A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

Abstract

Summary Background: Micelle formation of cholesterol with lecithin and bile salts is a key process for intestinal absorption of lipids. Some dietary fibers commonly used to reduce the lipid content in the body are thought to inhibit lipid absorption by binding to bile salts and decreasing the lipid solubility. Amongst these, α-cyclodextrin (α-CD) is reportedly one of the most powerful dietary fibers for decreasing blood cholesterol. However, it is difficult to believe that α-CD directly removes cholesterol because it has a very low affinity for cholesterol and its mechanism of action is less well understood than those of other dietary fibers. To identify this mechanism, we investigated the interaction of α-CD with lecithin and bile salts, which are essential components for the dissolution of cholesterol in the small intestine, and the effect of α-CD on micellar solubility of cholesterol. Results: α-CD was added to Fed-State Simulated Intestinal Fluid (FeSSIF), and precipitation of a white solid was observed. Analytical data showed that the precipitate was a lecithin and α-CD complex with a molar ratio of 1:4 or 1:5. The micellar solubility of cholesterol in the mixture of FeSSIF and α-CD was investigated, and found to decrease through lecithin precipitation caused by the addition of α-CD, in a dose-dependent manner. Furthermore, each of several other water-soluble dietary fibers was added to the FeSSIF, and no precipitate was generated. Conclusion: This study suggests that α-CD decreases the micellar solubility of cholesterol in the lumen of the small intestine via the precipitation of lecithin from bile salt micelles by complex formation with α-CD. It further indicates that the lecithin precipitation effect on the bile salt micelles by α-CD addition clearly differs from addition of other water-soluble dietary fibers. The decrease in micellar cholesterol solubility in the FeSSIF was the strongest with α-CD addition.

Low amounts of dietary fibre increase in vitro production of short-chain fatty acids without changing human colonic microbiota structure

“…CDs are cyclic oligosaccharides consisting of six (αCD), seven (βCD), or eight (γCD) α-1,4-linked glycopyranose units, with a hydrophilic hydroxyl group on their outer surface and a hydrophobic cavity in their centre. In these CDs, αCD is widely used as a water-soluble dietary fibre 8 . Addition of 1.5% αCD to mice has been shown to decrease the numbers of caecal bacteria belonging to the genus Clostridium 9 .…”

Anti-obesity effects of α-cyclodextrin-stabilized 4-methylthio-3-butenyl isothiocyanate from daikon (<i>Raphanus sativus</i> var. <i>longipinnatus</i>) in mice

“…Because of its interaction with lecithin precipitation, aCD decreased the micellar cholesterol solubility of dietary fat in intestinal fluid and prevented the absorption of cholesterol in the small intestine. (13,37,38) We expected that aCD would exert similar effects in this study. However, aCD did not alter HFD-induced increase in body weights and epididymal fat weight in our study.…”

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions

“…It has been shown that both bile salts and phospholipids can act as guest molecules in CD complexes. [216][217][218] As mentioned earlier in this review, in multicomponent systems, competition between different guest molecules may result in reorganization of complexes and in dynamic systems, such as the intestinal environment, complex composition (and, consequently, CD aggregation) can change over time. As a result, the aggregation behavior and overall performance of the formulation in biorelevant media and in pure water may strongly differ.…”