Mechanisms Underlying the Health Benefits of Plant Sterol and Stanol Ester Consumption

2015 ◽  
Vol 98 (3) ◽  
pp. 697-700 ◽  
Author(s):  
Jogchum Plat ◽  
Sabine Baumgartner ◽  
Ronald P Mensink
Keyword(s):  
Plant Sterol ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cvd Risk ◽  
Lower Serum ◽  
Intestinal Cholesterol Absorption ◽  
Target Drug ◽  
Stanol Ester

Abstract The recent IMPROVE-IT trial clearly showed that lowering serum low-density lipoprotein cholesterol (LDL-C) concentrations via inhibiting intestinal cholesterol absorption through ezetimibe effectively lowered the number of new cardiovascular disease (CVD) events. This supports the use of other (dietary) interventions that lower serum LDL-C concentrations via comparable mechanisms such as described for plant sterol and stanol ester enriched functional foods. Therefore it is tempting to suggest that these compounds may have the same effects on CVD outcome, as described for ezetimibe in the IMPROVE-IT trial. This has however not been proven so far. A possible advantage of plant sterol and stanol ester enriched foods over ezetimibe—a typical single-target drug—is that these dietary compounds act on multiple targets, since they not only lower serum LDL-C concentrations, but also lower serum triacylglycerol (TAG) concentrations in subjects with elevated serum TAG concentrations. In addition, they might influence the functioning of our immune system via a changed activity of the regulatory T-cells. This combination of effects makes these compounds highly attractive to decrease CVD risk.

Molecular Insights into the Mechanisms Underlying the Cholesterol- Lowering Effects of Phytosterols

2019 ◽  
Vol 26 (37) ◽  
pp. 6704-6723 ◽  
Author(s):  
Lídia Cedó ◽  
Marta Farràs ◽  
Miriam Lee-Rueckert ◽  
Joan Carles Escolà-Gil
Keyword(s):  
Bile Acids ◽  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Plant Sterols ◽  
Intestinal Lumen ◽  
Low Density ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Lowering

Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma Low-Density Lipoprotein-Cholesterol (LDL-C) levels when given 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 the blood to enterocytes and the 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.

Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study

2008 ◽  
Vol 33 (4) ◽  
pp. 728-734 ◽  
Author(s):  
Iwona Rudkowska ◽  
Suhad S. AbuMweis ◽  
Catherine Nicolle ◽  
Peter J.H. Jones
Keyword(s):  
Plant Sterol ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Individual Variability ◽  
Nucleotide Polymorphisms ◽  
Control Phase ◽  
Individual Variations ◽  
Niemann Pick

Plant sterol (PS) consumption decreases low-density lipoprotein cholesterol (LDL-C) levels; however, high variability of responsiveness of lipid levels to PS intervention has been observed. We hypothesized that common single-nucleotide polymorphisms (SNPs) in the genes for the ATP binding cassette proteins G5 (ABCG5) and G8 (ABCG8), Niemann-Pick C1-like 1 (NPC1L1), or other proteins of the cholesterol pathway, would underline inter-individual variations in response to PS. Twenty-six hyperlipidemic subjects completed a randomized trial of 3 PS phases and a control phase. Three non-responders were identified who failed on 3 consecutive occasions to decrease either total cholesterol or LDL-C level vs. control. It was observed that after 3 PS phases compared with a control phase, cholesterol absorption changed to a lesser degree (–7.7% ± 10.8%) in the non-responders than in the top 3 responders (–22.1% ± 8.8%); however, cholesterol synthesis rates did not differ between sub-groups. No common polymorphisms in ABCG8, ABCG5, or NPC1L1 were demonstrated between the 3 top responders and the non-responders. Yet, 1 non-responsive subject did demonstrate a rare SNP in NPC1L1. Results indicate PS intake did not decrease cholesterol absorption rates to the same degree in certain subjects, possibly clarifying the inter-individual variability in the cholesterol-lowering effect; hence, this work should be expanded.

scholarly journals Association ofCILP2andACEGene Polymorphisms with Cardiovascular Risk Factors in Slovak Midlife Women

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Lenka Luptáková ◽  
Dominika Benčová ◽  
Daniela Siváková ◽  
Marta Cvíčelová
Keyword(s):  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density Lipoprotein Cholesterol ◽  
Lower Serum ◽  
Entire Study ◽  
Pcr Rflp ◽  
Lower Serum Level ◽  
Lipid Parameters

The aim of this study is to assess the association of two polymorphisms, the cartilage intermediate layer protein 2 (CILP2) G/T and angiotensin converting enzyme (ACE) I/D, with blood pressure and anthropometrical and biochemical parameters related to the development of cardiovascular disease. The entire study sample comprised 341 women ranging in age from 39 to 65 years. TheCILP2genotypes were determined by PCR-RFLP and theACEgenotypes by PCR. The Bonferroni pairwise comparisons showed the effect of theCILP2genotype on high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), apoB-to-apoA1 ratio, the total cholesterol (TC)-to-HDL-C ratio, non-HDL-C, and the LDL-C-to-HDL-C ratio (P<0.05). Here, higher mean levels of HDL-C and lower mean levels of the remaining above mentioned lipid parameters were registered in the GT/TT genotype carriers than in GG carriers. Statistically significant association was identified between theACEgenotype and the following parameters: TC, LDL-C, and non-HDL-C (P<0.05). The II genotype can lower serum level of TC (B=0.40), LDL-C (B=0.37), and non-HDL-C levels. The results of this study suggest that the minor T allele ofCILP2gene and I allele ofACEgene have a protective effect against elevated serum lipid and lipoprotein levels.

scholarly journals Ezetimibe and Improving Cardiovascular Outcomes: Current Evidence and Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Akshyaya Pradhan ◽  
Monika Bhandari ◽  
Rishi Sethi
Keyword(s):  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cardiovascular Outcomes ◽  
Current Evidence ◽  
High Dose ◽  
Residual Cardiovascular Risk ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Absorption Inhibitor

Low-density lipoprotein lowering with statins has convincingly and consistently proven to reduce cardiovascular events in both primary and secondary prevention. However, despite high-dose statin therapy, residual cardiovascular risk remains and many patients also do not tolerate statins. Ezetimibe was initially projected as a frontline alternative to statin. It is an intestinal cholesterol absorption inhibitor with modest LDL lowering effects. But, major studies failed to demonstrate any beneficial effect of CV outcomes, and the drug was relegated to oblivion. IMPROVE-IT, a contemporary, large, and well-designed trial, unequivocally demonstrated reduction in CV outcomes with ezetimibe when added to statin therapy. The benefits are seen in both sexes, elderly, CKD, diabetes mellitus, and in patients with prior CABG. It also reduces biomarkers and induces plaque regression like statins. The drug has now established itself as an add-on therapy to statin when monotherapy fails to achieve LDL goals and when it is not tolerated. The combination therapy has excellent safety and efficacy record. It has now been endorsed by major guidelines too in management of dyslipidemia. Yes, ezetimibe can indeed improve cardiovascular outcomes!

scholarly journals Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways

2020 ◽  
Vol 11 ◽  
Author(s):  
Wen-wen Huang ◽  
Bi-hong Hong ◽  
Kai-kai Bai ◽  
Ran Tan ◽  
Ting Yang ◽  
...  
Keyword(s):  
Bile Acids ◽  
Palmitoleic Acid ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
High Dose ◽  
Intestinal Cholesterol Absorption ◽  
Preventable Risk Factor

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms whereby cis-palmitoleic acid (cPOA) and trans-palmitoleic acid (tPOA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects of cPOA and tPOA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administered cPOA or tPOA once daily for 4 weeks. tPOA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely, cPOA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed that cPOA ameliorated hepatic steatosis more effectively than tPOA. tPOA significantly reduced the expression of 3-hydroxy-3-methyl glutaryl coenzyme reductase (HMGCR), LXRα, and intestinal Niemann-Pick C1-Like 1 (NPC1L1) and increased cholesterol 7-alpha hydroxylase (CYP7A1) in the liver, whereas cPOA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest that cPOA and tPOA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore, tPOA, but not cPOA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dose tPOA and cPOA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1. tPOA and cPOA prevent hypercholesterolemia via distinct mechanisms.

scholarly journals Recent Molecular Mechanisms and Beneficial Effects of Phytochemicals and Plant-Based Whole Foods in Reducing LDL-C and Preventing Cardiovascular Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 784
Author(s):  
Salman Ul Islam ◽  
Muhammad Bilal Ahmed ◽  
Haseeb Ahsan ◽  
Young-Sup Lee
Keyword(s):  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Intestinal Cholesterol Absorption ◽  
Beneficial Effects ◽  
Treatment And Prevention ◽  
Whole Foods

Abnormal lipid metabolism leads to the development of hyperlipidemia, a common cause of multiple chronic disorders, including cardiovascular disease (CVD), obesity, diabetes, and cerebrovascular disease. Low-density lipoprotein cholesterol (LDL-C) currently remains the primary target for treatment of hyperlipidemia. Despite the advancement of treatment and prevention of hyperlipidemia, medications used to manage hyperlipidemia are limited to allopathic drugs, which present certain limitations and adverse effects. Increasing evidence indicates that utilization of phytochemicals and plant-based whole foods is an alternative and promising strategy to prevent hyperlipidemia and CVD. The current review focuses on phytochemicals and their pharmacological mode of actions for the regulation of LDL-C and prevention of CVD. The important molecular mechanisms illustrated in detail in this review include elevation of reverse cholesterol transport, inhibition of intestinal cholesterol absorption, acceleration of cholesterol excretion in the liver, and reduction of cholesterol synthesis. Moreover, the beneficial effects of plant-based whole foods, such as fresh fruits, vegetables, dried nuts, flax seeds, whole grains, peas, beans, vegan diets, and dietary fibers in LDL-C reduction and cardiovascular health are summarized. This review concludes that phytochemicals and plant-based whole foods can reduce LDL-C levels and lower the risk for CVD.

scholarly journals Ezetimibe: an update on its clinical usefulness in specific patient groups

2016 ◽  
Vol 8 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Daniel Hammersley ◽  
Mark Signy
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
The Body ◽  
Lipid Modification ◽  
Intestinal Cholesterol Absorption ◽  
Specific Patient ◽  
First Line Therapy ◽  
Risk Patients ◽  
Patient Groups

The aim of pharmacological lipid modification is to reduce low-density lipoprotein cholesterol (LDL-C) as a means of either secondary or primary prevention of cardiovascular disease. Statins are the first-line therapy for pharmacological lipid modification. Ezetimibe is a drug which reduces LDL-C by selectively inhibiting intestinal cholesterol absorption. This provides an alternative pharmacological approach to that of statin therapy to reduce LDL-C. Ezetimibe has been shown to significantly reduce levels of LDL-C and recently, as demonstrated in the IMPROVE-IT trial, to reduce the rate of cardiovascular events in high-risk patients. Ezetimibe therefore has an important role in pharmacological lipid modification. In this paper, we examine the body of research behind ezetimibe and assess its current clinical applications in different patient subgroups.

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