Oxysterol

Oxysterols are oxidized derivatives of cholesterol. They arise when cholesterol is modified by enzymatic processes or by non-enzymatic oxidation, and they can be found in tissues and circulating blood. Some oxysterols are produced inside the body, while others may form during the cooking and processing of foods.

Biosynthesis and sources include enzymatic routes such as cholesterol 25-hydroxylase (CH25H) yielding 25-hydroxycholesterol, cholesterol 27-hydroxylase (CYP27A1) producing 27-hydroxycholesterol, and cholesterol 24-hydroxylase (CYP46A1) generating 24-hydroxycholesterol mainly in the brain. Non-enzymatic oxidation by reactive oxygen species creates a range of products, including 7-ketocholesterol and 7β-hydroxycholesterol. Diet can contribute oxysterols formed during food processing, but endogenous production is typically the major determinant of circulating levels.

Biological roles are diverse. Many oxysterols act as signaling molecules, serving as ligands for liver X receptors (LXRα/β) and regulating cholesterol metabolism genes such as ABCA1, ABCG1, and APOE. They influence cholesterol efflux, transport, and metabolism. 24S-hydroxycholesterol is produced by neurons to help remove brain cholesterol, while circulating 27-hydroxycholesterol can cross the blood–brain barrier and participate in systemic signaling. Some oxysterols can be cytotoxic at high concentrations and may promote inflammatory responses in certain contexts.

Clinical relevance includes associations with cardiovascular and neurodegenerative diseases. Altered oxysterol levels can reflect oxidative stress and metabolic disturbances and may serve as biomarkers. Dysregulated oxysterol metabolism is also observed in certain inherited disorders.

Measurement and diet considerations: Oxysterols are quantified in plasma or tissue using GC-MS or LC-MS techniques. Because endogenous production dominates, circulating levels primarily reflect metabolic and oxidative processes rather than dietary intake.