Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice

Phytosterols and phytostanols are two classes of sterol derivatives naturally synthesised in plants, but not in humans. Structurally, phytosterols and phytostanols have a sterane ring in common, but phytostanols do not have a double bond between carbons 5 and 6. The therapeutic potential of phytoste...

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Main Authors: Massimiliano Ruscica, Wann Jia Loh, Cesare R. Sirtori, Gerald F. Watts
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Pharmacological Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1043661825001069
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author Massimiliano Ruscica
Wann Jia Loh
Cesare R. Sirtori
Gerald F. Watts
author_facet Massimiliano Ruscica
Wann Jia Loh
Cesare R. Sirtori
Gerald F. Watts
author_sort Massimiliano Ruscica
collection DOAJ
description Phytosterols and phytostanols are two classes of sterol derivatives naturally synthesised in plants, but not in humans. Structurally, phytosterols and phytostanols have a sterane ring in common, but phytostanols do not have a double bond between carbons 5 and 6. The therapeutic potential of phytosterols and phytostanols supplementation in cholesterol reduction is the main reason for its wide usage in an expansive food matrix, including milk, yoghurt, margarine, mayonnaise, chocolate, tartare, chips, esterification with omega-3, and recently, as a successful nutraceutical among athletes is its fortification with whey protein. The heterogeneous effect of phytosterols and phytostanols in cholesterol lowering appears to be related to whether the individuals’ inherent physiologic tendencies to “hyper-synthesise” cholesterol in the liver or “hyperabsorb” cholesterol via the small intestine. Individuals who are ‘hypersynthesizers” of cholesterol tend to have a good reduction in plasma low-density lipoprotein cholesterol (LDLc) in response to statin therapy. Conversely, “hyper-absorbers” of cholesterol show a greater LDLc lowering in response to phytosterols or phytostanols. The ratios of cholestanol to cholesterol and lathosterol to cholesterol are good biomarkers of intestinal absorption of cholesterol and hepatic cholesterol synthesis. Animal data and human observational data suggest that phytosterols and phytostanols may have anti-atherosclerotic activities, e.g. reduction of the formation of nitric oxide, antagonism to the formation of LDL aggregates and plaque formation. The absence of cardiovascular outcome trials using phytosterol or phytostanol supplementation, makes it difficult to confirm a wider use in clinical practice, especially with the rapidly expanding list of effective and safe lipid-lowering medications.
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spelling doaj-art-48988e29cc6844888b9b376b605ded592025-08-20T02:59:18ZengElsevierPharmacological Research1096-11862025-04-0121410768110.1016/j.phrs.2025.107681Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practiceMassimiliano Ruscica0Wann Jia Loh1Cesare R. Sirtori2Gerald F. Watts3Department of Pharmacological and Biomolecular Sciences ''Rodolfo Paoletti'', Università Degli Studi Di Milano, Milan, Italy; Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Corresponding author at: Department of Pharmacological and Biomolecular Sciences ''Rodolfo Paoletti'', Università Degli Studi Di Milano, Milan, Italy.School of Medicine, University of Western Australia, Australia; Department of Endocrinology, Changi General Hospital, Changi, Singapore; Duke-NUS Medical School, Singapore, Singapore; Correspondence to: Department of Endocrinology, Changi General Hospital, Changi, Singapore.Department of Pharmacological and Biomolecular Sciences ''Rodolfo Paoletti'', Università Degli Studi Di Milano, Milan, ItalySchool of Medicine, University of Western Australia, Australia; Departments of Cardiology and Internal Medicine, Royal Perth Hospital, Perth, Western Australia, AustraliaPhytosterols and phytostanols are two classes of sterol derivatives naturally synthesised in plants, but not in humans. Structurally, phytosterols and phytostanols have a sterane ring in common, but phytostanols do not have a double bond between carbons 5 and 6. The therapeutic potential of phytosterols and phytostanols supplementation in cholesterol reduction is the main reason for its wide usage in an expansive food matrix, including milk, yoghurt, margarine, mayonnaise, chocolate, tartare, chips, esterification with omega-3, and recently, as a successful nutraceutical among athletes is its fortification with whey protein. The heterogeneous effect of phytosterols and phytostanols in cholesterol lowering appears to be related to whether the individuals’ inherent physiologic tendencies to “hyper-synthesise” cholesterol in the liver or “hyperabsorb” cholesterol via the small intestine. Individuals who are ‘hypersynthesizers” of cholesterol tend to have a good reduction in plasma low-density lipoprotein cholesterol (LDLc) in response to statin therapy. Conversely, “hyper-absorbers” of cholesterol show a greater LDLc lowering in response to phytosterols or phytostanols. The ratios of cholestanol to cholesterol and lathosterol to cholesterol are good biomarkers of intestinal absorption of cholesterol and hepatic cholesterol synthesis. Animal data and human observational data suggest that phytosterols and phytostanols may have anti-atherosclerotic activities, e.g. reduction of the formation of nitric oxide, antagonism to the formation of LDL aggregates and plaque formation. The absence of cardiovascular outcome trials using phytosterol or phytostanol supplementation, makes it difficult to confirm a wider use in clinical practice, especially with the rapidly expanding list of effective and safe lipid-lowering medications.http://www.sciencedirect.com/science/article/pii/S1043661825001069PhytosterolsPhytostanolsLDL cholesterolCardiovascular riskPhytosterolemiaSitosterolemia
spellingShingle Massimiliano Ruscica
Wann Jia Loh
Cesare R. Sirtori
Gerald F. Watts
Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice
Pharmacological Research
Phytosterols
Phytostanols
LDL cholesterol
Cardiovascular risk
Phytosterolemia
Sitosterolemia
title Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice
title_full Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice
title_fullStr Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice
title_full_unstemmed Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice
title_short Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice
title_sort phytosterols and phytostanols in context from physiology and pathophysiology to food supplementation and clinical practice
topic Phytosterols
Phytostanols
LDL cholesterol
Cardiovascular risk
Phytosterolemia
Sitosterolemia
url http://www.sciencedirect.com/science/article/pii/S1043661825001069
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AT wannjialoh phytosterolsandphytostanolsincontextfromphysiologyandpathophysiologytofoodsupplementationandclinicalpractice
AT cesarersirtori phytosterolsandphytostanolsincontextfromphysiologyandpathophysiologytofoodsupplementationandclinicalpractice
AT geraldfwatts phytosterolsandphytostanolsincontextfromphysiologyandpathophysiologytofoodsupplementationandclinicalpractice