Proposed mechanisms of cholesterol-lowering action of plant sterols

Plant sterols (or phytosterols) are naturally occurring compounds structurally related to cholesterol with different side chain configurations. To date, numerous studies have shown that dietary intake of plant sterols either in their free form or as fatty acid esters is effective at lowering plasma total and low density lipoprotein cholesterol. The main mechanism responsible for the cholesterol-lowering effect of free and esterified plant sterols is the inhibition of intestinal cholesterol absorption. Several sites within the intestinal tract have been suggested where this inhibition might take place. Different mechanisms, such as competition with cholesterol for solubilisation in dietary mixed micelles, co-crystallisation with cholesterol to form insoluble mixed crystals, and interference with the hydrolysis process by lipases and cholesterol esterases are believed to contribute to the lowering of serum cholesterol concentrations by plant sterols. There is also emerging evidence that plant sterols interfere with transport-mediated processes of cholesterol uptake. The consequence of all these actions, although their individual contribution on the overall effect remains to be established, is that intestinal cholesterol absorption is reduced, while more cholesterol is excreted in the faeces. The aim of this review is to summarise the current understanding concerning the mechanism of action by which plant sterols affect cholesterol metabolism and thus exert their cholesterol-lowering effect. The review will focus on the gut, e.g. on the physico-chemical effects at the gastric-duodenal level, on absorptive site effects, and on intra-cellular trafficking, i.e. effects at the epithelial cell level.