Ketones are a backup fuel your body produces from fat when glucose is in short supply. They power your brain, heart, and muscles during fasting, low-carb diets, and prolonged exercise. Beyond fuel, ketones have therapeutic uses in epilepsy, emerging roles in heart failure research and athletic recovery, and surprising functions as signaling molecules that influence gene expression.
How Your Body Makes and Uses Ketones
When you haven’t eaten for a while or you’re eating very few carbohydrates, your liver breaks down fatty acids and converts them into ketone bodies. The two main types are beta-hydroxybutyrate and acetoacetate. These get exported into your bloodstream and picked up by organs that need energy, especially your brain and heart.
Your brain normally runs almost entirely on glucose because it can’t burn fat directly. But during prolonged fasting lasting days to weeks, ketones become the brain’s primary energy source, meeting up to two-thirds of its energy requirements. This shift is what kept humans alive during periods of food scarcity throughout evolution. The remaining third still comes from glucose, which the liver produces from protein and other non-carbohydrate sources.
The heart is also a major consumer. Cardiac muscle readily oxidizes ketones, and research from the American Heart Association shows that beta-hydroxybutyrate improves the efficiency of heart mitochondria, maintaining greater energy output per unit of oxygen consumed.
Nutritional Ketosis vs. Ketoacidosis
These two states involve ketones but are fundamentally different. Nutritional ketosis, the kind you enter through fasting or a ketogenic diet, produces blood beta-hydroxybutyrate levels between 0.5 and 5.0 mmol/L. Your body regulates this tightly through insulin, which acts as a brake on ketone production.
Diabetic ketoacidosis (DKA) is a medical emergency that occurs primarily in people with type 1 diabetes or severely uncontrolled type 2 diabetes. Without adequate insulin, there’s no brake. Ketone levels climb above 3 mmol/L while blood sugar spikes above 200 mg/dL, and the blood becomes dangerously acidic, with a pH dropping below 7.3. A healthy person with normal insulin function essentially cannot develop ketoacidosis through diet alone.
Treating Drug-Resistant Epilepsy
The ketogenic diet has been used to treat epilepsy since the 1920s, and it remains one of the most established therapeutic uses of ketones. It’s primarily prescribed for children and adults whose seizures don’t respond to medication.
The mechanisms work on multiple fronts. A ketogenic diet reduces glutamate, the brain’s main excitatory chemical, while boosting production of GABA, the brain’s main calming chemical. That shift in the ratio of excitation to inhibition makes seizures less likely to fire. The diet also reduces brain inflammation, which is significant because inflammation from infections or autoimmune conditions can trigger seizures on its own. Interestingly, research has found that the diet changes gut bacteria in ways that further promote a favorable GABA-to-glutamate ratio in the brain.
For seizure control, clinicians typically aim for blood beta-hydroxybutyrate levels of 0.8 mmol/L or higher. In cases where seizures persist, raising levels to 4.0 to 6.0 mmol/L may offer additional benefit, particularly when rapid seizure control is needed.
Heart Failure Research
Ketones are drawing significant attention in cardiovascular research. In people with heart failure where the heart pumps weakly, infusion of beta-hydroxybutyrate robustly increased cardiac output. The improvement correlated directly with blood ketone levels and was accompanied by a dramatic decrease in blood vessel resistance, making it easier for the heart to pump.
In animal models of heart failure, ketone supplementation improved the heart’s energy reserves without disrupting its ability to use glucose or fat. That’s a notable finding because a failing heart is essentially an energy-starved organ, and ketones appear to offer an additional fuel source rather than competing with existing ones. However, researchers caution that while ketones clearly boost total energy production in the struggling heart, the claim that they are inherently more “efficient” than other fuels hasn’t been definitively proven at the cellular level.
Athletic Recovery and Performance
Exogenous ketone supplements, typically ketone esters or ketone salts you drink, have become popular in endurance sports. The performance story is more nuanced than the marketing suggests, though.
For acute performance during exercise, the evidence is mixed at best. One early study showed improved cycling time-trial performance after ketone ester ingestion, but multiple follow-up studies with more realistic race conditions have reported either no benefit or a slightly negative effect. Taking ketones before or during a race doesn’t reliably make you faster.
Where ketones show more promise is in recovery after exercise. Post-exercise ketone supplementation has been shown to:
- Boost muscle repair signals: Ketones reduce protein breakdown while promoting muscle protein synthesis, which could help build muscle mass in response to training and reduce muscle wasting during injury-related inactivity.
- Increase erythropoietin (EPO): Taking ketones after exercise raised circulating EPO levels by roughly 25% for at least four hours. EPO drives red blood cell production, which is central to endurance performance and training adaptation.
- Improve glycogen resynthesis: Ketones may help muscles restock their carbohydrate stores faster after depleting exercise.
- Reduce overtraining symptoms: Recent studies found that post-exercise ketone supplementation blunted the development of overtraining signs and improved sleep quality.
The emerging picture is that ketones are more useful as a recovery tool than a mid-race performance enhancer.
Ketones as Signaling Molecules
One of the more surprising discoveries of the past decade is that ketones do far more than just supply energy. Beta-hydroxybutyrate acts as a signaling molecule that influences which genes your cells turn on and off.
It does this by blocking a family of enzymes called class I histone deacetylases, which normally suppress gene expression. When beta-hydroxybutyrate inhibits these enzymes, certain protective genes become more active. This is the same basic mechanism targeted by some cancer drugs and neurological medications, but ketones do it naturally at the concentrations reached during fasting or a ketogenic diet. Structurally, beta-hydroxybutyrate is nearly identical to butyrate, a short-chain fatty acid produced by gut bacteria that was the first known inhibitor of these same enzymes.
Beta-hydroxybutyrate also binds to receptors on cell surfaces that regulate fat breakdown, sympathetic nervous system activity, and metabolic rate. Through these receptors, ketones essentially tell your body to fine-tune how fast it burns energy and how aggressively it mobilizes fat stores. This dual role, as both fuel and signal, helps explain why ketones have effects that go well beyond simply replacing glucose.