The lipid-lowering effects and associated mechanisms of dietary phytosterol supplementation

Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation. Identification of single-nucleotide polymorphisms (SNP) in key cholesterol and TG regulating genes, in particular adenosine triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have provided insight into the potential of utilizing genomic identifiers as an indicator of PS responsiveness. While PS supplementation is deemed safe, expanding research into the atherogenic potential of oxidized phytosterols (oxyphytos-terols) has emerged with their identification in arterial lesions. This review will highlight the lipid-lowering utility and associated mechanisms of PS and discuss novel applications and future research priorities for PS pertaining to in utero PS exposure for long-term cardiovascular disease risk protection and combination therapies with lipid-lowering drugs.