Beta-Hydroxybutyrate (BHB) is the most abundant of the three primary ketone bodies produced by the liver. The body typically relies on glucose from carbohydrates for fuel, but when that supply is restricted, BHB becomes an alternative energy source for cells. This molecule signals a metabolic shift, indicating the body is utilizing stored fat for energy instead of circulating sugar. This change impacts cellular signaling and inflammatory responses, extending beyond simple energy provision.
How the Body Produces Hydroxybutyrate
The body initiates ketogenesis when circulating glucose and stored glycogen levels drop significantly. This metabolic shift is triggered by prolonged fasting, adherence to a very low-carbohydrate diet, or sustained, intense exercise. In response to this fuel scarcity, fat cells release fatty acids into the bloodstream, which travel to the liver for processing.
Inside the liver’s mitochondria, fatty acids undergo beta-oxidation, breaking them down into acetyl-CoA. When carbohydrate stores are depleted, the liver cannot feed all of this acetyl-CoA into the citric acid cycle, causing it to accumulate. Specialized enzymes then divert this excess acetyl-CoA to synthesize acetoacetate, which is readily converted into the more stable Beta-Hydroxybutyrate.
BHB is released from the liver into the bloodstream for distribution to other tissues. Unlike fatty acids, BHB efficiently crosses the blood-brain barrier, making it a primary fuel source for the central nervous system during carbohydrate restriction. The liver produces ketones but cannot use them for fuel itself, relying instead on fatty acid oxidation.
Beyond Energy: Hydroxybutyrate’s Functional Roles
Beta-Hydroxybutyrate functions as a signaling molecule with broad biological effects, in addition to being an alternative fuel. It serves as an efficient energy source, particularly for the brain and the heart, which prefer ketones over glucose when available. The heart muscle, for example, shows greater efficiency when fueled by BHB compared to its usual preference for fatty acids.
BHB’s regulatory function involves inhibiting histone deacetylases (HDACs). By inhibiting these enzymes, BHB helps maintain an open, or acetylated, state for specific DNA regions, which can increase the transcription and expression of protective genes.
BHB also plays a significant role in modulating the body’s inflammatory response by acting on the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. The NLRP3 inflammasome is a multi-protein complex that, when activated, triggers the release of pro-inflammatory cytokines, such as IL-1β. BHB actively suppresses this complex by blocking the outflow of potassium ions from the cell, a step required for the inflammasome’s activation. This inhibition of the NLRP3 inflammasome is considered a primary mechanism behind the anti-inflammatory effects observed in states of elevated ketosis.
Using Hydroxybutyrate Supplements
Exogenous ketone supplements are designed to increase the level of Beta-Hydroxybutyrate in the blood without requiring the fasting or carbohydrate restriction necessary for natural production. These products are used to boost mental clarity, enhance athletic endurance, or mitigate side effects associated with the initial phase of a ketogenic diet.
Ketone Salts
The most common supplemental forms are ketone salts, which bind BHB to mineral ions such as sodium, potassium, or calcium. They provide a modest elevation in blood BHB levels, often peaking around 0.5 to 1.0 mmol/L. Consuming large doses can lead to a significant intake of the associated mineral, which may be a concern for some users.
Ketone Esters
Ketone esters represent a more potent form, consisting of BHB bonded to a precursor molecule like 1,3-butanediol. Upon ingestion, the bond is rapidly broken, leading to a faster and more substantial increase in circulating BHB, frequently reaching levels between 3 and 6 mmol/L. While effective, esters are typically more expensive and often noted for having a strong, unpleasant taste.
MCT Oils
Medium-chain triglyceride (MCT) oils are another popular supplement, though they are not technically exogenous ketones. MCTs are specific fats that the liver converts into ketones, offering a less direct but effective method to support the body’s endogenous production.
Tracking and Measuring Ketone Levels
Individuals monitor their ketone status to confirm they have entered nutritional ketosis, defined by a blood BHB concentration of 0.5 mmol/L or higher.
Blood Ketone Meters
Measuring Beta-Hydroxybutyrate using a blood ketone meter requires a small finger-prick sample. This method provides the most accurate, real-time reading of the BHB circulating in the body.
Urine Strips
Urine strips measure the concentration of acetoacetate. While inexpensive and easy to use, they only indicate excess ketones being excreted, meaning they become less accurate as the body adapts and uses ketones more efficiently. Urine tests may show an increase in acetoacetate even as the metabolic state of DKA is resolving, due to the conversion of BHB to acetoacetate.
Breath Analyzers
A breath analyzer measures acetone, which is exhaled as a byproduct of acetoacetate breakdown. This non-invasive method offers immediate feedback and is useful for tracking trends, though the correlation with blood BHB levels can vary depending on the individual’s metabolic state. Measuring BHB in the blood is important for differentiating between benign nutritional ketosis and the high levels of ketones associated with diabetic ketoacidosis.