Ketones vs. Glucose: Which Fuel Source Is Better?

The human body is an adaptable machine capable of running on different energy sources. The two primary fuels it uses are glucose and ketones. While most people are familiar with glucose, ketones serve as an alternative energy source. Understanding how these fuels are produced and used by our cells provides insight into the body’s metabolic flexibility and how we power our daily activities.

Fuel Sources and Production

The body’s primary fuel is glucose, a sugar derived from carbohydrates in our diet. When we eat carbs, they are digested into glucose, which enters the bloodstream. This rise in blood sugar triggers the pancreas to release insulin, a hormone that allows glucose to enter cells for immediate energy.

If there is more glucose than needed, insulin signals the liver and muscles to store the excess as glycogen. These reserves act as a short-term energy buffer, converted back into glucose when energy demands increase or dietary intake is low.

When carbohydrate intake is significantly reduced, such as during fasting or on a very low-carb diet, glycogen stores become depleted. In response, the body enters a metabolic state called ketosis and begins to break down stored fat for energy.

This process, ketogenesis, occurs in the liver. The liver converts fatty acids from fat tissue into ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. These ketones are then released into the bloodstream to serve as an alternative fuel source.

Cellular Energy Conversion

Both glucose and ketones must be converted into adenosine triphosphate (ATP), the energy currency that powers cellular functions. For glucose, this starts in the cell’s cytoplasm with glycolysis, a series of reactions that quickly breaks down a glucose molecule for a small amount of ATP without needing oxygen.

For more sustained energy, the byproducts of glycolysis move into the mitochondria. Here, they enter the Krebs cycle and undergo oxidative phosphorylation. This process requires oxygen and generates a large amount of ATP from a single glucose molecule.

Ketone metabolism occurs almost entirely within the mitochondria. Ketones travel from the blood into cells and are converted into acetyl-CoA, the same molecule that glucose byproducts become before entering the Krebs cycle. From this point, the energy generation process is identical to that of glucose.

While glucose provides faster energy through glycolysis, ketone metabolism is more metabolically efficient. In terms of ATP produced per unit of oxygen consumed, ketones are a more potent fuel. For instance, one molecule of the ketone beta-hydroxybutyrate yields more ATP than one molecule of glucose.

Brain Metabolism

The brain is an energy-intensive organ, consuming about 20% of the body’s energy. Its primary fuel is glucose, requiring a constant supply from the bloodstream because it has limited storage capacity. Maintaining stable blood sugar is therefore important for cognitive function.

Glucose uptake is a “pull” system, drawn into brain cells based on energy demand. When a brain region is active, it uses more glucose, creating a deficit that pulls more in from the blood. This demand-driven mechanism ensures active areas receive fuel as needed.

During glucose scarcity, like prolonged fasting, the brain adapts by using ketones for energy. This survival mechanism allows the brain to remain functional when its main fuel is unavailable. In deep ketosis, the brain can source up to 70% of its energy from ketones.

In contrast, ketone uptake is a “push” system. The amount of ketones entering the brain is directly proportional to their concentration in the bloodstream. As blood ketone levels rise, more are pushed into the brain for use as fuel.

Implications for Physical Activity

Glucose and ketones are suited for different types of physical activity. For high-intensity, anaerobic exercises like sprinting or heavy weightlifting, glucose is the better fuel. These activities require rapid energy for short bursts, and glycolysis provides ATP much faster than ketone metabolism can.

For lower-intensity endurance activities like marathon running, ketones offer an advantage. Keto-adapted athletes can tap into the body’s vast fat reserves for a steady supply of energy. This spares the limited glycogen stored in muscles, preserving it for more intense moments like a final sprint.

By relying on fat and ketones, endurance athletes can maintain energy output over many hours without constant carbohydrate refueling. Studies show that keto-adapted athletes can burn more than twice as much fat during exercise compared to those on high-carbohydrate diets, allowing them to sustain performance longer.