Sterol absorption human intestine

The practical development of plant sterol drugs as cholesterol-lowering agents will depend both on structural features of the sterols themselves and on the form of the administered agent. For example, the unsaturated sterol sitosterol is poorly absorbed in the human intestine, whereas sitostanol, the saturated analog, is almost totally unabsorbable. In addition, there is evidence that plant sterols administered in a soluble, micellar form (see page 261 for a description of micelles) are more effective in blocking cholesterol absorption than plant sterols administered in a solid, crystalline form. 

Cholesterol absorption by intestinal cells is a key regulatory point in human sterol metabolism because it ultimately determines what percentage of the 1,000 mg of biliary cholesterol produced by the liver each day and what percentage of the... 

Like cholesterol, PS are absorbed in the proximal part of the small intestine after being incorporated into mixed micelles. Compared to cholesterol, the intestinal absorption of PS is low. While 40-60% of dietary cholesterol is absorbed, only about 5% of the PS are absorbed [18]. In addition, the efficiency of PS absorption is critically dependent on the structure of both sterol nucleus and side chain. For instance, the rate of plant sterol absorption was investigated in a human study... 

Phytosterols have cholesterol-lowering properties reducing cholesterol absorption in intestines, and may act in cancer prevention. Phytosterols naturally occur in small amount in vegetable oils, especially soybean oil. Sterols can reduce cholesterol in human subjects by up to 15% (Rossi S, 2006). 

The cholesterol-lowering properties of dietary plant sterols have been known for decades (Best et al., 1954 Peterson, 1951 Poliak, 1953), due specifically to reductions in cholesterol absorption. Inverse correlations between plant sterol intake and cholesterol absorption have been reported in animals (Carr et al., 2002 Ntanios and Jones, 1999) and humans (Ellegard et al., 2000). The exact mechanism by which plant sterols inhibit cholesterol absorption is unclear, and several mechanisms of action have been proposed, including (1) competition with cholesterol for solubilization in micelles within the intestinal lumen, (2) cocrystallization with cholesterol to form insoluble crystals, (3) interaction with digestive enzymes, and (4) regulation of intestinal transporters of cholesterol. 

The mechanism for the inhibition of cholesterol absorption is thought to involve competitive transfer to the micellar phase during absorption from the intestinal lumen. Phytosterols in the micellar phase may also act as emulsifying agents that selectively inhibit the transfer of cholesterol and other lipids (e.g., carotenoids and vitamins) and, thereby, limit their absorption. The exact kinetics governing the sterol competition for transfer are not known, but dietary sterols are absorbed differently in the digestive tract 40-50% for cholesterol, 12-16% for campesterol, 4-5% sitosterol, and <0.5% for phytostanols (37). Before absorption, esterified sterols are hydrolysed effectively in the upper intestine (191). Absorbed phytosterols are excreted by the liver into the bile but are hardly converted to bile acids (192). Numerous studies in animals and humans approved the safety of phytosterols and phytostanols (37). 

Recent data indicate that ezetimibe inhibits a specific transport process in jejunal enterocytes, which take up cholesterol from the lumen. The putative transport protein is Niemann-Pick Cl-hke 1 protein (NPCILI). In wild-type mice, ezetimibe inhibits cholesterol absorption by about 70% in NPCILI knockout mice, cholesterol absorption is 86% lower than in wild-type mice, and ezetimibe has no effect on cholesterol absorption. Ezetimibe does not affect intestinal triglyceride absorption. In human subjects, ezetimibe reduced cholesterol absorption by 54%, precipitating a compensatory increase in cholesterol synthesis, which can be inhibited with a cholesterol synthesis inhibitor such as a statin. There is also a substantial reduction of plasma levels of plant sterols (campesterol and sitosterol concentrations are reduced by 48 and 41%, respectively), indicating that ezetimibe also inhibits intestinal absorption of plant sterols. 

Phytosterols are nonnutrient bioactive substances and act as a structural component in the cell membranes, a role which in mammalian cells is played by cholesterol. The methyl or ethyl group at C-24 location makes them different from cholesterol [58]. They include plant sterols (unsaturated form) and plant stanols (saturated form). Both sterols and stanols are effective in lowering plasma total and LDL cholesterols and inhibit the absorption of cholesterol from the small intestine [59]. A wide spectrum of other biological activities in animals and humans has been reported, including anti-inflammatory [60], antibacterial [61], antioxidative [62], and anticancer activities [63]. P-Sitosterol, campesterol, stigmasterol, A -avenasterol, sitostanol, and campestanol are the most common representative members in this series. P-Sitosterol, campesterol, and stigmasterol are the major identified phytosterols in Brazil nut, with sitostanol, campestanol, and A -avenasterol present in trace amounts. 

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