One concept I have for food that really helps me is really thinking about the body's always trying to help me be satiated and trying to help reduce my cravings. I literally just have to give the body what it needs. I have to stimulate the body in a way that it will serve me in giving me satiety hormones to basically regulate my hunger.

And again, with visuals I think it's so helpful. I think about these cells lining our small intestine that literally have nutrient sensors and literal receptors on the cell membrane in the luminal side of the gut that's facing all the food that are just sitting there waiting to bind with these things in our food that will stimulate the cell to make the satiety hormone that poof, effortlessly makes us not hungry, gets rid of that grip of attachment to cravings that all of us are so plagued by.

And I think we have this intense conversation happening in society right now about GLP-1 analogs and Ozempic and Menjara and all these things, GLP-1 agonists, but we rarely talk about the fact that we have nutrient sensing cells of the gut, the L cells of the gut, that when stimulated appropriately will make GLP-1.

And when stimulated the way they want to be will secrete hordes of GLP-1 for us. And so how do we actually think about just literally giving the body what it needs to stimulate the satiety hormones? And the processed foods aren't giving us those things. You know, the things that are going to stimulate those cells – well, the things that will – I mean, this is kind of fascinating if you don't mind going down a little road.

No, please. Yeah. Please. With the GLP-1 conversation, I feel like so missing from the conversation is the idea that like from a first principles perspective, there's three ways our body could make more GLP-1. We make more cells that make it, L cells of the gut. Each of those cells makes more GLP-1, and importantly, we can also inhibit the inactivator of GLP-1, which is an enzyme called DPP-4.

So GLP-1 actually gets rapidly degraded by DPP-4 in the body. So if we can figure out how to inhibit DPP-4, we can raise our GLP-1 levels. What is DPP-4? It's an enzyme that breaks down GLP-1 rapidly. Got it. Thanks. I apologize. It's so fascinating. So how often have you seen in the headlines, "Oh, here's some strategies to inhibit your DPP-4." Never, because Ozempic is on track to be the highest grossing med in human history, and just like we talked about in the beginning of the episode, the whole industry, this $4 trillion healthcare industry, is desperate for us to not understand how to do the things that drugs could do for us.

So when we look at those three first principles approaches of how do we make more L cells, get them to produce more GLP-1 from each L cell, and then inhibit the breakdown through the inhibition of DPP-4, for the first one, we know that short-chain fatty acids, which of course are the byproduct of microbial fermentation of fiber in the diet, stimulates the differentiation of more L cells in the gut.

So more short-chain fatty acids, more L cells. Can we translate that into support the gut microbiome? Eat more fiber. Eat more fiber. And we had Justin Sonnenberg from Stanford on, a world expert in gut microbiome, and he was a big proponent of, based on work he's done with Chris Gardner and others at Stanford, so happens, of ingesting one to three servings of low-sugar fermented foods each day.

Things like sauerkraut, kimchi, again, low-sugar variety is probably best. Right. Not kombucha. Yeah. Maybe not. You said not kombucha? Yeah. Yeah. 'Cause that's gonna be like the highest sugar of the fermented foods, which people often go to, but now that's become soda. And often costly too. Yeah. And pretty costly.

I love sauerkraut. Oh, yeah. Tim Ferriss had a great recipe for this in "The 4-Hour Chef." You have to be careful because you can create some unhealthy ferment. You have to do it the way he describes. So check out the recipe. It's online. Or you can buy sauerkraut and the brines, drinking the brine off the sauerkraut, seems to be good for the gut.

That's such a great point, which is that ultimately we want the short-chain fatty acids, which is the medicine that the microbiome are making for us through the microbial fermentation process. And we can basically do that in three ways. One is we can eat more fiber, which is prebiotics. We can also eat more polyphenols because we're now learning that the microbiome actually processes, they ferment polyphenols from our, which is basically you'll find those in colorful fruits and vegetables, spices, teas, cocoa, things like that.

So fermentation of polyphenols and fiber to short-chain fatty acids, which then we absorb. And then, like you just said, in a fermented food, the bacteria in that food will be making short-chain fatty acids by fermenting the food in there. And then if we drink that, we're getting the short-chain fatty acids directly.

So that's the kimchi, sauerkraut, Greek yogurt, kvass, which I'm obsessed with, which is like low-sugar kombucha. It's like made with fermenting beets, basically. That's good stuff. It's such good stuff. Miso, natto. So that's one. That has been shown to differentiate more L cells in the gut. We also know that people with type 2 diabetes have much fewer L cells in the gut.

And it's hard to know what the causality is there, but I think a safe assumption is like if we keep our blood sugar under better control and sort of stay out of that diabetic range, it probably lends itself. I don't know what the chicken and the egg is there, but blood sugar stability, more L cell differentiation.

And then actually, ginseng has been shown to improve L cell differentiation. So that's just sort of one set of things. And I don't think the dose on ginseng has been settled, but very high antioxidant component plant. When we look at actually stimulating more GLP-1, you've talked about your Ramate, I think, having like a mild effect on GLP-1, but there's actually a lot of other things in the literature.

Protein, of course, very potently stimulates these nutrient receptor cells and specifically like valine and glutamine seem to have a potent stimulatory effect on GLP-1. So you're gonna find that in like meat and turkey and eggs and things like that. What are your thoughts on supplementing L-glutamine? It's controversial. I know that some people do it in an effort to relieve leaky gut, but there aren't any randomized control trials for that.

So depending on one stance on what's required for kind of a threshold for adopting something, some people will say that's crazy. Other people really swear by supplementing L-glutamine. Maybe it's through this route of increasing L-cells that some of the gut relief might exist. I guess we'd have to explore it.

So that's speculative, folks. So this is interesting. These are ways to increase the cells that then make GLP-1. So fiber, prebiotic, probiotic fiber, and fermented foods. Antioxidants, lowering blood sugar, ginseng. So those are kind of the L-cell ones. The actual secretion of more GLP-1, one of the most potent ones and the study that looks at this, like the bar graphs are very clearly statistically significant, lots of asterisks, is actually thylakoids.

Thylakoids. Tell me more about thylakoids. Thylakoids are so fascinating. Thylakoids are actually a structure in plants that are part of the chloroplasts. So chloroplasts, and this also is fascinating because chloroplasts are basically the plant version of mitochondria, essentially. And thylakoids are a molecule in the chloroplasts. And there's actually been research that shows that when you eat about 100 grams of spinach, which gives you 5 grams of straight thylakoid over 12 weeks daily, it led to a significant increase in GLP-1.

And again, I don't remember the exact, it was two or three-fold higher secretion. So that's a direct stimulatory effect of the L-cells. And so this equates to 3.5 ounces of spinach a day, which is like nothing. So just getting those... Raw spinach or cooked spinach? I don't think it actually...

It might have said in the methods, but I would imagine raw because you want to get those undenatured thylakoids in the gut. So just kind of another... Actually thylakoids do a lot of other interesting stuff. They inhibit lipase in the gut and so actually help more fat get down to the distal small bowel and promote satiety.

So this is one of the reasons why you talk about, oh, the people who eat all these healthy foods and greens, they're less hungry. It's like, it's biochemistry. There's stuff happening in there that is making the hunger signals go down through things like inhibiting lipase, improving GLP-1 secretion. So other things for GLP-1 secretion, the thylakoids, also fiber has been shown, specific amino acids, so high-protein foods, things that involve a lot of valine and glutamine, green tea, and specifically the ECGC that is one of the compounds in green tea, that's been shown to stimulate GLP-1, curcumin.

So there's several things that are all in that whole food, basically things you would associate with a healthy diet, but we actually know they stimulate GLP-1. So those are all things I try to include in my diet. And the last one is inhibition of DPP-4. And that one, there's just actually, when you look at the research, there's some kind of random foods that tend to inhibit DPP-4, black beans, Mexican oregano, other forms of oregano, rosemary, guava, and I wrote this one down because it's a word I hadn't seen very much before I started digging into this, but muricetin, which is found in berries, cranberries, and peppers, and Swiss chard.

So all that is to say, ultimately, many of us are gripped by cravings. And the idea of just not being constantly driven to eat more, which I would argue that about 80% of Americans are, feels really hard to overcome. But a lot of it is literally just communicating to your cells in a clear way through food to help you be satiated.

And the science can show us how to do this. And a lot of it comes down to eating, essentially, what you were talking about, how you eat, protein, healthy sources with nutrient density, and lots of colorful fruits, vegetables, spices, herbs, things like that. Thank you for tuning in to the Huberman Lab Clips channel.

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