BHB

Beta-hydroxybutyrate (BHB) is a ketone body produced mainly in the liver from fatty acids during periods of fasting, prolonged exercise, or carbohydrate restriction. It serves as an alternative energy source when glucose availability is limited, particularly for the brain, heart, and skeletal muscles. In humans, BHB is the predominant ketone produced during hepatic ketogenesis and is released into the bloodstream for use by peripheral tissues.

BHB exists as two enantiomers, the biologically dominant D-β-hydroxybutyrate and the less common L-β-hydroxybutyrate. It is a water-soluble molecule transported through the blood and across cell membranes by monocarboxylate transporters (MCT1–4). The liver lacks the enzyme succinyl-CoA:3-oxoacid CoA transferase (thiophorase) to utilize ketones, so it exports BHB and acetoacetate to other tissues that can use them for energy.

In peripheral tissues, BHB is converted back to acetyl-CoA via mitochondrial enzymes, entering the tricarboxylic acid cycle to produce energy. The D-enantiomer is the primary energy substrate; L-BHB is present in smaller amounts and is less efficiently used for energy. Beyond fuel, BHB functions as a signaling molecule, inhibiting histone deacetylases (affecting gene expression) and activating the receptor HCAR2 (GPR109A), with anti-inflammatory effects including inhibition of the NLRP3 inflammasome.

Medical and commercial interest surrounds ketosis, ketogenic diets, and exogenous BHB supplements (ketone salts and esters), which raise blood BHB to mimic fasting-like metabolic states. Safety considerations include the risk of ketoacidosis in insulin-deficient states and gastrointestinal effects from supplements.