Better Than Ozempic? 100% Natural Appetite Suppressor to Lose Weight Without Injections & Side-Effects

Nick Urban [00:00:07]:
Are you a high performer, obsessed with growth, and looking for an edge? Welcome to MINDBODY Peak Performance. Together, we’ll discover underground secrets to unlocking the full potential of your mind, body, and spirit. We’ll learn from some of the world’s leading minds, from ancient wisdom to cutting edge tools and everything in between. This is your host, Nick Urban. Enjoy the episode. Is there a safer natural alternative to the weight loss peptides like Ozempic and semaglutide, retrutide, and tirzepatide? Although these GLP one weight loss drugs are taking the world by storm because they work, is it possible that they come with downsides? And what if there’s an alternative that few people are discussing? Well, scientists, like the one we have on today’s podcast, say that there are. Join me and doctor Edward Walker from Kalocurb as we discuss a substance called amarasate, which is a powerful plant extract that naturally stimulates GLP 1, but significantly. It helps manage cravings and balances your metabolism without the risk of pharmaceuticals.

Nick Urban [00:01:29]:
But is it too good to be true? Stick around as we break down the science, the benefits, how you can start using it, and whether or not this more biocompatible substance really works. In this episode, we discuss the impact and side effects of things that increase GLP one, what scientists look for when they’re evaluating compounds that naturally increase GLP 1 because there’s a difference between a statistically significant increase and a clinically or outcome significant increase. We explore the benefits and side effects of amarasate and some different synergistic stacks you can use to increase GLP one levels and blunt cravings, increase satiety, and do everything else, potentially lose weight, and do everything else that people are turning to the GLP one drugs for. Doctor Ed Walker is a scientist and lecturer specializing in plant based nutraceuticals for health and wellness. He earned his PhD from the University of Auckland researching the antioxidant effects of berry fruits and now works at the New Zealand Institute For Plant and Food Research focusing on clinical validation of nutraceutical products. Most relevantly, his 13 year research on plant based appetite suppressants led to the development of amarosate, a New Zealand hops based suppressant with a mode of action similar to GLP 1 anti obesity drugs. Alright. To be clear, I think that the GLP 1 drugs that are so popular have their time and place, and they really can change lives when used by the right population.

Nick Urban [00:03:18]:
But for healthy populations, I think semaglutide and the newer analogs like Tirzepatide and Retrutide are overused, and the healthy folks have better options. If you want to explore the potential downsides that are less discussed about the powerful GLP one peptides, I will put a link to an article I wrote in the description of this episode. I also wrote an article listing over 45 different natural alternatives you can use instead of those peptides, one of which is caloCurb. I actually have it right here in front of me, but I actually didn’t notice much, if any, effect from one capsule. Yet when I increased my dose, all of a sudden, that changed. So we get into the nitty gritty of dosing and, bio individuality of it later in the show. After we recorded, I also just came across this study. Haven’t even read the whole thing yet, but it is titled effect of glucagon like peptide 1, GLP 1, receptor agonists and coagulists on body composition, systematic review, and network meta analysis.

Nick Urban [00:04:26]:
Although I haven’t read it yet and I’m looking forward to digging into it, the conclusions were that Tirzepatide and semaglutide, 2 of the most popular GLP 1 drugs, have a stronger weight loss effect but also cause a significantly increased loss of lean body mass. Now this is in comparison to the other GLP one drugs and well above what happens with standard weight loss. So, yes, these very powerful substances have their time and place. But before going to the big guns, they work incredibly different to the way natural GLP one works in the body. Consider the more natural approach. If you wanna learn more about this, you can find everything we discuss in the show notes for this episode, which will be at mind body peak dot com slash the number 193. And if you want more details on weight loss, the GLP ones, peptides, or any other topic, check out the free Mindbody Peak Performance AI chat. Go to mindbodypeak.com/ai and get all of your questions answered.

Nick Urban [00:05:36]:
It’s like having me and my guests available to you at all times. Alright. Ladies and gentlemen, sit back, relax, and enjoy this episode with Ed. Ed, welcome to the podcast.

Dr. Edward Walker [00:05:47]:
Hi. Thanks for having me.

Nick Urban [00:05:48]:
This one has been a long time in the making. We’re going to be discussing your discussing your star ingredient that you’ve been researching for nearly I think it’s a decade and a half at this point. Tell me how you got involved with the substance that is known as amarasate.

Dr. Edward Walker [00:06:05]:
Right. Yeah. So it all started back in, 2009. And what we had was, the New Zealand government put out a, basically, a call for research programs to develop a plant based treatment for obesity and appetite management. And so I was employed basically by a government institute to do that research. And we really what basically happened was we came up with a series of ideas about targeting the gastrointestinal tract to suppress appetite. We put in a grant. It was a 6000000, $20,000,000 government research grant.

Dr. Edward Walker [00:06:45]:
And we got the funding and it sort of kicked off 2010 and went from there. So, so I started there. Immediately before that, I just finished a PhD in molecular medicine looking at the health effects of berry fruit. So I sort of had, I guess, a background in plants and health and then straight into this, this weight loss project.

Nick Urban [00:07:04]:
Awesome. And I think you were one of the early researchers of a now famous class of drugs called the GLP 1 Agonists, the semaglutides and Wegovis and all that stuff of the world. What made you fascinated about this class when you started researching natural substances that may activate the same or similar pathways?

Dr. Edward Walker [00:07:29]:
Yeah. Yeah. Absolutely. So we had an idea, right, that we could suppress the appetite using using hormones from the gastrointestinal tract. So so every time you have a meal, right, your body will release a series of gut hormones that tell you you’re full and you’ve eaten. And they’re primarily CCK, PYY, GLP1. And they all have different sort of benefits and downsides to them. And CCK, for example, is a really amazing appetite suppressant.

Dr. Edward Walker [00:08:00]:
It kicks off really early, suppresses your appetite hugely, but it tends to have a rebound effect. It’s not very long lasting. So that’s not so much a really good drug target in isolation. When they did work on GLP-1, so GLP-1 was discovered sort of 1980s. What they found in mid mid nineties, they realized it was an appetite suppressant. What they found was when they did what they call infusion studies. So basically, they’ll get people to walk around with a bag of GLP-1 and they would infuse it into their blood over time. They found that they could hugely suppress appetite and it was long term.

Dr. Edward Walker [00:08:34]:
It would reduce their glucose levels as well, and it could even lead to weight loss. So there was a real, I guess, understanding from around the mid nineties that GLP-one was a really good target for weight management and weight loss. Now, the pharmaceutical side of things, what they said was they said basically, GLP 1 is not very stable. So in the body, what happens is you have a meal GLP 1 gets released, it gets released, gets released as soon as your meal is gone, goes back down again. And that that tells your body to eat again. So the pharmaceutical industry said, let’s stabilize it. Right? So let’s modify the GLP-one molecule and make it stable, make it last for a week rather than a few hours in the body. Now that’s great for a drug, but what it does is it takes a natural occurring hormone and changes it into something which is not following temporal profiles.

Dr. Edward Walker [00:09:27]:
It’s not going up and down with your body cycles. It’s not resetting at night. It’s just a constant high level, 24 hours a day, 7 days a week. And that’s not physiological. It causes your body to downregulate its natural hormones just just like, say, hormone replacement or steroid abuse would do. So, yeah, so there’s a series of downsides. So we really said, well, you know, pharmaceuticals doing that. That’s cool.

Dr. Edward Walker [00:09:50]:
Why don’t we look for a way just to get your body to produce more GLP-one and to release more GLP-one so that you can use your natural system, you can boost up your natural system rather than trying to just completely put something artificial version into it? And so that’s sort of, I guess, where we came in it from. And we we sort of thought about a few different ways of of trying to trigger GLP-one, and and and indeed these other appetite suppressing hormones. And we really came up with the idea that gastrointestinal bitterness was a really, I guess, potent way of triggering GLP one release, and that was sort of the the kickoff of the of the project for me.

Nick Urban [00:10:29]:
I wanna pause you there and go more into these substances that pharmaceutical companies have developed to potently increase GLP 1. Also, let’s back up a little bit. You mentioned the purpose of GLP 1. What are these peptides, the ones that I mentioned previously? Why have they become so popular?

Dr. Edward Walker [00:10:48]:
Do you mean the injectable peptides?

Nick Urban [00:10:50]:
Yeah. The injectable peptides and they’re now what was off label use is now probably their one of their main uses.

Dr. Edward Walker [00:10:57]:
So what GLP 1 does in the body, right, is it is a it is a signal to your body that you have consumed food and that you’ve likely to have glucose coming in and that you’re likely to not need to eat for a while. So it releases from your gut, right? Goes to your pancreas. It will stimulate insulin secretion to lower your glucose levels. It will go directly to your brain and it will trigger, suppress the appetite centers. It’ll also hit what’s called the vagus nerve, which is the nerve that runs from your gut to your brain and directly trigger that to suppress appetite. So what it is, is it’s a small peptide molecule, so small protein molecule. It’s around 30 or so peptides long, 3 to 37. So there’s different forms of it.

Dr. Edward Walker [00:11:39]:
But what it has on it is it has a, a cleavage site for an enzyme called DPP 4. Right? And what DPP 4 does is it cuts that GLP 1 into a non active form really quickly. So the half life in the body is 2 minutes. And what that means is that if you’re not actively releasing it And naturally, natural GLP-one. This is a natural one. Natural GLP-one, yep. So it lasts 2 minutes. So if you’re not producing it, it’s gone.

Dr. Edward Walker [00:12:04]:
And that’s really important for your body because it means that you can make yourself feel full after a meal, have a proper glucose response after a meal, but not have a constant stimulation of the system. So what the pharmaceutical industry did was they did a couple of different things. Firstly, they said, let’s stabilize it by binding it to albumin. So that’s like, you know, sort of some proteins in your blood. And if you bind it to albumin, it makes it harder for this enzyme to access it and cut it. And so that was liraglutide. So that was the first version of it, of the, I guess, you know, the commonly known GLP-one agonists or the the pharmaceutical versions. And so that increased the stability to half life to about a day, right, so about 24 hours around that.

Dr. Edward Walker [00:12:48]:
Then they may come up with semaglutides. And what semaglutide is is they actually actively modified the enzyme cleavage site. So they didn’t just bind it to the album to make it harder for the enzyme to access it. They modified it, modified the sites. The enzyme can’t really cut it very well. And that extended the half life to around a week. So you’ve gone from 2 minutes naturally to one day to one week for the sort of more recent semaglutide type drugs, the Wegovy. Yeah.

Nick Urban [00:13:18]:
And that right there is a huge difference. It might sound minor. I heard a doctor call the GLP one drugs like that one you just mentioned bioidentical to natural GLP one, except that it lasts a bit longer. And when you when something lasts 6000% longer, it’s not bio identical. It has totally different effects on the biology and all the different timings and rhythms that are naturally happening throughout every hour, day, even a week.

Dr. Edward Walker [00:13:46]:
Yeah. Yeah. Absolutely. I mean, you could you could say if someone comes along and says, well, you know, I’m an anabolic steroid user and it’s, you know, it’s exactly the same. You know, like, I can take TRIN, and it’s fine because it’s bio identical. I mean, everyone knows that’s ridiculous. And so that that comparison is is clearly not on not right. 1, then one that’s, you know, the the binding efficiency is much higher, so it’s stronger for starters and the temporal profile is completely different.

Dr. Edward Walker [00:14:11]:
Yeah. So so it’s absolutely, absolutely very, very different indeed. And I think that a lot of this was probably driven by marketing requirements because when you think about you’ve got an injectable drug, you’re asking yourself how frequently can we ask someone to inject a drug. So they could have and there were versions of of these, these pharmaceuticals or, you know, what, trial versions that were less stable, which might have had a stability of a number of hours or a number. But really, when you look at injectables once a week was sort of, I guess, the mind of well, my thought is this was the key. You know, someone will inject once a week, but they don’t really wanna do a lot more than that.

Nick Urban [00:14:51]:
What are some of the other effects this has in the body? You mentioned it also causes changes in the brain, which is why we’re also seeing it being used more for addictions. That’s one of the other hot use cases for it because I think it triggers what are called the POMC neurons.

Dr. Edward Walker [00:15:06]:
Yep. Yep.

Nick Urban [00:15:06]:
Breakdown of other effects. You mentioned that and the vagus nerve. And ironically, I’ve talked to a number of different users who, when they measure their vagus nerve via something called heart rate variability, they see dramatic reductions. And that’s not across the board, but for a lot of people, and I’ve seen research on this too, that they have impaired, resting heart rate and other proxies of recovery.

Dr. Edward Walker [00:15:28]:
Yeah. Yeah. So, I mean, the addiction is probably 2 fold the way it’s affecting that. And, yeah, there’s a POMC neurons and there’s also likely to be changes in some of the neurotransmitter levels that are that are linked to the addictive behavior, things like dopamine. And so certainly, there’s been indications of GLP-one being a target molecule for addiction, but also for things like behavioral disorders. So a long time ago, there were indications that GLP-one treatments by infusion. So this is the normal GLP-one, not the stabilized version, would cause a acute increase in anxiety and then a chronic decrease in anxiety. Right? So there was sort of like this, I guess, a U shaped response.

Dr. Edward Walker [00:16:13]:
And so the long term, there might be anti anxiety effects and long term, there’s likely to be anti addiction effects as well through those addiction pathways in the brain. And I think that’s one of the really strong, one of the reasons why it works so well, why these injectables anyway works so well is because they’re treating not just biological hunger triggers, but they’re also treating food addiction triggers. And that drives a lot of people because you can, if someone’s, if someone’s eating when they’re not hungry, then it’s really challenging to change their eating behavior. But if you manage to suppress that, then that’s really strong. Yeah. And for the vagus nerve, absolutely. So, changes in heart rate variation is something that you can measure. We were actually running a study right now that measures changes in heart rate variability.

Dr. Edward Walker [00:17:03]:
So we’re looking at giving and in one part this the Amarisade extract and we’re looking at changes in vagus nerve activation via a measure of heart rate, variability. And we’re also measuring neurotransmitter levels, peripheral measure of neurotransmitter. So looking if we can do the same kind of change with a natural product that you’re seeing with with pharmaceuticals. So, yeah, so it’s really exciting. And, yeah, so GLP 1’s amazing. Yeah. It really is.

Nick Urban [00:17:32]:
And there’s one other mechanism I wanna dig into with you because this is the one that when I saw, it gave me pause. I wrote an article, I wanna say, 3 years ago when I first started reading and research on these things. And the synthetic GLP ones that are modified to last way longer, they have an impact on insulin. And insulin in the longevity space is like public enemy number 1. Yet we also know this is stimulating insulin, and it’s doing so for a week. A 100 and 60 hours, I believe it is. Tell me about what this is doing. I actually have a paper up in front of me.

Nick Urban [00:18:04]:
It’s called Regulation of Adopacyte Formation by GLP 1 slash GLP 1R signaling. What happens when you signal GLP 1 and insulin like that for a 160 hours?

Dr. Edward Walker [00:18:19]:
Yeah. So it’s an interesting one. So, there’s there’s 2 aspects to GLP 1 insulin. And the the main one that people will talk about is the it’s an insulin stimulator. So you inject GLP-one and you stimulate insulin release. And that’s absolutely true and it’s really quite potent. There are some studies that also show that GLP-one is an insulin potentiator. What I mean by that is that it will increase the activity of the effectiveness of insulin release per unit of insulin.

Dr. Edward Walker [00:18:48]:
So if you have 10 units of insulin, the arbitrary number, it’s slightly better at removing blood glucose than it would otherwise be. And they do that based on some clamp experiments in rats. So they basically isolate part of the rats and they’ll put in a fixed volume of, glucose and then slim and add some GLP-one and see how quickly it’s removed. So there’s that aspect to it. But you’re absolutely right. There are questions around constant stimulation. And I think these likely feed into some of the reports of more rare side effects you may have with the GLP-one injectable. So if you think about your pancreas, your pancreas is used to getting GLP-one signal every time you have a meal for a few hours to release insulin.

Dr. Edward Walker [00:19:34]:
Now, if you take an injectable, it is getting that signal 24 hours a day, 7 days a week saying release insulin, release insulin, release insulin, release insulin. Right now, you do get reports of, pancreatitis, right, with the use of these. And they’re very rare, but they are, I guess I can’t comment on how related they are from a legal perspective. But from a scientific perspective, given that you’re stimulating the pancreas a lot, it’s possibly not unexpected that this might happen. You also have the same effect with delayed gastric emptying. So usually GLP-one will go to your gut or your stomach can tell it not to empty for a while. So usually that happens for a few hours. Now you’re getting it 7 days a week, 24 hours a day.

Dr. Edward Walker [00:20:22]:
And we do hear reports of, you know, gastroparesis type symptoms, really. We are occurring sometimes from injectables. And, again, you know, possibly not surprising this could occur if you’re getting a constant a constant signal. So, yeah, so so there’s absolutely there’s absolutely those. As far as things like adipocyte differentiation goes, yeah, I mean, absolutely. Yeah. So there’s certainly a potential for increasing adipocyte differentiation. You’re getting a lot of signals to your fat cells to basically say, hey, look, we’ve got nutrients to uptake.

Dr. Edward Walker [00:20:57]:
We need more of you to be there. So that’s not a surprising side effect. And I guess the concern comes in there for, and this is a concern I personally have is that if people are using injectables almost like a yo yo diet, right? So if they’re taking the GLP-one injectable, they’re losing the weight. Right. And then they’re going off it and they’re gaining the weight back. Have they have they just from using the injectable, sensitize their fat cells to be really responsive to uptaking nutrients? And if so, are they just going to make the yo yo dieting worse over time? So there’s absolutely, and you’re absolutely right. There are concerns around then around that, and we’ll know in the long term, I guess, what’s happening.

Nick Urban [00:21:44]:
So to summarize what you’re saying, is it possible that by using these, we’re actually making fat the fat cells in a way more aggressive towards uptaking things, towards growing more rapidly?

Dr. Edward Walker [00:21:55]:
Well, I mean, it’s absolutely it’s absolutely possible. Certainly, when you when you look at a cell and you want to you want to turn so if you if you go into what they call cell cultures, so you grow some some pre adipocyte in a lab and and and you want them to turn into a full adipocyte or a full set pet fat cell, you will use insulin to do that. Right? So if you’re stimulating your insulin levels, then, yeah, you know, that’s that’s entirely a possibility. Yeah.

Nick Urban [00:22:19]:
Yeah. And there’s a paper on this too called GLP 1 signaling in regulation of adipocyte fat cell differentiation and lipogenesis, which that’s a 2017 paper. So it’s been around for a little while, and I’m sure there’s more that I haven’t even seen yet.

Dr. Edward Walker [00:22:32]:
Yeah. Well, there’s, I mean, it’s an interesting, interesting comment you made there because it’s when you have a big pharmaceutical drug, there’s usually one paper that will show something, but then there’s not usually a lot of follow ups because it’s quite hard to get funding and the drug companies are not going to pay for it. So there’s also I mean, so the other so there’s that adipocyte differentiation issue, but there’s another one of down regulation of of your natural hormones. And, just like happens when you when you take when you take, say, exogenous hormones of some form. And you’d think there’d be a whole lot of papers on that, but there’s really just one. And it’s like, you know, and it came out about 2020 and it says, are you if you take liraglutide, your endogenous levels are suppressed within 3 days completely, pretty much. And you’re like, oh, well, that’s not surprising. But there’s no long term looking at how fast they rebound, whether you’ve got any changes in your, in your stem cells, in your gut.

Dr. Edward Walker [00:23:32]:
You know, these these these are all pieces of work I would do if I was developing a product. I’d be saying, okay. We’ve got no GLP 1 in the gut. Let’s just make sure that we’re not, we’re not changing our our gut stem cells so that they can’t produce GLP 1 in the future and that, you know, when we take someone off, it rebounds, but that data doesn’t exist yet.

Nick Urban [00:23:50]:
Yeah. Yeah. And these things can be life saving for people in certain circumstances. They can make dropping a £100 for someone who’s obese feasible, impossible, and it’s probably worse to walk around with an extra a 100, £150 on you than it is to use a peptide because we know very clearly that carrying around tons of extra body weight, especially if it’s a lot of visceral fat, is extremely unhealthy. And that’s one of, like, the big risk factors for all cause mortality. So there’s time and case for it, but I think there’s also a lot of other alternatives. Can you touch on the different generations? Because I know that there’s multiple different generations, and I think Retrotide is the new one that’s on the rise, and it’s not actually released yet, but it’s like a triple antagonist. Can you break down what what the different ones are? And

Dr. Edward Walker [00:24:38]:
Right. Yep. Yep. So initially, this was the GLP 1 based agonist. So they’re all based on, essentially just GLP-one. And that was liraglutide and then semaglutide, which has been more stabilized. They’ve got trizepatide. And what that is is that’s a GLP-one and it’s another gut hormone called GIP bound to it.

Dr. Edward Walker [00:25:00]:
So it’s basically a dual agonist. And what GIP does is kind of pretty similar to what GLP-one does to be fair. It also has insulin stimulating effects and it also has appetite suppressing effects. And I think that when you look at the combination of the 2, so if you look at the data on, say, efficacy, the 2 agonists, the dual agonists is more efficacious. But I really think that it’s more efficacious for a given side effect profile. So what you really see is you see that adding the extra agonist means that you can keep the side effects at a still quite a high level, but an acceptable level for more weight loss. And if you just gave more of a GLP-one, you’d probably, you know, or semaglutide, which is a single agonist, you’d probably be able to generate that same weight loss. You’ll just end up with more side effects.

Dr. Edward Walker [00:25:53]:
The reason for that is probably because when you look at, when you look at injectable, when they did studies with the endogenous hormones and they injected them, they got a profile of activity. So from, like, no effect to appetite suppression to GI side effects. And so if you imagine you’ve got one hormone, the higher you push it, you get appetite suppression, you get side effects. If you’ve got 2, you can have less of an effect on both of them. So it’s a bit more of a gentle way to do it. So then there’s this triagonist coming out now. I’ll see if I can remember. I think it’s an amylin.

Dr. Edward Walker [00:26:29]:
So there’s a few different ones, but then there’s GLP, GIP, and then I believe they’re adding amylin to 1, and there’s another one with, I believe, glucagon added to it as well. And so glucagon is, another GLP one related, peptide, which is, released from the, alpha cells of the pancreas. So it’s a pancreatic hormone. And again, it has, you know, sort of similar effects. So they’re really just they’re really just trying to, well, in some we have similar effects, but it’s almost like glucagon is almost like a, a balanced insulin as well. So in some ways that they may be adding this to try to counteract the overstimulation of insulin that they may be seeing or the overstimulation of insulinogenic effects. Right. And so we’re likely to see a again, an increase in efficacy and a slight decrease in side effects occurring when they introduce those those triagonists.

Nick Urban [00:27:24]:
Yeah. When I saw that, when I saw them adding glucagon activity, I thought that was interesting because it reminds me kind of like getting in a car and hitting the gas and the brakes at the same time because glucagon brings up blood sugar. It does the opposite of insulin.

Dr. Edward Walker [00:27:36]:
Yeah. Yeah. Absolutely. Yeah. And so that would be that would be what I I would think they were trying to do is trying to acknowledge that there’s maybe too much for if their target is weight loss, they’re probably getting too much insulinogenic activity, and they’re trying to basically pull it back a bit with the addition of the glucagon. Yeah.

Nick Urban [00:27:54]:
That’s interesting. Do you know have you seen any research on what other hormones these might affect? I’m wondering now if there’s gonna be an effect on cortisol or anything else that you wouldn’t necessarily wanna stimulate, especially not long term.

Dr. Edward Walker [00:28:06]:
Goodness. Yeah. So I can’t I can’t think of anything off the top of my head. I mean, it’s it’s pretty likely that those those will go up. I think that there’s not enough research to really show what the long term effects of these these hormones are. What I’d say is that, I mean, I would expect you to have probably a stimulation of cortisol, but but I can’t say I’ve seen a paper. I’d also guess be somewhat concerned, that you’re going to cause, I guess, a systemic suppression of some of your of your gut hormones all the way down and a downregulation of, not just the ones you’re targeting. So so, for example, when they gave on the one study they did looking at downregulation, they gave a GLP-one agonist and they saw complete down regulation of all the basically glucagon related genes in the gut.

Dr. Edward Walker [00:29:00]:
So so there’s, there’s sort of 2 pathways. Glucagon gets all the glucagon related genes get processed, 2 ones in the pancreas, ones in the gut. And so they saw GLP-one go down. They also saw GLP-two go down, which is, you know, they’re not injecting GLP-two, but it’s being downregulated anyway. So I would not be surprised if, as we expand the number of agonists that we put in, we’re seeing a more systemic down regulation of a wide variety of endogenous hormones. And there’s, I guess, a question mark over what the long term effects are gonna be.

Nick Urban [00:29:34]:
Alright. I’m with you on that. I wanna pivot now to amarsate, your ingredient, because when I came across this, I was immediately excited. It’s a needed substance in the world. I love it because of the more biomimetic half life and the dosing curve aligns much more closely with what you could naturally get. It’s a little it’s still a little more than you can get from a meal, and we’ll talk about that. But it also you’re not gonna be stimulating insulin late at night at 3 in the morning, 5 in the morning, 6 in the morning when you’re supposed to be sleeping. What sets Amarsate apart from the other powerful GLP one activators?

Dr. Edward Walker [00:30:13]:
Yeah. Yeah. So I mean, to go back to the, I guess, the start of the story, we we were looking for a GLP 1 booster and, we did a, we did this project called Foods for Appetite Control with the New Zealand government. So I’m a New Zealand government employee. I don’t I don’t work for the company that sells any products. And and what we found out was we found that, gastrointestinal bitterness was a good, I guess, target for stimulating GLP one release. So we we really wanted to boost up GLP one and we wanted to find a way to do it really potently. And so we did a pharmaceutical type approach.

Dr. Edward Walker [00:30:48]:
We screened a whole lot of extracts. We found, we found a hop extract that we named. We tested it in cells. We tested some people’s GLP-one release. Now, one of the things I guess that’s quite important when you look at, like nutraceutical GLP-one activators, what they call, is that, there is a, it’s really easy to get a cell in the lab to release GLP 1. Right? So if I grow what you call, enter endocrine l cell, which is the the human cell which releases GLP 1, What it is, it’s like a circle. It’s got these little vesicles in it. And if you put on a trigger like an RSAT, those vesicles will go and they will release into the gross media around the cell.

Dr. Edward Walker [00:31:35]:
Now, the other thing you can do is you can sprinkle some dust on that cell and it will die. They’re super fragile. When it dies, it will release all that GLP-one into the media. So, you know, you can you can publish a paper and if it’s not well done, you can show anything releases GLP-one. So you have to be very careful with the science. So if you see GLP-one release in a cell system, like so in a cell assay system, then that’s not really any proof to me that it’s going to work in a person like it’s preclinical, it’s like that’ll be interesting that if you’ve done it correctly go forward and do a clinical trial. So lots of the GLP-1 activators out there will have that sort of evidence, right? Where they’ve just done it in a cell and it may or may not be a real effect depending on how well they’ve done the science. What a marasade has, which is different, is we have fully double blind controlled placebo trial that shows potent GLP-one release and not just a small amount, not like you’ve given in, say, green tea extract and you’ve shown a 20% increase in GLP 1 levels, what we’re seeing is basically a doubling of your response to a meal.

Dr. Edward Walker [00:32:53]:
So usually when you have a meal, GLP 1 will go up by around 3 fold, and that’s exactly what we show in our study. But when you take a marasade an hour before that meal, it goes up by about 6 fold. Now, that difference is really important. And the reason it’s important, because if you look at the amount of GLP-one you need in your body to have an additional biological effect by itself, it’s around 4, 4 plus fold over baseline. So we’re in that bioactive range for GLP-one. We’re also in that bioactive range for some of the other gut hormones such as CCK, which suppresses appetite. And most of the time when you look at a study, it will not have anywhere close to that sort of change. So it’ll have this really small stimulation of GLP 1, and it’s just not enough to have a meaningful effect on people.

Nick Urban [00:33:41]:
Yeah. And I don’t think you know this, but I did some research on it. I did a roundup of all the different substances and foods I found that can stimulate GLP, GLP 1, and there’s, like, 45 of them that I came across that had, like, some level of improvements. But what you’re saying right now is really important. It’s not that it had a 5% or 10% or even 30% improvements in GLP one release because that’s not enough to actually cause a meaningful, like, clinical outcome. What you need is you need to have a massive four x spike over baseline to actually change behaviors in a way that, like, people are seeking when they’re using GLP one products.

Dr. Edward Walker [00:34:17]:
Yeah. Yeah. Absolutely. And and that that sort of it was really interesting when they and, I guess this is the benefit of having lots of history of research of GLP 1 is that we’re you know, you’re able to figure out the exact amount you need because they did the studies where they got a bag of GLP 1 and they infused it into people and they measured and they said, is it having an effect? Yes or no? And if they weren’t going up to 4 fold, then they didn’t do it. Yeah. So it’s, and that work was actually done by professor Sally Poppert or the the latest review article that sort of summarized it was. And she’s someone that I’ve worked with in the past, and she was actually involved in the in the development of AmaraSate as well.

Nick Urban [00:34:54]:
Yeah. Amazing. Tell me more about the actual use of AmaraSate because I’ve actually used one of the products called Callocurb. That’s an implementation of amarasite that can contains amarasite in it. I didn’t notice any major changes when I used I consumed one capsule about I think it was 60 to 90 minutes before a meal, but then I went up to 2 capsules and boom. It hit me. My appetite was very low. I could barely get through my my steak breakfast.

Dr. Edward Walker [00:35:21]:
Yeah. So it’s it’s an interesting one. So you what you what you’re saying is is not uncommon. And so we target the gastrointestinal tract. Right? So so what the way a marasite works is it goes past the stomach into the small intestine and it releases. And that’s where the the cells are, the l cells that will release the GLP-one. That’s why you need to have a half an hour, sorry, 60 minutes, 90 minutes before a meal because you want to get it through to that part of the gut. Now the benefit of targeting the gut is that there’s a safety profile so we don’t have to absorb it into the blood.

Dr. Edward Walker [00:35:56]:
So we don’t have to worry about things like liver and kidney toxicity. You have to worry so much about drug interactions. So there’s all these good safety profiles. The downside of targeting the gut is that the gut is much more variable between people than the blood volume is. So you imagine if you have someone and you’re absorbing a compound into the blood, people’s blood volumes are roughly the same. Right. So maybe a little bit high or low, but they’re roughly the same. So it’s quite easy to dose.

Dr. Edward Walker [00:36:24]:
With this, people’s guts are quite very different. And so dosing is a lot harder. And so what we find is that we find that the best way to approach it is to start low and to build it up because we just we just don’t know. There’s no good marker of when someone’s going to hit their sensitivity threshold. And that’s a little bit to do with, 1, how many basically taste receptors you have in your gut, but also how good your stomach is at emptying, how long your small intestine is, they’re all very variable things. Yeah. So, so what we do is we start off with 1 a day for a couple of days and we dose up to 2 a day. And then so some through, so 2 at a time.

Dr. Edward Walker [00:37:04]:
And then for some people, you may need to go to 3 at a time. Yeah. So it just it just depends a little bit. We get the odd person. So we’re just running a clinical trial right now, a 150 people. And we’ve found that in the in 2 people have been sensitive to the treatment so that we’ve had to give them a special half dose. So we’re looking at around, you know, like sort of, and they’ve, they finally got up to a full capsule, but, you know, they’re they’re sort of a little bit more sensitive. So there’s that sensitivity profile, and it’s just a it’s just a effect of how we’re targeting the gut and that variation.

Dr. Edward Walker [00:37:38]:
Yeah.

Nick Urban [00:37:38]:
Gotcha. So do people become less sensitive to a marcyte over time? Like, do you build up tolerance to it?

Dr. Edward Walker [00:37:46]:
Right. So we don’t see any evidence of that. What we know from, I guess, clinical research looking at how this mode of action works, so, so the the targeting bitterness to the gut and stimulating GLP-one. So what we know from clinical research is, one, people don’t become resistant to GLP-one at a physiological level anyway. So you don’t if you’re getting a stimulation and a reset, there’s no indications that GLP 1 becomes less effective. So we’re not worried about that side of things. If we talk about the bitter taste receptors, there’s not a lot of work done in the gut. But what we have what we have seen is that there is a if you trigger the taste receptors and cells anyway, they up regulate them rather than down regulate them.

Dr. Edward Walker [00:38:35]:
So if anything, there will be an expectation that sensitivity may increase over time rather than decrease. But you know, we’re not we’re not likely to see a decrease. Yep.

Nick Urban [00:38:49]:
So if sensitivity increases over time, how does the people you mentioned work their way up to 1 capsule when they work their way down from 1 capsule to half a capsule?

Dr. Edward Walker [00:39:00]:
Yeah. Yeah. So so I think there’s there’s 2 aspects. So if we’re talking about long term adaption, right, so so, you know, upregulation of of GLP 1, I guess, response, then that that’s a possibility. It’s only shown in cells, so we’re not we’re not talking about clinical trials here. We’re just talking about a cell. If we’re talking about the side effects that people get used to, the side effects tend to be a slightly different mode of action. Right? So you’ll get a few things like a direct delay in gastric emptying.

Dr. Edward Walker [00:39:32]:
So, if you get some leakage of the amylocyte from the small intestine up to the stomach, then the stomach will shut off. It’s business in the stomach will cause it to not empty. So that can cause bloating effects. If you get the MRSA slightly further down, you get a sensitization. You basically get an influx of water into the upper large intestine that can cause a flushing effect. And both of those appear to be and they’re not sort of a GLP-one mediated effect. They’re a secondary side effect, like from bitterness in different areas. And so those appear to people get used to them over time, whereas we’re hopeful that GLP one effect is not not diminished.

Dr. Edward Walker [00:40:17]:
Yeah.

Nick Urban [00:40:17]:
Yeah. And is that also why I couldn’t just break up one of the capsules in my mouth?

Dr. Edward Walker [00:40:22]:
Well, you can break it if you want. I mean, so if you if you put it directly into the stomach, what you’ll find is that, it will be one less effective, so you probably have to take more, and you’re more likely to have side effects as well. So this this side the the particularly sort of a bloating, and what it will do is it will, make your your stomach pump a bunch of acid into it and try to get rid of that bitterness, and so you can get bloating and and yes. So so it can still work if you take enough of it.

Nick Urban [00:40:51]:
That’s when you take it normally. If you break it open and put in your mouth, then it’s gonna do that? Or if you take it normally and is it breakdown in your stomach? Where does it breakdown in your stomach? No.

Dr. Edward Walker [00:40:59]:
No. It goes down to the small intestine. So what happens is occasionally, you people will get some reflux into the stomach and that’s when they tend to get that that sort of bloating stomach effect. Right. As it opens directly in the small intestine, then you shouldn’t get that. If you were to break it open and swallow it, you would get a stomach effect, which tends to be that bloating. You’d also have a horrifically horrible taste in your mouth. It is quite terrible.

Dr. Edward Walker [00:41:25]:
So we get, it’s quite an interesting story. So we get quite a, prolonged GLP-one response. So when we first did the work, we thought we’d get, like, a boost. You know, like, imagine this is a normal level. It’ll go up a bit, and then it will go back down normally. What we get is we get a sort of a doubling of response, but then an extension as well. So it’s lasting longer. And we think that’s because the business in the in the product, which is triggering the GLP-one release in the gut, is very, very persistent.

Dr. Edward Walker [00:41:55]:
So if you break it open on your tongue, what you get is you get the slow buildup of bitterness, and then it just will not go away. And you can’t wash it away. You can’t get rid of it. It just sits there for hours. Yeah. Yeah. And so I don’t recommend you do that. I mean, you’re welcome to.

Dr. Edward Walker [00:42:11]:
It’s not gonna cause you a problem. But, but you can’t you can’t wash it away with water. You can’t wash it away with alcohol. It’s, it’s, it’s really challenging.

Nick Urban [00:42:20]:
When you say bitter, I’m assuming you’re talking about more than, say, a grapefruit, more than berberine powder. It’s probably extreme.

Dr. Edward Walker [00:42:29]:
Yeah. So we did in the very first study, we did a, a test. We actually did an oral test before we enrolled people in the in the study. And because because people have, I guess, what you call, have you ever heard of a, super taster, like a bit of super taster? Yeah. So that’s what that is is there’s a taste receptor, one of the bitter taste receptors. It’s called Tas 2 r 38, but there’s, a few different genetic differences between people, and it causes some people to taste it and some people not to. And so we were we were concerned, I guess, that our our, you know, hop extract might be tasted by some people and not by others. So we got everyone enrolling in the study to make sure they could orally taste it, which meant if they could orally taste it, they got to taste it too.

Dr. Edward Walker [00:43:12]:
And we got them to fill in a form that said, how bitter do you think this is? And it was from not bitter at all to the most bitter thing I’ve ever tasted. And pretty much everyone was right at the top there. One person came back and contacted me the next day, and he said, I can still taste it on my tongue.

Nick Urban [00:43:30]:
Wow. Okay.

Dr. Edward Walker [00:43:31]:
Yeah. Yeah. So

Nick Urban [00:43:33]:
I will not be breaking it open and putting it on my tongue then.

Dr. Edward Walker [00:43:36]:
Yeah. Yeah.

Nick Urban [00:43:37]:
So the actual extract looks like, I wanna say, honey. It has, like, that color, and then it has that consistency. It’s not like a it’s not liquid. It’s not a powder. And, also, does the capsule have, like, an like, a liposomal or some kind of coating on it? How does it pass through the stomach without breaking down there?

Dr. Edward Walker [00:43:56]:
Right. So it’s a it’s a it’s a modified, cellulose capsule. So it’s technically a delayed release capsule. So it’s not a true enteric coated capsule. So you can get capsules that are resistant to stomach acid completely, but they tend to have some quite nasty chemicals in them. And so they’re not really, you know, you don’t really want to use them. So we have a modified cellulose, which is delayed release, which is pretty good at releasing in the small intestine. It’s not perfect, but it’s pretty good.

Dr. Edward Walker [00:44:26]:
When you look at the raw extract, what you find is that it’s quite waxy. So it’s almost like a wax in its raw state. And so when we did the before we did the clinical research, we did a series of, what we call an in vitro digestion model. So basically, we got a, we got sort of shakers and, I guess, enzyme solutions that mimic different parts of the gut, and we put the extract into those to see what would happen. And what we found was that if you if you lift it, in its raw form as a wax, it would just sit there and it wouldn’t disperse at all in the gut. So it has a, you know, like a formulation that’s been done to it that just allows a little bit of, so that’s why it’s a little bit runny, but not really. It’s still quite thick. So what what we’ve designed to do is to disperse in the gut a little bit enough so it can interact with the outside of your you see your gut lining, stimulate the release of those hormones, but progress through is quite a, I guess, what you call a bulbous mass.

Dr. Edward Walker [00:45:24]:
You can imagine it’s going down the gut as a bulbous mass triggering all of the hormones as it goes. If you were to leave it purely as that sort of wax, it just won’t disperse and won’t interact. And if you dilute it out too much, then then that efficacy becomes reduced, I guess. So as it’s going down the gut, it’s getting more dilute and fluid anyway. If you started off more dilute, then then it dies off more. And certainly in the clinical trials, when we’ve given a stomach targeted one, which would cause it to be more dilute and when it gets to the small intestine, the efficacy is not as long lasting. So it sort of dies off. So, yeah, So it’s quite, I guess, it’s, you know, it’s quite a careful formulation from that point of

Nick Urban [00:46:04]:
view. Clearly, a lot went into making sure that it’s delivered perfectly. Speaking of, since it’s so insanely bitter, will that interact with, like, the what should be pristine environment of the small intestine? Like, will it impact with any of the microbes that may or may not be there?

Dr. Edward Walker [00:46:18]:
Yeah. So, I mean, we you you shouldn’t really have a lot of, a lot of microbes in the small intestine. So what we what we know from so if you so the small intestine is probably pretty good. The more of the question becomes large intestine where you’ve got your your bacteria going. So we don’t have a lot of information on that. What we do know from animal studies is that if you give hop compounds in the, to, being done in rabbits, we didn’t do the studies. I’m not a big fan of animal studies, but previous people have done them and they’ve given these compounds to rabbits. What they’ve seen is they’ve seen that they are metabolized primarily in the colon and none of them come through in the feces.

Dr. Edward Walker [00:47:05]:
So there’s certainly no persistence in the gut. We don’t see any overt effects on intestinal health as far as we can tell. What I will say is we are likely to be triggering GLP2 release, or in fact, we almost certainly are. And GLP2 is a gut health hormone as well. So there’s there’s certainly some indications that we’re boosting up some of the gut health hormones, and they would hopefully offset any negative effects you might see in your colon.

Nick Urban [00:47:34]:
Nice. Yeah. There’s not much talk about GLP 2 yet, but perhaps there will there will be in handful of years, hopefully, not decades.

Dr. Edward Walker [00:47:42]:
Yeah. Well, again, and I think that’s one of the, one of the strengths of a product like this is that when you look at your your endocrine cells and causing this natural GLP 1 release because those cells and those little same secretory vesicles also have GLP-one, GLP-two. You’re secreting GLP-two. I mean, at some stage, I meant to be measuring some of our frozen blood samples to see it. But it’s sort of one of those things where you’re like, well, it’s gonna be there, so why am I why am I spending my time measuring it? So so we will we probably do that. But, again, for the injectables, because you’re suppressing that one paper says you suppressed GLP 1, but you also suppressed GLP 2 as well. And so that’s a negative on the gut health side for them, a potential negative where it’s potentially a positive for us.

Nick Urban [00:48:24]:
Would a MarsAT have any impact on the brain? Yes.

Dr. Edward Walker [00:48:28]:
I mean, again, if we’re triggering GLP1, then there’s likely to be effects. You’ll likely have possible effects on things like dopamine, serotonin levels, indeed a possibility, addictive behavior. There’s also likely to be changes in vagus nerve activation and heart rate variability. And we’re currently doing studies where we’re looking at that. I think that ultimately in the future, it would be really it would be really nice to do a big measurement on sort of addictive behavior with a product like this to say, can we, you know, can we do things like stop alcoholics from drinking or smoking? And we and we get, we get a lot of anecdotal evidence about, people reducing their urge to drink. And in this, I mean, in this study we’re currently running, so we’ve got a big weight loss study running. We’ve had that exact same comment from people who say, oh, you know, I was drinking 3 beers a day and suddenly I’m not, you know, I just don’t have the urge to drink the beer. So, certainly, in a subset of the population, we’re observing, you know, I guess, what you’d call brain effects linked to addictive behavior.

Nick Urban [00:49:31]:
Gotcha. And so if this has an impact on the vagus nerve, it seems like it would probably have a similar effect to the other GLP ones, and it might increase resting heart rate and lower heart rate variability. But because this has a shorter half life and it’s not gonna be a 160 hours, is it feasible that if you took this in the morning, those metrics could start to return to normal by the time you’re going to sleep?

Dr. Edward Walker [00:49:57]:
Yeah. Yeah. I mean, we’ll get we’ll get more information. But, also, this is a a much more gentle approach. So, I mean, I think that, you can we would be well, I’m hopeful we’re in a bit of a sweet spot where we’re because we’re doing a physiological approach rather than a pharmaceutical approach that we’re not really pushing a system into an area where it doesn’t want to go and having too many of these effects. You’re quite right that’s possible. We’ll get more information from that in one of the current studies we’re running, looking at heart rate variability. And, yeah, and, again, we’ve got resting heart rate measures, so full full spectrum of that treatment.

Nick Urban [00:50:33]:
Yeah. And since this is being used, it’s consumed, and goes through the gut and then into the small intestine, are you seeing a lot of differences between different like, men and women and then age ranges and, like, what are the different populations that seem to respond differently if there’s any general trends?

Dr. Edward Walker [00:50:51]:
Yeah. Yeah. It’s interesting. So, so we’ve done a couple of studies on, directly comparing men and women for hunger rates and during fasting, so during a 24 hour fasting trial. And what we see is we see effects in both men and women. We also see, to be fair, we see probably stronger effects in women when it comes to suppression of appetite, and that’s not entirely surprising. So what we what we see when it comes to hormone or appetite, weight loss related measures, women are more sensitive to the GLP 1 injectables. All right.

Dr. Edward Walker [00:51:27]:
So they’re they’re no more. So if you look at the other benefits, things like, you know, that’s the injectables anyway for things like heart protection and some glucose control, all of those men and women are the same. But when it comes to weight loss and appetite control, women have a bigger effect, due to GLP-one and that looks likely to be licked estrogen levels. So there’s actually a study in rats where they’ve given a GLP-one injectable and, they’ve conjugated it with estrogen. And if they conjugate it with estrogen, then it’s a lot more effective than if they give estrogen by itself or GLP 1 by itself. So there’s sort of a synergistic response. So that’s likely the mode of action. Women are also more sensitive to bitterness than men.

Dr. Edward Walker [00:52:10]:
So we’re likely because we’re targeting a a bitterness response, we’re likely seeing that elevated women as well. So what we’re seeing, I guess, is a fundamental likelihood that women have a slightly higher sensitivity to this product than men. What I’d say what I’d also say is that, if you’re a guy and you’re not feeling it, you can just dose it up a little bit more. Right? So it’s it’s, you know, it’s so there’s there’s no absolute reason. It’s not saying it won’t work in a guy. It’s just you may need to use a little bit more, and and that’s probably through through through 2 modes of action. Yeah. As far as things like with age go, we haven’t seen any overt effects of decreased effect with age.

Dr. Edward Walker [00:52:50]:
Certainly, I mean, you there are some studies that say that GLP-one is reduced with age. There’s also a study that shows that GLP-one in the gut has increased with age. So it may just be not a issue of, not having the GLP-one but not being able to release the GLP-one as you get older. If that if that in case if that’s true, then something that’s, you know, stimulating your endogenous GLP one is is probably quite a useful tool in older people. So so we’re not we’re not seeing any any issues with older people so far.

Nick Urban [00:53:21]:
Okay. And then if you were to design a stack to amplify some of these benefits, whether it’s satiety, it’s to reduce cravings, are there any foods or supplements or lifestyle behaviors that you consider for that?

Dr. Edward Walker [00:53:36]:
Goodness. A stack. Oh, interesting. I mean, so, what what I’d say is that I’m a, I’m a big fan. If if someone’s on a weight loss program, right, so you’re using this to control your, control your appetite and make healthier food choices. The biggest issue you get is muscle loss, right? Now, we’re hopeful that, that we won’t see as much muscle losses, as some of the other treatments because we’re more physiological, there’s other hormones being triggered, which which may, you know, have some sparing effects. But I would always, if someone wants to stack a supplement with with any weight loss program, I’d always recommend HMB. So I’m a big HMB fan.

Nick Urban [00:54:18]:
Yeah. HMB over a complete protein source or even essential amino acids?

Dr. Edward Walker [00:54:24]:
Yeah. Yeah. So so, I mean, so, I I mean, there’s no there’s no issue with taking complete protein source or, essential amino acids, or even a branch chain amino acid supplement. They all do a similar thing. HMB is just more focused. Right? So, And when you look at the data, HMB was used in hospitals to prevent muscle wastage during cancer and during for burn victims. And so they used to use that before they started using things like growth hormone, which growth hormones are more effective. But if a supplement is good enough to be used in a hospital, it’s usually a pretty good pretty good indication that it’s got bio efficacy.

Dr. Edward Walker [00:55:01]:
And when you look at HMB, you look at it’s a leucine metabolite. So you think of it I mean, for the people who are listening, if you don’t know, in your muscles, you’ve got 3 branched chain amino acids, leucine, isoleucine, valine that make up the main structure, and then you sort of have glutamine and taurine floating around as well. When your body breaks down your muscle, when it breaks down leucine, it turns it into HMB and HMB then signals basically, hey, you’ve broken down some muscle, don’t break any more down. Right? And so if you take that externally, then you can basically help prevent muscular breakdown during weight loss. The other thing I’d say is that there are, some some people have concerns around, dosing up too much protein because it may be pro aging. So there are things like mTOR activation. And I saw a study where they gave, they were looking at lifespan of rodents and they were giving, they were giving different amino acids and they didn’t show a decrease in lifespan when they gave leucine. Right? So obviously, if you’re giving leucine breaks down into HMB, so that HMB, but they did see it with the other branch chain.

Dr. Edward Walker [00:56:14]:
So it seemed to me that this particular branch chain, leucine derivatives, were more safe to use, and they have really good targeted ones. So so I’d recommend HMB for that reason. I take it all the time. I’m taking it now. What else to take with it? That’s a that’s a good that’s a good question.

Nick Urban [00:56:34]:
What about something like the dietary basics? Like, I know that fiber might work on different mechanisms to help increase satiety, perhaps maybe not supplementary fiber, but just a diet that contains fiber.

Dr. Edward Walker [00:56:47]:
If you’re looking at stimulating your gut so that your gut is more capable of releasing something like GLP-one, then, yeah, any sort of green veggies, yeah, are gonna be really good for that. They’re gonna they’re gonna increase it. If you wanna take a probiotic, absolutely. Probiotics and prebiotics will have moderate effects on, increasing GLP one levels and, particularly through and possibly even if you’re looking at fiber, possibly even increasing the number of, interendocrine cells of the cells that release the GLP one that are present in your gut. So that’s certainly, you know, something you could you could supplement and try with it as well. Yeah.

Nick Urban [00:57:23]:
What about postbiotics like butyrate or propionate? Any of those?

Dr. Edward Walker [00:57:27]:
Yeah. I mean, that they work in a in a completely different part of the the gut. So they’re really large intestinal rather than small intestinal. You can you can take them. I mean, very much they’d if you were supplementing it, I’d want it to be targeted to the colon. And then then they have some they can have some appetite suppressing effects and they can have some effects on the inter endocrine cells as well. There was, again, a study who must be close to 10 years ago where they, where they conjugated, the different short chain fatty acids, the butyrate, acetate, propidate to, to a fiber. So they would target it to the, to the large intestine, to the colon, in rats.

Dr. Edward Walker [00:58:10]:
And they could show that they would like suppress appetite and induce at least some, some weight loss with that sort of targeting. So as long as it’s targeted to the small and to the large intestine, yeah, they’re all good.

Nick Urban [00:58:22]:
How about exogenous ketones? I know those don’t directly impact the small intestine, but they do have an anti appetite effect also.

Dr. Edward Walker [00:58:29]:
Yeah. They’re they’re an interesting one. I haven’t read a lot about exogenous ketones, but they certainly appear to be an interesting option, for suppressing appetite. And really, again, telling you going to a point where you’re telling your body that you haven’t eaten and there’s no food around, so there’s no point making you hungry anymore. And I guess that sort of lines up with that whole fasting thing where people get an increase in hunger. Then if you fast for long enough, then that hunger goes away because there’s there’s simply, you know, there’s there’s no reason for producing it. But, yeah, there’d be no issue with taking those. Absolutely.

Nick Urban [00:59:06]:
Okay. So a little stack, amarosate containing supplement with HMB, some exogenous ketones, and perhaps a little extra fiber in the diet as, like, a simple way to reduce appetite.

Dr. Edward Walker [00:59:17]:
Yeah. Absolutely. Yeah. You’ll be, you’ll be super slim in no time. Because you’re winter there, so you don’t you’ve got plenty of time to to get lean for summer. Right?

Nick Urban [00:59:25]:
Yeah. Exactly. And then I know you spent most of your time researching what bitter substances impact GLP and that whole the whole class of incretins, those hormones. Are there any things outside of bitter that have you mind blown or at least fascinated?

Dr. Edward Walker [00:59:42]:
Yeah. So, I mean, we we looked at a few different approaches. So we looked at things like, for triggering things like GLP-one. We looked at carbohydrate malabsorption. So, you can trigger GLP-one release by getting, say, glucose into the very lower small intestine. And so we did some interesting studies on that where we wanted to say, well, how much glucose do you need to get into your small intestine in order to to stimulate GLP 1. So we got some, you know, young guys, you know, there was university students who volunteer for these studies, and we put a tube down their nose, down their throat, into their small intestine, and then squirted some glucose in and measured the GLP one response. So you can trigger it with glucose.

Dr. Edward Walker [01:00:26]:
It’s, you know, like, and if you do carbohydrate malabsorption, so, something like there’s a a pharmaceutical called AKABOS or AKABOS, which, you know, is a it’s slow to sort of a alpha amylase alpha glucosidase inhibitor. So it stops, you know, glucose, or starches and and more complex sugars breaking down into the the basic sugars that are absorbed in the gut. That can have an effect on GLP-one, and, it will be really, really interesting to see if we can get something natural that’s really effective enough to get someone some some, degree of malabsorption into the into the small intestine to really lower small intestine trigger that GLP 1 with carbohydrates. We’ve failed thus far. We’ve tried it, but, it’s not easy. But, you know, watch the space. It would be a nice synergy to get to get hold of if we could do it. Yep.

Nick Urban [01:01:17]:
And I’d love to see more safety information about, like, this doesn’t seem like it’s a mechanism that can naturally happen. I mean, it shouldn’t naturally happen if someone’s healthy. Is there a way that you could get a good amount of glucose down there that would be enough to stimulate GLP 1 release if someone’s healthy?

Dr. Edward Walker [01:01:35]:
Yeah. So, I mean, the what they what they’ll say is, like, the the proponents will will say, oh, well, it’s like if you had a really, really huge meal, you know, that your body is, you know, you’ve just eaten so much, your body can’t, can’t absorb with the glucose. I’m not, I’m not a fan of that. I don’t think that’s true. The the body has some pretty, major glucose absorption capacity. It’s really hard. And that’s why we’ve struggled to get it to work because we’ll get a supplement that sort of blocks like 90% of uptake and it’s just there’s still so much excess capacity to absorb glucose in the gut that you or carbohydrates in the gut that you can’t do it. So what we do know is that, if you look at from studies where people have had parts of their intestine removed and that you can like or they’ve got, you can you can really say that the likely safety issue is small intestinal bacterial overgrowth.

Dr. Edward Walker [01:02:31]:
So if you’re delivering glucose down to really far down, then you can stimulate the colonic bacteria to grow back up into the gut, which is not a good thing. It’s It’s quite easy to measure in a clinical trial. You can do like a breath test where you can measure changes in methane and, and carbon dioxide, and you can see whether you’re getting small intestinal, bacterial overgrowth. And you can also get what’s called, sort of, they call it dumping syndrome, which is a bit of a flushing effect as well. So there’s, I guess, 2, 2 quite good measures for safety that we would do if we were going forward in a clinical trial. But you’re quite right. It’s not likely to happen for a healthy individual.

Nick Urban [01:03:11]:
Yeah. What about other entirely different ways of approaching this? Like, for example, you mentioned earlier that DPP 4 is the enzyme that breaks down GLP, I believe. What if you were just to find something that would naturally inhibit that enzyme, and maybe that enzyme is also responsible for a lot more than just breaking down GLP? I’m not sure.

Dr. Edward Walker [01:03:29]:
It breaks down a few different, gut hormones. You can. So a lot of phytochemicals or plant compounds have DPP-four inhibition abilities. And certainly you could have, I guess, a degree of activation or degree of ability to inhibit. The problem there is that if you target the gut, you can get a compound as long as it’s acid stable and gets through the stomach. You can get it into the gut and it’s pretty much what you think it is. If you have to get it into the blood, then quite often compounds are changed. So the the the compound I like to think of is I call it the phytochemical gold molecule.

Dr. Edward Walker [01:04:11]:
It’s called quercetin. And quercetin is it is amazingly bioactive in the lab and it is somewhat bioactive in people. Right? And the reason for that is that quercetin is absorbed and as it’s absorbed into the blood it gets changed and it gets conjugated and it becomes quercetin, glucoside or quercetin glucuronate quercetin sulfate. It’s got and the bioactivity is different. So if you’re targeting DPP 4 and you’re trying to get your phytochemicals into the blood, chances are they will be changed. And so their DPP 4 activity may or may not exist. You also need to have quite major inhibition as well. So what you tend to find is that these enzymes in the body are usually, usually you’ll need to inhibit them quite a lot before you have a functional effect.

Dr. Edward Walker [01:05:01]:
And so, you know, you’d be asking a lot of a phytochemical to do it. In saying that, I mean, the Amarisade extract has d p four d p p four and an inventory effects as well. Right? So we’ve measured it. It doesn’t have a bit of 2. It doesn’t not a lot of it gets into the blood. So, you know, how much we’re actually getting there. But but you’re quite right. There are other other approaches.

Dr. Edward Walker [01:05:23]:
They work pharmaceutically. Watch the space. They may work with a phytochemical nutraceutical in the future.

Nick Urban [01:05:30]:
Ed, what’s in your stack, whether it’s for GLP or just in general?

Dr. Edward Walker [01:05:36]:
Alright. So what do I take? So right now I take I mean, I take a protein supplement, but I take, HMB. I’m taking a, a gram of resveratrol, 500 milligrams of quercetin. And I take the quercetin not to get into the blood, but try to help it get the resveratrol into the blood because resveratrol again is sulfated as it’s absorbed. And so if you take something like a quercetin or you could take something like a a biopiparone or something to try to try force it into the blood unmodified.

Nick Urban [01:06:07]:
Do you like resveratrol over something similar like terestilbene?

Dr. Edward Walker [01:06:11]:
Yeah. I mean, yeah, they’re they’re both good. They both probably work the same way. I like I like resveratrol because it’s I can get lots of it for inexpensive. But they all have similar similar effects. I also take some spermidine supplementation. I’ve done I did a really interesting one recently where I took a 16 chain long, fatty acid. Yeah.

Dr. Edward Walker [01:06:37]:
And it was sort of, it’s meant to have all sorts of, like it made me it made me bleed lots, actually. It was really weird. Apart from that, that’s all I’m on at the moment.

Nick Urban [01:06:46]:
Is that 16 chain fatty acid? It’s not c 15. C 15 is 15 chains.

Dr. Edward Walker [01:06:51]:
Yeah. C 15 is 15 chains. Yeah. It was, trying to think what name the supplement was. But but but, anyway, I I, yeah, I was it was it was one of these, science conferences. It was just being sold. I just gave it a go. It was really expensive.

Dr. Edward Walker [01:07:06]:
So, yeah, so there’s just those ones. I mean, in the past, I’ve taken a huge amount of supplements, but I’m really, I’m really good with my diet. So I’m not, you know, I’m not supplementing like vitamins and things like that. So I’ll eat my diet consists of green veggies, some lean meat, black or purple rice, So lots of anthocyanins, kiwifruit every day, berries. So it’s a lot of, I guess, what I’d call healthy foods and limited limited supplementation. And when I do supplement, I tend to take huge dosages. The other thing that I’ve taken in the past, which I which I’ll we use intermittently is obviously creatine, but, there’s a supplement, the Ectosterones. So I’m not sure if you’ve you’ve heard of those before.

Dr. Edward Walker [01:07:55]:
They’re estrogen beta agonist. And so they, they basically did some good studies showing they stimulate muscle growth. Yeah, but they are. They’re hard to get pure. So what we what yeah, what you find is that a lot of the time you’ll buy like a 100 milligram dose and it turns out it’s only got 1 milligram in it. And so I did a I did a really interesting thing where I’d read the paper, I read a paper where they showed if you took, if you took 200 milligrams or 600 milligrams of of 20 hydroxychisterone a day, you could generate, you know, like pretty decent muscular growth. So I went and bought some. I got some some pure, you know, through sort of scientific links.

Dr. Edward Walker [01:08:39]:
And and I and I thought, oh, well, they’re taking they’re taking, like, you know, 600. I’ll take a gram a day because, you know, I’ve got to up it a little bit. And I got terrible side effects. Yeah. And and so what happened was that, in the study, it turned out that the supplement they’d used was only I think it was only 10% pure. So it was only 10% what they said it was. So I wasn’t just taking more. I was taking like way, way more.

Dr. Edward Walker [01:09:04]:
And even though it was a, even though it was a estrogen beta agonist, which is muscular growth and things, it still has some estrogen receptor alpha antagonism, which is the demonizing one. And I was getting, like, itchy nipples and they were all sore. And I was like, what’s going on? And yeah. So so that works really well, but just careful on the dosage.

Nick Urban [01:09:24]:
That’s a good reminder in general that when you see something in research, not just to take the dosage and if it’s in animal models extrapolate to humans, but even if it’s in humans, that you have to be careful because their product they used as the reference in the study might not have been the same as the product that you’re getting.

Dr. Edward Walker [01:09:42]:
Yeah. Exactly. It might not be the same. And there’s no guarantee that just because they they used it, that their their numbers are accurate. And that’s that’s really a big thing because, I mean, one of the things that we do in Planet Food Research, which is whenever we’re doing health research, we’re required to do an, a chemical, you know, analysis of the product we’re using to make sure we know exactly what it is. And sometimes we’ll publish it with the paper, you know, like, or or refer back to it. And most studies won’t do that. So they’re just taking the supplier’s word for it or the you know, it could be a commercial product, the commercial product person’s word for it that that there’s actually what’s you know, it is what it is.

Dr. Edward Walker [01:10:21]:
Yeah.

Nick Urban [01:10:21]:
Wow. Well, Ed, if people want to follow your work to connect with you, is there anywhere that you’d like to point them?

Dr. Edward Walker [01:10:29]:
Yeah. So if you go to plant and food research, so plantandfooddot co.nz, and you search for either myself or for Amarasite, there’s links to the research we’ve been doing and there’s updates. And, if you’re interested in the, I guess, the commercial product that’s been made for my research, which, you know, I get no money from the sales from because I’m a government employee, and and no money no money from the patent that was made either. That that’s, the product is called CaliCurb, and you can and they they have lots of, like, social media type stuff you can read about there.

Nick Urban [01:11:01]:
Yeah. And I’ve used Kalicurb. 2 capsules works for me. I am an affiliate of theirs. So if you buy through my link and use the code urban, I do get a tiny commission. So I’ll put that in the show notes for this episode as well. But, Ed, this has been a blast. Thank you so much for joining me on the podcast today.

Dr. Edward Walker [01:11:18]:
Oh, it’s been a pleasure. Yeah. And, you have some great knowledge. It’s amazing, man. Good work.

Nick Urban [01:11:23]:
Yeah. Thank you for tuning in to this episode. Head over to Apple Music, Spotify, or wherever you get your podcasts and leave a rating. Every review helps me bring you thought provoking guests. As always, you can find the show notes for this one at mindbodypeak.com/andthenthenumberoftheepisode. There, you can also chat with other peak performers or connect with me directly. The information depicted in this podcast is for information purposes only. Please consult your primary health care professional before making any lifestyle changes.