Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion

Abstract

Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol.

Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes

“…The cholesterol lowering by the combination of plant sterols and glucomannan may involve a reduction in both cholesterol absorption and synthesis. Plant sterols have been shown to suppress intestinal cholesterol absorption by reducing dietary and biliary cholesterol incorporation into micelles (Ikeda et al, 1988;Nissinen et al, 2002). However, it has also been shown that the inhibition of the intestinal absorption is partially compensated for by an increase in hepatic cholesterol synthesis rate (Gylling et al, 1999;Jones et al, 2000).…”

“…The efficacy of sterols has now been unquestionably established through many earlier (Weststrate and Meijer, 1998) and recent studies (Hallikainen et al, 2000;Vanstone et al, 2002;Varady et al, 2004). It has been shown that plant sterols lower LDL cholesterol concentrations by inhibiting cholesterol absorption in the intestine (Ikeda et al, 1988;Nissinen et al, 2002).…”

Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols

“…However, in other studies with free plant sterols (Weststrate and Meijer, 1998;Hallikainen et al, 1999) or with plant sterol esters (Gylling et al, 1999;Hendriks et al, 1999;Mensink et al, 2002), there has been a significant (8-30%) reduction in b-carotene or a-tocopherol concentrations after lipid adjustment for reduced total or LDL cholesterol. It has been suggested that esterified plant sterols have a greater effect than free plant sterols on the reduction of fat-soluble vitamin absorption because the plant sterol esters partition into the oil phase of the intestine, whereas free sterols partition more frequently into the mixed micellar phase (Nissinen et al, 2002). Details of the regulation of the lipophilic nutrient absorption are largely unknown and this needs further investigation.…”

Are plant sterols and plant stanols a viable future treatment for dyslipidemia?

“…The only well-documented hypocholesterolemic mechanism of action of plant sterols/stanols is that when present in large enough quantities in the upper small intestine, they displace cholesterol from the mixed micelles so that cholesterol absorption is partially inhibited [3,4]. But how much dietary plant sterols/stanols are needed?…”