β-Hydroxybutyric acid is able to cross the blood-brain-barrier into the central nervous system. Levels of β-hydroxybutyric acid increase in the liver, heart, muscle, brain, and other tissues with exercise, calorie restriction, fasting, and ketogenic diets. The compound has been found to act as a histone deacetylase (HDAC) inhibitor. Through inhibition of the HDAC class I isoenzymes HDAC2 and HDAC3, β-hydroxybutyric acid has been found to increase brain-derived neurotrophic factor (BDNF) levels and TrkB signaling in the hippocampus. Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which induces promoters of the BDNF gene in the hippocampus. These findings may have clinical relevance in the treatment of depression, anxiety, and cognitive impairment.