Andrew Huberman explains the neuroscience of sugar cravings and practical tools to manage them
A solo episode of Huberman Lab Essentials in which Andrew Huberman covers the brain and body mechanisms behind sugar cravings and offers science-based strategies to control them.
Summary
Andrew Huberman, neuroscientist and professor at Stanford School of Medicine, presents a detailed breakdown of how the nervous system regulates sugar intake and appetite. He explains that two parallel neural pathways drive sugar-seeking behavior: one tied to the conscious perception of sweet taste and one tied to the subconscious, post-ingestive detection of blood glucose elevation in the gut. He argues that understanding these dual pathways — and the dopamine release they trigger — is the key to gaining control over sugar cravings rather than being controlled by them. He also identifies fructose, particularly from high fructose corn syrup, as especially problematic because it suppresses the hormones that would otherwise suppress ghrelin — thereby elevating ghrelin and driving hunger — meaning people eat more regardless of caloric intake. Practical tools discussed include lemon or lime juice, cinnamon, glutamine supplementation, berberine, and quality sleep, each explained through the lens of the underlying neuroscience.
Key Takeaways
FULL TRANSCRIPT
Introduction: What Happens When We Eat
Andrew Huberman: Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today we are going to discuss sugar — in particular, how our nervous system regulates our sugar intake and our seeking of sugar. We are going to place sugar into its proper context.
The way I want to start is to tell you a little bit about what happens when we eat and what the brain does to respond to those events. Let's take what I call a top-contour view of the hormonal response to ingesting food. Anytime we eat, that is the consequence of a number of things that happened before we ate. There's a hormone in our brain and body called ghrelin — spelled G-H-R-E-L-I-N. Ghrelin is a hormone that increases depending on how long it's been since we last ate. The longer it's been since we had a meal, the higher ghrelin levels will be. It essentially makes us hungry by interacting with particular neurons in an area of the brain called the arcuate nucleus of the hypothalamus, and some other areas as well, like the lateral hypothalamus. When we eat, ghrelin levels typically go down. It's a very logical system.
Now, when we eat — assuming we eat carbohydrates, but even if we just eat some protein and some fats — we will experience a slight or, in some cases, a large rise in blood glucose. Blood glucose is simply blood sugar. The body and brain, and particularly the nervous system, don't function well if blood sugar is too high or too low. As a consequence, we have another hormone released from the pancreas called insulin, which helps regulate the amount of glucose in the bloodstream.
Glucose as the Brain's Preferred Fuel
Andrew Huberman: One of the chief organs for glucose utilization is the brain. Neurons are tremendously metabolically active, and their preferred mode of metabolism is glucose metabolism. The same is also true for the neurons in your body. The way you are able to move the limbs of your body, the way you are able to perform exercise or movement of any kind, is because neurons called motor neurons send electrical potentials to the muscle fibers. Those neurons are also very metabolically demanding, especially when you're doing demanding types of physical work. Deliberate thought, deliberately controlling the way that your brain and body are moving, requires more glucose uptake — more energy in those very neurons.
This is also why, after doing a long bout of exercise, you might be tired. But also, if you do a bout of skill learning of any kind, or if you've been reading and thinking about what you're reading, or if you've had an intense conversation where you're really forcing yourself to listen, that's work. And that work requires glucose uptake by neurons both in the brain and in your body.
Fructose vs. Glucose: Key Differences
Andrew Huberman: Now that we've established that glucose is the preferred source of fuel for the nervous system, I'd like to concentrate on a few of the other types of sugars that we ingest on a common basis and the impact those have on brain and body function. I'd particularly like to focus on fructose. Fructose is found in fruit. It's also found in the infamous high fructose corn syrup, which we will talk about today. It's worth pointing out that the concentration of fructose in fruit is quite low compared to the concentration in high fructose corn syrup — typically anywhere from 1% to about 10% in fruit.
High fructose corn syrup is a different issue. Too much consumption of fructose can be a problem for the ways it impacts the neural circuits that process sugar. One of the key distinctions between glucose and fructose is that fructose most likely cannot directly access the brain. It actually needs to be converted into glucose in the liver. The way that conversion occurs feeds back to a set of hormones and neural pathways that have a lot to do with appetite.
To summarize what is now a lot of very solid data: fructose specifically has the ability to reduce certain hormones and peptides in our body whose main job is to suppress ghrelin. So although I — and I think pretty much everyone out there, save for a few individuals — agree that calories in, calories out is the fundamental principle of weight loss, weight maintenance, or weight gain, ingesting fructose shifts our hormone system and, as a consequence, our neural pathways within the hypothalamus, to make us hungrier regardless of how many calories we've eaten.
Current recommendations for most people are to eat more fruits and vegetables. But for those trying to control their hunger, ingesting a lot of fructose is probably not going to be a good idea. Certainly ingesting it from high fructose corn syrup is not going to be a good idea, because of the enormous percentages of fructose in high fructose corn syrup — 50% or sometimes even more.
The Two Parallel Neural Pathways for Sugar Seeking
Andrew Huberman: Fructose provides a bridge for us between a particular kind of sugar-hormone function — in this case ghrelin and the hypothalamus — which leads us to the next question: what is it about sugar that makes it such an attractive thing for us? Why do we like it so much? The obvious answer most people arrive at is that it just tastes really, really good. But that's actually not the way it works.
The rewarding properties of sugar — whether they come in the form of sucrose, fructose, or foods that increase glucose to a very high level — are not just related to the taste of the foods that produce that elevation. That's only part of the story. The rest of the story, once you understand it, can actually place you in a position to much better control your sugar intake of all kinds, and your food intake in ways that allow you to make much better choices about the foods you ingest.
I want to take us on a journey into the nervous system to explain the pathways in the brain and body that regulate our appetite for sugar. When we ingest foods, they're broken down into various components, and glucose is shuttled to the brain and to other neurons in our spinal cord and elsewhere, and to our muscles, in order for all of those cells, organs, and tissues to be able to function. The fact that so many cells, organs, and tissues require glucose in order to function has led to a situation where you have dedicated neural machinery — pieces of your brain almost entirely devoted to seeking out sugar or foods that contain sugars — to make sure that you not only seek those out, but that you know where those foods are and that you ingest more and more of them.
There are two main ways these neural circuits work. We can say there are two neural circuits entirely that work in parallel. In the case of sugar consumption, one pathway is related to the actual taste and perception of sweet tastes, which leads not just you but every animal we're aware of to seek more sweet-containing foods. The other parallel pathway is related to the nutritive component of sweet foods — meaning the degree to which a given food will raise blood glucose.
I want to repeat that: one pathway in your brain and body is devoted to getting you to seek out sweet-tasting things that you perceive as sweet, and another parallel pathway is devoted to getting you to seek out foods that lead to increases in blood glucose. It just so happens that the foods that lead to big increases in blood glucose are typically associated with that sweet taste.
This is distinctly different from the neural pathways that control seeking of savory, salty, spicy, or bitter foods. The sweet pathway is what we would call hardwired. It exists, as far as we know, in every mammal. Getting sweet stuff into the body might seem like it has a lot to do with taste, but it has just as much to do with the nutritive components that sweet-tasting foods carry and the fact that your nervous system and so many cells in your brain and body run on glucose.
If you recall, I said that even if you ingest fructose, it can be converted into glucose in the liver. The fundamental thing to understand is that when you think you want a piece of chocolate or a piece of cake, or you're craving something sweet, you are both craving the taste and your neurons are literally craving the nutritive components that arrive with that taste. Two parallel pathways.
Dopamine and the Conscious Taste Pathway
Andrew Huberman: One of the parallel pathways has to do with conscious perception. When you ingest something sweet, very quickly there are signals sent from neurons in your mouth to brain areas that cause you to seek out, or at least pay attention to, the source and abundance of those sweet things. They literally change your perception.
Does that mean you should never ingest anything sweet? No. Certainly I'm not saying that. Everyone has to decide for themselves what the appropriate amount of sugar intake is. But I find it remarkable when people say, "I need to get my sugar fix," or "I need to have my chocolate," or "I need to have a little bit of something to just take care of that sugar appetite." Because in taking care of that sugar appetite — maybe for the very disciplined of you, you can just have that one piece of chocolate and relish in it — it does shift the way that you perceive other foods as well.
The way it does that is through our probably now old friend, but incredible neuromodulator, dopamine. Dopamine is a molecule released from several places in the brain. There's the so-called mesolimbic reward pathway, which is a whole set of circuits designed to get us motivated, craving, and in pursuit of things. And then there are areas of the brain involved in movement that are linked up with those areas involved in motivation — which makes perfect sense. Why would you have a brain area involved in motivation if you couldn't actually do something with that motivation?
When we ingest something sweet, the perception of that sweet taste increases dopamine in the mesolimbic reward pathways, which are then conveyed to pathways for motor behavior and in general place us into modes of focused action toward getting more of whatever was sweet. But if you understand the way that dopamine works, you'll realize that when this dopamine pathway is triggered, it tends to create not the sensation of satiety — of feeling like something is enough — but rather the sensation of wanting more. In fact, the longer it's been since you've indulged in something you really enjoy or would like, the greater the dopamine you will experience when you finally engage in that behavior or ingest that thing.
I'm not saying you shouldn't pursue pleasurable things. These dopamine pathways are not evil. They're not bad. But once you understand the way they work, you can leverage them to your advantage, as opposed to them leveraging you to their advantage.
The Gut Pathway: Neuropod Cells and Post-Ingestive Reinforcement
Andrew Huberman: Now there's the second pathway. The second pathway is what's called the post-ingestive reinforcing properties of sugar — which is really just a fancy way of saying there are events that happen within your stomach, below your conscious detection, that are also driving you to seek out sweet-tasting things independent of their taste, and foods that increase blood glucose independent of their taste.
Here's how it works. We all have neurons within our gut. These neurons have a name: they are called neuropod cells. Neuropod cells were famously discovered by Professor Dr. Diego Bohórquez at Duke University. These cells respond to, among other things, the presence of sugar within the gut. Neuropod cells send electrical signals through a particular highway within the vagus nerve to the so-called nodose ganglion — a cluster of neurons. The nodose ganglion then sends information on to the nucleus of the solitary tract. The nucleus of the solitary tract is very important for understanding sugar preference.
We've all heard of hidden sugars — the sugars that manufacturers have put into foods and disguised with other flavors. Savory foods are often laden with these hidden sugars that we can't register as sweetness, but they trigger the neuropod cells, which then further trigger dopamine, which makes us want more of them. We may be able to resist eating more of them, but it makes us crave more food in general.
We will talk about ways to regulate this pathway, to intervene in this subconscious pathway. But for now, I'm hoping that just the understanding that we all have this pathway — that it is hardwired into our body — could potentially allow people to better understand why their cravings are so intense, and that it's not necessarily just about the taste of that food.
When you consider this, you start to realize that there are multiple mechanisms hardwired into us that make it especially hard not to eat the sweet thing or not to eat the food we're craving. We have two major accelerators — it's like a car with two accelerators — two ways that really get us into forward motion toward pursuing the consumption of sweet foods.
The Glycemic Index and How to Use It
Andrew Huberman: Some of you have probably heard of the so-called glycemic index, which is basically a measurement of how high, and to some extent how fast, blood sugar rises in response to ingesting particular foods. Very broadly speaking, low glycemic index foods are typically below 55; medium glycemic index foods go from about 55 to 69; and high glycemic foods are above 70. There's additional nuance related to glycemic load and many more features of the glycemic index.
A couple of things to understand about how the glycemic index is measured. Measurements of glycemic indices of foods are typically made by having people ingest those foods in isolation. In general, we can say that anytime we ingest fiber and/or fat along with a particular food, it will reduce the glycemic index of that food — either the absolute level of blood glucose that a particular food causes, or the rate at which that elevation in blood glucose occurs.
This is why there are some seemingly paradoxical aspects to sweet stuff in terms of glycemic index. For instance, ice cream has a lower glycemic index — provided it's ice cream that includes fat, which I hope it would, because that's the good-tasting ice cream in my opinion — compared to something like mangoes or table sugar. The glycemic index is not something to hold wholly in most cases, because most people are not ingesting foods in isolation.
Why am I telling you about the glycemic index? If we zoom out and take our perspective on all of this through the lens of the nervous system — reminding ourselves that neurons prefer glucose for energy, and that all sweet things, or things we perceive as sweet, but also sweet things ingested and registered by those neuropod cells in our gut, trigger the release of dopamine and trigger these neural circuits to make us want to eat more — what we start to realize is that a sharp rise in blood glucose, or a very high degree of elevation in blood glucose, is going to be a much more potent signal than a more moderate or slower rise in blood glucose.
For those trying to reduce sugar intake and wanting to do that through an understanding of how these neural circuits work — to shortcircuit some of the dopamine release caused by ingesting sugary foods — it can be advantageous to ingest sweet foods in combination with foods that reduce glycemic index or glycemic load. That might mean making different food choices: paying attention to sweet-tasting foods that can satisfy sugar cravings but do not cause as steep a rise in blood sugar. Or it could mean consuming other foods along with sweet foods in order to reduce the glycemic index and thereby slow or blunt the release of dopamine.
If you really wanted to adjust your sugar cravings and still want to ingest some sugary foods, you would probably be better off combining fiber with that sugary or sweet food. What we're really talking about is trying to reduce the dopamine signal that is the consequence of ingesting sweet foods — doing that through these different parallel pathways, not just by preventing sweet taste, but also by preventing the post-ingestive effects of sweet foods.
Practical Tools: Glutamine
Andrew Huberman: The backdrop to all of this is that most of us — not all of us — should probably be ingesting fewer refined sugars. So what are some ways that we can reduce our sugar cravings, ideally in ways that also benefit us nutritionally and from the neuroscience standpoint?
The fact that neuropod cells, and other neurons within the gut, respond very robustly to the presence of particular amino acids is also a potential lever by which one could reduce sugar cravings. There's an interesting literature around the amino acid glutamine in particular — supplementing with glutamine as it relates to sugar cravings, and certainly as it relates to other aspects of the gut, in particular leaky gut. The use of supplemental glutamine to try and treat leaky gut is not a new phenomenon.
Many people are experimenting with supplementing with glutamine — several grams per day, often five grams distributed through three or four different servings throughout the day — as a way to blunt their sugar cravings. There has not yet been a large-scale clinical trial using glutamine to reduce sugar cravings, but the results of the few studies I looked at, as well as my understanding of the logic of these neural circuits including the neuropod cells, bring us to a conclusion that it makes sense. If there's a population of neurons within our gut that responds very robustly to the presence of sugar, fatty acids, or amino acids, then the intake of particular amino acids would allow the dopamine pathways that might otherwise be triggered by sugar to be triggered by something like glutamine, which has very few or no calories.
I know some people who actually take glutamine mixed with full-fat cream and take it kind of like a shot — which sounds absolutely delicious. Glutamine is a little bit chalky, so it's not that great tasting on its own. If you do try this approach of ingesting glutamine to reduce sugar cravings, you want to increase the amount somewhat gradually. It can create some gastric distress if you take too much too quickly. Please also be aware that there's an entire literature devoted to the potential hazards of increasing glutamine if you have a pre-existing cancer. If you have cancer or are cancer-prone, I would really discourage you from this approach. As always, talk to your doctor.
Practical Tools: Lemon and Lime Juice
Andrew Huberman: There are other ways to reduce sugar cravings, and certainly ways to reduce the sharp rise in blood glucose that can occur when we ingest sugary or sweet foods, or even just an abundance of carbohydrate foods. I'm going to layer up through the ones that you might find in your cupboard or at the grocery store, and then get into some of the more esoteric ones, many of which can be quite potent.
The first is simple lemon juice or lime juice. There are now data pointing to the fact that lemon juice and lime juice — a couple of tablespoons or so — if ingested before, during, or even after consumption of sugary foods, or foods that sharply increase blood glucose, or large carbohydrate meals, can actually blunt the blood glucose response. I did see this when I did my own experiments on myself with a continuous glucose monitor. I preferred to do those experiments by eating somewhat larger meals of things that didn't contain a lot of sugar. I saw some big increases in blood glucose in certain instances, and then I would ingest some lemon juice or lime juice, typically mixed in with water, and sure enough you could see a blunting of the blood glucose response — and of course this was real-time, continuous blood glucose monitoring.
When you ingest lemon juice or lime juice, the mechanism by which it blunts blood glucose is probably twofold. One is probably through the post-ingestive effects of glucose in the gut — the way in which sugars are interacting with neurons and other components of your gut circuitry to impact things like gastric emptying time, and the firing of those neuropod cells and their signaling to the brain. But almost certainly it also has something to do with the perception of sour taste on the tongue.
You don't just have sweet taste receptors in your mouth. You also have bitter taste receptors, salty taste receptors, and sour taste receptors. If you ingest a substance that's just sweet or mostly sweet, that causes a certain set of effects on your blood glucose, but also on your brain, dopamine, and the other neural circuits. If you also ingest something sour, like lemon juice or lime juice, it adjusts the output of those neural circuits in your brain.
Again, we have a situation where we have two parallel pathways — one that's post-ingestive, coming from phenomena within our gut neurons and things like gastric emptying time, and one that operates simply through the perception of sour taste changing the way that sweet things impact your brain. The lemon juice and lime juice effect is not going to be magic. It's going to have everything to do with the way that ingesting sour foods can adjust the neural response to the taste of sweet foods. Based on the beautiful work of Charles Zuker at Columbia Medical School, we know that's exactly what happens.
Practical Tools: Cinnamon
Andrew Huberman: Some of you have probably heard that cinnamon can be a useful tool for controlling blood sugar. Indeed, that's the case. It's very clear that cinnamon can adjust the rate of glucose entry into the bloodstream, possibly by changing the rate of gastric emptying — slowing it and thereby also reducing the glycemic index of particular foods. I suppose if I were going to eat a mango and hadn't just done a bunch of hard training, I might sprinkle some cinnamon on it.
I do want to provide a cautionary note about cinnamon, however. Cinnamon contains something called coumarin, which can be toxic at high levels. You don't want to ingest more than about a teaspoon, maybe a teaspoon and a half, of cinnamon per day, because you'll start to exceed the threshold at which cinnamon could start to be problematic.
Practical Tools: Berberine and Other Potent Compounds
Andrew Huberman: Then of course we can venture into the more esoteric, or I would say the more advanced, tools for adjusting sugar intake. The one that comes to mind is berberine. Using berberine is a serious step. You should absolutely talk to your doctor about it. It is true that if you ingest berberine, your blood glucose will plummet. I point that out because I've actually tried it before. It gave me brutal headaches and I felt really dizzy and felt like I couldn't see straight — and actually I couldn't see straight. Why did it do that? It made me hypoglycemic. It actually drove my blood glucose down too far. The reason it did that is that I took berberine on an empty stomach. If I took berberine along with a very large meal that included a lot of carbohydrates, then I felt perfectly fine on even up to 750 milligrams or a gram of berberine. But again, talk to your doctor.
I would place berberine — and of course metformin and glibenclamide — in the category of heavy-hitting, potent tools for regulating blood glucose. There are some other substances, like sodium caprate, which are known to augment the effects of berberine via AMPK pathways — basically increasing the ability of berberine to have its glucose-lowering actions. But that is getting into the really potent, sharp-blade tools for controlling blood glucose.
Anytime you're dealing with blood glucose, you are dealing with the brain's preferred source of fuel. And anytime you're dealing with the brain's preferred source of fuel, you have to be especially cautious about depriving the brain of what it needs. Substances like berberine are very, very potent, and you need to take them seriously.
Sleep as a Tool for Sugar Metabolism and Cravings
Andrew Huberman: There is yet another tool for controlling sugar cravings and the neural circuits that regulate sugar craving and its downstream consequences. This tool is what I would call a high-performance tool, but one you probably didn't suspect: sleep.
What is the role of sleep in sugar metabolism, sugar hunger, and the way that the brain regulates those things? There's a really exciting study that came out just last year, published in a Cell Press journal — an excellent journal. The reason I love this study so much is that it involved having people sleep in the laboratory. What they did was measure metabolites from the breath of these people throughout the night, extracting information that allowed them to understand what sorts of metabolism were occurring in their bodies at different phases of sleep. They did this every ten seconds throughout the entire night.
What they discovered was that each stage of sleep was associated with a very particular signature pattern of metabolism. Particular phases of sleep are associated with sugar metabolism, others more with fat metabolism, and others with still other aspects of metabolism. The reason this study is important in the context of today's discussion is that many people have experienced the effects of disrupted sleep on their appetite. In particular, it's been reported that when people are sleep-deprived or the quality of their sleep is disrupted, their appetite for sugary foods increases.
We don't want to leap too far from this study to sugar metabolism and the neural circuits controlling it, but there is now a plethora of data pointing to the fact that getting quality sleep each night helps regulate not only appetite, but also the specific forms of metabolism that drive specific appetites. We can't overstate the importance of getting a regular, sufficient amount of high-quality sleep — at least 80% of the time — not just for immune system function or clear thinking, but also for properly regulating our metabolism, including our sugar metabolism.
Thank you for joining me for this discussion about sugar and the nervous system and how they are regulating each other in both the brain and body. And last but certainly not least, thank you for your interest in science.