Hydroxybutyrate

Hydroxybutyrate is a term that can refer to any hydroxy-substituted butyrate, but in physiology it most commonly denotes beta-hydroxybutyrate (β-hydroxybutyrate, BHB), a ketone body produced in the liver during fasting or carbohydrate-restricted states. The term can also refer to gamma-hydroxybutyrate (GHB), a distinct compound with sedative properties and abuse potential. BHB occurs as two enantiomers, D-β-hydroxybutyrate and L-β-hydroxybutyrate; the D form is the primary energy-carrying ketone produced in humans.

During fasting or ketogenic diet, fatty acids are oxidized in the liver to acetyl-CoA, which is converted into ketone bodies in a process called ketogenesis. The main products are acetoacetate and β-hydroxybutyrate; these are released into the bloodstream and transported to tissues via monocarboxylate transporters. In peripheral cells, β-hydroxybutyrate is oxidized back to acetoacetate and then to acetyl-CoA to fuel the tricarboxylic acid cycle.

β-hydroxybutyrate serves as an important energy substrate for the brain, heart, and skeletal muscle during prolonged fasting or low glucose availability. It can reduce the need for glucose and preserve muscle protein. In addition to metabolism, BHB acts as a signaling molecule, influencing gene expression and inflammation through mechanisms such as inhibition of histone deacetylases and activation of the G-protein–coupled receptor HCAR2.

Clinically, blood levels of ketone bodies, including β-hydroxybutyrate, are measured to assess ketosis or metabolic state; exogenous BHB supplements are available for research or dietary use. Gamma-hydroxybutyrate (GHB) is a separate compound with approved medical uses in some contexts but is also a controlled substance due to abuse potential.