[1][2] In humans, D-β-hydroxybutyrate can be synthesized in the liver via the metabolism of fatty acids (e.g., butyrate), β-hydroxy β-methylbutyrate, and ketogenic amino acids through a series of reactions that metabolize these compounds into acetoacetate, which is the first ketone body that is produced in the fasting state.

Ketogenesis occurs if oxaloacetate in the liver cells is depleted, a circumstance created by reduced carbohydrate intake (through diet or starvation); prolonged, excessive alcohol consumption; and/or insulin deficiency.

[13] Levels of β-hydroxybutyric acid increase in the liver, heart, muscle, brain, and other tissues with exercise, calorie restriction, fasting, and ketogenic diets.

[13] 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.

[13] Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which induces promoters of the BDNF gene in the hippocampus.

[13] In epilepsy patients on the ketogenic diet, blood β-hydroxybutyrate levels correlate best with degree of seizure control.