Stanol Research Articles

Recommended or high daily intakes of plant stanol esters do not affect ex vivo T-cell derived cytokine production in immunologically healthy volunteers.

A well-functioning immune system requires balanced immune responses. In vitro studies have shown that plant stanols contribute to restoring the T-helper (Th)1/Th2 ratio when it is imbalanced. However, effects of plant stanols on healthy immune responses are unknown. Therefore, we studied effects of recommended (2·5 g/d) or high (9·0 g/d) plant stanol intakes on the Th1/Th2 cytokine balance in immunologically healthy subjects. In two RCTs, peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and stimulated with 5 µg/ml Phytohemagglutinin-M to study ex vivo cytokine production. In the first study, twenty participants consumed margarines (2·5 g/d plant stanols) or control for three weeks. In the second study, nineteen participants consumed margarines and yogurts (9·0 g/d plant stanols) or control for four weeks. T-cell cytokine concentrations were measured in culture medium and in study 2 a standardized Th1/Th2 index was calculated. Serum lipids and non-cholesterol sterols were also measured. Compliance was confirmed by significant increases in serum total cholesterol (TC)-standardized sitostanol and campestanol levels in both studies. Changes in ex vivo cytokine production and Th1/Th2 index did not differ between intervention and control groups. In the first study, no statistically significant changes were observed in lipid and lipoprotein concentrations. In the second study, LDL cholesterol significantly decreased compared to control (-0·77 (-1·11, -0·42) mmol/l; P < 0·001). Recommended (2·5 g/d) or high (9·0 g/d) intakes of plant stanols did not alter PBMC ex vivo cytokine production in immunologically healthy subjects. This suggests that plant stanols might only affect immune function when Th1/Th2 immune responses are imbalanced.

The effect of water on the crystallization of phytosterols and phytostanols in organic solutions

Phytosterols (C29H50O), also known as plant sterols and stanols, are valuable biomolecules with a variety of applications in the pharma, food, and cosmetics industries. Phytosterols are typically manufactured from vegetable oil and tall oil feedstocks through a cooling crystallization process. Depending on the feedstock used, the composition regarding individual phytosterols and phytostanols (saturated analogs of phytosterols), also varies to a large extent. In the current research it was observed that by adding a small amount of water to the organic solvent [i.e., n(water)/n(acetone) of 0.17, n(water)/n(ethanol) of 0.13, and n(water)/n(ethyl acetate) of 0.10], the final phytosterol profile regarding phytosterol and phytostanol concentrations can be modified. This can be explained by the different solubility behavior of phytosterols and phytostanols in the studied solvent systems, based on experimental results obtained from transmissivity measurements. Phytostanols have surprisingly low solubility when compared to phytosterols in all the studied solvent systems. However, in the presence of water, phytosterol solubility decreased more compared to phytostanols. To the best of our knowledge, this is the first time that phytostanol solubility has been systematically studied. Moreover, phytosterol and phytostanol concentrations in a crystallized product with varying binary solvent systems containing water has not previously been reported. The measured experimental solubility data correlated well with the studied solubility models (van't Hoff, modified Apelblat, Buchowski-Ksiazaczak (λh), and polynomial equations). Understanding the solubility behavior of phytosterols and phytostanols allows to optimize the crystallization process itself toward a broader raw material selection, and better yield and quality in the production of phytosterols from plant-based raw materials. In addition, these findings can potentially be further utilized in phytosterol formulations for various applications.

Preparation and physicochemical evaluation of phytosterol‐enriched sesame oil microemulsions

AbstractSesame oil, known for its nutritional benefits, was selected as source for phytosterol extraction. Optimal conditions of 40°C, oil‐to‐solvent ratio of 1:25, and a saponification duration of 150 min were employed to separate the phytosterols from sesame oil. The extracted phytosterols were encapsulated using microemulsion method. Various variables, such as percent of sesame oil, surfactant‐to‐cosurfactant ratio, and presence of phytosterols, were evaluated to determine their impact on particle size, polydispersity, pH, viscosity, surface tension, and stability. The particle size and PDI demonstrated significant increase with increasing oil and addition of phytosterols. A higher S:C ratio resulted in the formation of smaller microemulsion droplets. The viscosity and surface tension of the microemulsions increased significantly with an increase in the oil percent. In conclusion, the optimal composition of the microemulsion was found to be 10 wt% sesame oil with an S:C ratio of 3:1. FESEM micrographs revealed a microstructure consisting of cylindrical micelles.Practical applicationsResearch has shown that consuming 2–3 g of plant sterols and stanols can lower blood cholesterol levels by 10% and LDL levels by 15%. However, incorporating phytosterols into food products is challenging due to oxidation, insolubility, and high melting point. Most phytosterols are esterified to enrich low‐fat foods but they can be expensive and impure. The synthesis of phytosterols often involves carcinogenic chemicals and requires additional purification. Extracting phytosterols from plant sources has been proposed as a solution. However, incorporating phytosterols into food products is challenging due to their susceptibility to oxidation, particularly during processing and storage at high temperatures, their insolubility in water, and their limited solubility in fats and oils. The main aim of this study was to enrich sesame oil microemulsions with phytosterols through encapsulation. Phytosterols were extracted from sesame seed oil, followed by purification, and finally, enriched microemulsions were prepared. The optimal formulation was determined based on the evaluation of several parameters, including the mean volume diameter of particles, polydispersity index, pH, viscosity, surface tension, and physical stability.

Plant stanol consumption increases anti-COVID-19 antibody responses, independent of changes in serum cholesterol concentrations: a randomized controlled trial

BackgroundPeople with overweight/obesity generally have impaired immune responses, resulting among others in increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined IgM/IgG antibody titers toward a hepatitis A vaccination in patients with allergic asthma, but the underlying mechanism is unknown. ObjectivesWe evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination. MethodsA double-blind, randomized, placebo-controlled trial was performed. Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4 g/d; provided as plant stanol ester) or control ≥2 wk before receiving their COVID-19 vaccination until 4 wk after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed. ResultsIgM concentrations against the COVID-19 Spike protein were increased in the plant stanol ester group compared with the control group, with the largest difference observed 2 wk after vaccination [31.2 (0.43, 62.1) BAU/mL, or +139%; Group × Time: P = 0.031]. Subjects that produced very low IgM antibodies produced, as expected, hardly any IgG antibodies. In those with IgG seroconversion, IgG Spike concentrations were also increased in the plant stanol ester group compared with the control group [71.3 (2.51, 140.1) BAU/mL; Group P = 0.043]. Stimulated cytokine concentrations decreased in the plant stanol ester group compared with the control group in all 3 cytokine domains (that is, proinflammatory, T helper [Th1]/Th17, and Th2/regulatory T cells). Between-group differences in serum LDL cholesterol or other metabolic markers were not observed. ConclusionsConsuming plant stanols (4 g/d) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increase. These effects are independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption.This trial was registered at clinicaltrials.gov as NCT04844346.

Plant Sterols and Stanols for Pediatric Patients with Increased Cardiovascular Risk.

The atherosclerotic process begins in childhood and progresses throughout adult age. Hypercholesterolemia, especially familial hypercholesterolemia (FH) and metabolic dysfunctions linked to weight excess and obesity, are the main atherosclerosis risk factors in pediatric patients and can be detected and treated starting from childhood. Nutritional intervention and a healthy-heart lifestyle are cornerstones and first-line treatments, with which, if necessary, drug therapy should be associated. For several years, functional foods enriched with plant sterols and stanols have been studied in the treatment of hypercholesterolemia, mainly as nutritional complements that can reduce LDL cholesterol; however, there is a lack of randomized controlled trials defining their long-term efficacy and safety, especially in pediatric age. This review aims to evaluate what the main published studies on sterols and stanols in pediatric subjects with dyslipidemia have taught us, providing an updated picture of the possible use of these dietary supplements in children and adolescents with dyslipidemia and increased cardiovascular risk. Nowadays, we can state that plant sterols and stanols should be considered as a valuable therapy in pediatric patients with hypercholesterolemia, bearing in mind that nutritional and lifestyle counseling and, when necessary, pharmacologic therapy, are the cornerstones of the treatment in developmental age.

Plant Sterols and Plant Stanols in Cholesterol Management and Cardiovascular Prevention.

Atherosclerotic cardiovascular disease (ASCVD) remains the major mortality cause in developed countries with hypercholesterolaemia being one of the primary modifiable causes. Lifestyle intervention constitutes the first step in cholesterol management and includes dietary modifications along with the use of functional foods and supplements. Functional foods enriched with plant sterols/stanols have become the most widely used nonprescription cholesterol-lowering approach, despite the lack of randomized trials investigating their long-term safety and cardiovascular efficacy. The cholesterol-lowering effect of plant-sterol supplementation is well-established and a potential beneficial impact on other lipoproteins and glucose homeostasis has been described. Nevertheless, experimental and human observational studies investigating the association of phytosterol supplementation or circulating plant sterols with various markers of atherosclerosis and ASCVD events have demonstrated controversial results. Compelling evidence from recent genetic studies have also linked elevated plasma concentrations of circulating plant sterols with ASCVD presence, thus raising concerns about the safety of phytosterol supplementation. Thus, the aim of this review is to provide up-to-date data on the effect of plant sterols/stanols on lipid-modification and cardiovascular outcomes, as well as to discuss any safety issues and practical concerns.

Use of phytosterol-fortified foods to improve LDL cholesterol levels: A systematic review and meta-analysis

AimsThe main objective was to assess if foods fortified with phytosterols (PS), including plant sterols and plant stanols, reduce low-density lipoprotein cholesterol (LDL-C) concentrations. The secondary objective was to determine the impact of different factors related to PS administration. Data synthesisThe search was carried out in MEDLINE, EMBASE, Web of Science, Scopus and The Cochrane Central Register of Controlled Trials (CENTRAL) databases up to March 2023. The meta-analysis was registered in the PROSPERO database (CRD42021236952). From a total of 223 studies, 125 were included. On average, PS lowered LDL-C 0.55 mmol/L [95% confidence interval (CI) = 10.82–12.67], and this decrease was significantly maintained for all analysed subgroups. A greater reduction in LDL-C levels was detected in relation to a higher daily PS dosage. The food format “Bread, biscuits, cereals”, conditioned a lower decrease of 0.14 mmol/L (95%CI -8.71 to −2.16) in LDL-C levels, compared to the predominant food format group of “butter, margarine, spreads”. No significant differences were detected with the other subgroups (treatment duration, intake pattern, number of daily intakes and concomitant statin treatment). ConclusionThe present meta-analysis supported that the use of PS-fortified foods had a beneficial effect on LDL-C lowering. In addition, it was observed that the factors that influence a decline LDL-C levels were PS dose as well as the food format in which they were consumed.

Plant sterol precipitation in system composed by fatty acids using in-situ synthesized ionic liquids

Plant sterols and stanols are bio-derived compounds used in functional foods because of their hypocholesterolemic effect. Currently, plant sterols and stanols are recovered from tall oil and vegetable oil waste streams by using high vacuum distillation and crystallization. The aim of this work was to explore the recovery and purification of plant sterols and stanols using ionic liquids. Particularly, in-situ protic ionic liquids were synthesized by mixing an amine and fatty/resin acids as a model system of tall oil and vegetable oil waste streams, then an anti-solvent precipitation was performed using alcohols and water. Precipitation temperature, alcohol concentration, water concentration, type of alcohol (methanol and ethanol) and structure of amine (triethylamine, butylamine, and methyldiethanolamine) strongly affect the precipitation from model systems. On the other hand, precipitation time (3–12 h) and type of fatty/resin acid (myristic acid, oleic acid, abietic acid) only slightly influence the precipitation. Results show that when myristic acid was used, the best combination of recovery and purity is reached using triethylamine and methanol with maximum experimental values of 79.9 % of purity and 99.4 % of recovery at 5 °C, 120 % alcohol, 30 % water, and 12 h. Unfortunately, the precipitation performance of plant sterols and stanols from tall oil (5.3 %) using triethylamine and methanol is significantly worse than the performance observed in model systems, achieving maximum experimental values of 70.5 % of recovery of and 76.5 % of purity. However, it was found that saponifying the tall oil before the precipitation significantly improve plant sterols and stanols recovery and purity.

Worldwide comparative efficacy of nutraceuticals on lipid profile. an updated systematic review and network meta-analysis

Abstract Introduction In case of patients without indications to statin therapy, those being close to the target and especially with statin intolerance, nutraceuticals might be an additional option of hypercholesterolemia therapy. Despite a large number of nutraceuticals, little is known on their comparative efficacy due to the paucity of head-to-head comparisons. We aimed to assess the lipid-lowering effect of various nutraceuticals by means of network meta-analysis. Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were carefully searched to identify eligible studies to the meta-analysis. We included parallel or crossover randomized clinical trials (RCT), comparing head-to-head or to placebo/no intervention, the following nutraceuticals: a) artichoke, b) berberine, c) bergamot, d) garlic, e) green tea extract, f) plant sterols and stanols, g) policosanols, h) red yeast rice (RYR), i) silymarin, j) spirulina. We did not include soy protein, fiber, and lupin trials, as unlike other nutraceuticals they are in fact dietary interventions. Due to strikingly inconsistent results of policosanols RCTs carried out in Cuba and other countries, we excluded Cuban trials from main analysis. Results From the initially identified 4151 articles we finally included 131 studies. As some studies reported clinically different groups separately, they were split and finally we included 136 records, 134 with data on total cholesterol (TC), 125 with data on low-density cholesterol (LDL-C), 127 that provided information on high-density cholesterol (HDL-c) and 129 that included data regarding triglycerides (TG). Pooled studies covered data for 6755 patients randomized to nutraceutical arms and 6370 randomized to receive placebo/no intervention. For reducing TC bergamot, was identified as the most effective approach (P-score = 1.0) followed by RYR (0.90) and berberine (0.76). For increasing HDL-C, bergamot (0.98), berberine (0.85), and RYR (0.77) were the most effective. While evaluating LDL-C reduction, bergamot (1.00) and RYR (0.90) showed the highest reduction efficacy. Reducing effect of investigated nutraceuticals on TG levels was the highest for bergamot (1.00) and RYR (0.78). Majority of reports regarding Cuban policosanol trials implicated very high effectiveness of those nutraceuticals, which was in contrast to trials conducted in other countries Conclusions Bergamot, berberine, and RYR seemed to be most effective nutraceuticals in terms of lipid-lowering efficacy. Alleged high effectiveness of policosanols was not confirmed in our analysis. This analysis might support the physicians and patients' decisions to use only those nutraceuticals of confirmed efficacy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice

Растительные стеролы и станолы, снижающие уровень холестерина липопротеинов низкой плотности

Objective: analyze and evaluate scientific literature data on the need for the use of plant sterols and stanols for the treatment of hypercholesterolemia in order to reduce the risk of coronary heart disease. Materials and methods. The article summarizes the information of scientific publications in the journals of search systems PubMed, Scopus, Google Scholar, as well as library databases (eLibrary). Results. Phytosterols (phytosterols), phytostanols, are lipid-like compounds found in foods of plant origin. Their structure is similar to cholesterol and therefore they successfully compete with it for absorption in the intestine, thus reducing the flow of cholesterol into the bloodstream. As a result of this therapy for hypercholesterolemia, the risk of coronary heart disease is reduced. The factors influencing the efficacy of sterols/stanols and ways to improve therapy with their use are discussed in the review. The effect of stanols on the immune system is also presented. Conclusion. Food products enriched with sterols and stanols (yoghurt, kefir, milk, spreads, etc.) are promising tools in the complex of non-medicinal measures to reduce LDL cholesterol levels, an established risk factor for CHD, and their introduction into the diet will contribute to the prevention of CHD among the Russian population.

Association of dietary patterns and components with atherosclerosis risk biomarkers in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a relatively common genetic disorder associated with elevated atherosclerotic risk. Dietary interventions can modulate processes associated with cardiovascular risk and potentiate the impact of pharmacological lipid-lowering therapies. This review evaluates recent findings of dietary patterns and their components on risk biomarkers in people with FH. Diets lower in saturated fatty acids (SFA) may reduce low-density lipoprotein-cholesterol (LDL-C); however, their effects seem to be modest. A Mediterranean style diet apparently exerts more robust effects on plasma LDL-C, apolipoprotein B and C reactive protein concentrations than one restricted in SFA. Supplementation of plant sterols and stanols reduces LDL-C especially in children with FH. Caloric restricted diets may reduce weight and improve triglyceride levels in individuals with FH and excess body weight. Despite the strong impact of genetic variants, dietary patterns mostly low in SFA and especially the Mediterranean diet may influence risk biomarkers in FH. However, most available studies are limited by cross-sectional design, small number of study subjects and short-term follow-ups. Robust interventional studies are necessary to test the impact of dietary patterns in people with FH.

Gene-diet interaction in plasma lipid response to plant sterols and stanols: A review of clinical trials

• PS reduce plasma LDL-C levels by 6–12%. • LDL-C response to PS intake modulated by variants in cholesterol metabolism genes. • Only CYP7A1 c. −204C > A variant offered an hypocholesterolemic effect. • Standardization of clinical trials evaluating gene-diet interaction is necessary. Plant sterols and stanols (PS) are well known for their cholesterol-lowering effect by reducing intestinal absorption of cholesterol. However, genetic factors modulate the low-density lipoprotein cholesterol (LDL-C) response to PS therapy. This review examines clinical trials evaluating the impact of the main genes associated with response of plasma lipid concentrations to PS intake: APOE, CYP7A1, ABCG5/G8, NPC1L1, CETP, APOA4/A5, SCARBI, HMGCR, PPARα, LIPC, MTHFR and LPA. Evidence indicates that carriers of mutant allele of the CYP7A1 c. −204 A > C variant experience a greater plasma cholesterol reduction after PS intake, although there is discrepancy for the rest of genetic variants studied. Thus, it is necessary to standardize the design of these studies to validate the use of genetic information as a predictor marker of the response to the intervention with PS, to scientifically validate the use of these data in the personalized dietary advice.

Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review.

Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.

Plant stanol esters might optimise the immune response and improve the SARS-CoV-2/COVID-19 vaccine efficacy in overweight and obese subjects.

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Anti-Inflammatory Effects of Dietary Plant Stanol Supplementation Are Largely Dependent on the Intake of Cholesterol in a Mouse Model of Metabolic Inflammation.

The prevalence of metabolic disorders characterized by chronic inflammation has been on a sharp rise for decades. As such, tools that address metabolic and inflammatory dysregulation are of great importance. Plant stanols are well-known for reducing intestinal cholesterol absorption and may also have direct anti-inflammatory effects. In this study, our aim was to investigate to what extent the benefits of dietary plant stanol supplementation depend on dietary cholesterol intake in an experimental mouse model for cholesterol-induced metabolic inflammation. Here, we used Ldlr−/− mice transplanted with Npc1nih-derived bone marrow, featuring feature bone marrow-derived immune cells characterized by chronic inflammation induced by lysosomal lipid accumulation. Npc1nih- and Npc1wt-transplanted mice were placed on either a high fat, high cholesterol (HFC) or on a chow diet low in cholesterol, with or without 2% plant stanols supplementation. At the end of the study, the metabolic and inflammatory status of the mice was analyzed. Plant stanol supplementation to the HFC diet reduced liver cholesterol levels and improved lipid metabolism and liver inflammation, particularly in Npc1nih-tp mice. In contrast, plant stanol supplementation to the chow diet did not significantly improve the aforementioned parameters, though similar reductive trends to those in the HFC diet setting were observed regarding liver cholesterol accumulation and liver inflammatory markers. The effects of dietary plant stanol supplementation on dietary cholesterol-induced inflammation are largely dependent on dietary cholesterol intake. Future research should verify whether other models of metabolic inflammation exhibit similar stanol-related effects on inflammation.

Obesity Does Not Interfere with the Cholesterol-Lowering Effect of Plant Stanol Ester Consumption (as Part of a Heart-Healthy Diet).

Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This ad hoc analysis was based on earlier results of a cross-over, randomized controlled trial of postmenopausal women consuming rapeseed oil-based margarine without or with plant stanol ester (3 g plant stanols/day) for seven weeks. We classified the subjects as normal-weight (BMI ≤ 25 kg/m2, n = 9, mean 22.6 kg/m2) or overweight/obese (BMI > 25 kg/m2, n = 11, mean 28.4 kg/m2), and recalculated the results, focusing on cholesterol absorption, cholesterol synthesis, and fecal steroid outputs. Serum cholesterol levels were similar in the groups during the control diet. Plant stanol ester reduced serum cholesterol by 0.63 ± 0.19 mmol/L (11%) in normal-weight and by 0.75 ± 0.13 mmol/L (12%) in overweight/obese subjects (p < 0.05 for both), and cholesterol absorption was reduced in both groups. However, relative and dietary cholesterol absorption were more effectively reduced in normal-weight subjects. In conclusion, overweight/obesity did not interfere with the serum cholesterol response to plant stanol ester consumption despite substantial differences in cholesterol metabolism between the groups.

Sustainable and Green Synthesis of Stanol Esters from Oil Wastes.

The recombinant lipase ofOphiostoma piceae (OPEr) is characterized by its prominent sterol esterase activity. The protein was immobilized on magnetic nanoparticles, giving four enzyme variants that have been tested in solvent-free transesterification of methyl oleate and sitostanol. The yields of stanol esters reached 85%, and the catalysts can be reused. Stanol esters were also obtained in a two-step cascade reaction; a mixture of fatty acid methyl esters was enzymatically synthesized from cooking oil wastes and then used for stanol transesterification. An 85% conversion was achieved in 2 h from the second cycle onward, maintaining the activity over 5 cycles. The biocatalysts can be safely used since they don't release toxic compounds for HeLa and A549 cell lines. These procedures comply with the principles of green chemistry and contribute to the sustainable production of these nutraceuticals from secondary raw materials, like the lipid fraction from industrial or agricultural residues.

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

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.

Lowering Low-Density Lipoprotein Cholesterol Concentration with Plant Stanol Esters to Reduce the Risk of Atherosclerotic Cardiovascular Disease Events at a Population Level: A Critical Discussion.

Atherosclerotic cardiovascular diseases (ASCVDs) cause every fifth death worldwide. However, it is possible to prevent the progression of ASCVDs by reducing circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Recent large meta-analyses demonstrated that by reducing the dietary intake of saturated fat and cholesterol, it is possible to reduce the risk of ASCVD events. Plant stanols, as fatty-acid esters, were developed as a dietary adjunct to reduce LDL-C levels as part of a heart-healthy diet. They reduce cholesterol absorption so that less cholesterol is transported to the liver, and the expression of LDL receptors is upregulated. Ultimately, LDL-C concentrations are reduced on average by 9–12% by consuming 2–3 g of plant stanol esters per day. In this review, we discuss recent information regarding the prevention of ASCVDs with a focus on dietary means. We also present new estimates on the effect of plant stanol ester consumption on LDL-C levels and the risk of ASCVD events. Plant stanol esters as part of a heart-healthy diet plausibly offer a means to reduce the risk of ASCVD events at a population level. This approach is not only appropriate for subjects with a high risk of ASCVD, but also for subjects at an apparently lower risk to prevent subclinical atherosclerosis.

Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids: The BLOOD FLOW Randomized Intervention Study.

Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. Approach and Results: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm, P=0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index<25 kg/m2. Decreased LDL aggregation susceptibility was associated with decreased proportion of LDL-sphingomyelins and increased proportion of LDL-triacylglycerols. LDL binding to proteoglycans was decreased in the plant stanol ester group, the decrease depending on decreased serum LDL-cholesterol concentration. Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01315964.