Mohamed D, Ramadan AA, Mabrok HB, Hamed I. Phytosterols in human health: Biochemical mechanisms of action and disease-modulating effects. World J Biol Chem 2026; 17(2): 121685 [DOI: 10.4331/wjbc.v17.i2.121685]
Corresponding Author of This Article
Doha Mohamed, PhD, Professor, Department of Nutrition and Food Science, Food Industries and Nutrition Institute, National Research Centre, 33 El Buhouth Street, Dokki, Cairo 12622, Egypt. dohaabdomohamed@gmail.com
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Biochemistry & Molecular Biology
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review-article
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Mohamed D, Ramadan AA, Mabrok HB, Hamed I. Phytosterols in human health: Biochemical mechanisms of action and disease-modulating effects. World J Biol Chem 2026; 17(2): 121685 [DOI: 10.4331/wjbc.v17.i2.121685]
World J Biol Chem. Jun 5, 2026; 17(2): 121685 Published online Jun 5, 2026. doi: 10.4331/wjbc.v17.i2.121685
Phytosterols in human health: Biochemical mechanisms of action and disease-modulating effects
Doha Mohamed, Asmaa A Ramadan, Hoda B Mabrok, Ibrahim Hamed
Doha Mohamed, Asmaa A Ramadan, Hoda B Mabrok, Ibrahim Hamed, Department of Nutrition and Food Science, Food Industries and Nutrition Institute, National Research Centre, Cairo 12622, Egypt
Author contributions: Mohamed D, Ramadan AA, Mabrok HB, and Hamed I contributed equally to the review; All authors read and approved the final version of the manuscript to be published.
AI contribution statement: We would like to respectfully clarify that the manuscript was not generated by AI. The scientific content, literature review, interpretation of evidence, and conclusions were prepared by the authors. The manuscript was also professionally edited by a native English language editor, and the editing certificate was uploaded during submission. All reviewer responses, scientific explanations, literature interpretation, and revisions were prepared and evaluated by the authors. AI tools were not used to independently generate scientific responses or academic content. Limited AI-assisted language tools were occasionally used to improve grammar, sentence clarity, readability, and general language expression. All figures and images were prepared by the authors and were not generated using AI tools.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Doha Mohamed, PhD, Professor, Department of Nutrition and Food Science, Food Industries and Nutrition Institute, National Research Centre, 33 El Buhouth Street, Dokki, Cairo 12622, Egypt. dohaabdomohamed@gmail.com
Received: March 30, 2026 Revised: May 3, 2026 Accepted: May 25, 2026 Published online: June 5, 2026 Processing time: 66 Days and 13.6 Hours
Abstract
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.
Core Tip: Phytosterols are well-established cholesterol-lowering agents, but emerging evidence highlights their broader biological roles. This review provides a comprehensive synthesis of molecular mechanisms underlying phytosterol action, including modulation of liver X receptors, peroxisome proliferator-activated receptors, and AMP-activated protein kinase signaling, membrane lipid organization, and gut microbiota-bile acid interactions. These integrated pathways contribute to improved lipid and glucose metabolism, reduced inflammation, and enhanced cardiometabolic health, supporting the potential of phytosterols as multifunctional dietary bioactives beyond lipid lowering.
