Molecular insights into the mechanisms underlying the cholesterol-lowering effects of phytosterols.

Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma low-density lipoprotein- cholesterol (LDL-C) levels when given at 2 g/day. Since this dose has not been reported to cause health- related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into very-low-density lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the transintestinal cholesterol excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from blood to enterocytes and intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.

• Publication year

  2019

• Venue

  Current Medicinal Chemistry

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.2174/0929867326666190822154701PMID 31438826
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2017cited by this paper
• Developments in intestinal cholesterol transport and triglyceride absorption

  2017cited by this paper
• Fat type in phytosterol products influence their cholesterol-lowering potential: A systematic review and meta-analysis of RCTs.

  2016cited by this paper
• The Farnesoid X Receptor: Good for BAD

  2016cited by this paper
• 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents.

  2016cited by this paper
• Fat type in phytosterol spreads influence their cholesterol-lowering potential: A systematic review and meta-analysis of RCTs

  2016cited by this paper
• Transintestinal Cholesterol Transport Is Active in Mice and Humans and Controls Ezetimibe-Induced Fecal Neutral Sterol Excretion.

  2016cited by this paper
• Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1

  2015cited by this paper
• Micellar lipid composition affects micelle interaction with class B scavenger receptor extracellular loops

  2015cited by this paper
• Postprandial plasma oxyphytosterol concentrations after consumption of plant sterol or stanol enriched mixed meals in healthy subjects.

  2015cited by this paper
• Phytosterols, Phytostanols, and Lipoprotein Metabolism

  2015cited by this paper
• Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

  2015cited by this paper
• Ezetimibe added to statin therapy after acute coronary syndromes

  2015cited by this paper
• A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion.

  2015cited by this paper
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• Relative roles of ABCG5/ABCG8 in liver and intestine

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• Inter-individual Variability in Response to Plant Sterol and Stanol Consumption.

  2015cited by this paper
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  2014cited by this paper
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  2014cited by this paper
• Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease.

  2014cited by this paper
• Sitosterolemia: Diagnosis, Investigation, and Management

  2014cited by this paper
• The role of the gut in reverse cholesterol transport--focus on the enterocyte.

  2013cited by this paper
• Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease

  2013cited by this paper
• Intestinal cholesterol secretion: future clinical implications.

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  2013cited by this paper
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  2013cited by this paper
• Effects of plant sterol- or stanol-enriched margarine on fasting plasma oxyphytosterol concentrations in healthy subjects.

  2013cited by this paper
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• Role of the gut in lipid homeostasis.

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• Inhibition of Cholesterol Absorption: Targeting the Intestine

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• Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present.

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  2011cited by this paper
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  2011cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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