Controlling Sugar Cravings & Metabolism with Science-Based Tools

The episode opens with Andrew Huberman, who introduces himself as a professor of neurobiology and ophthalmology at Stanford School of Medicine, framing sugar as a two-way story: the nervous system regulates how much sugar we take in and seek out, and sugar in turn regulates the nervous system. He says it does this through two main mechanisms. The first is sweet taste, which is rewarding in itself. He notes that most people prefer sweet to bitter even if they are not particularly drawn to sweets, and he admits he is not. Sweetness is described as strongly reinforcing: it activates neurons in the brain and body that make us want more of the sweet substance, and, he adds, more of other foods as well.

The second mechanism is independent of sweetness. It depends on sugar's nutritive, caloric content and on how sugar interacts with the nervous system at a subconscious level. According to the host, this route also shapes craving and seeking of both sugar and other foods, without our being aware of it.

The host also sets up a tension the episode comes back to. Sugar is described as such a powerful brain fuel that neurons function less well when people don't ingest enough of it or when blood glucose drops too low. At the same time, he says, "there are conditions of very low blood sugar in which neurons can function even better." He says the goal is to help listeners judge how much sugar to eat, whether to avoid sugars they currently eat, and which fuel sources the brain depends on.

The discussion begins with a disclaimer: "there's nothing inherently bad about sugar." The host also says it is widely accepted that eating a lot of refined sugars, especially high-fructose corn syrup, has many bad effects on the brain and body. He presents the calories-in-calories-out principle as common ground and calls it a principle of thermodynamics. If we take in more energy than we burn, we gain weight. If we take in less, we generally lose weight. If the two balance, weight stays the same.

His argument is that energy balance is not the whole picture. Particular nutrients, sugar in this case, change how the brain works so that we seek more of them. He says eating sugar engages at least two mechanisms that drive craving for more sugar. Sugar also affects neural circuits in ways that can make us more or less focused, agitated, or happy, and "more or less depressed in some cases." He links this to goals such as thinking, exercising, and gaining or losing weight. Sugar plays a critical role in reaching those goals, but taken in excess, at the wrong times, or in the wrong forms, it can get in the way of them.

To set the context, the host gives what he calls a "top-contour view" of the hormonal response to eating, and points to his earlier episode on metabolism for the full cascade. The first hormone is ghrelin. Ghrelin rises the longer it has been since we last ate and makes us hungry by acting on neurons in the arcuate nucleus of the hypothalamus and other areas, such as the lateral hypothalamus. When we eat, ghrelin typically falls, which he calls "a very logical system."

Eating, especially carbohydrates but also protein and fat, raises blood glucose slightly or sometimes a lot. The host says the nervous system doesn't function well when blood sugar is too high or too low. Insulin, released from the pancreas, helps regulate glucose in the bloodstream. In his example, even an eight-ounce cup of pure table sugar, in someone with a normal insulin response who is not diabetic, would be met by insulin that clamps blood glucose to prevent damage.

He explains why this clamping matters. Very high blood sugar is "actually toxic to neurons and other cells of your body, it can kill them off," and neurons of the brain and spinal cord do not come back once they die. Type 1 diabetics, who don't make insulin, take it when they eat foods that raise blood sugar in order to avoid this neurotoxicity and other harms. In his summary, ghrelin drives hunger, eating suppresses it and raises glucose, and the body smooths out glucose peaks and valleys by storing glucose or delivering it to cells that use it.

The brain is presented as one of the main organs that use glucose. Neurons are described as very metabolically active, and glucose metabolism is their preferred mode. The host adds a caveat right away.

In other words, neurons basically run on sugar, which is not to say that you should eat a lot of sugar.

He notes that people in fasted states often report great mental clarity while their blood glucose is quite low. So it is "simply not the case" that more sugar means better brain function. His more limited claim is that people who are not on, or adapted to, ketogenic or very low-carbohydrate diets rely on glucose so that their neurons can fire, meaning send electrical signals along their length to other neurons.

He states the scope of his remarks: unless he says otherwise, he assumes a typical diet with fats, proteins, and carbohydrates. He acknowledges low-carbohydrate, moderate-carbohydrate, and carnivore eaters. He describes himself, at 46, as a lifelong "proud omnivore" who tries to eat high-quality, unprocessed foods, avoids highly processed ones, and might someday try a carnivore or vegan diet.

The main evidence in this section is a recent study, published in the Cell Press journal Neuron, which the host says builds on a long history of similar work. He first explains orientation tuning in the visual cortex. Whether neurons are recorded with an electrode or activity is measured with fMRI, some neurons respond best to vertical bars of light, others to horizontal bars, and others to 45-degree bars. He calls this "a cardinal, classic feature" of how the visual system is built.

He explains why this matters for perception. Face-responsive neurons deeper in the brain depend on input from these orientation-tuned cells, arranged in a "hierarchical representation." He says these cells are the building blocks for recognizing faces, reading, and everything else we see. Tuning sharpness can be measured: a vertical-preferring neuron typically also responds to lines about 10 degrees off vertical on either side, maybe 20, but usually not much more.

The study asked whether the precision of this tuning depends on blood glucose. As the host reports it, when subjects were well-fed, vertical-preferring neurons responded strongly to vertical lines and hardly at all to lines 10 or 20 degrees off. Horizontal-preferring neurons showed the same pattern. When subjects were fasted, tuning became much broader, and neurons that usually responded only to vertical also responded to other angles.

The host says the broader tuning is a loss of precision, not a gain in versatility: "in the fasted state, your perception of the outside world is actually distorted. It's blurred." He specifies that by "fed" he really means a state "when glucose is available to neurons."

The host does not treat the study as a case against fasting, and he describes his own routine. He usually eats his first meal around 11:00 a.m. and his last around 8:00 p.m., plus or minus an hour. He is not strict about it and sometimes eats earlier when very hungry. He feels most focused in the morning while fasted, with water and caffeine about 90 minutes after waking, and notes that many others report mental clarity when fasted.

He explains that during fasting, neurons use fuels derived from the previous day's food, such as glycogen, blood sugar from storage sites, and proteins and fats converted into usable fuel. He adds that "You don't actually use fat as a fuel source for neurons under typical conditions." His reading of the study is that well-fed conditions deliver glucose to the brain in a way that lets neurons work best.

To reconcile the two observations, he points to other features of the fasted state, "in particular the elevations in things like epinephrine and norepinephrine," also called adrenaline and noradrenaline. He suggests these may produce the mental clarity that people seek from fasting. He still concludes that glucose is the brain's preferred fuel and that the study is one of many linking nutritional or blood glucose status to neuronal tuning and function.

And it really points to the fact that ultimately, your brain as an organ is a glucose-consuming machine.

The host explains that glucose from digested carbohydrates cannot enter the brain directly. It has to be carried across the blood-brain barrier, and its metabolism and delivery to neurons are handled by astrocytes. He describes astrocytes as the most abundant cell type in the brain "and maybe even in your entire nervous system." They are a kind of glial cell, a name meaning glue, but he argues against reading that as mere structural support.