Can cholesterol absorption be reduced by phytosterols and phytostanols via a cocrystallization mechanism?

The formation of mixed water-insoluble poorly absorbable crystals between cholesterol (CH) and phytosterols (PS) or phytostanols (PSS) in the intestinal lumen has been considered for a long time as a plausible mechanism of the PS/PSS-induced reduction of serum CH concentration. In this report, we demonstrated with the use of the powder X-ray diffraction (XRD) and the differential scanning calorimetry (DSC) techniques that mixed CH:beta-sitosterol (SI) crystals can be formed by recrystallization of corresponding mixtures from melts and also from mixed CH:SI solutions in triglyceride oil. Formation of mixed CH:SI crystals takes place in a wide interval of CH:SI ratios, from approximately 10 up to approximately 75 wt.% of SI in the mixture. Formation of mixed CH:sitostanol (SS) crystals from melts and solutions in triglyceride oil was also detected, but in a more narrow interval of CH:SS ratios. However, during the lipolysis of model dietary emulsions under in vitro conditions, the formation of crystalline material was not detected due to the relatively high solubility of free sterols/stanols in products of fat hydrolysis. We found that the solubility of free CH, SI, and SS raises upon the increase in the solvent polarity, i.e. free fatty acid > diglycerideoil > triglyceride oil. Therefore, we believe that the cocrystallization mechanism of phytosterol-induced serum CH lowering has relatively low importance, unless the diet is specially designed to include relatively little amounts of dietary fats. The presented experimental evidence demonstrates that it is unlikely that the formation of poorly absorbable mixed crystals largely affects the intestinal absorption of CH and, therefore, that this is a prime mechanism by which PS and PSS effect CH absorption.