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.

scholarly journals Diet and Cardiovascular Disease Risk Among Individuals with Familial Hypercholesterolemia: Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Fotios Barkas ◽  
Tzortzis Nomikos ◽  
Evangelos Liberopoulos ◽  
Demosthenes Panagiotakos
Keyword(s):  
Fatty Acids ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plant Sterols ◽  
Low Density ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Lowering

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.

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 Diet and Cardiovascular Disease Risk Among Individuals with Familial Hypercholesterolemia: Systematic Review and Meta-Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2436
Author(s):  
Fotios Barkas ◽  
Tzortzis Nomikos ◽  
Evangelos Liberopoulos ◽  
Demosthenes Panagiotakos
Keyword(s):  
Fatty Acids ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plant Sterols ◽  
Low Density ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Lowering

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the eligibility of the included trials and their bias risk and extracted the data which was independently verified by other colleagues. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the assessed risk parameters. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference (MD): −0.27 mmol/L, 95% confidence interval (CI): −0.47 to −0.07, p < 0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: −0.34, 95% CI: −0.68 to 0, mmol/L, p = 0.05) and low-density lipoprotein cholesterol (MD: −0.31, 95% CI: −0.61 to 0, mmol/L, p = 0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: −0.62 mmol/L, 95% CI: −1.13 to −0.11, p = 0.02) and low-density lipoprotein cholesterol (MD: −0.58 mmol/L, 95% CI: −1.08 to −0.09, p = 0.02). The same was by plant sterols (MD: −0.46 mmol/L, 95% CI: −0.76 to −0.17, p < 0.01 for cholesterol and MD: −0.45 mmol/L, 95% CI: −0.74 to −0.16, p < 0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the efficacy of cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in patients with familial hypercholesterolemia.

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