A review on chemical and physical modifications of phytosterols and their influence on bioavailability and safety.

Phytosterols have been shown to lower cholesterol levels and to have antioxidant, anti-inflammatory and other biological activities. However, the high melting point and poor solubility limit their bioavailability and practical application. It is advantageous to modify phytosterols chemically and physically. This article reviews and discusses the chemical and physical modifications of phytosterols, as well as their effects on the bioavailability and possible toxicity in vivo. The current research on chemical modifications is mainly focused on esterification to increase the oil solubility and water solubility. For physical modifications (mainly microencapsulation), there are biopolymer-based, surfactant-based and lipid-based nanocarriers. Both chemical and physical modifications of phytosterols can effectively increase the absorption and bioavailability. The safety of modified phytosterols is also an important issue. Phytosterol esters are generally considered to be safe. However, phytosterol oxides, which may be produced during the synthesis of phytosterol esters, have shown toxicity in animal models. The toxicity of nanocarriers also needs further studies.

Sterols and Sterol Oxidation Products: Effect of Dietary Intake on Tissue Distribution in ApoE-Deficient Mice.

Sterols and sterol oxidation products (SOPs) are well-known dietary factors influencing atherosclerosis; however, their distribution in vivo after dietary sterol/SOP intake is still unclear. Here, we investigated the tissue distribution of sterols and SOPs in ApoE-/- mice after dietary exposure to diets supplemented with phytosterols (PS), phytosterol oxidation products (POPs), or cholesterol oxidation products (COPs). The results showed that PS intake reduced cholesterol in serum and the liver but increased cholesterol in the brain. PS intake increased the levels of PS in vivo and the levels of 7-keto- and triol-POPs in serum and the liver. COP intake elevated the level of all COPs in serum but did not change the 7-keto-cholesterol level in the liver and brain. All POPs in serum and parts of POPs in the liver and brain increased after dietary POP exposure. Our study indicated that dietary PS and SOPs accumulated in vivo with varying degrees and influenced cerebral cholesterol metabolism.

Impact of thermooxidation of phytosteryl and phytostanyl fatty acid esters on cholesterol micellarization in vitro.

The effects of thermooxidation of a phytosteryl/-stanyl and a phytostanyl fatty acid ester mixture on cholesterol micellarization were investigated using an in vitro digestion model simulating enzymatic hydrolysis by cholesterol esterase and subsequent competition of the liberated phytosterols/-stanols with cholesterol for incorporation into mixed micelles. As a first step, relationships between different doses of the ester mixtures and the resulting micellarized cholesterol were established. Subsequent subjection of the thermooxidized ester mixtures to the in vitro digestion model resulted in three principal observations: (i) thermal treatment of the ester mixtures led to substantial decreases of the intact esters, (ii) in vitro digestion of cholesterol in the presence of the thermooxidized ester mixtures resulted in significant increases of cholesterol micellarization, and (iii) the extents of the observed effects on cholesterol micellarization were strongly associated to the remaining contents of intact esters. The loss of efficacy to inhibit cholesterol micellarization due to thermally induced losses of intact esters corresponded to a loss of efficacy that would have been induced by an actual removal of these amounts of esters prior to the in vitro digestion. The obtained results suggest that in particular oxidative modifications of the fatty acid moieties might be responsible for the observed increases of cholesterol micellarization.