A Plant-Based Diet for Weight Loss: Boosting GLP-1 and Restoring Our Natural Satiety Circuit

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Why does our natural GLP-1 satiety mechanism fail, and what can we do about it?

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Vegetarian diets appear to offer significant benefits for weight reduction. Might the appetite-suppressing hormone GLP-1 have anything to do with that? Let’s compare the GLP-1-inducing effects of a meaty meal versus a plant-based one, with the same number of calories, on gastrointestinal hormone responses. I mean, we know the intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity, and leads to increased oxidative stress. However, its effect on the secretion of after-meal gut hormones, like GLP-1, has been unclear. So, what happens when people either with or without diabetes eat a pork burger with cheese, versus a plant-based burger made with couscous and oats?

For those with diabetes, there was a doubling of GLP-1 half an hour after the plant-based burger was eaten, compared to the meat burger. But if you compare the two meals, although they were matched for calories, they were not matched for macronutrients. The meaty meal had more protein and fat, and fewer carbohydrates. And since different macros can affect GLP-1 differently, the difference in GLP-1 secretion may have had more to do with the macros than the meat. Okay, so, how about using a tofu burger that’s macronutrient matched? People with diabetes had a significantly higher increase in GLP-1 release after the veggie meal, compared to the meat meal, just like in the last study. But if you remember, in the last study, the veg meal only seemed to boost GLP-1 secretion in those with diabetes. Was that because of the macro mismatch as well? There’s only one way to find out.

A randomized crossover trial tested the effects of two meals, matched in calories and macronutrients, using the same tofu burger versus a conventional meat burger. And compared to the meat meal, the vegan meal boosted GLP-1 levels by 42 percent in those with diabetes, and was about just as effective in boosting GLP-1 in those without diabetes.

Does that actually translate into improving satiety, though? Yes: “A plant-based meal increases gastrointestinal hormones and satiety more than an energy- and macronutrient-matched processed-meat meal in type 2 diabetic, obese, and healthy men.” Satiety was greater in all participants after the vegan meal compared to the meaty one. And since enhancing satiety is one of the major challenges in the dietary treatment of obesity and type 2 diabetes, plant-based meals may be an effective strategy in solving this problem.

But does this actually translate into eating less? Researchers had study participants consume a pasta lunch at an all-you-can-eat buffet with ground plant-based meat versus ground beef, and participants consumed significantly fewer calories of the pasta with the plant-based burger meat. Yet, despite eating less, they felt just as satisfied, full, and satiated. But this was unlikely to be a GLP-1 effect, since rather than GLP-1 driving lower food intake, lower food intake appeared to drive lower GLP-1.

If you look at the effects of mycoprotein, which make up meat substitutes like Quorn, made from the mushroom kingdom rather than the plant kingdom, mycoprotein not only shows a decrease in caloric intake at an all-you-can-eat meal, but so suppresses subsequent appetite that there’s a decrease in intake over the entire day. When researchers compared it to eating chicken, they saw a significantly decreased calorie intake during the mycoprotein meal that was not compensated for later in the day, which led to an average caloric reduction over the whole day by 188 calories. And, this was accomplished without altering GLP-1.

So, GLP-1 may not be the reason plant-based meals tend to be more satiating, or why whole food plant-based diets apparently achieve greater weight loss than any other diet. Maybe it’s because plant-based diets are associated with an improved gut microbiome, increased insulin sensitivity, better metabolism, and reduced calorie density. Dietary fiber alone can improve your microbiome and reduce calorie density, and a few types of fiber may be able to also boost GLP-1.

L-cells, the specialized cells lining our digestive tract that produce appetite-suppressing hormones like GLP-1, have receptors on their surface that respond to carbohydrates, proteins, and fats––as well as detect bitter compounds, like the quinine in tonic water that I’ve talked about before, as well as pungent molecules, as I detailed in my video on spices. But if these cells churn out appetite-suppressing hormones in response to detecting carbs, proteins, and fats, why do we have an obesity epidemic? Why are so many people gaining so much weight?

The problem is the majority of GLP-1-producing L cells are located at the lower part of our digestive tract, way at the end of our small intestine, known as the distal ileum, and especially in our colon. Unfortunately, the majority of digested nutrients are absorbed in the upper GI tract high in our small intestine, so don’t reach the distal ileum and colon, where L-cells are highly abundant. And so, we may rarely activate a natural satiety mechanism known as the ileal brake, which you may remember from my Evidence-Based Weight Loss presentation.

The ileal brake is the intestinal feedback mechanism that tamps down our hunger. As soon as calories reach the ilium, the end of our small intestine, L-cells are activated, and GLP-1 is produced, which puts the brakes on eating more. Our appetite is dialed down, and the rate at which food leaves our stomach slows. This can be shown experimentally. If you insert a nine-foot tube down people’s throats and drip in any calories––fat, protein, or sugar––you can activate the ileal brake. Then, when they sit down to an all-you-can-eat meal, (compared to individuals in the placebo group who had just gotten a squirt of water through the tube), they eat over 100 calories less. With the ileal brake on, you just don’t feel as hungry. You feel just as full, eating significantly less. That’s the ileal brake in action.

But our natural GLP-1 satiety mechanism fails, because most food components are rapidly digested and absorbed at the beginning of our small intestine, and don’t make it way down to the end of the small intestine where our GLP-1-secreting cells are concentrated. Well, that’s dumb. Why would our body design an appetite regulation system based on calories ending up in our colon, when most calories get absorbed way before that, no matter how much we eat?

Because when we were evolving there was no such thing as table sugar. There was no such thing as Wonder Bread. No such thing as vegetable oil. For the millions of years before we began to sharpen spears, mill grains, or boil sugarcane, our entire physiology is presumed to have evolved in the context of eating what our great ape cousins did: a diet comprised of leaves, roots, fruits, and nuts. We started using tools during the Paleolithic period, which only goes back about two million years, but we and other great apes have been evolving since the Miocene era, which goes back as far as 20 million years. So, for as much as the first 90 percent of our hominoid existence, our body evolved on mostly whole plant foods.

Here’s why that matters. Animal cells are encased only in easily digestible membranes, which allow the enzymes in our gut to effortlessly liberate the calories within a steak, for example. Plant cells, on the other hand, have cell walls that are made out of fiber, which acts as an indigestible physical barrier; so, many of those calories remain trapped until the good gut bugs in our colon eat that fiber and spill out the contents of plant cells to signal GLP-1 release.

When we get our calories, our protein, fat, and carbs (like the sugars in milk) from animal foods, they get absorbed early in the small intestine, and never get to activate many of the satiety cells that secrete GLP-1 hormones, which are concentrated farther down. It’s the same when you consume processed plant foods. Chug down sugar water, white flour, and oil, and the exact same thing happens. But what if you walled off your calories––in other words, tried to make sure as many of your calories as possible (your protein, your carbs, your fat) were encased in cell walls? In other words, from whole, intact, plant foods?

Let’s say you eat a nut. No matter how well you chew, little bits of nut containing hundreds of thousands of intact cells are going to make it down to your colon, where the fat can be released by fiber-eating bacteria to activate GLP-1 secretion. You can see the bacteria breaking into the cells and nom-nomming all the goodies. The same happens when you eat an apple or steel-cut oats. Instead of all the sugar and starch getting absorbed earlier, like if you drank apple juice or ate a cracker, some of the carbs spill out further down to activate your satiety hormones.

Even though the milling of whole grains into flour can break open all the grains’ cell walls, whole-grain bread is still better than white bread, because whole-grain at least has extra fiber that makes it down to our colon. There, our good gut bugs can turn the fiber into short-chain fatty acids that can activate GLP-1 secretion on their own. And, fiber has a gelling property that can trap other calories in the meal, and pull them further down the intestine. Chug a third-of-a-cup (80 ml) of oil on a high-fiber diet, and more than twice as much fat makes it to your colon than when you have the same amount of oil on a low-fiber diet. In other words, even if you ate a donut on an otherwise high-fiber diet, some of the donut calories could still make it far enough to help dial down your hunger.

So, we have to make sure our calories get all the way down to the end of our small intestine for a sustained release of GLP-1. And dietary fiber can help do that by slowing the digestion and absorption of the calories we eat to maximize their activity in sustaining the secretion of GLP-1.

So, part of the “slow digestion strategy” to sustain GLP-1 secretion is dietary fiber to slow down the digestion of nutrients. This strategy has been proposed as a dietary approach to mimic the function of bariatric surgery. Because certain procedures can entail literally cutting out part of your small intestine, nutrients get dumped further down, causing a big GLP-1 ileal brake response.

So, the modern medical solution to this mismatch between the foods we were built to eat, that naturally activate satiety circuits, and the processed junk we’re now being sold is to physically, surgically change our anatomy to force it to the end of our gut, or inject GLP-1 mimicking drugs, so we get GLP-1 activation regardless of what we eat.

It’s funny, you’ll read how “almost no nutrients” make it down to where the GLP-1 producing cells are, “under normal situations.” But by “normal” they mean, donuts for breakfast. When, really, normal-for-our-species is eating so many unprocessed plant foods that we’re knocking down triple-digit grams of fiber every day. That entails massive amounts of whole plant foods. So, to restore our natural satiety circuits, we can go under the knife, under the needle, or just eat the way nature intended.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Vegetarian diets appear to offer significant benefits for weight reduction. Might the appetite-suppressing hormone GLP-1 have anything to do with that? Let’s compare the GLP-1-inducing effects of a meaty meal versus a plant-based one, with the same number of calories, on gastrointestinal hormone responses. I mean, we know the intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity, and leads to increased oxidative stress. However, its effect on the secretion of after-meal gut hormones, like GLP-1, has been unclear. So, what happens when people either with or without diabetes eat a pork burger with cheese, versus a plant-based burger made with couscous and oats?

For those with diabetes, there was a doubling of GLP-1 half an hour after the plant-based burger was eaten, compared to the meat burger. But if you compare the two meals, although they were matched for calories, they were not matched for macronutrients. The meaty meal had more protein and fat, and fewer carbohydrates. And since different macros can affect GLP-1 differently, the difference in GLP-1 secretion may have had more to do with the macros than the meat. Okay, so, how about using a tofu burger that’s macronutrient matched? People with diabetes had a significantly higher increase in GLP-1 release after the veggie meal, compared to the meat meal, just like in the last study. But if you remember, in the last study, the veg meal only seemed to boost GLP-1 secretion in those with diabetes. Was that because of the macro mismatch as well? There’s only one way to find out.

A randomized crossover trial tested the effects of two meals, matched in calories and macronutrients, using the same tofu burger versus a conventional meat burger. And compared to the meat meal, the vegan meal boosted GLP-1 levels by 42 percent in those with diabetes, and was about just as effective in boosting GLP-1 in those without diabetes.

Does that actually translate into improving satiety, though? Yes: “A plant-based meal increases gastrointestinal hormones and satiety more than an energy- and macronutrient-matched processed-meat meal in type 2 diabetic, obese, and healthy men.” Satiety was greater in all participants after the vegan meal compared to the meaty one. And since enhancing satiety is one of the major challenges in the dietary treatment of obesity and type 2 diabetes, plant-based meals may be an effective strategy in solving this problem.

But does this actually translate into eating less? Researchers had study participants consume a pasta lunch at an all-you-can-eat buffet with ground plant-based meat versus ground beef, and participants consumed significantly fewer calories of the pasta with the plant-based burger meat. Yet, despite eating less, they felt just as satisfied, full, and satiated. But this was unlikely to be a GLP-1 effect, since rather than GLP-1 driving lower food intake, lower food intake appeared to drive lower GLP-1.

If you look at the effects of mycoprotein, which make up meat substitutes like Quorn, made from the mushroom kingdom rather than the plant kingdom, mycoprotein not only shows a decrease in caloric intake at an all-you-can-eat meal, but so suppresses subsequent appetite that there’s a decrease in intake over the entire day. When researchers compared it to eating chicken, they saw a significantly decreased calorie intake during the mycoprotein meal that was not compensated for later in the day, which led to an average caloric reduction over the whole day by 188 calories. And, this was accomplished without altering GLP-1.

So, GLP-1 may not be the reason plant-based meals tend to be more satiating, or why whole food plant-based diets apparently achieve greater weight loss than any other diet. Maybe it’s because plant-based diets are associated with an improved gut microbiome, increased insulin sensitivity, better metabolism, and reduced calorie density. Dietary fiber alone can improve your microbiome and reduce calorie density, and a few types of fiber may be able to also boost GLP-1.

L-cells, the specialized cells lining our digestive tract that produce appetite-suppressing hormones like GLP-1, have receptors on their surface that respond to carbohydrates, proteins, and fats––as well as detect bitter compounds, like the quinine in tonic water that I’ve talked about before, as well as pungent molecules, as I detailed in my video on spices. But if these cells churn out appetite-suppressing hormones in response to detecting carbs, proteins, and fats, why do we have an obesity epidemic? Why are so many people gaining so much weight?

The problem is the majority of GLP-1-producing L cells are located at the lower part of our digestive tract, way at the end of our small intestine, known as the distal ileum, and especially in our colon. Unfortunately, the majority of digested nutrients are absorbed in the upper GI tract high in our small intestine, so don’t reach the distal ileum and colon, where L-cells are highly abundant. And so, we may rarely activate a natural satiety mechanism known as the ileal brake, which you may remember from my Evidence-Based Weight Loss presentation.

The ileal brake is the intestinal feedback mechanism that tamps down our hunger. As soon as calories reach the ilium, the end of our small intestine, L-cells are activated, and GLP-1 is produced, which puts the brakes on eating more. Our appetite is dialed down, and the rate at which food leaves our stomach slows. This can be shown experimentally. If you insert a nine-foot tube down people’s throats and drip in any calories––fat, protein, or sugar––you can activate the ileal brake. Then, when they sit down to an all-you-can-eat meal, (compared to individuals in the placebo group who had just gotten a squirt of water through the tube), they eat over 100 calories less. With the ileal brake on, you just don’t feel as hungry. You feel just as full, eating significantly less. That’s the ileal brake in action.

But our natural GLP-1 satiety mechanism fails, because most food components are rapidly digested and absorbed at the beginning of our small intestine, and don’t make it way down to the end of the small intestine where our GLP-1-secreting cells are concentrated. Well, that’s dumb. Why would our body design an appetite regulation system based on calories ending up in our colon, when most calories get absorbed way before that, no matter how much we eat?

Because when we were evolving there was no such thing as table sugar. There was no such thing as Wonder Bread. No such thing as vegetable oil. For the millions of years before we began to sharpen spears, mill grains, or boil sugarcane, our entire physiology is presumed to have evolved in the context of eating what our great ape cousins did: a diet comprised of leaves, roots, fruits, and nuts. We started using tools during the Paleolithic period, which only goes back about two million years, but we and other great apes have been evolving since the Miocene era, which goes back as far as 20 million years. So, for as much as the first 90 percent of our hominoid existence, our body evolved on mostly whole plant foods.

Here’s why that matters. Animal cells are encased only in easily digestible membranes, which allow the enzymes in our gut to effortlessly liberate the calories within a steak, for example. Plant cells, on the other hand, have cell walls that are made out of fiber, which acts as an indigestible physical barrier; so, many of those calories remain trapped until the good gut bugs in our colon eat that fiber and spill out the contents of plant cells to signal GLP-1 release.

When we get our calories, our protein, fat, and carbs (like the sugars in milk) from animal foods, they get absorbed early in the small intestine, and never get to activate many of the satiety cells that secrete GLP-1 hormones, which are concentrated farther down. It’s the same when you consume processed plant foods. Chug down sugar water, white flour, and oil, and the exact same thing happens. But what if you walled off your calories––in other words, tried to make sure as many of your calories as possible (your protein, your carbs, your fat) were encased in cell walls? In other words, from whole, intact, plant foods?

Let’s say you eat a nut. No matter how well you chew, little bits of nut containing hundreds of thousands of intact cells are going to make it down to your colon, where the fat can be released by fiber-eating bacteria to activate GLP-1 secretion. You can see the bacteria breaking into the cells and nom-nomming all the goodies. The same happens when you eat an apple or steel-cut oats. Instead of all the sugar and starch getting absorbed earlier, like if you drank apple juice or ate a cracker, some of the carbs spill out further down to activate your satiety hormones.

Even though the milling of whole grains into flour can break open all the grains’ cell walls, whole-grain bread is still better than white bread, because whole-grain at least has extra fiber that makes it down to our colon. There, our good gut bugs can turn the fiber into short-chain fatty acids that can activate GLP-1 secretion on their own. And, fiber has a gelling property that can trap other calories in the meal, and pull them further down the intestine. Chug a third-of-a-cup (80 ml) of oil on a high-fiber diet, and more than twice as much fat makes it to your colon than when you have the same amount of oil on a low-fiber diet. In other words, even if you ate a donut on an otherwise high-fiber diet, some of the donut calories could still make it far enough to help dial down your hunger.

So, we have to make sure our calories get all the way down to the end of our small intestine for a sustained release of GLP-1. And dietary fiber can help do that by slowing the digestion and absorption of the calories we eat to maximize their activity in sustaining the secretion of GLP-1.

So, part of the “slow digestion strategy” to sustain GLP-1 secretion is dietary fiber to slow down the digestion of nutrients. This strategy has been proposed as a dietary approach to mimic the function of bariatric surgery. Because certain procedures can entail literally cutting out part of your small intestine, nutrients get dumped further down, causing a big GLP-1 ileal brake response.

So, the modern medical solution to this mismatch between the foods we were built to eat, that naturally activate satiety circuits, and the processed junk we’re now being sold is to physically, surgically change our anatomy to force it to the end of our gut, or inject GLP-1 mimicking drugs, so we get GLP-1 activation regardless of what we eat.

It’s funny, you’ll read how “almost no nutrients” make it down to where the GLP-1 producing cells are, “under normal situations.” But by “normal” they mean, donuts for breakfast. When, really, normal-for-our-species is eating so many unprocessed plant foods that we’re knocking down triple-digit grams of fiber every day. That entails massive amounts of whole plant foods. So, to restore our natural satiety circuits, we can go under the knife, under the needle, or just eat the way nature intended.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

I mentioned my Evidence-Based Weight Loss presentation. Check it out. 

This is the seventh video in my series on Ozempic. If you missed the previous ones, see: 

Stay tuned for the last two videos in the series: Using Prebiotics, Intact Grains, Thylakoids, and Greens to Boost Our GLP-1 for Weight Loss and Obesity: Is a GLP-1 Deficiency Its Cause, and How to Treat It Without Ozempic and Other Drugs.

Don’t want to wait? Get my new book, OZEMPIC: Risks, Benefits, and Natural Alternatives to GLP-1 Weight-Loss Drugs, available as an ebook, audiobook, and softcover (currently on sale for 20% off) 

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