Phytosterols in human health: Biochemical mechanisms of action and disease-modulating effects

Phytosterols are plant-derived sterols structurally similar to cholesterol and present in vegetable oils, seeds, legumes, and whole grains. Their best-established health effect is lowering circulating low-density lipoprotein cholesterol, mainly through inhibition of intestinal cholesterol absorption. Beyond this classical role, recent studies suggest that phytosterols may influence biological processes relevant to human health. Proposed mechanisms include changes in membrane lipid organization, modulation of nuclear receptors such as liver X receptors and peroxisome proliferator-activated receptors, activation of AMP-activated protein kinase, and regulation of metabolic and inflammatory signaling pathways. Experimental and human evidence indicates possible effects on adipose tissue function, hepatic lipid accumulation, insulin sensitivity, inflammation, oxidative stress, and immune responses. These findings have increased interest in the relevance of phytosterols to obesity, metabolic dysfunction-associated steatotic liver disease, type 2 diabetes, and immune-mediated disorders such as rheumatoid arthritis. Interactions with the gut microbiota and bile acid metabolism may provide additional pathways linking phytosterol intake with systemic effects, although human evidence remains limited. Antioxidant and anti-inflammatory actions have also been linked to neuroprotective and anticancer effects, but current support is mainly from preclinical studies. This review critically summarizes mechanistic and translational evidence, with emphasis on bioavailability, interindividual variability, safety, and remaining research gaps.