Ketone bodies are a group of three molecules your liver produces from fat when glucose is in short supply. They serve as backup fuel for your brain, heart, and muscles during fasting, prolonged exercise, or very low-carbohydrate diets. The three ketone bodies are acetoacetate, beta-hydroxybutyrate (BHB), and acetone. Far from being just a metabolic byproduct, ketone bodies are efficient energy sources and, as scientists have more recently discovered, powerful signaling molecules that can influence gene expression throughout the body.
The Three Types of Ketone Bodies
Your liver produces acetoacetate first. From there, the molecule can take one of two paths: it can be converted into BHB by an enzyme, or it can spontaneously break down into acetone. Each of the three plays a slightly different role.
BHB is the most abundant ketone body in the blood and the one most commonly measured in clinical and home testing. Acetoacetate is the central molecule in ketone metabolism, acting as the starting point for the other two. Acetone is the simplest and smallest of the three. Because of its low molecular weight, it easily diffuses from blood into the air spaces of the lungs and gets exhaled. That’s the source of the fruity or nail-polish-remover smell on the breath of someone in deep ketosis.
How and Why Your Body Makes Them
Ketone production, called ketogenesis, happens in the liver’s mitochondria. The trigger is straightforward: when carbohydrate supply is limited and insulin levels drop, your liver starts breaking down fatty acids and certain amino acids into ketone bodies. This process kicks in during prolonged fasting, starvation, intense exercise, or when following a very low-carbohydrate (ketogenic) diet.
The underlying logic is about glucose conservation. Your body stores only a limited supply of glycogen (the stored form of glucose), enough for roughly 24 hours of normal activity. Once those reserves run low, the liver ramps up ketone production to provide an alternative fuel, sparing whatever glucose remains for cells that absolutely require it, like red blood cells. A ketogenic diet mimics this state by keeping carbohydrate intake so low that the body shifts into fat-burning mode even without actual food restriction.
Ketones as Brain Fuel
One of the most important things ketone bodies do is feed the brain. The brain can’t burn fat directly because fatty acids are too large to cross the blood-brain barrier. Ketone bodies, however, cross that barrier through specialized transporters on brain cells. Unlike glucose transport, which ramps up when neurons fire, ketone uptake depends simply on how much is circulating in the blood: higher blood ketone levels mean more fuel reaching the brain.
The contribution is dramatic depending on how long you’ve been fasting. After an overnight fast, blood ketone levels typically sit below 0.5 mmol/L and supply less than 5% of the brain’s energy. But during prolonged fasting of five to six weeks, ketone levels rise enough to cover nearly 60% of the brain’s total energy needs, effectively replacing glucose as the primary fuel source.
Energy Efficiency Compared to Glucose
Gram for gram, ketone bodies actually produce more cellular energy than glucose. For every 100 grams of fuel burned, glucose generates about 8.7 kg of ATP (the molecule cells use for energy). The same amount of BHB yields roughly 10.5 kg of ATP, and acetoacetate produces about 9.4 kg. This higher energy density is one reason athletes and researchers have become interested in ketones as a performance fuel, and it helps explain how the brain can maintain normal function even when glucose is scarce.
Signaling Beyond Energy
BHB does more than just power cells. It acts as a signaling molecule that can alter gene expression, lipid metabolism, neuronal function, and metabolic rate. One of its most studied actions is blocking a family of proteins called class I histone deacetylases. These proteins normally keep certain genes switched off by tightening the way DNA is packaged. When BHB inhibits them, specific genes become more active.
In animal studies, rising BHB levels during fasting increase the activity of a stress-response gene called Foxo3a, which is linked to longevity in multiple species. BHB also boosts expression of a brain growth factor (BDNF) after exercise, which supports neuron health and may partly explain the cognitive benefits some people report during ketosis. BHB binds to receptors on cell surfaces, modifies proteins after they’re built, and influences ion channels. These effects broadly connect nutritional status to how genes behave, which is why researchers are investigating ketones in aging, neurodegeneration, and metabolic disease.
Nutritional Ketosis vs. Ketoacidosis
There’s an important distinction between the safe, regulated rise in ketones that happens during fasting or a ketogenic diet and the dangerous, uncontrolled buildup that occurs in diabetic ketoacidosis (DKA). Nutritional ketosis is defined by a blood BHB concentration between 0.5 and 5.0 mmol/L. In this range, the blood stays at a normal pH and the body uses ketones efficiently.
DKA is a medical emergency that primarily affects people with type 1 diabetes (and occasionally type 2). It requires three things happening at once: high blood sugar at or above 200 mg/dL, BHB levels at 3 mmol/L or higher, and acidic blood with a pH below 7.3. In severe DKA, BHB can exceed 6 mmol/L, blood pH drops below 7.0, and consciousness may be impaired. The key difference is insulin: in a healthy person, even modest insulin production puts a ceiling on ketone production. Without that brake, ketones accumulate to toxic levels and overwhelm the body’s buffering systems.
How Ketone Levels Are Measured
Three testing methods exist, each measuring a different ketone body with different levels of accuracy.
- Blood meters measure BHB directly from a finger prick, using a small test strip. A reading above 0.5 mmol/L is considered positive for ketosis. Blood testing is the gold standard because BHB is the most abundant and clinically relevant ketone body.
- Urine strips detect primarily acetoacetate. They’re inexpensive and easy to use, but they have a notable limitation: they’re less sensitive to BHB, which is the first ketone to rise in conditions like DKA. Compared to blood testing, urine strips have a sensitivity of only about 64% for detecting diabetic ketosis. They can also become unreliable if kidney function is impaired or if your body has adapted to using ketones efficiently (in which case fewer spill into urine).
- Breath meters measure exhaled acetone, the ketone body that diffuses into your lungs. Breath testing is noninvasive and repeatable, with a sensitivity of about 91% for detecting ketosis, higher than urine strips. The trade-off is slightly lower specificity (around 77%), meaning occasional false positives.
Medical Uses: Epilepsy and Beyond
The therapeutic use of ketones has a surprisingly long history. The ketogenic diet has been used to treat drug-resistant epilepsy since the 1920s, and animal studies dating back to the 1930s showed that ketone bodies could protect against seizures. Medium-chain triglycerides, a type of fat that the liver converts rapidly into ketones, have been used as an epilepsy therapy in children since the early 1970s. For children and adults whose seizures don’t respond to medication, a medically supervised ketogenic diet remains one of the most effective non-drug options available.
Researchers are now exploring ketone-based therapies for neurodegenerative conditions like Alzheimer’s disease, partly because the aging brain often has trouble using glucose efficiently but can still metabolize ketones. The signaling effects of BHB on gene expression and brain growth factors add another layer of interest, though clinical applications beyond epilepsy are still being studied.