Plant sterols and stanols: Their role in health and disease

Abstract

Mammalian physiological processes, and likely any organism with a biliary tree, can distinguish between dietary cholesterol and non-cholesterols, retaining very little of the non-cholesterol in their bodies. Historically, the distinction between plant sterols and cholesterol has been known about for a century or more. That plants sterols were not 'absorbed' has been investigated for almost half a century. Indeed, the oral of plant sterols in gram quantities was shown to interfere with cholesterol absorption and is one of the oldest pharmacological therapies for hypercholesterolemia. Although the basis for the latter was shown to be caused by exclusion of cholesterol from intestinal micelles by plant sterols, it was not until the identification of the a rare genetic disease, sitosterolemia, first described in 1974, that led to the hypothesis that specific molecular mechanism(s) governed both the entry and excretion of sterols by the body. This talk will cover the physiology of dietary sterol metabolism, genetics and pathophysiology of sitosterolemia. Additionally, the role of plant sterols in normal and abnormal metabolism in humans as well as selected animal models will be discussed.

Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia

“…1 Although 20% to 80% of dietary cholesterol is absorbed, 2 dietary plant sterols, which include stigmasterol, campesterol, and sitosterol, are normally actively excreted, resulting in less than 1% retention. 3 Clues that a specific molecular mechanism was involved in the selective removal of phytosterols were first provided by Bhattacharyya and Conner in a 1974 description of extensive tendon xanthomas and unusually high levels of b-sitosterol with normal cholesterol levels in 2 sisters suffering from what is now most commonly known as sitosterolemia.…”

High Fibre Diets and Alzheimer’s Disease

“…2 g per day associated with reduction in cholesterol absorption with effects on membrane cholesterol molecular mechanisms [97][98][99].…”

“…Brain cholesterol homeostasis and phytosterol intake are closely interlinked and diets with specific composition of phytosterols are possibly important in the maintenance of liver, brain and oxysterol metabolism [97][98][99][100][101][102][103][104][105][106]. Phytosterols such as campesterol and stigmasterol inhibit intestinal cholesterol absorption and beta-sitosterol and stigmasterol act on the liver to reduce cholesterol levels (Figure 2, ref [97,99,101]).…”

“…The membrane interactions of Aβ require cholesterol for clearance and metabolism with the increase in the membrane cholesterol involved in the regulation of Aβ assemblies [125][126][127]. The role of caloric restriction in activation of HDAC genes which control membrane cholesterol and the role of phytosterols and phytostanols (Figure 4 [99][100][101][102] have become of central interest since membrane interactions with cholesterol and Aβ may be required for the clearance and metabolism of Aβ. Increasing membrane phytosterol contents may control unstable protein/lipid complexes with the composition of phytosterols essential for neuron number and survival.…”

Do clinical and experimental investigations support an antiatherogenic role for dietary phytosterols/stanols?

“…PS lowers plasma cholesterol by 10-15% when the PS intake is 0. .0 g/day (9). Several trials have shown that 2 g/day of phytostanols can lower plasma lowdensity lipoprotein (LDL)-cholesterol (LDL-C) from 9 to 14% (6).…”