Phase behavior of cholesterol in mixtures with hypo- and hypercholesterolemic lipids

Some lipidic bioactives are largely reported to present hypocholesterolemic effects, for example, oleic acid, α-tocopherol, and octacosanol, found in rice-bran, olive, and sunflower oils. In contrast, some saturated and trans-unsaturated lipids found in animal fats or partially hydrogenated oils have been associated with the opposite effect. However, the mechanisms in which these lipids act for lowering or increasing cholesterol are not fully understood. In this context, this work was aimed at a fundamental physicochemical comprehension of how cholesterol phase behavior is affected in mixtures with these compounds. The complete solid-liquid equilibrium (SLE) phase diagrams of these mixtures were depicted by differential scanning calorimetry and microscopy, and also evaluated by the SLE thermodynamic theory. The minimal melting temperature (eutectic points) of the mixtures followed the order: α-tocopherol < oleic acid < elaidic acid < stearic acid < octacosanol. Among all biocompounds, stearic and trans-oleic acids promoted few changes in the normal thermodynamic behavior of cholesterol when in a mixture. In contrast, α-tocopherol induced a significant temperature depression in the system. Furthermore, at high concentrations of cholesterol (>90% molar fraction), the formation of solid solution was observed in all other systems, to a higher degree for oleic acid. The higher interactions of these beneficial compounds and the formation of solid solution that literature associates with the alteration of cholesterol enteric absorption probably correlates with their hypocholesterolemic effects.