title: Quantification of Cholesterol Solubilized in Dietary Micelles: Dependence on Human Bile Salt Variability and the Presence of Dietary Food Ingredients.
abstract: The solubility of cholesterol in bile salt (BS) micelles is important to understand the availability of cholesterol for absorption in the intestinal epithelium and to develop strategies to decrease cholesterol intake from the intestinal lumen. This has been the subject of intense investigation, due to the established relation between the development of diseases such as atherosclerosis and high levels of cholesterol in the blood. In this work we quantify the effect of BS variability on the amount of cholesterol solubilized. The effect of some known hypocholesterolemic agents usually found in the diet is also evaluated, as well as some insight regarding the mechanisms involved. The results show that, depending on the bile salt composition, the average value of sterol per micelle is equal to or lower than 1. The amount of cholesterol solubilized in the BS micelles is essentially equal to its total concentration until the solubility limit is reached. Altogether, this indicates that the maximum cholesterol solubility in the BS micellar solution is the result of saturation of the aqueous phase and depends on the partition coefficient of cholesterol between the aqueous phase and the micellar pseudophase. The effect on cholesterol maximum solubility for several food ingredients usually encountered in the diet was characterized using methodology developed recently by us. This method allows the simultaneous quantification of both cholesterol and food ingredient solubilized in the BS micelles even in the presence of larger aggregates, therefore avoiding their physical separation with possible impacts on the overall equilibrium. The phytosterols stigmasterol and stigmastanol significantly decreased cholesterol solubility with a concomitant reduction in the total amount of sterol solubilized, most pronounced for stigmasterol. Those results point toward coprecipitation being the major cause for the decrease in cholesterol solubilization by the BS micelles. The presence of tocopherol and oleic acid leads to a small decrease in the amount of cholesterol solubilized while palmitic acid slightly increases the solubility of cholesterol. Those dietary food ingredients are completely solubilized by the BS micelles, indicating that the effects on cholesterol solubility are due to changes in the properties of the mixed micelles.
authors.affiliation: Chemistry Department, University of Coimbra Rua Larga , Largo D. Dinis, 3004-535 Coimbra, Portugal.|Coimbra Chemistry Center, CQC, Rua Larga, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Filipe M
authors.initials: FM
authors.lastname: Coreta-Gomes
authors.affiliation: Chemistry Department, University of Coimbra Rua Larga , Largo D. Dinis, 3004-535 Coimbra, Portugal.|CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa , Lisbon, Portugal.
authors.forename: Winchil L C
authors.initials: WL
authors.lastname: Vaz
authors.affiliation: Coimbra Chemistry Center, CQC, Rua Larga, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Emeric
authors.initials: E
authors.lastname: Wasielewski
authors.affiliation: Department of Life Sciences, Faculty of Science and Technology, University of Coimbra 3000-393 Coimbra, Portugal.|Coimbra Chemistry Center, CQC, Rua Larga, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Carlos F G
authors.initials: CF
authors.lastname: Geraldes
authors.affiliation: Chemistry Department, University of Coimbra Rua Larga , Largo D. Dinis, 3004-535 Coimbra, Portugal.|Coimbra Chemistry Center, CQC, Rua Larga, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Moreno
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D002784:Cholesterol / Q000032:analysis* / Q000737:chemistry*; D004032:Diet; D000074385:Food Ingredients / Q000032:analysis*; D006801:Humans; D008823:Micelles; D010840:Phytosterols / Q000737:chemistry; D012995:Solubility
chemical_list: D001647:Bile Acids and Salts; D000074385:Food Ingredients; D008823:Micelles; D010840:Phytosterols; D002784:Cholesterol