Episode 346: Semaglutide, Ozempic, GLP-1, Glucagon, Gastric Emptying, Muscle Loss, Insulin Resistance, Exclusion Zone Water, The Mind Blown Podcast, And More!

Intermittent Fasting


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Dec 04

Welcome to Episode 346 of The Intermittent Fasting Podcast, hosted by Melanie Avalon, author of What When Wine Diet: Lose Weight And Feel Great With Paleo-Style Meals, Intermittent Fasting, And Wine and Vanessa Spina, author of Keto Essentials: 150 Ketogenic Recipes to Revitalize, Heal, and Shed Weight.

Today's episode of The Intermittent Fasting Podcast is brought to you by:

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Listener Q&A: Candice - This is potentially a strange question, but I’m wondering how semaglutide works.

Listener Q&A: Sunny - What do you think about ozempic & the ilk for weight loss?

Semaglutide for the treatment of overweight and obesity: A review 

Berberine Attenuates Hyperglycemia by Inhibiting the Hepatic Glucagon Pathway in Diabetic Mice

Antidiabetic Properties of Berberine: From Cellular Pharmacology to Clinical Effects

Berberine promotes glucagon-like peptide-1 (7–36) amide secretion in streptozotocin-induced diabetic rats 

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Melanie Avalon: Welcome to Episode 346 of The Intermittent Fasting Podcast. If you want to burn fat, gain energy, and enhance your health by changing when you eat, not what you eat, with no calorie counting, then this show is for you. I'm Melanie Avalon, biohacker, author of What When Wine and creator of the supplement line AvalonX. And I'm here with my cohost, Vanessa Spina, sports nutrition specialist, author of Keto Essentials and creator of the Tone Breath Ketone Analyzer and Tone LUX Red Light Therapy panels. For more on us, check out ifpodcast.com, melanieavalon.com, and ketogenicgirl.com. Please remember, the thoughts and opinions on this show do not constitute medical advice or treatment. To be featured on the show, email us your questions to questions@ifodcast.com. We would love to hear from you. So, pour yourself a mug of black coffee, a cup of tea, or even a glass of wine if it's that time and get ready for The Intermittent Fasting Podcast.

Hi, everybody and welcome. This is Episode number 346 of The Intermittent Fasting Podcast. I'm Melanie Avalon and I'm here with Vanessa Spina. 

Vanessa Spina: Hello, everyone.

Melanie Avalon: How are you today, Vanessa?

Vanessa Spina: I'm doing wonderfully. How are you? 

Melanie Avalon: I am good. We are recording this so far in advance. I'm looking at the week that this comes out, which is the first week of December and I think I don't want to jinx it. Well, man, there might be multiple products coming out and multiple things coming out for me this month, but I think this is the week that I might be releasing my third podcast. Maybe that's the plan. So, I'm going to go ahead and say what it is. So, Scott Emmens, the fabulous Scott Emmens at MD Logic. He's been on this show multiple times. He and I are just like friends for life. And it's kind of a problem because we have a lot of business calls because we're constantly creating supplements together. And we actually have another side project we might be doing, which is very exciting, but we tend to just go on these really random tangents and talk for an hour about not work-related things.

And so, we realized one day that we should maybe have a podcast about all of this. Actually, started when we had a crazy theory about the Mandela Effect that we realized. So, we're going to be launching the Mind Blown Podcast hopefully this week. It's been so fun recording it thus far. Basically, each episode, it's so fun. So, each episode we start off by, we bring to the table a mind blown fact to share. So, we share one and then we rate each other's mind blown facts and we talk about it, and then we have the topic. Like I said, the first two episodes, it was going to be one episode, but of course, with Scott and I, it ended up going longer. So, it's a two parter about the Mandela Effect and our crazy theory surrounding it. And then yeah, there's some really good episodes after that, each episode will be an a la carte, like, mind blown topic. 

Vanessa Spina: That's so exciting. Congrats. 

Melanie Avalon: Thank you. It's really fun to be podcasting, not about something health related. [chuckles] I mean, I'm sure some of it will be health related, but it's a different genre. 

Vanessa Spina: That's so fun.

Melanie Avalon: So yeah. Do you think you'll start your other podcast some time?

Vanessa Spina: I think about it. Right now, I like it just as a thought you know.

Melanie Avalon: Yeah.

Vanessa Spina: It's like a happy thought. I'm like, “I love to do a podcast on that. I feel like I have so much to share,” but then I'm like, today I was like, “I could do a podcast about how to create products because there're just so many different topics that would be fun to get into.” But yeah, I think doing one on consciousness and mindset and consciously, deliberately cultivating a beautiful life, that's the one that I think would be just, like, a pure pleasure to do. So yeah, it's a happy thought right now, but whenever I mention, like, definitely listeners of my current podcast are like, “Oh, I would love to hear about that.” So, I can feel the joy of launching it. And I'm so happy for you and Scott because I feel like it's just going to just bring more joy to your life. 

Melanie Avalon: Thank you. Yeah, it is so fun. It's really wonderful that I just so thoroughly enjoy all the podcasting stuff. Like, it's just so fun and they all fulfill different needs in a way. Like with the Melanie Avalon I'm learning, and I'm getting to learn about these topics and talk to amazing guests and meet new people. And then this one is my besties, friendship, nourishing for the soul and then talk about fasting. And I feel like the audience here, actually they've been here for so long, so it's kind of like family and friend’s adventure. And then with Scott thing, it's just kind of like a new, really fun. 

Vanessa Spina: That's wonderful. I'm so happy for you both. 

Melanie Avalon: Thank you. I also might be releasing, hopefully this month, our next supplement. Hopefully we're getting the final formulation figured out right now.

Vanessa Spina: Is this the spirulina one? 

Melanie Avalon: Yes. So, I'm really excited because yes, we're releasing spirulina. We're working the final formulation right now, trying to get the best formulation, but there are so many health benefits to spirulina and I'm obsessed with it. It's basically, like, just one of the most nutrient-rich things you can get in a tiny little package, and it's great for detox and trace minerals and just so many things. It's like a superfood. I don't like that word, but I'm excited about it. But that's just a teaser because we're figuring it out all out right now, even though by the time this airs, I probably will have been talking about it a lot at that point. So yes, so listeners, if they would like to get updates about that, which I am so, so excited about. They can go to avalonx.us/emaillist. I'm just so excited. I can't wait till it manifests. And I really want the packaging. I love design. Like, Vanessa, we've talked about this. Like, we love packaging design and such.

Vanessa Spina: I just finished doing that today for the new Tone Device. So, like, I've been buzzing all day about it.

Melanie Avalon: Isn't it fun? 

Vanessa Spina: It's the best. But today we’re doing because the cover-- the boxes are already fully designed with the new second generation but today I got the samples, so I got touch them and feel them and see them. And the main difference is that it says Generation 2. But were also just adding all the logos because we finished doing all the third-party lab testing. And I'm now an expert [laughs] on third party lab testing for electronics. Because after the past few years of doing it, it's always a little bit nerve wracking because you're like, “What if the test fails or it comes back with like there's some kind of issue?” And we just got everything back. Everything is fully, fully certified and approved. But there's a lot of different regulations because I sell in multiple markets. So, the US has FCC for electronics and there's a whole bunch of them. But, like, in Europe, you have EN standards and RoHS. And then there's also UL testing for safety. And there's another one. Oh, and then there's like, California Proposition 65 that nothing in your products. Devices can have any of the certain materials or you have to disclose it. And it's not just the product, it's also the packaging. 

So, it's a lot of stuff, but everything is fully approved. And we thought it would because the first generation all was-- so there wasn't any concern with it, but always just feels good to get everything, get all the certificates and then officially put all of those logos on the box and put all the details and everything. We were just finishing that. But I love it. [chuckles] I love that part. I love that part of design. I just love the creation process and getting the packages. And I'm now selling an accessory, which is the charging cable, because almost every week someone emails me and says that they lost their charging cable. So, I decided, like a year ago to just start making them and selling them as an accessory. And then we made this cute box with it. But I just got the actual finished box today, so it was really fun to get that and get it photographed and yeah, I just love it so much. I love all the design, the testing. I just love all the aspects of creating products. I don't know, since I was a little kid.

Melanie Avalon: I was just about to say, “Same here.” I was thinking, “We're so similar.” And I was thinking, ever since I'm like a little kid, I was, like, creating stuff. 

Vanessa Spina: Yes, same. That's what my mom used to always say. I was just so creative. I was creating or inventing things and then selling them. Like, trying to sell them either, like, on the street [laughs] that sounds weird, on our sidewalk. 

Melanie Avalon: What were some of the things you tried to sell?

Vanessa Spina: So, I would make jewelry. Like, at first, I started out with just friendship bracelets. And when my parents would go play tennis at their tennis court, I would go and sell them to people for, like, a dollar, and everyone would buy one, I guess because I was, like, a kid and you want to support kids. And then I upgraded because my mom would go on business trips to the Philippines and she'd bring back all these beads. She'd bring up these big bags of beads that she would get at the markets there. So, I would make all this jewelry earrings and necklaces, and I would sell them around whenever there was block parties or garage sales or things like that. But I had individual little plastic bags for each one. And then I printed a logo on the computer, like, in paint [chuckles] onto stickers--

Melanie Avalon: Paint. Windows 95. 

Vanessa Spina: Doesn't that make you happy to think about Paint? 

Melanie Avalon: Oh, man, I'm getting hit with, like, memories. Oh, the memories are flooding in. They're flooding. Do you remember Kid Pix? Did you ever use that? 

Vanessa Spina: No. [laughs] What's that one? 

Melanie Avalon: That was like software with-- but it was similar to Paint but upgraded.

Vanessa Spina: Yeah, that stuff makes me so happy to think about. I loved paint. Such simple times. [laughter]

Melanie Avalon: I know, all the colors. Do you remember, like, the color wheel? It was like, ah, you could pick the colors.

Vanessa Spina: It was so good. Like, I want to do Paint right now. I’ve got to google some old-time machine version of Paint. It was so much fun. 

Melanie Avalon: You would have loved Kid Pix.

Vanessa Spina: It sounds similar. 

Melanie Avalon: It was like Paint, but it was, like, for kids. And it had more stuff. 

Vanessa Spina: Every time you say it, I'm like I feel like I played that at one of my friend's houses or something. 

Melanie Avalon: You probably did. Do you remember going to computer class? I wonder do they still do that? 

Vanessa Spina: Yeah, I loved computer class. I think it was one of my favorites. 

Melanie Avalon: I always thought it was so, like, they were talking down to us. I was like, “I know how to do this. This is not complicated.” [chuckles] Why are we here?

Vanessa Spina: Computer class is probably just class now. Whereas, like-- 

Melanie Avalon: It probably is.


Vanessa Spina: But even you saying computer class makes me happy. I'm like, “Oh, I loved computer class.” 

Melanie Avalon: I know. Did you do the typing games to learn how to type? 

Vanessa Spina: Yes, typing tutor. There was typing tutor. I think we had one called

Melanie Avalon: I did JumpStart. 

Vanessa Spina: It was so much fun. 

Melanie Avalon: It was stressful, though. Okay, that was, like, the one computer game, because it was like, you have to type the things fast. I was really stressful, especially when it was in class and you had to type words fast enough. I don't know. I didn't like the pressure of that. I'd rather just learn it on my own. Oh, do you know why? Oh, this was something. Oh, wait, there's like a fun fact and I don't know the answer. Did you know with the keyboard, the way it is set up is not the most efficient way? It doesn't really make sense the way it's set up right now. And so, they've tried to change it because I was reading something about how hard it is to change things in society, and they've tried to change it to make it more efficient, but you just can't because people are so used to the way it is now that they won't use a new manifestation, even if it's better.

Vanessa Spina: Yeah, that makes sense. I've also heard that about our mathematical system, like the Egyptian system or something was way better and made a lot more sense. And the way that we learn it now is weird and kind of clumsy.

Melanie Avalon: It's kind of upsetting. Like, if you're just in too deep, you just can't--

Vanessa Spina: Paradigm shifts are really hard, are really hard. Like the most mind-blowing thing-

Melanie Avalon: Oh, good. Let me add this to my list. 

Vanessa Spina: Oh, you definitely should. Gerald Pollack. I'm not sure if you've interviewed him or heard about him,-

Melanie Avalon: Yes, reading about him. 

Vanessa Spina: -The Fourth Phase of Water. His book was the biggest mind-blowing thing that I've read about the fact that we have this gel like water that forms inside our cells, and it forms these sheets of honeycomb. They're like honeycomb, like hexagonal or is that hexagonal? These honeycomb layers around structures and so it's called structured water. It's kind of like a snowflake, but it's really amazing because we can actually charge it. And infrared heat charges that water. And so, he discovered this and he was basing it on the work of some of his colleagues and predecessors, and it's really, really fascinating. So, they have this fourth phase water that they actually put two electrodes into charged water and it was able to light a light bulb.

So, our bodies are actually batteries and we have this water inside of us that is like a gel and we basically can charge it up by going into the sun. Like, the sun is 50% infrared and infrared energy is all around us. Like, if you had infrared goggles on, you could see energy coming from everything around you. But the sun gives us a lot of charge and it charges up that water. So that water, he also calls it exclusion zone water and it expands. And when you-- this is the part that, okay, that already blew my mind, because it's like, okay, we need to redo all of science and redo all of biology with this understanding. When you do cold exposure, like cold plunging, you basically are doing it a lot of ancient cultures or Northern European cultures, they do it in the winter because there's no sun. And by getting cold, it then forces our bodies to generate infrared heat from our core and that charges up our cells and gives us the same kind of energy that we would get from the sun in the summer, which is like, amazing, but also red-light therapy. The infrared on that also charges up and so does infrared sauna. But it's so amazing. I got to interview him on my podcast. 

Melanie Avalon: You did? 

Vanessa Spina: Yeah, and I was just-- 

Melanie Avalon: Oh, I want to interview him. That's amazing. When did you interview him? 

Vanessa Spina: Was like maybe six or eight months ago. 

Melanie Avalon: Oh, recently? 

Vanessa Spina: Yeah. And you will love him. He's one of the kindest, most down to earth people I've ever interviewed. And it's amazing because you and I talk about this all the time, but you have these-- I don't know if you can even call him a scientist-

Melanie Avalon: Legend.

Vanessa Spina: -yeah, legend who've done so much, made these incredible discoveries, and you'll talk to them and they're just like the most down to earth people in the world, even though you wouldn't expect that. And then you talk to other people who haven't really accomplished that much and they're like not down, you know what I mean? They have overinflated egos and stuff. So, it's so nice when you meet someone like that and yeah, he's just so incredible. You have to interview him and read his books because what's really fascinating too, is apparently Russian scientists had discovered it a long time ago and then when it was sort of like challenged by the international scientific community-

Melanie Avalon: They didn't get backlash?

Vanessa Spina: -yeah, there was a lot of backlash. And so, at the time, Russia was embarrassed. So, they made the scientists who discovered it publicly say that he was wrong. But Gerald Pollack worked with his mentee or someone who was like an assistant or mentee of his, and he said that he knew that he was right and he knew that he was right until the time that he died. But he had to publicly say that he was wrong just to not bring shame on the country. And so, thankfully, Dr. Pollack has taken on the work. But it's really fascinating. Absolutely fascinating, because our bodies do get energized by the light. We are learning that. We do get energy in other ways. And it all kind of goes back to the mitochondria, because this exclusion zone water forms inside the mitochondria. And that's one of the reasons the mitochondria cristae have all those folds, because the more folds there are, the more exclusion zone water can form around those structures. So, it's most mind-blowing thing I learned in 2023. [laughs] 

Melanie Avalon: I love that.

Vanessa Spina: Paradigm shift. It's like we need to redo all understanding of biology and physiology and medicine everything based on this. But are we going to? That the quantum sort of like the whole quantum physics, quantum biology sphere that we now have technology to learn about, but it's teaching us things that we have to rebuild everything. And that's so hard to do. 

Melanie Avalon: It's kind of like the book I just finished and I'm interviewing him on Monday. It's called, What's Gotten Into You: The Story of Your Body's Atoms, from the Big Bang Through Last Night's Dinner. And it's basically, the history of molecular physics and quantum physics and atoms and everything, like I just said, from the Big Bang to you. And my takeaway from that book, which I've been listening to while putting sequins on my Taylor Swift outfit, it's a nice contrast, is that we have no idea about anything. And it's crazy, the history of people finding ideas and having theories and being discredited or looked down upon, but then they turn out to be right, but then we still don't even know. And there's so much cognitive bias that's kind of like a theme of his throughout the book, is that it's really hard to see beyond biases based on preexisting evidence or what we want to see. And I don't know, I walked away from the book feeling both very excited and empowered and also feeling like we don't know anything.

Vanessa Spina: Yeah, I know the feeling. [laughs] It's like the more you know the more you realize you don't know. And it's an interesting-- it's like mixed emotions for sure. But I think it's also a sign that you are actually learning more. Like, the more humbled you become of how little we know. [chuckles] But I also love to listen to audiobooks while I'm doing stuff around the house. I love that. 

Melanie Avalon: Oh, it's so fun. It's so satisfying because doing stuff around the house or putting sequins on Taylor Swift outfits or cleaning is, like, satisfying in and of itself. But then listening to learning knowledge is so satisfying. I don't want to just sit there and listen. Not that it's wasted time. Not that we need to be multitasking super productive 24/7 but and I do feel really nice when I combine them. So, you get all the dopamine from the learning and the cleaning, ah, so fun.

Vanessa Spina: One thing I learned from Alison Armstrong is women get a lot of oxytocin release from repetitive hand motions. So, if you're doing some kind of fine work, like detailed work, like, needlepoint or putting sequins or knitting, you actually get a lot of oxytocin from that. So that's probably extra.

Melanie Avalon: Wow. So, when I’m adding those sequins.

Vanessa Spina: Yeah.

Melanie Avalon: Wow. Okay, I should stop this train, but I'm just thinking about little things when I was little, did you do the thing with the bright, like, the rainbow? It was like stretchy rubber band things and you put them on like what's it called? 

Vanessa Spina: Like a loom. 

Melanie Avalon: A loom, [laughs] okay. 

Vanessa Spina: A 100%.

Melanie Avalon: And you like braid it, they braid it together. 

Vanessa Spina: It made me so happy. 

Melanie Avalon: I was never quite sure what the purpose was of the finished product. But you made this thing, but what do you do with it? It was like just a thing. Kind of like [chuckles] one of the things I would make is when I discovered making glue chips. Did you make these? You put glue in a cup and then you take paint and swirl it in and you can make like, rainbow glue chips. But what do you do with these glue chips? 

Vanessa Spina: It's just the activity, the intrinsic value of the activity itself.

Melanie Avalon: And then like, the artifact created from it. Oh, how about the spinney paper thing where you drop the paint in and it makes-- 

Vanessa Spina: That gives me goosebumps. It makes me so happy to think about.

Melanie Avalon: Oh, so happy. Like with a color that drops it, but then when it stops, it never quite looked as brilliant as you thought it was going to-- I didn't think it ever looked as brilliant as I thought it was going to look while in the spinning phase.

Vanessa Spina: Yeah, there was one with detergent and water and color drop.

Melanie Avalon: Oh, it jumped away from each other.

Vanessa Spina: Yeah, all that stuff. We had this one book and it was like activities for kids that are like sciencey. And I was always like, “Can we do it.” [laughs] But makes me happy to think about them. I got to redo all them with Luca. 

Melanie Avalon: Oh. Oh, yes. Did you have the craft series of books? Craft kids or something. 

Vanessa Spina: Probably. It sounds really familiar. 

Melanie Avalon: That was my favorite. They had a lot of great science books as well. Shall we jump into some fasting-related topics? 

Vanessa Spina: I would love to. 

Melanie Avalon: So, to start things off, Vanessa and I are so excited to talk about this. We have had multiple questions come in about Ozempic and semaglutide. So here are two of them and then we're just going to talk about the topic in general. These are both from Facebook. Sunny asked, “What do you think about Ozempic and the elk for weight loss? Effective and presumably safe or scary with three question marks.” She says, “And what are the safe alternatives that will give results if your insurance won't cover it?” And then Candice, also from Facebook, asked she said, “Hi, I love the podcast. This is potentially a strange question, but I'm wondering how semaglutide works. I am not interested in taking it. I asked because one of my parents started taking it. I looked into how it worked and based on what I know about insulin, it makes no sense to me. My parents had been doing IF and saw great results. Then he got really sick, had to stop IF to recover, and he gained a lot of weight. One of his doctors put him on semaglutide. He lost no weight in two months on it. Now he's been back doing IF for two months and is gaining weight. Did he become insulin resistant? I'm truly baffled.” Okay, I have so many thoughts about this. Vanessa, would you like to tell us a little bit about semaglutide? 

Vanessa Spina: I would love to. I did a whole episode on semaglutide this summer on my podcast. I was doing a bunch of research for it, but it's really fascinating to learn about the actual mechanism of action. So semaglutide itself is a peptide and it actually is sold under two main brand names. So, the one that you mentioned is Ozempic and that was actually first approved in 2017 as a treatment for type 2 diabetes. But in 2021, the FDA approved the same drug under a different brand name, which is Wegovy. Everyone talks about Ozempic, so Wegovy is the brand that basically is for weight loss, but they're both the same thing. They're both semaglutide and they're both made by a pharmaceutical company called Novo Nordisk.

So, what's really interesting about them in terms of how they work, which I think is a big question that's on everyone's mind. And so, when it comes to weight loss and weight gain, it's really about energy balance. And so, you have to create either a deficit or unbalance that energetic balance by either consuming less calories, less energy intake, or generating more energy expenditure. And the way that semaglutide works is actually reducing caloric intake because it suppresses appetite, like to the point where people have not much interest in food at all. And so, it suppresses appetite, but it also has a number of other mechanisms of action that are really fascinating. So, most people are losing weight because they're just not hungry and so they're consuming fewer calories. And so that is creating a loss of body weight/body fat, because I'm going to get into that as well, because it's not necessarily all body fat, which is the concerning-- One of the concerning parts about it, because I find it to be more so scary than anything else.

And so, there is a peptide in the body called GLP-1. It's glucagon like peptide and it's basically a glucagon like peptide receptor agonist. So, drugs either come in the category of agonist or antagonist. So, an agonist binds to the receptor on a cell in the same way that the actual molecule would in the body. So semaglutide mimics the action of glucagon like peptide 1 or GLP-1. And so, it binds to the receptors in the same way that the body actually perceives it to be GLP-1, even though it's not GLP-1. [chuckles] So that's why it is an agonist, whereas antagonist will also bind to the receptor but actually blocks the action or the mechanism. So, the reason that you can't actually just use GLP-1 is GLP-1 has a really short half-life, it's like 2 minutes, whereas semaglutide extends that half-life to about seven days. So that's why people get an injection once a week if they are taking it regularly. Their chemical formula is very, very similar. GLP-1 is a polypeptide that has either 36 or 37 amino acids with a chemical formula that's very similar to semaglutide, which is a polypeptide with 31 amino acids. But the basics of it is that semaglutide is similar enough to GLP-1 that the body recognizes it as GLP-1.

So, the way that it works is GLP-1 is actually a hormone that is released from the gastrointestinal tract or the gut when you eat. And one of the roles, just one of the roles of GLP-1 is to prompt the body to release more insulin and produce more insulin. So that actually reduces blood glucose by increasing glucose uptake in the muscles so that secretes insulin or produces more insulin. And that then pushes some of our glucose into the muscles, gets it out of the bloodstream, and it also decreases glucose production in the liver. So, it inhibits glucagon which is the antagonist hormone to insulin, because glucagon causes glycogen breakdown in the liver, which actually raises our blood glucose levels. So some of the effects that take place because of the GLP-1 secreted by the gut really reduce blood sugar spikes after eating by stimulating this insulin secretion and inhibiting the glucagon. But that's not the only thing it does.

GLP-1 also slows gastric emptying. So that's the time it takes for food to empty out of the stomach. And so, it takes longer for the food that you eat that ends up in your stomach to then go to the small intestine, where most of the food is then absorbed into the body. So, if you delay gastric emptying, you also slow down and stabilize blood glucose responses to your meal, which is another way that GLP-1 limits blood glucose spikes during that post mealtime. And because the blood sugar is going to be so stable, you're not going to have that blood glucose spike. And then the fall, which is what makes people typically feel really hungry, is when their glucose spikes and then crashes afterwards. Another thing that GLP-1 does is it actually acts on the brain. And there's some really aggressive research that is taking place right now. University of Florida researchers are currently researching that GLP-1 that is secreted by the gut is different from GLP-1 secreted by the brain. And so, they're suppressing eating via two independent circuits, which is one of the reasons it is so powerful as an appetite suppressant.

So, the main reason that people need to take semaglutide is, again, because of that short half-life of GLP-1, when it only lasts for 2 minutes as opposed to seven days. In terms of side effects, this is one of the many scary aspects of this to me. But the list of side effects is so massive. Nausea, diarrhea, vomiting, constipation, abdominal pain. It goes on and on and on, but one of the ones that's been getting a lot of headlines is this paralysis of gastric emptying. So, people are having, like, their stomachs are becoming paralyzed from using semaglutide, which doesn't surprise me because you're using something that is-- like if you think of a half-life being 2 minutes compared to seven days, it's so much more powerful than our endogenously produced GLP-1. So, it does cause a lot of weight loss. There were five big studies that were done on semaglutide called the STEP trials. And unfortunately, one of the big things that is really alarming and scary about these peptides is that people are losing a lot of weight, but it's not all fat. So, this is my Peter Attia quote he said-- I'm not sure when exactly he said this, but he said, “That almost every patient that we put on this drug semaglutide has lost muscle mass at a rate that alarms me.”

So not all of the studies, the STEP trials measured body composition, but there was one of them in particular that did. And in that one, the proportion of their weight loss was 39% from lean body mass, so almost 40%. Whereas standard weight loss, if you're doing it well, you're losing at the most 25% lean body mass. Like you do not want to be losing 39% or 40% of your lean body mass and only 60% coming from body fat. So, in the STEP 1 study, the subjects who were on the semaglutide, they lost 43% body fat and lost 57% of their lean body mass, which is absolutely massive. And then there was one other study where body composition was measured and it was called the SUSTAIN 8 trial. It had 178 people and the average proportion of lean body mass reduction was 40%. So, people are losing huge amounts of weight, but a lot of it is coming from their lean body mass. And that big part of that is muscle which you don't want to lose, especially after the age of 40. But there're only certain situations where people are morbidly obese where these kinds of rates of lean body mass loss are less of a risk because someone has that much body fat, it's more likely to come from body fat. But people who are taking this, who are not morbidly obese are going to be losing a lot of lean body mass. 

So, there're a lot of studies that have come out where they compared semaglutide to a placebo group. And like I said, the amount of weight loss with semaglutide was pretty high. There was one study that was two years long, was really interesting because they did like 104 weeks and most of the weight loss happened in the first year and the second year they just maintained. So, I'm not sure what's happening, but a lot of people have concerns about what happens when they go off it and I think that's something that we have yet to see because in this study that was two years, the participants lost an average of 35 pounds in the first year. But the second year they just maintained and sometimes went up a little bit and they're still on it. So, what happens when they go off it? The chances that they're going to be able to maintain the weight loss I think are pretty slim. And so, you may end up in a situation where you lose a bunch of weight, 40% of it is lean body mass and then when you go back to your normal appetite levels, when you're no longer injecting yourself once a week, you're just going to gain fat back. And that's how people end up with really poor body composition where their body fat levels are super high, body fat percentages is really, really high. 

So, there've been a lot of headlines lately about the side effects. There was one I think on CNN saying hundreds of thousands of people are having this paralysis of their digestion which is just like unimaginable to me, like your stomach is just not emptying at all. I'm not sure how severe that is, how easy it is to fix. But also, in the studies people had a lot of adverse events and most of them were gastrointestinal and really not pleasant. So that's really how it works in terms of the specific questions, in finding something that's a safe alternative. The thing that stands out the most to me about these drugs or these peptides is like well that's what a lot of the stuff that we do in terms of lifestyle and nutrition, that's what they do for me, like prioritizing protein suppresses my appetite. And it's because of the satiety hormones released from the gut and released from the brain. So doing a lot of these kinds of strategies, intermittent fasting for me, carbohydrate restriction, prioritizing protein, all of this stuff really works for me to get these same benefits at the same time teaching me healthy habits that I can maintain easily without a risk of side effects without a risk of losing tons of lean body mass. So, for me, I don't know of any pharmaceutical safe alternatives, but I think that's what we try to talk about a lot on this podcast is the safe alternatives that are more lifestyle, nutrition oriented that I think over the long term are going to be much more beneficial. 

And as far as Candice, when you were asking about your family member who did not lose any weight in two months on semaglutide and then going back to intermittent fasting and gaining weight, potentially becoming insulin resistant in terms of the mechanisms, you know semaglutide is pushing out more insulin and causing the body to produce more insulin. So, it's possible that some, like the basal insulin levels could have been raised through going on it. I'm surprised that he didn't lose any weight. But a lot of people, like, some people lose a ton of weight and some people don't. So, it kind of seems to be very dependent on the person. It could have given him potentially some kind of higher basal insulin resistance or sorry, higher basal insulin, which can be measured by fasting insulin. So, you could have his fasting insulin tested to see what that's at because that might help shed some light on it. 

Melanie Avalon: Wow. Awesome. Okay, thank you for all of that information. I love talking about all of this. I'll put a link in the show notes and it's so interesting because I didn't realize the name. You said the company was Nordisk, right? 

Vanessa Spina: Novo Nordisk.

Melanie Avalon: Because I'll put a link into the show notes. There's a January 2023 review published in Diabetes, Obesity, and Metabolism called Semaglutide for the treatment of overweight and obesity: A review and it provides an overview of the I think now there's actually been 8 STEP trials on semaglutide. And what's funny, because that was the first thing I read when I sat down to research this. And reading it, I was like, “Oh, wow, this is really impressive,” [chuckles] because it talks about the weight loss throughout the trials and compared to placebo and the beneficial effects on blood sugar and potentially even cardiovascular benefits, then it really minimizes the side effects. I think basically it says that around 75% have GI side effects, but that few discontinue the treatment. The numbers it gives across the different trials, I mean, they're losing around 14.9% to 17.4% weight loss compared to the placebo groups, which is really low, anywhere from like, 0.8% up to 4.5%.

I didn't realize this when reading it, but I scrolled down to the bottom after you said the name of the company. It says that basically it was funded by Novo Nordisk. So, like, oh, that makes sense [laughs] that it's the company creating these drugs that is funding this research. Something I wanted to comment on, for Candice's question about the insulin issue and Vanessa was touching on this a little bit. I was also just like, at the beginning, confused about this because we talk so much about how we want to reduce insulin release and so much of our diet and our lifestyle and fasting is all about minimizing insulin release. So how can something a glucagon like peptide 1, a GLP-1, a hormone that is increasing insulin release, how is that a potentially beneficial thing for weight loss? And what's really interesting about the context of this and Vanessa was talking about this, but just to dive a little deeper into it, that insulin glucagon connection. 

Diving into this, I'm actually thinking it's kind of crazy. We don't talk about glucagon more like we're so focused on insulin. But the primary issue of hyperglycemia, so high blood sugar in diabetes, it's not from well, technically, way down the line, it's from the food you ate, but it's not from the food you just ate. It's from the liver producing it. That's the majority of the burden of the blood sugar. So, glucagon releasing blood sugar is the, I don't want to say the primary issue, but it is a huge issue. And there's been even rodent trials where they have inhibited the rodent's ability to produce glucagon in diabetic rodents, not change their insulin levels, and it normalizes their diabetes. So, the role of glucagon is huge. And so, if you have glucagon releasing blood sugar and then insulin trying to keep it down, if you have that battle going on 24/7, A, it's very exhausting for your pancreas and your insulin. And B, it creates a state where you're constantly having to release insulin to mitigate your high resting blood sugar levels in the fasted state as well as after you're eating. 

And what's really, really interesting about GLP-1, peptides, hormones, is that the effect on glucagon, so they reduce glucagon, which is creating this issue of high fasted blood sugars. The effect on insulin is glucose dependent, so they don't cause the pancreas to release insulin in the fasted state. It's from when the body is metabolizing glucose. So basically, the benefit of GLP-1 is it's actually creating helping your body. I'm not saying this as an advertisement for semaglutide, but GLP-1, which semaglutide is acting like is helping create the ideal state of insulin and glucagon in your body. It's helping create a state where you're not releasing blood sugar all the time, not having high fasting blood sugar. And then you are releasing insulin when you need it, when you're eating carbs and sugar, and you're able to properly store that and it increases insulin sensitivity. So, I think that can help explain why it's actually helpful with the insulin release. There's like some context to it. And then what's interesting as well about the muscle piece is because I read an article also by Peter Attia, I was looking at it again, I think it was-- so you said you listened to him talk about that on a podcast, right? 

Vanessa Spina: Yeah. It was from a podcast I think or from an article that he wrote about a podcast, maybe transcript. 

Melanie Avalon: I think that's, yeah, because I was reading that article as well because he was talking about that 8 trial that you mentioned. 

Vanessa Spina: SUSTAIN 8. Yeah. 

Melanie Avalon: Yeah. The SUSTAIN 8. He also mentioned. I find this really interesting because I agree that the muscle loss is very scary. I have two thoughts to complicate it further because I think okay, step back. I think the majority of people, and I don't know this as a fact, but I would assume the majority of people, a majority of people going on semaglutide for weight loss on their own rogue or with the doctor, they might not be prioritizing protein, they might just be taking it and not eating. So, [chuckles] they’re just like losing weight, fat and muscle. What's really interesting is apparently, despite those shockingly high muscle losses that were seen in the STEP trials in these STEP 1 patients, even though they lost a ton, they actually increased their lean mass to body fat mass proportion by 3%. And in the SUSTAIN 8, they increased their lean mass to fat mass proportion ratio by 1%. So, while it was a shocking amount of weight loss and muscle loss, their body composition was actually slightly better in the muscle to fat ratio.

That said and this is what Peter talks about in his article, he talks about how maybe that muscle loss is something that I don't want to say is okay, but people who are severely obese or overweight, they can afford it if they maintain muscle thereafter. But for people who are-- so many people are like normal weight and using this or they're only a little bit overweight and they're trying to use this to lose weight. And I just think the muscle loss is a big concern and especially if you're not prioritizing maintaining muscle. I would be so curious. I would love to see studies on semaglutide in people on a very high protein diet. So, people who are like and who are resistant training-- I'd be really curious if they experience the muscle loss or not. I don't know if we have studies on that. So, stepping back from all of it and I didn't know I'm so glad you talked about that. I did not know that, Vanessa, about the half-life and the long-term effects, you were talking about people like the stomach paralysis. That's terrifying. When I first learned about semaglutide and I learned that it makes your stomach, like, delays gastric emptying, I mean, I have such a fear of constipation. I was like, “Nope.” I was like, “You cannot pay me to put that in my body.” That is terrifying to me. So, to step back from all of it, GLP-1 as a natural substance, that's so interesting Vanessa, about the 2 minutes, you said 2 minutes is what the normal half-life is compared to seven days. 

Vanessa Spina: So short. [chuckles] 

Melanie Avalon: That's concerning that you're-- yeah, 2 minutes versus seven days.

Vanessa Spina: But that's the whole point, like you said, is the people who are taking semaglutide are the people who are not prioritizing protein and that's probably why they're struggling and they're probably not doing resistance training and so they are the most at risk for that muscle loss. And again, if you're like morbidly obese, it's probably worth it and you'll probably be fine because like you said those ratios will even out and a lot of the people in those studies were obese. But if you're taking it and you're taking it as like a vanity drug or something and you are not morbidly obese, that also puts you at a higher risk for losing more lean mass, right? 

Melanie Avalon: Yeah. I really personally would only take it, I think, if I was obese and if I did not have a fear of constipation and if I was hardcore prioritizing protein and resistance training during that weight loss phase. I just think that's so, so important. So many people are just trying to take it off label, which is legal. Doctors can prescribe it for weight loss, it's just considered off label. It's only approved for-- Vanessa mentioned the different things it's approved for. And even with the weight loss one that's approved, you actually have to technically have another condition, another metabolic issue as well alongside it or cardiovascular issue. But the thing is, a lot of people who are very obese probably have metabolic syndrome, so they probably do have one of the criteria.

Vanessa Spina: One of the weird things about it that I've been hearing lately is that it's popping up in malls. And even there was one person who said that their nail salon or it was either nail salon or hair salon is now offering it. So, I think it's just like people are seeing that it's selling so well. It's so popular that there's probably going to be those kinds of unregulated situations showing up. It's the same thing as maybe like getting Botox, like where you get your nails done or whatever. You definitely would want to see a physician about it or your physician who can track you and make sure that it's something that's potentially safe for you. But the side effects of it are so scary to me. I would not let anyone in my family or friends go on it because the risk of your stomach becoming paralyzed. I mean, I don't have anyone right now in my family who's morbidly obese. 

You probably have to weigh the risks if that's like your situation and if you feel like you've tried everything and nothing has worked for you. I just think that there are so many healthy alternative ways of getting a lot of the benefits of appetite suppression, for example, that don't have the risk of these side effects and ultimately are more long term. Like, the results will be more long term. Because my biggest concern is what is going to happen to these people when they stop taking it, if you have to take it for a whole year after just to maintain, what's going to happen when they stop injecting themselves every week or do they have to do it for the rest of their lives? 

Melanie Avalon: Well, to that point, kind of like with Candice's question, because it sounds like her dad was doing IF, he was doing well, he got sick, he had to stop IF and he gained weight, so probably stopping the IF is the reason he gained weight, because the IF was working with him to either maintain or lose weight. So, then he goes on semaglutide. It sounds like then he started maintaining his weight. He didn't lose weight, but he wasn't gaining. And so, it sounds like maybe semaglutide was keeping him from gaining weight, and then he stopped the semaglutide goes back on IF and is gaining weight. It could be multifactorial. It could be a long-term effect, like Vanessa was saying earlier and just now. Now he's no longer on this drug and might be having residual side effects that have made it worse than before being on it. And now he's gaining weight even though he's doing IF. So I will say and I agree completely with Vanessa that the lifestyle way is how I would go this and actually so is there a natural compound that increases GLP-1 naturally in your body? Yes.

So, berberine, which I have a berberine by AvalonX and I am obsessed with my berberine. So, it's a plant alkaloid. There're a lot of studies on it for its beneficial effects on blood sugar control, glucose metabolism, its effects on insulin and the mitochondria and even AMPK. And there are quite a few studies showing that it increases GLP-1 in the intestines and has positive effects on glucose metabolism. And that's been theorized that might be one of the ways that it works so well for diabetes and blood sugar control. And then it has a lot of benefits beyond that for blood sugar control but it does directly affect GLP-1. So, what I would suggest, I think is you can take something like berberine. So Berberine is not going to make you lose weight because it's not going to have that effect of semaglutide where you're just not eating and your stomach is paralyzed. But if you want to get these GLP-1 enhancing benefits, you could take something like berberine and then use your dietary approach and lifestyle to address the natural calorie restriction and reduced appetite, like fasting. 

So fasting will do that on a high protein diet, a whole foods-based diet, that's what I would do. And that's completely sustainable. And berberine is going to have benefits and it's been used for thousands and thousands of years in traditional Chinese medicine and ayurvedic medicine. So that's what I would personally do. That would be my semaglutide hack. Again, it's not going to wipe out your appetite and make you stop eating but you will get some of that GLP-1 enhancing effect. 

Vanessa Spina: I love that. [chuckles] It is awesome. Another one that does it is protein. So, one of the reasons consuming protein is so satiating is when you consume dietary protein, you get GLP-1 secreted from the gut. You get CCK, you get peptide YY and all of these are secreted in the gut, as we talked about and they diminish and suppress appetite and they also decrease ghrelin levels or the gremlin. My friend, Dr. John Lemanski always calls it the gremlin hormone. The ghrelin which is the hunger hormone, you know, just prioritizing protein can also be a semaglutide hack, maybe with some berberine together [chuckles] too, but also intermittent fasting, fasting doing-- I know you eat more of a higher carb diet but there're a lot of benefits to doing restricted carbohydrate. It's one option for people that does really suppress hunger with the ketones. There're just so many ways that you can get the benefits that are very similar to these peptides without having to take on all the risks.

Melanie Avalon: Sounds like we're on the same page. 

Vanessa Spina: Love the questions. I'm so glad we got to talk about this, it's so topical right now. 

Melanie Avalon: Me too. And if listeners would like to get my berberine, they can go to avalonx.us and the coupon code MELANIEAVALON will get you 10% off. You can get a 20% off code if you text AVALONX to 877-861-8318. Okay. Anything from you, Vanessa, before we go? 

Vanessa Spina: Make sure to sign up for Tone Protein at [laughs] toneprotein.com as well. 

Melanie Avalon: Oh, yes. Oh, yes. Which by the time this comes out, will that be?

Vanessa Spina: It should be out, yes. So, if you are signed up at Tone Protein, you will get the launch discount for it. Yeah, it should be out and available by then. So that's toneprotein.com.

Melanie Avalon: Awesome. Well, this has been absolutely amazing. If listeners would like to submit their own questions for the show, they can directly email questions@ifpodcast.com or they can go to ifpodcast.com and submit questions there. The show notes will have links to everything that we talked about and a transcript. That is at ifpodcast.com/episode346. And you can follow us on Instagram. We are @ifpodcast, I am @melanieavalon, and Vanessa is @ketogenicgirl. I think that's all the things. Anything from you, Vanessa, before we go?

Vanessa Spina: I had so much fun with you and can't wait to record more next week. 

Melanie Avalon: Me too. This was so fun. I will talk to you next week.

Vanessa Spina: Sounds great. Bye.

Melanie Avalon: Bye.

Thank you so much for listening to The Intermittent Fasting Podcast. Please remember everything we discussed on this show does not constitute medical advice and no patient-doctor relationship is formed. If you enjoyed the show, please consider writing a review on iTunes. We couldn't do this without our amazing team, administration by Sharon Merriman, editing by Podcast Doctors, show notes and artwork by Brianna Joyner, transcripts by SpeechDocs, and original theme composed by Leland Cox and re-composed by Steve Saunders. See you next week.

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