Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice.

Phytosterols and phytostanols are two classes of sterol derivatives naturally synthesised in plants, but not in humans. Structurally, phytosterols and phytostanols have a sterane ring in common, but phytostanols do not have a double bond between carbons 5 and 6. The therapeutic potential of phytosterols and phytostanols supplementation in cholesterol reduction is the main reason for its wide usage in an expansive food matrix, including milk, yoghurt, margarine, mayonnaise, chocolate, tartare, chips, esterification with omega-3, and recently, as a successful nutraceutical among athletes is its fortification with whey protein. The heterogeneous effect of phytosterols and phytostanols in cholesterol lowering appears to be related to whether the individuals' inherent physiologic tendencies to "hyper-synthesise" cholesterol in the liver or "hyperabsorb" cholesterol via the small intestine. Individuals who are 'hypersynthesizers" of cholesterol tend to have a good reduction in plasma low-density lipoprotein cholesterol (LDLc) in response to statin therapy. Conversely, "hyper-absorbers" of cholesterol show a greater LDLc lowering in response to phytosterols or phytostanols. The ratios of cholestanol to cholesterol and lathosterol to cholesterol are good biomarkers of intestinal absorption of cholesterol and hepatic cholesterol synthesis. Animal data and human observational data suggest that phytosterols and phytostanols may have anti-atherosclerotic activities, e.g. reduction of the formation of nitric oxide, antagonism to the formation of LDL aggregates and plaque formation. The absence of cardiovascular outcome trials using phytosterol or phytostanol supplementation, makes it difficult to confirm a wider use in clinical practice, especially with the rapidly expanding list of effective and safe lipid-lowering medications.