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A Review on the Role of Phytosterols: New Insights Into Cardiovascular Risk
Abstract
Phytosterols, which are structurally related to cholesterol, are found in all plant foods with highest concentration occurring in vegetable oils and nuts. Phytosterols are known to reduce serum low-density lipoprotein cholesterol level without changing high-density lipoprotein cholesterol or triglyceride levels. Daily consumption of phytosterols-enriched foods is widely used as a therapeutic option to lower plasma cholesterol and atherosclerotic disease risk. The cholesterol-lowering action of phytosterols is thought to occur, at least in part, through competitive replacement of dietary and biliary cholesterol in mixed micelles, which undermines the absorption of cholesterol. The aim of this review is to provide a general overview of available evidence regarding the effects of phytosterols on cholesterol metabolism and addressing issues related to efficacy as dose, length, frequency of consumption, type of phytosterol (sterols versus stanols) or food matrix. Furthermore, we will explore the factors that influence the response of individuals to phytosterol therapy and evaluate their safety and the possibility that elevated plasma phytosterol concentrations contribute to the development of premature coronary artery disease.
... According to Cohn et al. [186], phytosterols primarily reduce intestinal cholesterol absorption by 30 to 50%, which lowers LDL-C levels. Several mechanisms, including competition with cholesterol through solubilization in mixed micelles in the intestinal lumen, may be responsible for this reduction in the quantity of cholesterol accessible for absorption [187]. Additional mechanisms that have been proposed are: firstly, alteration in the expression of genes that encode sterol-carrying proteins, like the Niemann-Pick C1-like 1 (NPC1-L1) protein, which reduces the amount of cholesterol transported to the enterocyte; secondly, ATP-binding cassette transporters (ABCG5 and ABCG8), which promote the efflux of cholesterol from the enterocytes to the intestinal lumen; thirdly, decreased rate of cholesterol esterification in the enterocyte; and fourthly, increased removal of cholesterol from the body through the transintestinal cholesterol excretion (TICE) system [121]. ...
Functional lipids are dietary substances that may have an impact on human health by lowering the risk of chronic illnesses and enhancing the quality of life. Numerous functional lipids have been reported to have potential health benefits in the prevention, management, and treatment of cardiovascular disease, the leading cause of death in the United States. However, there is still insufficient and contradictory information in the literature about their effectiveness and associated mechanisms of action. The objective of this review, therefore, is to evaluate available literature regarding these functional lipids and their health benefits. Various studies have been conducted to understand the links between functional lipids and the prevention and treatment of chronic diseases. Recent studies on phytosterols have reported that CLA, medium-chain triglycerides, and omega-3 and 6 fatty acids have positive effects on human health. Also, eicosanoids, which are the metabolites of these fatty acids, are produced in relation to the ratio of omega-3 to omega-6 polyunsaturated fatty acids and may modulate disease conditions. These functional lipids are available either in dietary or supplement forms and have been proven to be efficient, accessible, and inexpensive to be included in the diet. However, further research is required to properly elucidate the dosages, dietary intake, effectiveness, and their mechanisms of action in addition to the development of valid disease biomarkers and long-term effects in humans.
... Alkaloids, on the other hand, have a high potential as anticancer agents and are known to be the basis of drug development for various diseases, such as antitumor, anti-inflammatory, and antibacterial [19,20] . Steroid compounds have also been found to possess pharmacological activities, such as antioxidant, neuroprotective, and antihypercholesterolemic activities [21] . ...
Colon cancer and cervical cancer are types of cancer with a high prevalence, contributing 10% and 3.1% respectively of the total new cancer cases. Nutrition and dietary factors play an important role in human carcinogenesis. Natural plants contain substances that can be beneficial to human health. One such plant is the pumpkin (Cucurbita moschata). Pumpkin seeds are thought to have many biological activities for health, such as antioxidant, anticancer, and anti-inflammatory effects. This study aimed to determine the cytotoxic activity of n-hexane extract of pumpkin seed against colon (WiDr) and cervical (HeLa) cancer cells using the MTT Assay method. The method used in this study consisted of the preparation of plant extracts, phytochemical screening, total content of metabolites. The results proved that the n-hexane extract of pumpkin seed was observed containing flavonoids, alkaloids, and steroids. The content of highest total content, namely flavonoid compounds as much as 616.46 mg/L. The n-hexane extract of pumpkin seed showed cytotoxic activity for WiDr cells and HeLa cells with an IC50 value of 193.44 µg/mL and 237.702 µg/mL, respectively. The results of this study can be concluded that n-hexane extract of pumpkin seed can be used as a chemopreventive agent, due to the moderate cytotoxic test results.
Functional yogurt contains a variety of nutritional components that offer numerous health benefits, with limitations that can potentially be overcome.
Edible oils and fats are derived from plants and animals and have several health benefits. Edible oils and fats consist of many health-promoting bioactive compounds such as polyunsaturated fatty acids, monounsaturated fatty acids, polyphenols, flavonoids, phytosterols, vitamins, and inorganic compounds. The chemical compounds present in edible oils and fats are known for their possible health risks such as coronary heart disease and metabolic diseases, which is why there is a need to check the quality, purity, and safety of edible oils and fats. Bioactive Compounds of Edible Oils & Fats: Health Benefits, Risks, and Analysis provides an overview of different edible oils and fats, health benefits, associated risks, and analytical techniques for qualitative and quantitative guidelines for ensuring their quality and safety using modern analytical tools and techniques. This book will provide an important guideline for controlling quality, safety, and efficacy issues related to edible oils and fats.
Key Features:
Provides a detailed overview of different edible oils and fats of plant and animal origin, chemistry, and identification methods.
Describes their health benefits, risks, and the use of different analytical techniques in quality control.
Describes the applicability of sophisticated analytical techniques such as GC-FID, GC-MS, and HPLC for quality control of edible oils and fats.
Emphasizes the use of recent techniques such as LC-MS and FTIR-chemometrics in the analysis and quality control of edible oils and fats.
Bioactive natural compounds possess several health benefits in humans. Edible oils and fats are a major source of bioactive compounds, and these compounds are mainly categorized into triglycerides, saturated and unsaturated fatty acids, polyphenolics and phenolic acids, flavonoids, phytosterols, phospholipids, vitamins, minerals, etc. These bioactive compounds have several health benefits in humans; however, excess consumption of saturated and trans fatty acids poses a risk for cardiovascular diseases. Unsaturated fatty acids such as omega-3 fatty acids and omega-6 fatty acids specifically linoleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are known for their cardioprotective, anticancer, anti-inflammatory, and immunomodulatory activities. Edible oils and fats are obtained from seeds of many plant species such as olive oils, peanut oils, canola oil, sunflower oil, soybean oil, flaxseed oil, corn oil, mustard oil, coconut oil, peanut oil, and linseed oil, and animal products such as fish oils, ghee, and butter also contain edible oils and fats. The current book chapter comprehensively compiles data on different plant and animal sources of edible oils and fats. The chapter also focuses on different classes of bioactive compounds present in these edible oils and fats.
Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV–vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.
This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov.
A plant-based diet (PBD) includes multiple dietary patterns such as vegetarianism, veganism, lacto-ovo-vegetarianism, etc. A well-balanced PBD has positive effects on body mass index, hyperlipidemia, and type 2 diabetes, and it is associated with decreased risk of cardiovascular diseases. Due to its high fiber content, which lowers levels of low-density lipoprotein cholesterol, high antioxidant content, which prevents capillary wall damage; the presence of polyunsaturated fatty acids, which have an anti-inflammatory effect, improvement in glucose homeostasis through improved insulin sensitivity, and impact on the gut microbiota, it has been proven to be beneficial for the heart. Despite their possible benefits, PBDs can be low in essential nutrients such as vitamin B12, zinc, vitamin D, iodine, and amino acids. This review aims to analyze the influence of PBDs on the cardiovascular system and associated disease progression.
The phytochemical and proximate properties of cucumber (Cucumber Sativus) seed oil had been evaluated and characterized for its suitability in pharmaceutical, foods, and skin-care product formulations. The seed-oil was isolated using acetone and ethanol with an automated soxhlet extractor, while, the triplicate values of the oil yield were calculated, according to AOAC standard. The moisture content of 7.21 %; ash content of 5.48 %; crude fibre of 27.8 %; crude protein of 4.50 %; crude fat is 2.143 %, carbohydrate content of 52.86 %, and other physiochemical properties of the oil were determined. Some good health support inorganic elements identified include, Potassium (6.830 ± 0.0040); Sodium (7.2287 ± 0.0058); Iron (6.2213 ± 0.0043) and Arsenic(3.1113 ± 0.0003). Major phytochemical compounds identified in both ethanol and acetone extracts are saponins, terpenoids, phytosterols and flavonoids. The Viscosity of 7.066, Specific gravity of 0,882 g/cm 3 , Bulk density of 0.393 g/cm 3 and Tapped density 3 0.680 g/cm 3 , are good properties of edible oil, if further purified. The Phytochemicals and other inorganic elements identified revealed that cucumber seed oil can serve as raw materials for pharmaceutical and cosmetic formulations.
HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications, have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity.
To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking.
A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Subjects were provided (i) control margarine with each meal; (ii) 1.8 g/day plant sterols in margarine with breakfast (single-BF) and control margarine with lunch and supper or (iii) 1.8 g/day plant sterols in margarine divided equally at each of the three daily meals (three times per day).
Relative to control, end point plasma low-density lipoprotein (LDL) cholesterol concentrations were lower (P<0.05) after consuming plant sterols three times per day but were not different when consumed once per day (3.43+/-0.62, 3.22+/-0.58 and 3.30+/-0.65 mmol/l, control, three times per day and single-BF, respectively). Relative to the control, end point LDL level was 0.21+/-0.27 mmol/l (6%) lower (P<0.05) at the end of the three times per day phase. Cholesterol fractional synthesis rate was highest (P<0.05) after the three times per day phase (0.0827+/-0.0278, 0.0834+/-0.0245 and 0.0913+/-0.0221 pool/day, control, single-BF and three times per day, respectively). Cholesterol-absorption efficiency decreased (P<0.05) by 36 and 39% after the three times per day and single-BF phase, respectively, relative to control.
Present data indicate that to obtain optimal cholesterol-lowering impact, plant sterols should be consumed as smaller doses given more often, rather than one large dose.
Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.
A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules).
In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below.
The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …
The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
A 5-year-old girl with a recent history of recurrent abdominal pain presented with acute respiratory distress that rapidly became asystolic. She then could not be revived. At autopsy, widespread yellow aortic xanthomas were seen, with severe atheromatous narrowing of both coronary ostia (Figure 1). The right and left anterior descending arteries showed focal marked atheromatous narrowing. Grossly and microscopically, there were no specific myocardial changes. Atheromas were also seen on the surfaces of the mitral valve leaflets and within the pulmonary artery. Aortic lesions extended to the level of the superior mesenteric artery, and atheromas …
This clinical trial was carried out with the objective of a preliminar evaluation of the hypocholesteremic effectiveness of a dietary dairy product currently marketed in Spain in the form of drinkable yogurt. Thirty-two adult male and female patients with LDL cholesterol higher than 120 mg/dl were recruited in a pilot, randomized as parallel groups, double-blind, and placebo-controlled clinical trial. Patients consumed during 3 weeks (a bottle a day) Kaiku's Benecol® containing 2 g/bottle of plant stanol esters, or a placebo consisting of the same product without plant stanol. Furthermore, all participants carried out some dietary standards. At the beginning and the end of the treatment LDL cholesterol, total cholesterol, and HDL cholesterol were assessed; LDL/HDL index was also calculated.
At the end of the treatment in the active group a significant decline (p < 0.01) with regard to the initial levels was observed in LDL cholesterol (157 ± 30 to 140 ± 34, mg/dl, mean ± SD) levels, total cholesterol (235 ± 34 to 219 ± 35) levels, and LDL/HDL index (3,2 ± 1,0 to 3,0 ± 1,2), without significant changes in HDL cholesterol (48 ± 15 to 53 ± 29); in the placebo group there were no significant changes (LDL cholesterol: 168 ± 25 to 164 ± 23; total cholesterol: 245 ± 31 to 237 ± 23; HDL cholesterol: 51 ± 12 to 51 ± 12; LDL/HDL index: 3,4 ± 0,6 to 3,3 ± 0,8).
In short, consumption of a yogurt a day containing 2 g of stanol reduces significantly the cholesterol levels and this effect is not observed with the placebo.
Objectives To determine the long-term effects of phytotherapy with β-sitosterol (the trade name for β-sitosterol used in this study is Harzol®) for symptomatic benign prostatic hyperplasia (BPH).
Patient and methods At 18 months after enrolment in a 6-month multicentre double-blind placebo-controlled clinical trial with β-sitosterol (reported previously), patients were re-evaluated using the modified Boyarsky score, the International Prostate Symptom Score and quality-of-life index, the maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR). In this open extension of the original trial (after 6 months of treatment or placebo), patients were free to chose their further treatment for BPH.
Results In all, 117 patients (59%) were eligible for analysis during the follow-up. Of the formerβ-sitosterol group, 38 patients who continued β-sitosterol treatment had stable values for all outcome variables between the end of the double-blind study and after 18 months of follow-up. The 41 patients choosing no further therapy had slightly worse symptom scores and PVR, but no changes in Qmax. Of the former placebo group, 27 patients who started β-sitosterol after the double-blind trial improved to the same extent as the treated group for all outcome variables. The 18 patients choosing no further therapy showed no signs of improvement.
Conclusion The beneficial effects of β-sitosterol treatment recorded in the 6-month double-blind trial were maintained for 18 months. Further clinical trials should be conducted to confirm these results before concluding that phytotherapy with β-sitosterol is effective.
Phytosterols have been proposed to be atherogenic. This research investigates whether plasma concentrations of phytosterols correlate with the manifestation of coronary heart disease.
The CORA study compares clinical, biochemical, and lifestyle factors in consecutive pre- and postmenopausal women with incident coronary heart disease to those in age-matched population-based controls. Controls (n=231) had significantly higher plasma concentrations of the major phytosterol species than cases (n=186) (4.649mg/l vs. 4.092mg/l; p<0.001). Cases had a higher dietary intake of phytosterols, but the ratio of lathosterol over sitosterol did not significantly differ. Phytosterols correlated with cholesterol concentrations of LDL and HDL, the phytosterol-carrying lipoproteins. The age-adjusted odds ratio for the association of total phytosterols and risk of coronary heart disease was 0.69 per 5mg/dl (95% CI 0.46-0.99). After adjustment for LDL- and HDL-cholesterol the odds ratio approached 1 (0.89; 95% CI 0.61-1.30), which was reached after additional adjustment for major risk factors, particularly those reflecting the metabolic syndrome (1.05; 95% CI 0.64-1.97).
Healthy controls had higher unadjusted concentrations of plasma phytosterols, but the adjusted odds ratio for coronary heart disease did not point to an impact of plasma phytosterols on coronary heart disease.
Sitosterolemia is characterized by elevated plasma levels of plant sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD develops in some subjects with sitosterolemia, despite having normal plasma cholesterol levels, suggesting that high circulating levels of plant sterols may be atherogenic. We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified mice and in middle-aged men and women.
Wild-type and hypercholesterolemic female mice with >20-fold higher plasma levels of plant sterols because of inactivation of the ATP-binding cassette (ABC) half transporters G5 and G8 (G5G8-/-mice) were fed chow or Western diets for 7 months. No significant differences in aortic lesion area were found when the sitosterolemic mice were compared with littermate controls. To determine whether plasma levels of plant sterols were associated with coronary atherosclerosis in humans, the relationship between plasma plant sterols and coronary calcium (detected by electron beam computer tomography) was examined in 2542 subjects aged 30 to 67 years. Plasma levels of cholesterol, but not sitosterol or campesterol, were significantly higher in subjects with coronary calcium.
The results of this study do not support an association between elevated plasma levels of plant sterols and atherosclerosis.
To determine if plant stanols and plant sterols differ with respect to their low-density lipoprotein cholesterol (LDL-CH) lowering efficacies across a continuous dose range.
Dose-response relationships were evaluated separately for plant stanols and plant sterols and reductions in LDL-CH, using a first-order elimination function.
Altogether, 113 publications and 1 unpublished study report (representing 182 strata) complied with the pre-defined inclusion and exclusion criteria and were included in the assessment. The maximal LDL-CH reductions for plant stanols (16.4%) and plant stanol ester (17.1%) were significantly greater than the maximal LDL-CH reductions for plant sterols (8.3%) and plant sterol ester (8.4%). These findings persisted in several additional analyses.
Intakes of plant stanols in excess of the recommended 2g/day dose are associated with additional and dose-dependent reductions in LDL-CH, possibly resulting in further reductions in the risk of coronary heart disease (CHD).