So, we have all of those strains in there that do the two steps of that reaction, plus Akkermansia. And, really, what we found in our clinical data was that you did need this entire consortia. We had an arm where we only had a subset of them. So, you needed the entire consortium to get statistically significant data. And so, in a placebo-controlled double-blinded randomized trial, we found that people who were on product versus placebo had an A1C lowering of 0.6% and a lowering of blood glucose spikes by 34%.  And that’s a really meaningful product for somebody with type-2 diabetes as you know. But it’s all natural. It’s all these naturally occurring strains and a prebiotic in there.

Dr. Weitz:            Since GLP agonists now are being looked at as longevity molecules or potential longevity molecules, perhaps Akkermansia could be part of that mix.

Colleen:               Well, in fact, I think this theory that this whole thing is operating upstream of GLP-1 is that you get these butyrate producers when they combine to the right GPCRs, they then stimulate GLP-1 release. And we actually have in vitro data showing that we can do that. But our chief medical officer once we had this theory about how the product worked, we went and we grabbed Dr. Orville Kolterman who was previously the CMO at Amylin Pharmaceuticals that put out multiple GLP-1 agonists. That company got acquired for something like $7 billion from BMS. He was retired actually. And I met with him and I said, “If you want to really get in on the next frontier of diabetes therapeutics, it’s the microbiome.”  And he went up and did his own research and came back and said “All right. I’m in.” And he’s really guided all of our pre-clinical and clinical development. And you’re right these GLP-1 agonists are really showing up. I think at the core of it is that your ability to manage your blood glucose and to metabolize glucose properly is actually at the core of a lot of health issues that we previously didn’t know were related to each other. I don’t know if you have theories about how these systems are related to glucose control.

Dr. Weitz:            You mean how the gut is related to glucose control?

Colleen:               Well, if you have mismanaged glucose control, it can show up in a variety of ways beyond just type-2 diabetes. I don’t know if you have people talking about fatigue or-

Dr. Weitz:            Sure. But the only thing we really know about that I’ve heard people talk about is the way in which glucose molecules glom onto proteins in the body, glycogen storage stuff.

Colleen:               Yeah. Absolutely. And I think this is what happens is when you can’t manage your glucose response properly, we know this. You have these free sugars kind of floating around binding to red blood cells and all these proteins and…

Dr. Weitz:            Right. Like hemoglobin A1C is sugar molecules binding to red blood cells. And then, these sugar molecules bind to all these other proteins. And that accounts for a lot of the damage that occurs with diabetes.

Colleen:               Exactly.

Dr. Weitz:            So, anything we can do to reverse that is good. And especially for people in the natural world who are looking for ways to hack longevity and who are not that thrilled with the idea of taking medicines like GLP-1 agonists, some natural way of doing it is very, very appealing.

Colleen:               Yeah. And I’ll tell you this. I don’t have diabetes or pre-diabetes. But I take the pills because I actually feel that I have more energy throughout the day when I take them. And I actually wore a continuous glucose monitor on myself and saw that when I was on product versus placebo, of course, I’m a scientist so I had to run the experiment on myself, that actually it helped me with my sugar spikes and crashes. It helped just to minimize those. And for me, that shows up as sustained energy throughout the day, better workouts, and things like that. And so, I’m on it. My mom is on it. My kids are on it. My husband’s on it because it’s a natural product and being able to manage blood glucose is important for everybody.

Dr. Weitz:            Another thing you might look into is could this play a role in non-alcoholic fatty liver, which has to do with sugar storage in the liver.

Colleen:               Oh, you’re right on.  So, actually in the trial that we published, we did see that people’s ALT and AST numbers were improved, so, their liver enzymes.

Dr. Weitz:            Oh, interesting.

Colleen:               Yes. It wasn’t one of the primary outcomes. So, it’s kind of buried in the paper.  But, yeah, you’re right.  That’s something super interesting to look into.

Dr. Weitz:            Cool.  So, what about the effect of Akkermansia on the gut and gut conditions, say like, IBS?

Colleen:               Yeah.  Just to be clear, we haven’t done a clinical trial in IBS.  But what we found that’s interesting is that our customers who are taking the product, we have nine out of 10 people saying they’re getting lowered blood sugar spikes and lowered A1Cs.  But we also have nine out of 10 people saying they have improved GI symptoms.  And so, this isn’t something that we studied in our clinical trial.  But it’s something that we’re definitely hearing from people.  And, certainly, as you’re saying, there’s a lot of research to imply that Akkermansia might be doing that.  And so, you’re stepping into what we’re looking at next which is really IBS and things like that.

Dr. Weitz:            You’d have to pivot really quickly. But it would be interesting to see patients with long COVID symptoms that are GI related if this could be beneficial for them, because there’s a huge amount of inflammation in the gut that happens with some patients who get COVID.

Colleen:               Yeah. And I think understanding the role of Akkermansia in these inflammatory responses and these inflammatory miss-responses, I think, is going to be a really important part of discovery.

Dr. Weitz:            So, how does Akkermansia reduce inflammation in the gut?

Colleen:               Well, the idea is again that you have a mucin layer inside of your gut. And the thickness of that layer is relevant. And so, I think about it like a fence in your backyard. So, I have a wooden fence in my backyard. When we first moved in, oh, it’s beautiful. The planks were perfectly polished. What was supposed to be inside was inside. What’s supposed to be outside was outside. But what happens to these over time where you get sun and snow and just weather in years and times is that those-

Dr. Weitz:            And termites.

Colleen:               And termites, exactly. Those planks can start to deteriorate. And, sometimes, you might lose a plank or two. And then, all of a sudden now, all the outside things can come in. And the inside things are leaking out. And so, your gut lining is just like that fence. And the mucin layer is really like your planks that you’re trying to keep together to keep that solid gut lining. And so, when you lose that, the reason the inflammatory process gets stimulated is because now small molecules are not where they’re supposed to be, and your body responds to that. And that’s really kind of the underlying issue with not having the right gut lining.

Dr. Weitz:            Now, I was looking at some of the research. I was reading one of the studies. And there seemed to be some evidence that Akkermansia plays some role in the way that metformin works, that metformin is for most of you listening if you’re not familiar, is the most commonly prescribed drug for patients with type-2 diabetes. And yet, there’s been some controversy over exactly the mechanism by which it works.  And so, some of the evidence seems to indicate it has to do with its effect on the microbiome, and that Akkermansia may play some positive role in the way that metformin works. Can you talk about that?

Colleen:               Yeah. I think your use of the word controversial is spot on because basically there have been studies showing that I do believe that metformin is impacting the microbiome. I think that seems quite consistent. The way in which it’s impacting the microbiome is unclear. And you have publication saying it increases certain strains. And then, you’ll have publications saying it decreases the same strains. And so, I think it’s not clear. And, to be honest, there’s probably a little bit of a personalized component to this of what metformin is doing based on your microbiome and your ecosystem there. And so, I don’t think there’s any clarity on exactly what metformin is doing to the microbiome and what benefits, therefore, it could be conferring.

Dr. Weitz:            So, how can your product be used for type-2 diabetics? Is it better for patients with pre-diabetes with the beginning stages of type-2 diabetes? Does it matter. And then, how should it be administered and in what dosage?

Colleen:               So, the trial that we did was really in people with type-2 diabetes. And most of them were on metformin. And so, the efficacy is on top of metformin. It’s a bottle of pills that you store in your refrigerator. And you take two pills a day. And that really gets your microbes. And to your point earlier, it’s sort of an ongoing thing unless you’re one of those very special people that’s able to colonize it. You really do keep taking. And people can take microbiome tests to know whether things are colonizing or not.  And we really encourage people to do that. We give people free A1C testing because we want you to see the results. We’re not here to scam anybody. Actually, we have a money-back guarantee that if the product doesn’t work for you, we’ll give you your money back. We really believe in it. And we really want to help people.

So, the work is really done into type-2 diabetes. But as you know, metabolic syndrome is a sort of ongoing continuum from type-2 diabetes to pre-diabetes to obesity. And underlying all of that is the continued inability to metabolize glucose. And GLP-1 has been shown to be effective across those different states. And so, even though we didn’t do our trial and anybody other than people with type-2 diabetes, we certainly have a lot of customers who have pre-diabetes or obesity and are really using the product and seeing benefit. And so, that’s been that’s one of the benefits, I think, of the consumer route as opposed to the drug route.

Dr. Weitz:            And when should they take the two capsules? Should they split them up? Is it better to take it with the meal, without a meal, in the morning, in the evening?

Colleen:               Well, this is a kind of a big unknown. So, I’ll start with that. We don’t exactly know. But here’s what we do know, is that in trial work, we have people take one in the morning and one in the evening because we don’t know what people eat during the day. And we don’t really know what their schedules are like. And so, we were just trying to hedge to say, “If you eat breakfast that has fiber in it, this is great. If you eat a dinner that has fiber in it, we’ll catch you on either end.”  But the truth is actually we have a lot of customers including myself that can’t really remember to do something twice a day, we’re lucky if I remember something once a day. So, I take both my pills in the morning and call it a day. But the trial was really one in the morning and one in the evening to try to capture the effect of your diet on the microbiome.

Dr. Weitz:            And do you think it’s better with the meal or apart from the meal? It sounds like you’re saying it’s better with the meal.

Colleen:               Yeah. We’ve recommended people take it with a meal. The capsules are actually enteric coated so that they can get through the stomach acid and where they need to get to. But as you know, your stomach has a really low pH. And so, when you eat a meal, it does help to raise that pH. And so, the idea is that it will help those enteric-coated capsules not be dissolved in the stomach. So, although I’ll also admit this is terrible that I take my two in the morning with a cup of coffee. And I oftentimes skip breakfast. But what we do recommend people take it with a meal.

Dr. Weitz:            Well, you’re doing intermittent fasting.

Colleen:               Yes. Exactly. Exactly. I don’t want to mess up that part of my routine. So, you can’t take them on an empty stomach.

Dr. Weitz:            Right. Now, I did notice in your study that even though it lowered hemoglobin A1C that there was no change in fasting glucose. Why do you think that is? And did you also look at fasting insulin?

Colleen:               Yeah. That was a little bit of an anomaly. I think one of the things that’s been more interesting to us is actually the use of continuous glucose monitor technologies. It’s really hard with these fasting glucose numbers especially when you’re doing them in clinic because people don’t always fast before they come in and give you their fasting glucose numbers.  And so, wearing continuous glucose monitor enables people to kind of freely live their life the way that they want. And you can get that fasting glucose number before a meal is consumed which you can clearly see through a spike. We definitely have customers who have seen improvements in their continuous glucose monitor data and in their fasting glucose. So, we don’t really actually understand that phenomenon.

Dr. Weitz:            I think maybe in one of your future studies, you should consider measuring the level of butyrate that’s produced if that’s one of the mechanisms.

Colleen:               Oh, now, you’re really getting an all my secret bag of tricks. So, we just presented at the ADA conference data showing that in fact people who were on formulation had increased butyrate levels in their plasma. And so, that is data that has not been published yet.

Dr. Weitz:            All right. So, do you plan to come out with a separate Akkermansia outside of this formula? By the way, the other ingredients, the other probiotics in your formula, talk about those for a few minutes.

Colleen:               Sure. So, the other strains include anaerobacterium [inaudible 00:31:13], Clostridium butyricum, Bifidobacterium infantis and Clostridium beijerinckii. Now, you’re testing my ability to pronounce all of these strains. And so, again, these are really in that pathway of metabolizing fiber into butyrate. These are strains which we found to be kind of in vitro to have a lot of activity on that butyrate production.

And I would say that we’re not quite done yet because the product doesn’t work for everybody. And I think there’s an underlying belief that not all these strains are going to be able to have their functions in your microbiome versus my microbiome. And so, I think that the key thing is these functions and that there’s potentially new strains that we can develop that will help people that have different microbiome issues. And so, all of those strains really do function together along with we have inulin in the pill too. They really all function together to demonstrate efficacy.

Dr. Weitz:            What do we know about Akkermansia as a percentage of the microbiome in younger people versus older people, women versus men, people live in the United States as opposed to Africa or Europe or Asia? Do we know anything about that?

Colleen:               Yeah. I think that there’s still a lot of data being collected. So, it’s still emerging and trying to understand what are the trends with Akkermansia is certainly really an exciting place where there’s been a lot of discovery. So, I think one of the biggest trends that we’ve seen with Akkermansia is that healthy people tend to have a ton of it. It’s one of the most prevalent strains in the stool of people that are healthy.  But as you go down the line and you look at these different disease states from type-2 diabetes to Crohn’s disease to IBS to even autism and some neurological diseases, you see that there’s a depletion of Akkermansia. And so, it doesn’t appear to isolate to men versus women. But there does appear to be an aging component to it. So, as we age, unfortunately, I think many of us remember a time where we could eat and drink whatever we wanted to. We didn’t have to worry about anything.  And part of what happens over aging is you lose some of these key microbes including Akkermansia. And so, the question is if you give them back to your longevity question, if you give them that, will you now have a better functioning engine inside your body.

Dr. Weitz:            Are there similar benefits to taking supplements of butyrate? Do you know?

Colleen:               Interestingly, the butyrate supplements have really strong pre-clinical evidence in them. But there’s been a real struggle to show that butyrate delivery in humans actually has the same impact. And the theory is that because butyrate is used by all of the colon cells and we were discussing this earlier, but your colon cells are the only cells in your body that use butyrate instead of glucose for their sugar, for their energy source.

And so, every colon cell wants butyrate. And so, I sort of think of it like if I were going to give you, Dr. Weitz, a million dollars, would you rather me bring it to your door in a suitcase and hand it to you or would you rather me call you and say, “I let it go all over 101, the freeway. And you can go pick it up there.” The problem with giving butyrate is that you’re just like releasing this on the 101. And every car is going to stop, and people are going to grab this money before it ever gets to your house.

And so, this is why the strains that colonize in the right location in the microbiome produce the butyrate right next to the receptor where it needs to bind to is far more effective than just delivering the butyrate molecule to your colon.

Dr. Weitz:            What about the other short-chain fatty acids like propionate?

Colleen:               Yeah. Propionate and acetate are two other short-chain fatty acids that also are quite abundant. And I think there’s good emerging evidence that they’re also important. And in our hypotheses around butyrate production and having the different enzymes or the different bacteria that perform these enzymatic functions, now, you’re seeing my biochemist kind of bias emerging here. They’re strains, not enzymes. We do actually also produce acetate and propionate because as you know they can be upstream of butyrate. And then, one more modification turns acetate into butyrate. And so, I think trying to understand the role of those other short-chain fatty acids is still emerging. But butyrate has the most, I think, evidence behind it.

Dr. Weitz:            Are you looking into producing… There’s another keystone species that’s anaerobic called fecal bacterium [inaudible 00:35:48] that’s also not available on the market. Are you looking into possibly producing that?

Colleen:               Well, I can’t tell you what’s in our freezer that we’re working on producing. It’s definitely a strain of interest to many people.

Dr. Weitz:            Right. Okay. Great. I think those are my questions that I had. Any other thoughts that you’d like to leave our listeners with?

Colleen:               I think I would just say that as people are out there trying to do the right thing for their bodies and trying to be more healthy and standing in front of these shells filled with probiotics and prebiotics and whatever other marketing gimmicks are being thrown our way and trying to figure out what works or doesn’t work, that it’s really important that they talk to their healthcare professionals.

So, people like you, anybody that they’re seeking advice from to sort of really approach the microbiome more as a science about what are the functions and what are the strains that make sense for me. What is the problem I’m trying to solve? And I think it’s really important that you and the rest of the healthcare professional community starts to become at the leading edge of being educated and being able to guide people on not just probiotics, but what probiotics and what functions are their patients really trying to solve for and being that guiding light because you’re the only ones who can understand the clinical trial data. You’re the only ones who kind of know the problems people are coming at you. And being able to connect those is really in your arena. So, I encourage people to really go talk to their HCPs.

Dr. Weitz:            Now, can practitioners and we have a fair amount of practitioners that list listen, can we get a professional account with your company and sell these to our patients or how do we get these to our patients?

Colleen:               Absolutely. And, actually, this is something we’ve just started with different physician groups and naturopath groups, people who really kind of do understand the microbiome and understand what these trains are doing. And we are absolutely thrilled to get to work with healthcare professionals. And so, anybody can contact us. You go to our website, pendulumlife.com. We can get discount codes specifically for you and your patients. And we have programming set up to also educate you as well as things that you can handle your patients on what to expect. And so, we’re really excited to get to work with healthcare professionals to bring this product to life.

Dr. Weitz:            So, can we buy this product at wholesale and store it in our office and sell it to our patients or not?

Colleen:               If you contact us, we will sell it to you wholesale, and any of your colleagues that’s excited about that. Yeah. I mean we’re an early stage startup company. So, we’re just starting to delve into this.

Dr. Weitz:            Okay. I see.

Colleen:               But we are selling it wholesale to a few partners. And I think that that’s a really big opportunity. I mean you’re seeing patients and you have the ability to really influence them on what they should be doing. So, we want to enable you. And so, the answer is yes. Just reach out to us.

Dr. Weitz:            Sounds good. So, we go to the website or can we call? What’s the best way for us to contact you?

Colleen:               Yeah. If you go to the website and just put something a note into the contact us, it’ll immediately get shunted to our marketing and BD teams that can help set that up immediately. And so, we’re very excited about that. And you had asked earlier if we had thought about selling an Akkermansia-only product. And so, I will tell you that we literally just launched this product a couple of days ago. And so, yeah, You should come work for us because you got all the ideas and the next things to do.  And so, if people are doing these microbiome tests and they’re finding that they’re low in Akkermansia and they just want Akkermansia, we now sell that. And so, we can also distribute that wholesale to physicians as well.

Dr. Weitz:            And so, the website, one more time, is what?

Colleen:               It’s pendulumlife.com.

Dr. Weitz:            Excellent. Thank you, Colleen.

Colleen:               Yup. Thank you so much. And one more thing is that all your listeners get a discount code Weitz 20 for them to try product. And that’ll apply to also the Akkermansia-only product.



Dr. Weitz:            Oh, that’s great. Thank you. Thank you. Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple podcast and give us a five-star ratings and review. That way, more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts.  And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition Clinic. So, if you’re interested, please call my office, 310-395-3111, and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you and see you next week.


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