#104 Dr. Ben Bikman: How To Reverse Insulin Resistance Through Diet, Exercise, & Sleep

“maybe first you can explain just, you know, generally how these GLP-1 agonists work and why they're causing weight loss and how they affect metabolic health, but also whether they're addressing the underlying root cause of obesity.”

“looking at the study of incretins by a drug company. And so I've long been familiar with GLP-1 and the other incretins, incretin being a word to describe these gut-derived hormones that have metabolic effects. But it's been interesting for me to note the evolution in their use because originally they were only used as anti-diabetic drugs.”

“So at the lower dose, originally used, these GLP-1 activators worked, actually by inhibiting glucagon. So back to the alpha cell that I mentioned earlier, we come back to them now, where in type 2 diabetes,”

“Now, some people have the very mistaken view that semaglutide or GLP-1 activators also release insulin. That is not true. That has been shown to happen in isolated cell cultures, but in humans, there's no evidence.”

“He's one of the absolute authorities on the subject. He's published multiple papers in humans showing that no amount of GLP-1 elicits an insulin release. So we need to put that idea to bed. In humans, that does not happen. GLP-1 does not act as what's called an insulin secretagogue or a drug that forces the beta cell to make insulin.”

“or a drug that forces the beta cell to make insulin. GLP-1 inhibits glucagon, which helps correct blood glucose. Now, as the dose starts to go up higher, I guess just for the sake of time, I'd mention two effects, which is one in the guts and then one central.”

“my concern is that the dose of GLP-1 that we're using now has gone, it's just a little too much of a good thing. What is the dose range that you were referring to, talking about? Yeah, yeah. So I think that the commonly used doses are going to be in the order of,”

“Okay. Of GLP-1. So that to me is too high. And two and a half milligrams being the low dose. That is the, yeah, that's the low dose of what is used now. Right. Mm-hmm.”

“I am, as much as people will hear me describe this and think that I'm being just universally opposed, I actually do think there's a place for these GLP-1 drugs. A paper was published in 1996 that looked at the changes in GLP-1 in two populations. They took otherwise healthy humans and split them up and they noticed changes in the obese group and the lean group.”

“um, of, of these different deal, GLP-1 agonists, um, a lot of most of the people end up gaining weight back because it, you know, they go back to their old habits. Yeah. And I think that's because they're not framing. I think a part of it's the narrative or the story,”

“you know, the, I guess it's pretty well known now is that when people are rapidly losing weight, whether it's on a GLP-1 agonist or it's from caloric restriction, they can lose a lot of muscle along with the fat. Yeah. It's not just all fat. Um, particularly if people are not getting enough dietary protein, which is a big signal for muscle protein synthesis.”

“Yeah. Um, this, this kind of, there's another interesting point here and that is like GLP-1 receptors. And I mean, they're all over many different organs. The muscle has them. And so does bone. Bone. Yeah. Right.”

“And so does bone. Bone. Yeah. Right. Yeah. So that is, that is an interesting question. Neurons do. Yeah. I mean, and it also starts to touch on the broader use of GLP-1 drugs where you and I both know people are using them, uh, well beyond the, as much as I bemoan the fact that it's now an obesity drug where it was once just a diabetic drug.”

“And in, you have to wonder like, is, is this a, is there a direct effect of, you know, agonizing these GLP-1 receptors on different tissues, or is this just an indirect effect of weight loss and improved metabolic health? Yeah. Yeah. Yeah. So I, I don't know, but we, what I can speak to is our unpublished results right now in muscle cells.”

“more than doubles in people on high dose GLP-1s. It was just, a paper was just published. So you look at the degree of blindness that occurs in adults and those using the drug, it was more than twice the risk.”

“I truly don't mean to suggest the drug is causing blindness. No more than someone could say the drug is promoting longevity. Although you actually can do a hard outcome with blindness, you can't really do the hard outcome with when does the person die very well. But there's so many variables that get worked in here that I cannot say it's because of the drug.”

“all the more reason to come back to these kind of metabolic first principles. And so looking at insulin sensitivity and glucose control, and I would just say the same thing with GLP-1, while we may find that GLP-1 has a direct effect of, say, activating autophagy, maybe it could, and that could be a mechanism whereby it promotes longevity.”

“Yeah. In fact, they're not measuring insulin, but glucose. Yeah. Right. Yeah. So to answer the question very directly, I'm an enormous advocate of CGM use. The more we democratize access to CGMs, I think the better we put individuals in a position to be their own coach.”

“They don't need to have someone like you berating them and telling them to change their habits and eat a little better. When you see how your body's responding to what you're eating and the CGM enables that, you end up making your own lifestyle changes. So with the use of the CGM, fasting glucose isn't going to be the best indicator.”

“aren't back down to normal by about two hours, that suggests a problem. So in my mind, the greatest utility of the CGM is to monitor the dynamic changes rather than the static, where am I at every morning? That has less value. The dynamic changes are what has value.”

“In fact, people wearing CGMs may notice this, that the CGM may reveal that they're starting to get a cold or a flu because they notice that their glucose levels, they're having a much harder time controlling them, even though their habits haven't changed.”

“Yes. Well, everything you just said, I am nodding to because I can relate. Where I, when I've worn CGMs, I absolutely see that the single most predictive variable of my glycemia in any given day is how did I sleep? Nothing that I've played around with, nothing has even come close.”

“So, you know, you hear everything from magnesium to Alpha-lipoic acid to berberine, apple cider vinegar. Yeah. And if there's any merit to that or taking it before a meal or is this just like dropping like a drop of water in the pool to like try to fill the pool up?”

“It's constantly pushing the liver to make more glucose. Apple cider vinegar will inhibit that. And so it helps the blood glucose by just having the liver dump less glucose into the blood. But it also stimulates AMPK. And you'd mentioned GLUT4 at the muscle.”

“Including mitochondrial biogenesis and a little bit of uncoupling. Where apple cider vinegar is one of my favorites. Where if you take a couple tablespoons. Before your most starchy meal. You absolutely could compare the glucose curve from one day to the next.”

“But with regards to beta-hydroxybutyrate, even exogenous ketones. That wasn't one you mentioned, but there are increasing studies showing that you can have. There was just a study in women with PCOS. The only intervention was to give them exogenous ketones. And every outcome related to metabolic markers and PCOS got better. And the only change was the supplementation with exogenous ketones.”

“ketones. Well, this is where exogenous ketones, I think, become so helpful. Where if you have someone who just says, I just don't want to do the ketogenic diet, but I still would like some of the benefits. There are so many good options nowadays.”

“dose of ketones to activate, you know, these beneficial signaling pathways, but also to make sure that you're not, like, dipping too low, like your glucose doesn't go too low, where you're kind of like, what's going on here?”

“I would maybe counter or not counter by just stating that those also in nature, when you have the omega-6 linoleic acid, you often also have an omega-3 that comes with it. That to me is key that if you're, and often it'll have some degree, even minuscule levels of vitamin E.”

“of a nuanced view of linoleic acid in that it's everywhere. But when we get it in nature, it'll come with an omega-3 and it'll come with some amount of often vitamin E, which will help prevent the linoleic acid from going down the pathway of becoming a villain, which it can.”

“Seeds have linoleic acid in it, but they also come with other things like a degree of vitamin E and an omega-3 to some degree. And those help to varying degrees reduce the pathogenicity. Even if the linoleic acid had the potential to be harmful, which it does through peroxidation”

“carbs, I think if you're talking about the low glycemic load carbs, like cruciferous vegetables and berries and citrus fruits, for example, now there's almost nothing. And then you've chased that down with a tablespoon of coconut oil, the most concentrated form of saturated fat on the planet.”

“calories consumed globally, it's about 60%. And in the U.S. are carbohydrates. And they're not coming from leafy greens and berries and, you know, citrus fruits. It's coming from bags and boxes with barcodes. But nevertheless, that's an interesting finding. My criticism of that is, one, it's an extremely short-term study.”

“think that I'm the best dad in the world and I want them to be healthy. And I don't really bring a lot of cereal into the home. I make breakfast for the kids every morning for the most part. And it's a mix of various meals that I make. And they think, wow, my dad just loves me so much. Yes, I do. I love you all my little darling babies, but I do it because I don't”

“And then I think I need six bowls of cereal right now. And so then I will eat myself sick. And like a true addict, I will tell myself, I'll just have one bowl. What's the problem with one bowl? And then yet there's this little shoulder angel telling me, oh, but you know, you're not going to stop at one bowl. But then there's the addiction side of me saying, yeah, I am. I want this.”

“leading to the hyperglycemia that defines the diabetic state. At this low dose, semaglutide inhibits the alpha cell. It inhibits glucagon. And by inhibiting glucagon, you're helping correct blood glucose. So it was an effective anti-diabetic.”

“Now that is itself a big pool, but some of it would be muscle and bone mass, but I have not seen data that has determined whether it is a direct effect of the semaglutide. In other words, is the drug actually harming muscle and bone or is it just an artifact of the poor nutrition?”

“And the short chain in the human diet, as much as we eat a lot of fat, most of it is from seed oils and soybean oil. But we lose out on the full spectrum of fats because we don't really eat a lot of fermented foods anymore.”

“Because of how we eat them, we eat them from refined seed oil sources. Dr. Christopher Ramsden at the NIH a number of years ago, published a report finding that soybean oil has become the number one consumed source of fat calories in the human diet. That's not good. And so I think it's appropriate for us to call them seed oils rather than linoleic acid”

“I actually described this in my book, Why We Get Sick”

“My pleasure. People, so you mentioned your book. Yep, yeah, Why We Get Sick. Yeah, Why We Get Sick and then a follow-up companion, How Not To Get Sick. How Not To Get Sick, that's to be coming soon.”

“if you are simply living in an inner city area and there's just pollution there's nothing you can really do about it you can't do maybe you can replace your internal in-home air filter more frequently and get one and but those aren't cheap either so I'm very mindful of the financial constraints of the person who we may be fictionally talking about”

“Sugary fruits and vegetables or the starchy fruits and vegetables. So the tropical fruits we said, please be careful with like bananas, pineapples, mangoes, and then the starchy, if the vegetable grows in the ground, eat less of it relatively, but all other fruits and vegetables, and that's still a lot enjoy liberally and then prioritize protein and don't fear the fat that comes with that protein.”

“So, you know, you hear everything from magnesium to Alpha-lipoic acid to berberine, apple cider vinegar. Yeah. And if there's any merit to that or taking it before a meal or is this just like dropping like a drop of water in the pool to like try to fill the pool up?”

“even some medications like birth control medications don't work anymore, for example, because you've so changed how long it takes that drug to get from the stomach into the small intestine”

“Yep. I mean, all these different short chain fatty acids. Well, the short chain fatty acids that you're getting from foods. And then there's another. Malate's also in like blueberries. Malic acid. Yeah. Malic acid's in them. And then. So just my sort of wheels are turning here when you're mentioning that because it'd be so fascinating to see if there's a common mechanism.”

“and which is not going to break your fasted state. Even if you put a little butter, I don't consider that as breaking a fasted state because I define fast as the endocrinology, the nutrients rather than the calories. But that's a topic for another time.”

“It's the potato chip. Because it's been fried. But what's it been fried in? It's been fried in corn oil or whatever. So you not only have a concentrated source of omega-6, but it's undergone this superheating. And now it's absolutely gone through some peroxidation.”

“controlled trial on creatine for Alzheimer's disease. We believe that you won't find this information anywhere else, and I encourage you to subscribe today so you can receive the very next email newsletter. You can find that at foundmyfitness.com forward slash newsletter.”

“carbs, I think if you're talking about the low glycemic load carbs, like cruciferous vegetables and berries and citrus fruits, for example, now there's almost nothing. And then you've chased that down with a tablespoon of coconut oil, the most concentrated form of saturated fat on the planet.”

“I don't know. So we have just the whole animal data so far, and then the next step will be isolating individual particles to try to find out, all right, which culprit, if one culprit, is more to blame with regards to the e-cig exposure versus the cigarette because it is different chemicals.”

“But we lose out on the full spectrum of fats because we don't really eat a lot of fermented foods anymore. So we don't get the medium chain fats. And because we don't eat any much fermentation. Fermented foods, we don't get any short chain fats for the most part.”

“They are. And is there something that would be so interesting to look at? To see if there's something going on with lactate, acetate, malate, right? Like that's in like a Granny Smith apple or something. Like the more sour apple, right? Yep. I mean, all these different short chain fatty acids.”

“I'd say there are better ways to do it. Like, not that I'm endorsing any intervention like this, but you'd be better off just focusing on growth hormone than you would injecting yourself with insulin. So I am not a fan. Now, I appreciate some big yoked bodybuilder looking at relatively svelte, small Ben Bickman and saying, well, what do you know?”

“Yeah, Why We Get Sick and then a follow-up companion, How Not To Get Sick.”

“ability to eat something like this, something sweet, like an ice cream or a cereal and just have a little bit of it and be done. I can't do that. She is a moderator and I am an addict when it comes to these kinds of things, which is one of the reasons why I don't love a lot of the modern things.”

“Sugary fruits and vegetables or the starchy fruits and vegetables. So the tropical fruits we said, please be careful with like bananas, pineapples, mangoes, and then the starchy, if the vegetable grows in the ground, eat less of it relatively, but all other fruits and vegetables, and that's still a lot enjoy liberally and then prioritize protein and don't fear the fat that comes with that protein.”

“I probably should have mentioned this earlier when we were talking about the late-night snacking, but the fact that melatonin shuts down insulin production in the pancreatic beta cells is probably Yeah, hyperglycemia disrupts melatonin too. So even back to the glucose mechanism, another reason to not go to bed hyperglycemic is it disrupts the melatonin rhythm at the same time.”

“People are consuming these seed oils in processed foods, right. They're all in processed foods versus eating some, like you said, meats, you know, walnut. I mentioned nuts because they have a higher ratio, but they also. You know, have omega-3s as well. So I do think it's a nuanced topic as well.”

“the diabetic who's gone hypoglycemic can just drink a cup of orange juice. And within minutes, it'll start to, you know, that's such a concentrated load of fructose”

“And they would still have food in their stomach even though they hadn't eaten for 24 hours. So this results in what people colloquially just call ozempic burps, where they just have putrid breath and burping and just stomach nausea. But because of the change in gastric emptying,”

“Sugary fruits and vegetables or the starchy fruits and vegetables. So the tropical fruits we said, please be careful with like bananas, pineapples, mangoes, and then the starchy, if the vegetable grows in the ground, eat less of it relatively, but all other fruits and vegetables, and that's still a lot enjoy liberally and then prioritize protein and don't fear the fat that comes with that protein.”

“and the cell will burst. Wow. I was just starting to think about prunes, because prunes are, like, high in sorbitol. Yeah, so what's funny, though, when I teach this concept to my students, you can tell I'm the... I'm an ultimate professor here. I teach all these ideas.”

“you can tell I'm the... I'm an ultimate professor here. I teach all these ideas. I actually have my students, as a funny little assignment, look up the customer reviews of sugar-free gummy bears. And it's so funny, because these derivatives of glucose, like sorbitol or mannitol, they can't move across cell membranes.”

“rapid weight loss and weight loss that's made very easy by taking GLP-1 agonist drugs, things like Ozempic and Wegovy”

Also filed under GLP-1 Agonists