phytosterols and Hypercholesterolemia

The aim of this study was to assess the potential value of the measurement of plasma xenosterols (or phytosterols) concentrations in clinical practice.. Recent genetic studies suggest that individuals with elevated plasma phytosterol concentrations due to monogenic and polygenic variants are at an increased risk of coronary artery disease. This supports early observations that elevated plasma phytosterol concentrations are per se atherogenic.. Measurement of plasma phytosterols can identify individuals with xenosterolemia (or phytosterolemia). This may be clinically useful in four ways: Establishing a diagnosis and informing management of patients with homozygous phytosterolemia; Providing a comprehensive differential diagnosis for familial hypercholesterolemia; Providing an index of cholesterol absorption that may inform personalized pharmacotherapy; and Informing more precise assessment of risk of cardiovascular disease.

Topics: Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols

Phytosterols (PSs) have been reported to improve blood lipids in patients with hypercholesterolemia for many years. However, meta-analyses of the effects of phytosterols on lipid profiles are limited and incomplete. A systematic search of randomized controlled trials (RCTs) published in PubMed, Embase, Cochrane Library, and Web of Science from inception to March 2022 was conducted according to the 2020 preferred reporting items of the guidelines for systematic reviews and meta-analysis (PRISMA) statement. These included studies of people with hypercholesterolemia, comparing foods or preparations containing PSs with controls. Mean differences with 95% confidence intervals were used to estimate continuous outcomes for individual studies. The results showed that in patients with hypercholesterolemia, taking a diet containing a certain dose of plant sterol significantly reduced total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (TC: Weight Mean Difference (WMD) [95% CI] = -0.37 [-0.41, -0.34],

Topics: Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Humans; Hypercholesterolemia; Hyperlipidemias; Lipids; Phytosterols; Randomized Controlled Trials as Topic; Triglycerides

The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease.. Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia. Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.

Topics: Atherosclerosis; Cholesterol; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Xanthomatosis

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.

Topics: Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol; Humans; Hypercholesterolemia; Phytosterols

The exploration of lipid-lowering resources, such as phytosterols, for the complementary nutritional treatment of hypercholesterolemia is relevant to reduce cardiovascular risk. The use of phytosterols in capsules or tablets can bring advantages in the context of diet therapy, but such format is still less studied when compared to fortified foods.. Systematically review randomized clinical trials on the effects of phytosterol supplementation, in capsules or tablets, on the lipid profile and its use in the treatment of hypercholesterolemia in adults.. A systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, with a PROSPERO protocol registered under number CRD42021249539. The process was conducted by two independent reviewers. Only randomized clinical trials with phytosterol supplementation in adult individuals with hypercholesterolemia were included. The terms were searched in the databases: PubMed/MEDLINE, Cochrane Library/CENTRAL, Embase, LILACS and Web of Science, without restriction of time and language. The manual search was also performed through the list of references of articles included in this review.. The searches resulted in 977 articles. 22 articles were selected, whose full text was read, and according to the eligibility criteria 10 were incorporated into the review. The studies were separated into groups according to the association of the intervention with changes in lifestyle and the characteristics extracted from the studies were summarized and displayed in tables. Most studies have revealed a positive association between phytosterol supplementation and cholesterol reduction, despite the short duration of interventions.. The analyzed studies showed that phytosterol supplements can be useful to modulate the lipid profile, helping to reduce the plasma concentration of LDL cholesterol. However, more research with the aforementioned supplementation in such pharmaceutical formats should be encouraged.

Topics: Adult; Capsules; Dietary Supplements; Humans; Hypercholesterolemia; Phytosterols; Randomized Controlled Trials as Topic; Tablets

A 17-year-old boy with acute coronary syndrome was admitted to our hospital. He had xanthomas over his elbow and Achilles tendon and a high level of low-density lipoprotein cholesterol; therefore, his initial diagnosis was familial hypercholesterolemia. However, a genetic analysis revealed a compound heterozygous mutation in the ABCG5 gene with a high serum level of sitosterol, leading to the diagnosis of sitosterolemia. After lipid-lowering treatment, percutaneous coronary intervention was performed. Furthermore, a persistently high C-reactive protein level and images of large arteries led to a diagnosis of Takayasu arteritis. To our knowledge, this is the first case of sitosterolemia complicated by Takayasu arteritis.

Topics: Acute Coronary Syndrome; Adolescent; ATP Binding Cassette Transporter, Subfamily G, Member 5; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols; Takayasu Arteritis

Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized.. Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described.. Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only.. The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.

Topics: Adolescent; Adult; Aged; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Child; Child, Preschool; China; Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Mutation; Phytosterols; Young Adult

Inherited hypercholesterolemias include monogenic and polygenic disorders, which can be very rare (eg, cerebrotendinous xanthomatosis (CTX)) or relatively common (eg, familial combined hyperlipidemia [FCH]). In this review, we discuss familial hypercholesterolemia (FH), FH-mimics (eg, polygenic hypercholesterolemia [PH], FCH, sitosterolemia), and other inherited forms of hypercholesterolemia (eg, hyper-lipoprotein(a) levels [hyper-Lp(a)]). The prevalence, genetics, and management of inherited hypercholesterolemias are described and selected guidelines summarized.

Topics: Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols

Coronary heart disease is the leading cause of mortality worldwide. Elevated blood cholesterol levels are not only the major but also the best modifiable cardiovascular risk factor. Lifestyle modifications which include a healthy diet are the cornerstone of lipid-lowering therapy. So-called functional foods supplemented with plant sterols lower blood cholesterol levels by about 10-15%.. In the recent revision of the ESC/EAS dyslipidemia guideline 2019, plant sterols are recommended for the first time as an adjunct to lifestyle modification to lower blood cholesterol levels. However, the German Cardiac Society (DGK) is more critical of food supplementation with plant sterols and calls for randomized controlled trials investigating hard cardiovascular outcomes. An increasing body of evidence suggests that plant sterols per se are atherogenic. This review discusses this controversy based on findings from in vitro and in vivo studies, clinical trials, and genetic evidence.

Topics: Cardiovascular Diseases; Dietary Supplements; Dyslipidemias; Humans; Hypercholesterolemia; Phytosterols

In this review, we summarize the genetics and mechanisms of sitosterolemia and sterol trafficking, and provide an update on the understanding of the prevalence of ABCG5 and ABCG8 variants and their role in human disease.. Defects in ABCG5/G8 result in the accumulation of xenosterols. It had been previously thought that near total LoF of one of the proteins was required to cause pathology. However, recently there was the first report of a patient with Sitosterolemia who was heterozygous for mutations in both genes. Moreover, large population studies have demonstrated the even simple heterozygous carriers are associated with altered lipid profiles and cardiovascular risk. Broader screening has added to the rapidly growing list of gene variants indicating that the prevalence of ABCG5/G8 variants is higher than previous thought, especially in patients with hypercholesterolemia.. These findings support a strategy of measuring xenosterol levels in patients with hypercholesterolemia to screen for ABCG5/G8 variants, and then tailoring treatment with a sterol absorption inhibitor, like ezetimibe, where indicated. Xenosterol trafficking affects remnant clearance and maybe pathogenically linked to the increased risk of atherosclerosis.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Sterols

Sitosterolemia is a lipid disorder characterized by the accumulation of dietary xenosterols in plasma and tissues caused by mutations in either

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cholesterol; Enterocytes; Hepatocytes; History, 21st Century; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Mutation; Phytosterols

Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.

Topics: Disease Management; Humans; Hypercholesterolemia; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Phytosterols

To carry out a systematic review on the effects of phytosterol supplementation on the treatment of dyslipidemia in children and adolescents.. Review in the SciELO, Lilacs, Bireme, PubMed and Web of Science databases, with no time limit. Descriptors: phytosterols or plant sterols and dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, in English and Portuguese. The articles included were published in Portuguese, English or Spanish and evaluated the effect of phytosterol supplementation in pediatric patients with dyslipidemia. Documents that involved adults or animals, review papers, case studies and abstracts were excluded. Two authors performed independent extraction of articles. Of 113 abstracts, 19 were read in full and 12 were used in this manuscript.. Phytosterol supplementation to reduce cholesterol levels has been shown to be effective in reducing LDL-cholesterol levels by approximately 10%, with reductions above 10% in LDL-cholesterol levels observed after 8 to 12 weeks of intervention. Studies have not shown significant changes in HDL-cholesterol and triglyceride levels. Based on the absence of adverse effects, its use seems to be safe and of good tolerance in children and adolescents.. Phytosterol supplementation seems to be of great therapeutic aid for the treatment of hypercholesterolemia in children and adolescents. Further studies assessing the long-term effect of phytosterol supplementation are necessary.

Topics: Adolescent; Anticholesteremic Agents; Child; Child, Preschool; Cholesterol, LDL; Food, Fortified; Humans; Hypercholesterolemia; Phytosterols; Randomized Controlled Trials as Topic

The ABCG5/G8 heterodimer is the primary neutral sterol transporter in hepatobiliary and transintestinal cholesterol excretion. Inactivating mutations on either the ABCG5 or ABCG8 subunit cause Sitosterolemia, a rare genetic disorder. In 2016, a crystal structure of human ABCG5/G8 in an apo state showed the first structural information on ATP-binding cassette (ABC) sterol transporters and revealed several structural features that were observed for the first time. Over the past decade, several missense variants of ABCG5/G8 have been associated with non-Sitosterolemia lipid phenotypes. In this review, we summarize recent pathophysiological and structural findings of ABCG5/G8, interpret the structure-function relationship in disease-causing variants and describe the available evidence that allows us to build a mechanistic view of ABCG5/G8-mediated sterol transport.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Biliary Tract; Catalysis; Cholesterol; Homeostasis; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Liver; Phytosterols

Sitosterolemia is a recessive inherited metabolic disorder of unknown prevalence, characterized by increased levels of plasma plant sterols. It is caused by 28 and 31 variants in ABCG5 and ABCG8 genes, respectively, and is characterized by a predisposition to hyperabsorption and accumulation of toxic levels of plant sterols in plasma. Its clinical picture is extremely heterogeneous. The main clinical features are tendinous and cutaneous xanthomas, arthritis or arthralgia, premature cardiovascular disease and atherosclerosis. These characteristics are shared with familial hypercholesterolemia (FH), making it possible for sitosterolemia to be misdiagnosed as homozygous FH, especially in pediatric patients. In such cases, a specific chromatography-based laboratory method is essential to differentiate sitosterol and cholesterol. Hematological abnormalities (hemolytic anemia and macrothrombocytopenia) may be present in 25-35% of patients, in whom it is usually associated with the main clinical features, as occurs in the 70% of the cases. In this context, the peripheral blood smear is essential and reveals giant platelets and stomatocytes. Only 21 causative variants in ABCG5/ABCG8 are associated with macrothrombocytopenia. Most physicians still do not recognize these hematological abnormalities or relate them to sitosterolemia. Patients may suffer long-term misdiagnosis of immune thrombocytopenia and be at high risk of receiving harmful therapies or of not benefitting from a low-cholesterol diet and/or from the gold standard treatment with ezetimibe. This drug reduces the levels of plasma plant sterols, provokes regression of xanthomas, and can alleviate hematological abnormalities. Finally, to identify genetic defects, recent advances in high-throughput sequencing, especially in the use of targeted sequencing of pre-specified genes, have begun to be incorporated in the first-line approach in the field of genetic disorders.

Topics: Animals; Cardiovascular Diseases; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols

Plant sterols and stanols (PS) are natural, non-nutritive molecules that play a structural role in plant membranes similar to that of cholesterol in animal membranes and abound in seeds and derived oils. PS exert their physical effect of interference with micellar solubilization of cholesterol within the intestinal lumen and are marginally absorbed by enterocytes, with negiglible increases in circulating levels. The physiological role of PS in plants and their natural origin and non-systemic action, together with their cholesterol-lowering effect, make them an attractive option as non-pharmacological agents for the management of hypercholesterolemia. Recent meta-analyses have summarized the results of >100 controlled clinical trials and have firmly established that the consumption of PS-supplemented foods in different formats at doses of 2-3 g per day results in LDL-cholesterol reductions of 9-12%. PS are both effective and safe cholesterol-lowering agents and have many clinical applications: adjuncts to a healthy diet, treatment of common hypercholesterolemia, combination therapy with statins and other lipid-lowering drugs, and treatment of metabolic syndrome and diabetes. The cholesterol-lowering efficacy is similar in all clinical situations. PS are also useful agents for treatment of hypercholesterolemic children who are not yet candidates to statins or receive low-doses of these agents. In the setting of statin treatment, the average LDL-cholesterol reduction obtained with PS is equivalent to up- titrating twice the statin dose. However, information is still scarce on the efficacy of PS as an add-on therapy to ezetimibe, fibrates, omega- 3 fatty acids, or bile acid binding resins. The consistent scientific evidence on the cholesterollowering efficacy and safety of functional foods supplemented with PS has led several national and international scientific societies to endorse their use for the non-pharmacologic treatment of hypercholesterolemia as adjuncts to a healthy diet. There is, however, a lack of clinical trials of PS with outcomes on cardiovascular events.

Topics: Animals; Food, Fortified; Humans; Hypercholesterolemia; Phytosterols

Sitosterolemia is a rare autosomal recessive disorder of dyslipidemia due to mutations of genes ABCG5 and ABCG8, leading to highly elevated plasma levels of plant sterols and expanded body pools of cholesterol.. We present a 9-year-old and a 7-year-old Chinese boy with hypercholesterolemia and xanthomas of sitosterolemia due to ABCG5 gene mutations. We also make a literature review of another 30 sitosterolemic children cases that have been reported with virulence ABCG5 gene mutations.. We took peripheral blood samples from 2 patients and their parents to conduct genetic analysis by next-generation sequencing (NGS) technologies.. The 2 patients received dietary modifications without pharmaceuticals treatment.. A c.1166G>A (Arg389His) homozygosis mutation in exon 9 was observed in case 1, whereas a c.751C>T (Gln251*) homozygosis mutation in exon 6 was found in case 2. Literature review found another 30 pediatric cases with sitosterolemia due to ABCG5 gene mutation. The lipid profile was normalized and xanthomas got smaller with combined therapy of a combined low-cholesterol and low-phytosterols diet.. These suggested that in patients (especially Asian patients) with multiple xanthomas, severe hypercholesterolemia, or elevated low-density lipoprotein-cholesterol, sitosterolemia should be considered in the differential diagnosis. Early diagnosis is important, and restriction of both cholesterol and phytosterols diet should suggested for these patients.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; Child; Diagnosis, Differential; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Phenotype; Phytosterols

Sitosterolemia or phytosterolemia is a rare autosomal recessive hereditary lipid storage disorder. It is caused by homozygous or compound heterozygous mutations in one of the two ABCG5 and ABCG8 genes encoding the intestinal and hepatic heterodimer ABCG5 (sterolin 1)/ABCG8 (sterolin 2) efflux transporters. These mutations lead to intestinal hyperabsorption and reduced hepatic secretion of cholesterol and plant sterols with subsequent accumulation of phytosterols and cholesterol in plasma and deposition in tissue (xanthoma). Phytosterols are found mainly in vegetable oils, margarine, nuts, grains, soybeans and avocados. Patients with sitosterolemia show extreme phenotypic heterogeneity from almost asymptomatic individuals to those with combined severe hypercholesterolemia at a young age, leading to increased atherosclerosis and premature cardiac death. Early abnormalities include hemolytic anemia with stomatocytosis, macrothrombocytopenia and splenomegaly. In addition to strict avoidance of phytosterol-containing foods, the use of the sterol absorption inhibitor ezetimibe, possibly in combination with the bile acid-binding resin cholestyramine, is the most effective treatment option.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Mutation; Phytosterols

Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease.. Mutations in multiple alleles responsible for low-density lipoprotein regulation could contribute to the development of familial hypercholesterolemia, especially among patients with mutation-negative familial hypercholesterolemia. In oligogenic familial hypercholesterolemia, multiple rare genetic variations contributed to more severe familial hypercholesterolemia.. Familial hypercholesterolemia is a relatively common 'genetic' disorder associated with an extremely high risk of developing coronary artery disease. In addition to monogenic familial hypercholesterolemia, different types of familial hypercholesterolemia, including polygenic and oligogenic familial hypercholesterolemia, exist and have varying degrees of severity. Clinical and genetic assessments for familial hypercholesterolemia and clinical risk stratifications should be performed for accurate diagnosis, as should cascade screening and risk stratification for the offspring of affected patients.

Topics: Animals; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Risk Assessment

Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively) gene mutations. Recent advances in genetics have revealed that the prevalence of subjects with deleterious mutations in ABCG5 and/or ABCG8 genes could be more than 1 in ~200,000 individuals among the general population. Furthermore, accumulated evidence, including infantile cases exhibiting progression/regression of systemic xanthomas associated with LDL cholesterol levels, have shown that the elevation of LDL cholesterol seems to be the major cause of development of atherosclerosis and not the elevation of sitosterol. Regarding therapies, LDL apheresis, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, could be useful for sitosterolemia, in addition to ezetimibe and/or colestimide. In this study, we provide the current understanding and future perspectives of sitosterolemia, which is currently considered an extremely rare disorder but is expected to be much more prevalent in clinical settings.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Coronary Artery Disease; Heterozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Mutation; Phenotype; Phytosterols; Polymorphism, Genetic; Proprotein Convertase 9; Sitosterols

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.

Topics: Anticholesteremic Agents; Canada; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Congresses as Topic; Diet; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols

Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed. Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia. High-throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias. Accurate characterization of sitosterolemia helps us determine appropriate management.. Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.

Topics: Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; DNA Mutational Analysis; Ezetimibe; Female; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Middle Aged; Mutation; Phenotype; Phytosterols; Sitosterols; Spain; Thrombocytopenia; Xanthomatosis

Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation. Identification of single-nucleotide polymorphisms (SNP) in key cholesterol and TG regulating genes, in particular adenosine triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have provided insight into the potential of utilizing genomic identifiers as an indicator of PS responsiveness. While PS supplementation is deemed safe, expanding research into the atherogenic potential of oxidized phytosterols (oxyphytosterols) has emerged with their identification in arterial lesions. This review will highlight the lipid-lowering utility and associated mechanisms of PS and discuss novel applications and future research priorities for PS pertaining to in utero PS exposure for long-term cardiovascular disease risk protection and combination therapies with lipidlowering drugs.

Topics: Animals; Clinical Trials as Topic; Dietary Supplements; Dyslipidemias; Humans; Hypercholesterolemia; Lipids; Phytosterols

A consumption of 2 grams per day of plant sterols produces an inhibition of intestinal absorption of cholesterol and reduces the plasma concentration of c-LDL (cholesterol associated with low-density lipoprotein) by around 10%, which has determined its incorporation into different food products like margarines or dairy. The plant sterols develop their action in the intestine, where they reduce the absorption of cholesterol increasing their elimination fecal. In clinical practice, the use of functional foods with plant sterols at the recommended doses can be considered as a complement to lifestyle modifications, in individuals with hypercholesterolemia and low cardiovascular risk but who do not require hypocholesterolemic pharmacological treatment, and also in those patients receiving pharmacological treatment with lipid-lowering drugs and who do not get the therapeutic goals of c-LDL. The hypocholesterolemic effect of plant sterols is additive to that achieved with changes in lifestyle and/or other lipid-lowering agents. Coadministration with statins generates a hypocholesterolemic effect usually greater than that obtained when the statin dose is doubled.. Un consumo de 2 gramos diarios de esteroles vegetales produce una inhibición de la absorción intestinal de colesterol y reduce la concentración plasmática de c-LDL (colesterol asociado a lipoproteínas de baja densidad) alrededor de un 10%, lo que ha determinado su incorporación a diferentes productos alimenticios como margarinas o lácteos. Los esteroles vegetales desarrollan su acción en el intestino, donde dificultan la absorción del colesterol aumentando su eliminación a través de las heces.En la práctica clínica, la utilización de alimentos funcionales con esteroles vegetales a las dosis recomendadas se puede considerar como complemento de las modificaciones del estilo de vida, en individuos con hipercolesterolemia y riesgo cardiovascular global bajo, pero que no precisen tratamiento farmacológico hipocolesterolemiante, y también en aquellos pacientes que reciben tratamiento farmacológico con hipolipemiantes y que no alcanzan los objetivos terapéuticos de c-LDL. El efecto hipocolesterolemiante de los esteroles vegetales es aditivo al alcanzado con los cambios del estilo de vida y/o con otros hipolipemiantes. La coadministración con estatinas genera un efecto hipocolesterolemiante habitualmente superior al obtenido cuando se dobla la dosis de estatina.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Phytosterols; Plant Preparations

Phytosterols are bioactive compounds found in foods of plant origin, which can be divided into plant sterols and plant stanols. Clinical studies consistently indicate that the intake of phytosterols (2 g/day) is associated with a significant reduction (8-10%) in levels of low-density lipoprotein cholesterol (LDL-cholesterol). Thus, several guidelines recommend the intake of 2 g/day of plant sterols and/or stanols in order to reduce LDL-cholesterol levels. As the typical western diet contains only about 300 mg/day of phytosterols, foods enriched with phytosterols are usually used to achieve the recommended intake. Although phytosterols decrease LDL-cholesterol levels, there is no evidence that they reduce the risk of cardiovascular diseases; on the contrary, some studies suggest an increased risk of atherosclerosis with increasing serum levels of phytosterols. This review aims to address the evidence available in the literature on the relationship between phytosterols and risk of cardiovascular disease.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypercholesterolemia; Phytosterols

Hypercholesterolaemia is a major cardiovascular risk factor. A healthy diet and a healthy lifestyle reduces cardiovascular risk. 'Functional foods' supplemented with phytosterols are recommended for the management of hypercholesterolaemia and have become a widely used non-prescription approach to lower plasma cholesterol levels. Two billion euros are spent world-wide each year on various functional foods, which have regulator-approved health claims for the management of elevated cholesterol levels. While international societies, such as the European Atherosclerosis Society or the National Heart Foundation in Australia, still advise phytosterols as an additional dietary option in the management of hypercholesterolaemia, recently released guidelines such as those from the National Institute of Health and Clinical Excellence in the United Kingdom are more critical of food supplementation with phytosterols and draw attention to significant safety issues. This review challenges whether an intervention with phytosterol supplements is beneficial. We summarize the current evidence from genetic diseases, genetic association studies, clinical trial data and data from animal studies.. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Dietary Supplements; Functional Food; Humans; Hypercholesterolemia; Phytosterols; Practice Guidelines as Topic; Risk Factors

The prevalence of premature atherosclerosis and cardiovascular disease (CVD) is constantly increasing worldwide. It has been proved that LDL-cholesterol (LDL-C) plays causal role in the development of coronary atherosclerosis. The fact that atherosclerosis is a chronic and progressive disease which onsets during the first three decades of life bores questions what to do to maintain LDL-C at low levels throughout life and thus to delay and/or prevent the progress this disease. Currently, most of public health expenses are spared on treatment, but not on prophylaxis.. This is a review article summarizing novel reports concerning the efficacy of sterols/stanols as lipidlowering agents, assessing their influence on cardiovascular risk and safety.. It has been suggested that sterols and stanols are effective in the lowering of low-density cholesterol levels and diminishing cardiovascular risk. However, the results of other studies suggest that phytosterols may not exert positive effects during atherogenesis. Firstly, patients with phytosterolaemia (genetic disease in which high plant sterol plasma concentrations are observed) develop malignant premature atherosclerosis. Moreover, several epidemiological studies demonstrated the association between upper normal plasma concentrations of plant sterols and increased risk of cardiovascular events. Finally, the supplementation with plant stanols and plant sterols may be not beneficial due to their incorporation in various tissues and potentially resulting in adverse effects.. Despite the worldwide promotion of sterols as health improving supplements, it seems that in some people responding with relatively high phytosterol serum levels after its consumption such additives may turn out to be as good as it has been believed.

Topics: Cardiovascular Diseases; Cholesterol; Humans; Hypercholesterolemia; Hypolipidemic Agents; Phytosterols

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics.

Topics: Apolipoprotein B-100; Cholesterol Ester Storage Disease; Diagnosis, Differential; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Proprotein Convertase 9; Proprotein Convertases; Receptors, LDL; Serine Endopeptidases; Xanthomatosis, Cerebrotendinous

The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%-10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be diminished.

Topics: Animals; Dietary Fats; Dietary Supplements; Humans; Hypercholesterolemia; Intestinal Absorption; Kinetics; Lipoproteins; Liver; Particle Size; Phytosterols; Postprandial Period; Treatment Outcome

There is broad evidence that lowering low-density lipoprotein (LDL) cholesterol will reduce cardiovascular risk. However, in patients on maintenance hemodialysis treatment, lowering LDL cholesterol is not as effective in preventing cardiovascular complications as in the general population. Cholesterol is either endogenously synthesized or absorbed from the intestine. It has been suggested that the benefit of using statins to prevent atherosclerotic complications is less pronounced in people with high absorption of cholesterol. Recent data indicate that patients on hemodialysis have high absorption of cholesterol. Therefore, these patients may benefit from dietary counseling to reduce cholesterol intake, from functional foods containing plant sterols and stanols, and from drugs that interfere with intestinal absorption of sterols (i.e., ezetimibe, bile acid resins, and sevelamer). This review discusses cholesterol homeostasis and the perspective of personalized treatment of hypercholesterolemia in hemodialysis.

Topics: Azetidines; Cardiovascular Diseases; Cholesterol, Dietary; Cholesterol, LDL; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Kidney Failure, Chronic; Phytosterols; Polyamines; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Sevelamer

Sitosterolemia is an autosomal recessive disorder characterized by increased intestinal absorption of plant sterols. It is caused by mutations in genes encoding ATP-binding cassette, subfamily G5 (ABCG5) or G8 (ABCG8), and clinical features include elevated plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, patients with sitosterolemia also hyperabsorb cholesterol, and serum cholesterol levels tend to be elevated.. We report an infant with sitosterolemia who presented with severe hypercholesterolemia and intertriginous xanthomas.. A 15-month-old Korean girl presented with yellow dermal plaques over flexural areas including the wrist, neck, and gluteal folds, which were consistent with intertriginous xanthomas. The lesions were first noticed at 3 months of age when she was being exclusively breastfed. Her total cholesterol and low-density lipoprotein-cholesterol levels were 675 and 540 mg/dL, respectively. A low-fat/low-cholesterol diet and cholestyramine therapy were introduced. Unexpectedly, her serum cholesterol level decreased dramatically and normalized in 2 months. Cholestyramine was tapered off. The xanthomas also regressed and disappeared by 3 years of age. Gas chromatography-mass spectrometric analysis was performed with serum drawn at 3 years of age when her low-density lipoprotein-cholesterol was 118 mg/dL, which revealed striking elevation of her sitosterol level at 19.36 mg/dL. Direct sequencing for ABCG5 revealed compound heterozygous null mutations c.904+1G>A (p.Met302Asnfs*82) and c.1336C>T(p.Arg446*).. Our case suggests that sitosterolemia can present with severe hypercholesterolemia and intertriginous xanthomas. Sitosterolemia should be suspected when a patient with hypercholesterolemia shows unexpectedly good response to dietary modification or bile acid sequestrant therapy.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP-Binding Cassette Transporters; Diet, Fat-Restricted; Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Treatment Outcome; Xanthogranuloma, Juvenile

Phytosterols (PS, comprising plant sterols and plant stanols) have been proven to lower LDL-cholesterol concentrations. The dose-response relationship for this effect has been evaluated in several meta-analyses by calculating averages for different dose ranges or by applying continuous dose-response functions. Both approaches have advantages and disadvantages. So far, the calculation of averages for different dose ranges has not been done for plant sterols and stanols separately. The objective of the present meta-analysis was to investigate the combined and separate effects of plant sterols and stanols when classified into different dose ranges. Studies were searched and selected based on predefined criteria. Relevant data were extracted. Average LDL-cholesterol effects were calculated when studies were categorised by dose, according to random-effects models while using the variance as weighing factor. This was done for plant sterols and stanols combined and separately. In total, 124 studies (201 strata) were included. Plant sterols and stanols were administered in 129 and fifty-nine strata, respectively; the remaining used a mix of both. The average PS dose was 2.1 (range 0.2-9.0) g/d. PS intakes of 0.6-3.3 g/d were found to gradually reduce LDL-cholesterol concentrations by, on average, 6-12%. When plant sterols and stanols were analysed separately, clear and comparable dose-response relationships were observed. Studies carried out with PS doses exceeding 4 g/d were not pooled, as these were scarce and scattered across a wide range of doses. In conclusion, the LDL-cholesterol-lowering effect of both plant sterols and stanols continues to increase up to intakes of approximately 3 g/d to an average effect of 12%.

Topics: Adult; Anticholesteremic Agents; Cholesterol, LDL; Dietary Supplements; Evidence-Based Medicine; Functional Food; Humans; Hypercholesterolemia; Phytosterols; Randomized Controlled Trials as Topic

To provide an update on recent advances made in our mechanistic and pathophysiological understanding of the rare human disease Sitosterolemia, the role of ABCG5/ABCG8 in sterol trafficking and how newer data implicate a more wider role in the body.. Sitosterolemia is caused by a genetic defect of sterolins (ABCG5/ABCG8) mapped to the STSL locus. Polymorphic variations in STSL have been linked to lipid levels and gallstone disease in whites. Newer studies now link this locus to a more diverse ethnic group for gallstone disease, susceptibility to biliary cancer, and show variants that alter sterolin function. Intriguingly, carriers of a mutant allele seem to show protection against carotid wall disease. Although the 'promoter' region of the STSL is minimal, regulatory regions responsive to liver X receptor have remained elusive, but no longer; two intronic regions in ABCG8 have now been identified. Xenosterol accumulation leads to loss of abdominal fat, infertility, and premature death. Xenosterol accumulation in mouse platelet membranes leads to platelet hyperactivation, increased microparticle formation, and reduced αIIbβ3 surface expression. In humans, phytosterols may promote liver injury in parenteral nutrition-associated liver disease.. Progress in understanding sterolin function is beginning to show that xenosterols can be toxic and are involved on pathogenesis, and the role of ABCG5/ABCG8 may extend into other metabolic processes by altering intracellular sterol metabolism.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Biological Transport, Active; Blood Platelets; Cell Membrane; Genetic Loci; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Liver X Receptors; Mice; Mutation; Orphan Nuclear Receptors; Phytosterols; Polymorphism, Genetic; Promoter Regions, Genetic; Sterols

Sitosterolemia is a rare autosomal recessively inherited disease caused by mutations affecting ABCG5 or ABCG8, which are located on human chromosome band 2p21. Around 100 cases have been reported in the literature. Sitosterolemic patients typically exhibit a 30-fold to 100-fold increase in plasma concentrations of plant sterols. The clinical manifestations include xanthomas, premature atherosclerosis, hemolytic anemia, and macrothrombocytopenia. It is noteworthy that abnormal hematological parameters may be the only clinical feature of sitosterolemic patients, suggesting that sitosterolemia may be more frequent than previously thought. Severe accumulation of plant sterols in mouse models of sitosterolemia induced complex cardiac lesions, anemia, and macrothrombocytopenia, disrupted adrenal and liver cholesterol homeostasis, and caused infertility and hypertriglyceridemia. It remains unclear whether all disease traits are present in sitosterolemic patients. The drug ezetimibe appears to be effective in reducing plasma plant sterol levels, promotes xanthoma regression, and improves the cardiovascular and hematological signs in sitosterolemic patients.

Topics: Anemia, Hemolytic; Animals; Anticholesteremic Agents; Atherosclerosis; Azetidines; Ezetimibe; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Mice; Phytosterols; Thrombocytopenia; Xanthomatosis

Hypercholesterolemia is a major contributor for disease burden in both the developed and developing world and an important risk factor for cardiovascular diseases (CVD). Phytosterols (PhS) and dietary fiber (DF) act as low density lipoprotein cholesterol (LDL-C) lowering agents, offering an effective treatment against high blood cholesterol and CVD. The aim of this review was to consider clinical evidence that analyzed the combination of PhS and DF in a cereal carrier for lowering LDL-C. Electronic database searches were carried out to identify peer-reviewed journal articles, from which five intervention studies that combined both components in a cereal carrier were identified and included in the present review. LDL-C lowering effects varied widely among studies, due to large heterogeneity in study design, subject baseline characteristics, length of the interventions, PhS and DF dosage and type of DF used. In relation to a time of intake, three studies suggested a frequency or distribution of the product's consumption during the day, while two studies did not consider this factor. Overall, the selected studies found significant differences on LDL-C concentrations, although not all of them reached the expected outcomes. Future research should be conducted to explore the effect that different types of DF exert on LDL-C when combined with PhS, and to analyze the effect of the product's time of intake in order to suggest an optimal moment of the day for its consumption.

Topics: Cholesterol, LDL; Dietary Fiber; Humans; Hypercholesterolemia; Phytosterols

According to the American Diabetes Association and the Adult Treatment Panel III, the starting point for treating metabolic syndrome (MS) is a change of lifestyle. In addition, action on the main symptoms of MS by means of dietary supplements, can be helpful in view of the chronic course of the disease. The term 'phytosterols' refers to sterols and stanols composed of lipophilic triterpenes, a family that is widely distributed in the plant kingdom and whose cholesterol-lowering properties have been amply demonstrated. In the light of the recent literature, the key points for maximum effectiveness and safety of sterols are the following. (A) Plant sterols should be taken with meals: clinical trials have shown that when plant sterols are consumed close to mealtimes, low-density lipoprotein cholesterol may decrease by 9.4%, while when they are taken between meals, the reduction is about 6%. (B) The optimal dosage is 2-2.5 g day(-1) in a single dose. More than 3 g day(-1) has not been found to have any additional beneficial effect and increases the risk of side effects. (C) The food matrix used to dissolve the phytosterols should contain a certain amount of fat. A milk-based matrix appears optimal from this point of view.

Topics: Dose-Response Relationship, Drug; Humans; Hypercholesterolemia; Hypolipidemic Agents; Metabolic Syndrome; Phytosterols

The research focuses on effective supply of phytosterols in human nutrition. Their beneficial influence concerning the lowering effect on the concentration of LDL cholesterol is underlined and the occurring changes in serum concentrations of the fractions related to cholesterol absorption and synthesis are pointed out. It seems that the use of phytosterols in human nutrition may be the factor playing an important role in preventing the development of dyslipidemia.

Topics: Cholesterol; Cholesterol, LDL; Dietary Supplements; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Plant Extracts

Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Diet; Dietary Fats; Fatty Acids, Unsaturated; Functional Food; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Plant Extracts; Sitosterols

Sitosterolemia (STSL) is a rare autosomal recessive disease, manifested by extremely elevated plant sterols (PS) in plasma and tissue, leading to xanthoma and premature atherosclerotic disease. Therapeutic approaches include limiting PS intake, interrupting enterohepatic circulation of bile acid using bile acid binding resins such as cholestyramine, and/or ileal bypass, and inhibiting intestinal sterol absorption by ezetimibe (EZE). The objective of this review is to evaluate sterol metabolism in STSL and the impact of the currently available treatments on sterol trafficking in this disease. The role of PS in initiation of xanthomas and premature atherosclerosis is also discussed. Blocking sterols absorption with EZE has revolutionized STSL patient treatment as it reduces circulating levels of non-cholesterol sterols in STSL. However, none of the available treatments including EZE have normalized plasma PS concentrations. Future studies are needed to: (i) explore where cholesterol and non-cholesterol sterols accumulate, (ii) assess to what extent these sterols in tissues can be mobilized after blocking their absorption, and (iii) define the factors governing sterol flux.

Topics: Absorption; Atherosclerosis; ATP Binding Cassette Transporter, Subfamily G; ATP-Binding Cassette Transporters; Azetidines; Cholesterol; Disease Progression; Ezetimibe; Humans; Hypercholesterolemia; Intestinal Diseases; Kinetics; Lipid Metabolism, Inborn Errors; Membrane Proteins; Membrane Transport Proteins; Phytosterols; Sitosterols; Sterol O-Acyltransferase; Sterol O-Acyltransferase 2; Sterols; Xanthomatosis

Reducing intestinal cholesterol absorption with plant sterol consumption is a well-characterized strategy to lower LDL-C and potentially reduce cardiovascular disease risk. However, over 50 years of clinical research demonstrate that there is significant heterogeneity in the individual LDL-C lowering response to plant sterol therapy. A clear understanding of why plant sterols work effectively in some individuals but not in others will ensure optimal integration of plant sterols in future personalized nutritional lipid-lowering strategies. This review will examine the current knowledge base surrounding the metabolic and genetic determinants of LDL-C lowering in response to plant sterol consumption.

Topics: Animals; Anticholesteremic Agents; Cholesterol, LDL; Humans; Hypercholesterolemia; Individuality; Phytosterols

Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

Topics: Anticholesteremic Agents; beta-Glucans; Cholesterol, HDL; Cholesterol, LDL; Diet; Dietary Fats; Dietary Fiber; Energy Intake; Fatty Acids, Monounsaturated; Food; Food Preferences; Humans; Hypercholesterolemia; MEDLINE; Nuts; Phytosterols; Sitosterols; Solubility; Soybean Proteins

Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C) levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose-response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for consumption including spreads and yoghurt type drinks. In conclusion, a dose-effect relationship of plant stanols in higher doses than currently recommended has been demonstrated by recent clinical studies and a meta-analysis. Further studies are called for to provide confirmatory evidence amenable for new health claim applications and dietary recommendations.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Plant Oils; Sitosterols; Yogurt

Phytosterols/stanols (PS) enriched food products have been shown to consistently lower plasma cholesterol levels. The intake of 2g/d of PS decreases LDL-cholesterol by about 10%. With respect to the association of LDL-cholesterol lowering with reduction in the cardiovascular (CV) risk, it is likely that supplementation in PS reduces the incidence of CV disease. In addition, the vast majority of animal studies have shown that oral administration of PS reduces the progression atherosclerosis. However, it has been recently suggested that an increase in PS plasma concentrations may increase CV risk. Evidence to support this hypothesis come mainly from observations in sitosterolemic patients who hyperabsorb PS and cholesterol and display very high levels of PS, which may be associated with a premature atherosclerosis. Some epidemiological studies in non-sitosterolemic subjects have shown a positive correlation between PS plasma levels and coronary heart disease. However, these are observational studies and some of them present major methodological bias. In addition, recent studies with a larger number of subjects have indicated, either an absence or a negative relationship between PS and the incidence of CV disease. The guidelines of several French and international institutions recommend the use of PS enriched food in association with other classical recommendations in hypercholesterolemic subjects. However, further studies are highly encouraged to examine the CV benefit of PS enriched food.

Topics: Animals; Atherosclerosis; Humans; Hypercholesterolemia; Phytosterols

Recommendations about the use of plant stanol/sterol esters have not been updated since 2001. There have been many developments in medicines for lipid-lowering since 2001. In this review, the use of margarines containing stanol or sterol esters, to lower LDL cholesterol is considered in the 2011 setting. Firstly, there is a brief overview of the effects of the stanols/sterols on LDL cholesterol, which shows that these agents have a modest ability to lower LDL cholesterol, and are not effective in all conditions. Secondly, the relevance of the stanols/sterols in 2010/1 is questioned, given they have not been shown to reduce clinical endpoints, and have no effects on HDL cholesterol or triglyceride levels. Finally, there is a section comparing the stanols/sterols with the present day prescription lipid lowering medicines. Prescription drugs (statins, ezetimibe, and niacin) have a much greater ability to lower LDL cholesterol than the stanol/sterol esters, and also increase levels of HDL cholesterol and decrease levels of triglycerides. The statins and niacin have been shown to reduce cardiovascular clinical endpoints. Except in borderline normo/hypercholesterolemia, prescription drugs should be preferred to stanol/sterol esters for lowering LDL cholesterol in 2011.

Topics: Anticholesteremic Agents; Azetidines; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Ezetimibe; Fibric Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Margarine; Micronutrients; Niacin; Phytosterols; Sitosterols; Triglycerides

Inflammation is a strong risk factor for cardiovascular disease. Dietary plant sterols are known to reduce plasma cholesterol levels and thereby reduce cardiovascular risk. Recent observations from animal and human studies have demonstrated anti-inflammatory effects of phytosterols. For example, several animal and human studies report reductions in the levels of proinflammatory cytokines, including C-reactive protein, after consumption of dietary plant sterols. Although the cholesterol-lowering effects of phytosterols in humans are well documented, studies on the effects of phytosterols on inflammatory markers have produced inconsistent results. This review summarizes and discusses findings from recent animal and human studies with regard to the potential anti-inflammatory effects of dietary phytosterols. Findings on the effects of plant sterols on inflammation remain limited and confounding. Future research using better-designed and well-controlled laboratory studies and clinical trials are needed to fully understand the mechanisms through which phytosterols influence inflammation. Additional well-designed placebo-controlled studies are needed to better understand how and to what extent dietary plant sterols may modify the immune system and the production of inflammatory markers.

Topics: Animals; Anti-Inflammatory Agents; Humans; Hypercholesterolemia; Hypolipidemic Agents; Phytosterols

Topics: Anemia, Hemolytic; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Thrombocytopenia

Hypercholesterolemia is a major risk factor for cardiovascular disease. The HMG-CoA-reductase inhibitors, statins, reduce plasma cholesterol and, as a consequence, decrease cardiovascular morbidity and mortality. Data from a subgroup analysis of the 4-S Study, however, indicate that patients with high cholesterol absorption may not benefit from statin treatment. Furthermore, there is accumulating evidence that lower hepatic synthesis and higher intestinal absorption markers are associated with increased cardiovascular risk. Therefore, prospective clinical trials are needed to evaluate whether subjects with altered cholesterol homeostasis may benefit from treatment strategies that reduce cholesterol absorption in addition to statin treatment.

Topics: Absorption; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Coronary Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Mucosa; Liver; Phytosterols; Risk; Sterols

Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1 by increasing raft content will increase signaling through these receptors, as has been experimentally demonstrated. Moreover, additional reports indicate ABCA1, and possibly SR-BI, another HDL receptor, may directly act as anti-inflammatory receptors independent of their lipid transport activities. Finally, we give an update on the progress and pitfalls of therapeutic approaches that seek to stimulate the flux of lipids through the RCT pathway.

Topics: Animals; Atherosclerosis; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Cholesterol; Coronary Vessels; Hepatocytes; Humans; Hypercholesterolemia; Inflammation; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Models, Biological; Myocardial Infarction; Phenotype; Phytosterols; Tangier Disease

Coronary heart disease (CHD) is the leading cause of mortality worldwide. With increasingly urbanized lifestyles in developing countries and the aging populations, the major risk factors for CHD such as obesity, diabetes mellitus, and hypercholesterolemia are likely to increase in the future. In the current report, we reviewed the evidence on the effect of cholesterol lowering using pharmacological agents.. A PubMed/Medline systematic search was performed over the past 12 years (1998-2009 inclusive) and relevant papers written in the English language were selected. We used key phrases including, "risk factors for hypercholesterolemia," "management of hypercholesterolemia," "guidelines for management of hypercholesterolemia," and "pharmacological management of hypercholesterolemia.". There were a total of over 3500 reports. We selected key publications on the effect of cholesterol lowering using different pharmacological agents.. Several options exist with regards to pharmacological management of hypercholesterolemia. There is a substantial body of evidence to support the effect of a population shift towards a favorable risk profile, which has huge potential in reducing the burden of CHD globally.

Topics: Anticholesteremic Agents; Azetidines; Cholestyramine Resin; Coronary Disease; Drug Therapy, Combination; Evidence-Based Practice; Ezetimibe; Fatty Acids, Omega-3; Gemfibrozil; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Niacin; Patient Selection; Phytosterols; Practice Guidelines as Topic; Primary Prevention; Risk Assessment; Risk Factors; Risk Reduction Behavior; Secondary Prevention; Treatment Outcome

This paper explores how users of foods containing phytosterols are 'configured' within biomedical research and writing on these substances. A growing range of such foods have been launched and marketed on the basis that they actively lower cholesterol. They are among the most prominent examples of a set of foods designated as 'functional foods'. The paper is based on an analysis of biomedical journal articles which address the use of phytosterols as a cholesterol lowering agent in humans. These include both original research papers and commentaries such as review articles, letters, editorials, news items and professional guidelines. My analysis suggests that users are constituted variously as autonomous, self-motivated consumers, patients and publics needing advice, people resistant to pill use, and practitioners looking for something to offer their patients. I characterise the imagined uses of the products as healthy/holistic, lazy/busy/contemporary, and incompetent use. These varying portrayals of users and their use of these food products entail different ways of understanding health identities and different allocations of responsibilities between the technology, user and health care professionals. I conclude that, while experts and regulators may attempt to configure 'correct' uses of these products, relatively little is known about the rationales and practices of actual users.

Topics: Anticholesteremic Agents; Biomedical Research; Cholesterol; Functional Food; Health Behavior; Humans; Hypercholesterolemia; Phytosterols

To examine experimental evidence that has examined association of phytosterols and the reduction of the risk of cardiovascular disease and cancer.. Phytosterols exist as naturally occurring plant sterols that are present in the nonsaponifiable fraction of plant oils. Phytosterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra methyl or ethyl group; however, phytosterol absorption in humans is considerably less than that of cholesterol. In fact, phytosterols reduce cholesterol absorption, although the exact mechanism is not known, and thus reduce circulating levels of cholesterol. The efficacy of phytosterols as cholesterol-lowering agents have been shown when incorporated into fat spreads as well as other food matrices. In addition, phytosterols have been combined with other beneficial dietary components including fish and olive oils, psyllium and beta-glucan to enhance their effect on risk factors of cardiovascular disease. Phytosterols appear not only to play an important role in the regulation of cardiovascular disease but also to exhibit anticancer properties. A side effect associated with the consumption of phytosterols is that they reduce the blood levels of carotenoid. Nevertheless, it has been suggested that compensation for this impact on serum carotenoid levels can occur either by increasing the intake of carotenoid-rich foods or by taking supplements containing these carotenoids.. Dietary phytosterols appear to play an important role in the regulation of serum cholesterol and to exhibit anticancer properties.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Carotenoids; Cholesterol; Humans; Hypercholesterolemia; Neoplasms; Phytosterols

This article discusses specific dietary factors as well as dietary patterns that affect the major coronary heart disease (CHD) lipid risk factors (ie, LDL-C, HDL-C, and TG). Based on a very large evidence base, it is clear that diet and lifestyle practices can markedly affect these major CHD lipid risk factors, and consequently decrease CHD risk substantively.

Topics: Alcohol Drinking; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet; Diet, Fat-Restricted; Diet, Mediterranean; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Glycine max; Humans; Hypercholesterolemia; Hypertriglyceridemia; Life Style; Motor Activity; Phytosterols; Triglycerides; Weight Loss

Plant sterols are an important but underused dietary component in the treatment of elevated blood cholesterol.. This review discusses the background to plant sterol use and reviews evidence about its use in clinical practice.. When consumed in the recommended amounts, sterols alone decrease low density lipoprotein cholesterol; in combination with other dietary changes, low density lipoprotein can be further lowered. Most patients, whether they are on cholesterol lowering drugs or not, would benefit from using plant sterols, which are now available in milk and yoghurt as well as spreads. In animal models, plant sterols have been shown to reduce atherosclerosis despite an elevation in the blood level, however there is no hard end point data for this in humans.

Topics: Anticholesteremic Agents; Australia; Cholesterol; Cost-Benefit Analysis; Humans; Hypercholesterolemia; Phytosterols

A number of studies have raised the possibility of circulating plant sterols being a risk factor in the pathogenesis of atherosclerosis. Evidence in support of this hypothesis comes mainly from observations in sitosterolemic patients, who hyperabsorb plant sterols and suffer premature atherosclerosis. Accordingly, the atherogenicity of plant sterols of dietary origin is currently under debate, in view of the widespread use of cholesterol-lowering functional foods enriched with these compounds. Although some reports have suggested the vascular perils of small increases in plasma plant sterol concentrations, other prospective and large population-based studies have indicated otherwise. Further, the potential risk of plant sterol-enriched foods may be counterbalanced by the notable reduction in plasma cholesterol. This review summarizes the current evidence on the possible impact of plant sterols as a risk factor for atherosclerosis.

Topics: Atherosclerosis; Dose-Response Relationship, Drug; Humans; Hypercholesterolemia; Incidence; Phytosterols; Prognosis; Risk Factors

The objective of this work is to conduct a systematic review that investigates the efficacy of phytosterols/stanols in lowering lipid concentration in individuals with non-familial hypercholesterolemia. Randomized controlled intervention trials were identified through selected international journal databases and reference lists of relevant publications. Two researchers extracted data from each identified trial and only trials of sufficient quality were included in the review. Main outcomes of interest were differences between treatment and control groups in terms of low density lipoprotein cholesterol, total cholesterol, high density lipoprotein cholesterol and triacylglycerol. Of the studies reviewed, 20 out of 76 studies were of sufficient quality. The results of the systematic review indicated that phytosterols/stanols could significantly decrease low density lipoprotein cholesterol, total cholesterol and triacylglycerol in treatment groups compared with control groups and that the mean differences were [-0.35 mmol/L, 95%CI(-0.47, -0.22), p<0.00001], [-0.36 mmol/L, 95%CI(-0.46, -0.26), p<0.00001] and [-0.1 mmol/L, 95%CI(-0.16, -0.03), p=0.004] respectively. Foods enriched with 2.0 g of phytosterols/stanols per day had a significant cholesterol lowering effect.

Topics: Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Humans; Hypercholesterolemia; Lipids; Phytosterols; Randomized Controlled Trials as Topic; Sitosterols; Triglycerides

Topics: Cholesterol; Humans; Hypercholesterolemia; Phytosterols; Severity of Illness Index; Treatment Outcome

To characterize the effect of plant sterols/stanols on serum lipids in hypercholesterolemic patients on concurrent statin therapy, we conducted a meta-analysis of randomized controlled trials.. A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through May 2008. Trials were included in the analysis if they were randomized controlled trials evaluating the use of plant sterols/stanols in combination with statins in hypercholesterolemic patients that reported efficacy data on total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval (CI) was calculated as the difference between the mean in the plant sterol/stanol groups and the control groups, using a random-effects model.. Eight studies (n = 306 patients) met the inclusion criteria. Upon meta-analysis, the use of plant sterols/stanols in combination with statin therapy significantly lowered total cholesterol (WMD, -14.01 mg/dL [95% CI, -18.66 to -9.37], p < 0.0001) and LDL cholesterol (WMD, -13.26 mg/dL [95% CI, -17.34 to -9.18], p < 0.0001) but not HDL cholesterol or triglycerides.. Based upon the current literature, we can only say that plant sterols/stanols, when administered in addition to statins, favorably affect total and LDL cholesterol with 95% confidence. Randomized trials examining the impact of plant sterols/stanols in combinatation with statins on patient morbidity and mortality are needed.

Topics: Anticholesteremic Agents; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Phytosterols; Phytotherapy; Randomized Controlled Trials as Topic; Treatment Outcome

Hypercholesterolemia is a predominant risk factor for atherosclerosis and associated coronary and cerebrovascular diseases. Control of cholesterol levels through therapeutic drugs, notably statins, have significantly reduced the risk for developing atherosclerosis and associated cardiovascular diseases. However, adverse effects associated with therapeutic drugs warrant to find other alternative approaches for managing hypercholesterolemia, especially for those with borderline cholesterol levels. Food supplements have increasingly become attractive alternatives to prevent or treat hypercholesterolemia and reduce the risk for cardiovascular diseases. This review summarized current patents on food supplements with claims of hypocholesterolemic effects. They can be mainly divided into four categories based on the active ingredients in the supplements: 1) plant sterols or stanols; 2) fiber or polysaccharides; 3) microorganism-derived; and 4) soy protein and phytoestrogens. The efficacy, mechanisms of action and potential side effects are reviewed for each of the four categories. The hypocholesterolemic effects of plant sterols, fiber, Monascus products and soy protein preparations have been consistently demonstrated in clinical trails whereas the efficacy of some probiotic bacteria and phytoestrogens-containing supplements remains to be established. Accumulative clinical data show that plant sterols, fiber, soy protein and phytoestrogen are generally considered safe and cause no obvious side effects. However, additional clinical studies are required to establish the safety profiles of certain probiotic bacteria as food supplements.

Topics: Anticholesteremic Agents; Atherosclerosis; Bile Acids and Salts; Dietary Fiber; Humans; Hypercholesterolemia; Lipoproteins, HDL; Lipoproteins, LDL; Monascus; Phytoestrogens; Phytosterols; Polysaccharides; Probiotics; Sitosterols; Soybean Proteins

Topics: Cholesterol; Humans; Hypercholesterolemia; Intestinal Absorption; Margarine; Phytosterols; Sitosterols; Treatment Outcome

Epidemiological studies have demonstrated that elevated levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the major risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) and a low ratio of TC to HDL-C are protective against CHD. A relationship between plasma TC and the risk of CHD is well established at concentrations above 240 mg/dL. In addition to the use of three main classes of cholesterol-lowering medications, including HMG-CoA reductase inhibitors, anion-exchange resins, and fibrates, a nutritionally balanced diet that reduces saturated fat and cholesterol intake has traditionally been the first goal of dietary therapy in lowering plasma TC. In recent years, nutraceuticals and functional foods have attracted much interest as possible alternative therapies for lowering plasma TC, especially for hypercholesterolemia patients, whose blood cholesterol level is marginally high (200-240 mg/dL) but not high enough to warrant the prescription of cholesterol-lowering medications. This review summarizes the findings of recent studies on the production, application, efficacy, and mechanisms of popular cholesterol-lowering nutraceuticals and functional foods.

Topics: Animals; Anticholesteremic Agents; Catechin; Cultured Milk Products; Dietary Fiber; Dietary Supplements; Fagopyrum; Flavonoids; Garlic; Humans; Hypercholesterolemia; Naphthalenes; Oryza; Phenols; Phytoestrogens; Phytosterols; Polyphenols; Tea

This study examined the effect of plant sterols added, together with an emulsifying agent, to a low-fat yoghurt on the serum lipid and plant sterol values in moderately hypercholesterolaemic volunteers. Study I was a randomized double-blind, cross-over trial. For 4 weeks, 15 volunteers consumed yoghurt containing 1 g plant sterols or a placebo yoghurt. Study II was a randomized, double-blind, parallel-group study. For 8 weeks, the sterol group (n = 12) ingested daily two yoghurts (2 g/day plant sterols) and the placebo group (n = 14) ingested two yoghurts without plant sterols. Study I: compared with the placebo, the sterol yoghurt reduced serum total cholesterol by 0.15 mmol/l (2.2%, P=0.235) and low-density lipoprotein (LDL) cholesterol by 0.19 mmol/l (4.3%, P=0.082), and increased serum campesterol by 0.26 mg/100 ml (P=0.006) and sitosterol by 0.11 mg/100 ml (P=0.015). Study II: compared with the placebo, the sterol yoghurt reduced serum total cholesterol by 0.41 mmol/l (6.3%, P=0.167) and LDL cholesterol by 0.28 mmol/l (6.4%, P=0.306), and increased serum campesterol by 0.28 mg/100 ml (P=0.016) and sitosterol by 0.40 mg/100 ml (P=0.206). Meta-analysis: the pooled treatment difference was -0.34 mmol/l (5.2%, P=0.173) in total cholesterol and was -0.26 mmol/l (-5.8%, P=0.261) in LDL cholesterol, when the sterol yoghurt was compared with the placebo. A low-fat yoghurt enriched with 1-2 g/day plant sterols reduced serum cholesterol levels in moderately hypercholesterolaemic subjects. Campesterol and sitosterol serum levels increased, but their concentration remained in the range of normal values.

Topics: Adult; Analysis of Variance; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Sitosterols; Yogurt

The cholesterol-lowering effect of phytosterols has been extensively studied, and consumption of phytosterols is among the recommendations to lower LDL-cholesterol concentrations. Due to their structural similarity with cholesterol, phytosterols may undergo oxidative processes comparable to those involved in cholesterol oxidation. Consumption of phytosterols could therefore lead to increased systemic concentrations of oxidized phytosterols (oxyphytosterols) via increased dietary intake or in vivo formation from non-oxidized phytosterols. While the biological effects of oxidized cholesterol (oxycholesterol) have been well studied, the amount of biological research on oxyphytosterols is scarce. Most reports on oxyphytosterols cover their quantitative analysis. Whether oxyphytosterols may play similar biological roles as compared to oxycholesterol has not been fully elucidated. The usual perception about oxyphytosterols is that these components present a concern in terms of food quality and health. This perception originates from the parallel that is made with oxycholesterol. Yet, in line with results for oxycholesterol, recent data suggest that oxyphytosterols--depending on the type of oxidation product--may also have beneficial biological properties. Therefore, the objective of this review is to summarise the current understanding of the biological effects, next to identifying future research needs that will help to clarify the possible impact of oxyphytosterols on human health.

Topics: Androgen Antagonists; Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, Dietary; Humans; Hypercholesterolemia; Immunosuppressive Agents; Liver; Medicine, Traditional; Oxidation-Reduction; Phytosterols

Plant sterols, naturally occurring in foods of plant origin, reduce cholesterol absorption. Experimental studies show plant sterols to be an important part of the serum-cholesterol lowering effect of certain diets and dietary components. Epidemiological data show that individuals with higher intakes of plant sterols from their habitual diets have lower serum-cholesterol levels. To date, the role of naturally occurring plant sterols for lowering serum cholesterol has probably been underestimated. The consumption of dietary plant sterols should be a part of dietary advice to patients with hypercholesterolemia and the general public for the prevention and management of coronary heart disease.

Topics: Anticholesteremic Agents; Cholesterol; Diet; Humans; Hypercholesterolemia; Intestinal Absorption; Phytosterols; Phytotherapy

Lowering lipid levels in the cardiovascular prevention we confine ourselves to measure the cholesterol level and care less for the background effects. Namely blood cholesterol level beyond the amount consumed with the diet highly depends on balance of intestinal absorption/secretion and synthesis. Studying the rate of absorption and synthesis has come only recently into the foreground of interest. Many observations proved that using even the strongest cholesterol lowering drug - beyond reducing the synthesis in the liver - may be associated with an up to 50 percent increase of the intestinal cholesterol absorption. When studying the effectiveness of statins in everyday practice we measure only the decrease of serum cholesterol level as the final result, and do not examine the changes in the synthesis and absorption. The amount of cholesterol synthesized or absorbed can be determined in an indirect way by measuring that of the non-cholesterol sterols (phytosterols). The absorption markers are campesterol, sitosterol, avenasterol as well as cholestanol. The biosynthesis of cholesterol correlates with the level of lathosterol, cholestanol, desmostenol. In practice the concentration of lathosterol or lathosterol/cholesterol can be considered the marker of synthesis and the campesterol or campesterol/cholesterol ratio the marker of absorption. So recent study results show that while inhibiting the cholesterol synthesis with statin the cholesterol absorption increases and the absorption inhibitor ezetimibe is associated with boost of synthesis. The increase in absorption caused by statins can be reduced or prevented by combining with ezetimibe. These data confirm that combination of statin and ezetimibe, inhibiting simultaneously both the synthesis and absorption provides the most effective cholesterol-level lowering with the least side-effects.

Topics: Anticholesteremic Agents; Azetidines; Biomarkers; Cholestanol; Cholesterol; Cholesterol, Dietary; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Phytosterols; Sitosterols

Many dietary recommendations which try to lower the concentration of total, respectively LDL cholesterol, force us to look back to vegetable-based diet. The plants synthesize many compounds similar to cholesterol, called phytosterols and phytostanols, and these sterols are consumed in average Western diet in amounts ranging from 200 to 500 mg/day. Phytosterols and phytostanols share the mechanisms of absorption with cholesterol molecule and influence the cholesterol metabolism inside the enterocytes. Both types of phytoanalogs of cholesterol were proven to be potent cholesterol-reducing agents; their daily intake about 2 g/day reduces the LDL-cholesterol by 15%. The underlying mechanisms involve the prevention of cholesterol absorption from the gut lumen and slower esterification rate of phytosterols (phytostanols) inside the enterocytes. In contrary to phytostanols, phytosterols are absorbed with yet-to-be-considered efficiency, appearing in plasma with concentrations reaching as much as 1% that of total cholesterol. The hypocholesterolemic effect of phytosterols (phytostanols) can be further supported with the combination of dietary (n-3 polyunsaturated fatty acids, fibre) regimen as well as pharmacological intervention (statins). To conclude, plant sterols represent safe dietary approach to lowering of plasma total cholesterol with the attention paid to the intake of lipid soluble vitamins.

Topics: Cholesterol, LDL; Food, Fortified; Humans; Hypercholesterolemia; Phytosterols

Topics: Atherosclerosis; Cholesterol, LDL; Diet; Humans; Hypercholesterolemia; Hypertension; Phytosterols

Daily cholesterol consumption in western countries reaches as much as 400 mg. According to the health recommendations the daily intake should not exceed 300 mg and in the case of people with cardiovascular disease it should be less than 200 mg. For 50 years it is known that phytosterols can decrease the level of cholesterol in blood. One of the mechanisms is based on the fact that phytosterols stop absorption of cholesterol in digestive tract, which results in the decrease of the concentration of cholesterol in blood. The second mechanism is based on the fact that cholesterol is pumped back out of enterocytes into the lumen of small intestine by ABC transporter and phytosterols increase this process. The above merftioned mechanisms are different than the way statins can lower cholesterol level and they are commonly used as hipocholesterolemic medicine. Because different mechanisms are implemented both statins and fitosterols can be used in therapy of hipercholeserolemia. The people taking statins who still have increased level of total cholesterol and LDL-cholesterol in blood can include phytosterols in their diet what can lead to the decrease of its level.

Topics: Cholesterol, Dietary; Cholesterol, LDL; Diet; Enterocytes; Food, Fortified; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Margarine; Phytosterols; Yogurt

Prompted by current dietary recommendations for the control of serum cholesterol to new targets to reduce the risk of coronary heart disease (CHD), and by the CHD risk reduction claims made for certain foods or food components, studies are now being undertaken using combinations of cholesterol-lowering foods in one diet (eg, a dietary portfolio) rather than single foods to achieve more effective dietary control of serum cholesterol. This approach has increased the potential relevance of dietary therapy and may yield nutrition strategies that bridge the gap between what is regarded as a good diet and drug therapy.

Topics: Cardiovascular Diseases; Cholesterol, LDL; Coronary Disease; Diet; Dietary Fiber; Food; Health Behavior; Humans; Hypercholesterolemia; Hyperlipidemias; Lipids; Nuts; Phytosterols; Risk Factors; Risk Reduction Behavior; Soy Foods

At present, dyslipidemia is most commonly treated with lipid-altering pharmacological therapies. However, safety concerns regarding the use of these agents have prompted the need for safe and efficacious nonpharmacological lipid-altering interventions. One such natural therapy is the combination of plant sterols and endurance training. This combination lifestyle intervention has been shown to decrease total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride concentrations while increasing high-density lipoprotein (HDL) cholesterol concentrations. However, the mechanisms that underlie these positive lipid alterations have yet to be clarified. Thus, the purpose of this review is to evaluate individual effects of plant sterols and exercise training on lipid levels while attempting to elucidate the possible independent and synergistic mechanisms of action responsible for these modulations. Results reveal that plant sterols decrease both total and LDL cholesterol levels by reducing exogenous cholesterol absorption by way of cholesterol displacement in the intestinal lumen. Additionally, the intestinal membrane transport proteins, ABCG5, ABCG8, as well as NPC1L1, have also been implicated in plant sterol-mediated cholesterol lowering. Conversely, exercise decreases triglyceride levels by reducing hepatic very low-density lipoprotein secretion and increasing skeletal lipoprotein lipase activity. In addition, endurance training was shown to increase HDL cholesterol levels by way of HDL subfraction alterations, in conjunction with changing reverse cholesterol transport enzyme activities. Moreover, plant sterols and exercise may work synergistically to alter lipid levels by modulating lipoprotein transport, composition, release and metabolism. In sum, the present review lends further insight as to the metabolic benefits of adopting a healthy lifestyle, including plant sterols and endurance training, in the treatment of dyslipidemia.

Topics: Absorption; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Exercise; Humans; Hypercholesterolemia; Physical Endurance; Phytosterols; Triglycerides

A low-density lipoprotein (LDL) cholesterol goal of less than 100 mg/dl is recommended for patients at moderate to high risk of cardiovascular disease with an optional LDL goal of less than 70 mg/dl for patients at a very high risk of cardiovascular disease. Most patients will require reductions in LDL of more than 50% in order to achieve these more aggressive goals. Only a few agents will lower LDL by at least 50%. This review will focus on the efficacy and safety ezetimibe/simvastatin coadministered as a therapy with enhanced LDL-lowering efficacy, while minimizing the adverse effects of statins in a wide range of patients. Ezetimibe 10 mg/simvastatin 80 mg lowers LDL by approximately 60% and has been demonstrated to be superior to the highest doses of atorvastatin and rosuvastatin for lowering LDL and raising high-density lipoprotein.

Topics: Anticholesteremic Agents; Atorvastatin; Azetidines; C-Reactive Protein; Cardiovascular Diseases; Drug Therapy, Combination; Ezetimibe; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Lipoproteins, LDL; Phytosterols; Pravastatin; Pyrroles; Simvastatin

Topics: Anion Exchange Resins; Anticholesteremic Agents; Diet, Fat-Restricted; Dietary Fiber; Drug Combinations; Drug Monitoring; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Life Style; Liver Function Tests; Patient Selection; Phytosterols; Risk Factors; United States

The inhibition of cholesterol synthesis by a statin enhances intestinal absorption of both cholesterol and various phytosterols. The atherogenic role of phytosterols, well proven in hypersitosterolemia, is now suspected in patients with premature coronary artery disease. The cholestanol/cholesterol ratio can be used as a marker of intestinal cholesterol absorption. Individuals with elevated ratio ("high absorbers") have less favourable cholesterol-lowering response and cardiovascular protection with statin therapy as compared to individuals with low ratio ("high synthesizers"). They may benefit of an adjunct therapy with phytostanols or ezetimibe, both being capable to reduce plasma concentrations of cholesterol and of phytosterols.

Topics: Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Phytosterols

The development of cholesterol-lowering drugs (including a variety of statins, bile acid-binding resins and recently discovered inhibitors of cholesterol absorption) has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined targets for LDL cholesterol concentrations. Combination therapy with drugs that have different or complementary mechanisms of action is often needed to achieve lipid goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to conventional drug treatment and remain at high risk for the development and progression of atherosclerotic cardiovascular disease and alternative approaches are needed. The discovery and development of ezetimibe (a novel, selective and potent cholesterol absorption inhibitor) has advanced the treatment of hypercholesterolaemia. New agents including the phytostanol preparation FM-VP4 and inhibitors of acyl coenzyme A:cholesterol acyltransferase, the apical Na(+)-dependent bile acid transporter and microsomal triglyceride transfer protein may also play a future role in combination therapy. This review focuses on the recent progress in the molecular mechanisms of intestinal cholesterol absorption and transport, and novel therapeutic approaches to inhibit the cholesterol absorption process.

Topics: Acetyl-CoA C-Acyltransferase; Animals; Anticholesteremic Agents; Atherosclerosis; Azetidines; Bile Acids and Salts; Carrier Proteins; Cholesterol, Dietary; Drugs, Investigational; Ezetimibe; Humans; Hypercholesterolemia; Intestinal Absorption; Phytosterols

Phytosterols are chemical homologs of cholesterol that are found in most plant foods and are particularly abundant in vegetable oils and whole grains. They interfere with the micellar solubilization of cholesterol in the intestine and reduce the efficiency of cholesterol absorption. The net absorption of phytosterols themselves is very small and most clinical studies suggest that consumption is safe. Phytosterols naturally present in foods appear to be bioactive, but many commercial phytosterol supplements are comprised of purified crystals with limited bioavailability. Proper formulation to improve bioavailability is critical for phytosterol supplements. Phytosterols appear to be quantitatively as important to cholesterol lowering as reducing saturated fat consumption, and they provide an additional tool for regulation of circulating cholesterol through lifestyle changes.

Topics: Absorption; Cholesterol; Humans; Hypercholesterolemia; Phytosterols; Treatment Outcome

In this article we briefly review the evidence on the effect of different "natural" products on cholesterolemia. Plant stanols and sterols reduce cholesterol intestinal absorption and decrease total and LDL cholesterol by approximately 10%. Polycosanol is a mixture of saturated alcohols that seem to inhibit cholesterol hepatic synthesis and decrease total and LDL cholesterol by up to 25%. The effects on the cholestorolemia of soy and soluble fiber are modest.

Topics: Dietary Fiber; Fatty Alcohols; Glycine max; Humans; Hypercholesterolemia; Phytosterols; Plant Preparations; Sitosterols

Plant sterol-enriched foods are an effective dietary adjuvant in reducing cardiovascular risk by lowering total cholesterol and low density lipoprotein-cholesterol (LDL-C) in serum by up to approximately 15%. The mechanism of action of plant sterols is different from those of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) and thus their effect is additive. Combining plant sterols with other dietary components known to reduce cholesterol in a portfolio approach has proven to be most effective for reduction of hypercholesterolemia and provide an alternative treatment option for clinicians. Plant sterol-enriched foods provides clinicians with a relatively cheap, safe, and effective way to help patients manage their cardiovascular risk.

Topics: Animals; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Diet; Dietary Supplements; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Phytosterols; Phytotherapy; Practice Guidelines as Topic; Risk Factors

The recent discovery of transporters in the intestinal mucosa and the canalicular membrane has given new insights into the regulation of intestinal absorption as well as the biliary output of cholesterol and plant sterols. The 2 adenosine triphosphate (ATP)-binding cassette (ABC) half-transporters ABCG5 and ABCG8 are expressed in the mucosa cells and the canalicular membrane, and they resecrete sterols, especially absorbed plant sterols, back into the intestinal lumen and from the liver into bile. Defects of either of these cotransporters lead to the rare inherited disease of phytosterolemia, which is clinically defined by hyperabsorption and diminished biliary excretion of plant sterols. Furthermore, it has been recently demonstrated that the Niemann-Pick C1-Like 1 (NPC1L1) transporter is most likely responsible for the transport of cholesterol and plant sterols from the brush border membrane into the intestinal mucosa. Ezetimibe interferes with NPC1L1, reducing the intestinal uptake of cholesterol and plant sterols. These new findings contribute to our understanding of cholesterol and plant sterol concentrations in serum, and the effect of dietary and drug intervention to reduce serum concentrations of sterols.

Topics: Absorption; Anticholesteremic Agents; ATP-Binding Cassette Transporters; Azetidines; Cholesterol; Diet; Ezetimibe; Humans; Hypercholesterolemia; Membrane Proteins; Membrane Transport Proteins; Microvilli; Phytosterols; Proteins

Incorporation of plant stanol esters into margarine is among the first examples of a functional food with proven low-density lipoprotein (LDL) cholesterol-lowering effectiveness. Recently, there have been many studies on the effects of plant stanols/sterols on cholesterol metabolism. It has been found that the serum LDL cholesterol-lowering effect of plant stanols/sterols originates from reduced intestinal cholesterol absorption, a process in which changes in micellar composition are thought to play a major role. However, recent findings suggest that there is an additional process in which plant stanols/sterols actively influence cellular cholesterol metabolism within intestinal enterocytes. Furthermore, in response to the reduced supply of exogenous cholesterol, receptor-mediated lipoprotein cholesterol uptake is probably enhanced, as shown by increased LDL receptor expression. At recommended intakes of about 2 to 2.5 g/day, products enriched with plant stanol/sterol esters lower plasma LDL cholesterol levels by 10% to 14% without any reported side effects. Thus, plant stanols/sterols can be considered to be effective and safe cholesterol-lowering functional food ingredients.

Topics: Cholesterol, LDL; Humans; Hypercholesterolemia; Intestinal Absorption; Phytosterols; Phytotherapy; Sitosterols

Normal serum contains small amounts of noncholesterol sterols, including those reflecting cholesterol absorption and those that are markers of cholesterol synthesis. Absorption marker sterols include serum plant sterols, whereas cholesterol precursor sterols correlate with whole-body synthesis of cholesterol. Thus, serum noncholesterol sterols, and especially their ratios to cholesterol, can be used to evaluate the major features of cholesterol metabolism (ie, synthesis and absorption). Statin treatment reduces serum cholesterol precursors but increases serum plant sterols severalfold, especially in subjects with high-absorption marker sterol levels indicative of efficient cholesterol and sterol absorption in general. Statin therapy is most effective in subjects with high serum cholesterol precursor levels. In subjects with high-absorption sterol markers, dietary cholesterol absorption inhibition (eg, with plant stanol and sterol ester margarine) needs to be combined with a statin to achieve effective serum cholesterol reduction. However, whereas dietary plant stanol esters reduce statin-induced elevations of serum plant sterol levels, serum plant sterol levels remain elevated during dietary plant sterol ester consumption. The clinical implication of high serum plant sterol levels is under active investigation.

Topics: Cholesterol, LDL; Diet; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Phytosterols; Sitosterols

Use of plant stanols/sterols in forms that are sufficiently bioavailable for therapeutic effect should be a key element of maximal dietary therapy. This principle was recognized by National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and has been amply confirmed by experimental studies in humans. Since the introduction of statins, dietary therapy for control of elevated low-density lipoprotein (LDL) cholesterol levels has received less attention. The time has come, however, to reassert the importance of maximal dietary therapy as a cost-effective means for treatment of elevated LDL concentrations and for lifetime prevention of coronary heart disease.

Topics: Cholesterol, LDL; Combined Modality Therapy; Coronary Artery Disease; Cost-Benefit Analysis; Humans; Hypercholesterolemia; Phytosterols; Sitosterols; Treatment Outcome

Statin trials have indicated that effective reduction of serum cholesterol should last up to one year before reduced risk of cardiovascular diseases can be detected. This observation can be applied most probably also to the use of plant stanol/sterol ester spreads for the treatment of hypercholesterolemia. However, despite the fact that the two spreads lower serum cholesterol similarly in short term studies, a comparison of one year results reveals an inconsistent effect of plant sterol spread as compared with that of plant stanol spread on cholesterol concentration in both men and women. This favors the use of plant stanol ester spread for long-term lowering of serum cholesterol. Doses of about 2 g/day of plant stanols as fatty acid ester spread enhances fecal elimination of cholesterol, but not of bile acids, through inhibition of cholesterol absorption by about 40%. This lowers serum total and low density lipoprotein (LDL) cholesterol despite enhanced compensatory increase in cholesterol synthesis by about 10% and 15% as compared with control spread, respectively, and by up to 20% as compared with the baseline diet. About one-third of mildly hypercholesterolemic subjects reach an accepted cholesterol level. A small dose of statin should be added to treatment in individuals resistant to monotherapy with plant stanol ester spread. A life-long consumption of plant stanol ester spread has been predicted to lower coronary events by about 20%.

Topics: Animals; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Margarine; Models, Animal; Phytosterols

Plant sterol and stanol esters are called "functional" compounds due to their hypocholesterolemic properties. The objective of this review is to update recent findings concerning the effect of phytosterols in the blood cholesterol, emphasizing the results from experimental and human studies. The hypocholesterolemic effect is observed with the intake of 2.5g/day of phytosterols or phytostanols. Daily intake, usually of stanols, for 4 weeks has shown to to be effective in lowering blood total- as well as LDL-cholesterol by about 10%. The mechanism of action in lowering blood cholesterol comes from their structural similarity to cholesterol, hence they act by competing with cholesterol at the luminal absorption site. The adverse effects of a high intake of phytosterols and phytostanols are the lower absorption of some liposoluble vitamins and antioxidants.

Topics: Anticholesteremic Agents; Cholesterol, Dietary; Food, Fortified; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Plant Preparations; Sitosterols; Stigmasterol

Over the past decade, the possibility of using phytosterols as ingredients in functional foods has led to numerous research studies in relation to their ability to reduce blood cholesterol. Many different types of carriers have been tested, with good results. The main conclusion is that the effective doses were between 1.5 and 3g/day, leading to reductions between 8% and 15% in LDL-cholesterol. The principal mechanism of action is based on interference with the solubilisation of the cholesterol in the intestinal micelles and, thus, absorption is reduced. Work has also been done on the optimal pattern of administration, and it has been found that ingesting phytosterols in a single dose per day or between meals are equally effective methods. The only side effect is that they can interfere with the absorption of carotenoids, but this can be compensated for in the diet or by adding these compounds in appropriate carriers. It has also been reported that phytosterols have anticancer properties and act as immune system modulators. There are several possible future lines of research: alternative sources with a high phytosterol content must be found, industrial processes must be implemented which minimise their loss, phytosterols must be included in food composition tables, the potential of the different types of phytosterols must be discerned, the genetic bases of their action must be elucidated, synergic effects with other compounds must be studied, side effects must be minimised, and the effects of long-term treatment must be defined precisely.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypercholesterolemia; Phytosterols; Treatment Outcome

Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Sitosterols

Topics: Food, Fortified; Humans; Hypercholesterolemia; Myocardial Ischemia; Phytosterols; Stroke

Coronary heart disease is a major health problem in developed countries. Many studies have shown that elevated serum concentrations of total or low-density-lipoprotein cholesterol (LDL cholesterol) are high risk factors, whereas high concentrations of high-density-lipoprotein cholesterol (HDL cholesterol) or a low LDL to HDL cholesterol ratio may protect against coronary heart disease. Plant sterols and stanols derived from vegetable oils or wood pulp have been shown to lower total and LDL cholesterol levels in humans by inhibiting cholesterol absorption from the intestine. These findings may lead to new therapeutic options to treat hypercholesterolemia. In addition, phytosterols may influence cell growth and apoptosis of tumor cells. However, they can interfere with the absorption of fat soluble vitamins and carotenoids.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, HDL; Humans; Hypercholesterolemia; Molecular Structure; Phytosterols

FM-VP4 is a phytosterol analog under development by Forbes Medi-Tech for the potential treatment of hyperlipidemia and hypercholesterolemia. By March 2002, FM-VP4 had entered phase I clinical trials and phase II trials were underway by late 2002.

Topics: Animals; Cholesterol, LDL; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Molecular Structure; Phytosterols; Randomized Controlled Trials as Topic; Structure-Activity Relationship

Topics: Anticholesteremic Agents; Azetidines; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Patient Selection; Phytosterols; Treatment Outcome

The benefits of lipid lowering therapy on coronary heart disease have been clearly established in many clinical trials on primary and secondary prevention. Despite the availability of potent lipid lowering drugs, many patients do not reach the current treatment goals. This paper reviews new therapeutic approaches in lipid lowering drugs focusing on compounds which lower cholesterol absorption. The role of plant sterols and stanols, new acyl-CoA:cholesterol O-acyl transferase (ACAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, and ezetimibe are summarised. Although the lipid lowering effect of plant sterols and plant stanols is only moderate, their use as functional foods is beneficial for patients with mild hypercholesterolaemia and is able to enhance the lipid lowering effect of HMG-CoA reductase inhibitors (statins). The role of ACAT inhibitors that might also inhibit cholesterol absorption remains unclear. Avasimibe, the first oral bioavailable ACAT inhibitor, has entered phase III trials. However, the presently available data in humans do not indicate a clear clinical benefit. The role of MTP inhibitors, which exhibit remarkable effects on all plasma lipids, also remains unclear, as safety concerns must first be addressed. Ezetimibe, the first available 2-azetidinone, succeeded in phase III trials showing remarkable effects in inhibition of cholesterol absorption as well as cholesterol lowering. The synergistic effect of co-administration of ezetimibe with statins seemingly offers a new approach in reaching the therapeutic goals.

Topics: Anticholesteremic Agents; Azetidines; Cholesterol; Clinical Trials as Topic; Drug Synergism; Ezetimibe; Humans; Hypercholesterolemia; Phytosterols; Sterol O-Acyltransferase; Sterol O-Acyltransferase 2; Structure-Activity Relationship

Topics: Anticholesteremic Agents; Cholesterol, LDL; Diet; Humans; Hypercholesterolemia; Phytosterols

Topics: Anticholesteremic Agents; Cholesterol, LDL; Coronary Disease; Diet, Fat-Restricted; Feeding Behavior; Humans; Hypercholesterolemia; Nutritional Requirements; Phytosterols; Practice Guidelines as Topic; Risk Reduction Behavior; United States

Topics: Anticholesteremic Agents; Azetidines; Cholesterol, LDL; Cholestyramine Resin; Combined Modality Therapy; Drug Therapy, Combination; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Margarine; Phytosterols

Statins effectively inhibit cholesterol synthesis and are currently the most commonly used drugs for the treatment of hypercholesterolemia. However, patients with familial hypercholesterolemia and those unwilling to take, or who cannot tolerate statins, and patients with combined hyperlipidemia require a combination treatment. Statins combined with cholesterol malabsorption, caused, e.g., by plant stanol esters or ezetimibe (Schering-Plough Corp/Merck & Co Inc), or with bile acid malabsorption, caused by bile acid binding resins or guar gum, inhibit compensatory increases in cholesterol synthesis and effectively lower LDL cholesterol levels. Combination therapy of statins with fibrates should be controlled by lipidology experts. Recent information on indications and advantages of combining statins with n-3 fatty acids, hormone replacement therapy, or niacin, will also be discussed.

Topics: Animals; Drug Therapy, Combination; Hormone Replacement Therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Phytosterols

Plant sterols have recently been recommended by the National Cholesterol Education Panel for use with the more traditional approaches of limiting saturated fat and cholesterol intakes, maintaining a healthy body weight and engaging in regular exercise, as a non-pharmacological approach to reduce low-density lipoprotein cholesterol levels. Recent data confirm the original observation that approximately 1.6 g of plant sterol esters per day results in a maximal low-density lipoprotein cholesterol lowering of approximately 10%. Few side-effects of plant sterols have been reported, with the exception of decreased levels of circulating carotenoids.

Topics: Absorption; Anticholesteremic Agents; Carotenoids; Cholesterol, LDL; Humans; Hypercholesterolemia; Lipids; Phytosterols; Treatment Outcome

Blood cholesterol levels are affected by diet and in particular by the type and amount of fat intake. In recent years, vegetable oil spreads containing plant sterols/stanols (as their fatty acid esters) have been developed. Numerous clinical trials on spreads with added plant sterols/stanols have shown that they have much greater cholesterol-lowering properties than conventional vegetable oil spreads. Plant sterols decrease both dietary and biliary cholesterol absorption in the small intestine, with a consequential increase in excretion of cholesterol. It is also recognized that plant sterol/stanol-enriched, cholesterol-lowering spreads, if consumed regularly, may induce a 10-20% decrease in plasma carotenoids, adjusted for changes in plasma lipids. A 10-20% decrease in plasma carotenoids falls well within the seasonal variation observed in individuals. Our current understanding of the physiological functions of carotenoids does not indicate any health risk associated with the slight decrease in their blood levels due to the intake of plant sterol/stanol. The questions that have been raised, though, are how plant sterols/stanols affect plasma carotenoid levels, and in addition, what quantity of fruits and vegetables (the richest dietary sources of carotenoids) would have to be consumed to improve plasma carotenoid levels? The current mini-review covers the cholesterol-lowering effect of plant sterols, their mechanisms of action and effect on blood carotenoids, and concludes with the potential heath benefits of daily intake of plant sterol-enriched spreads.

Topics: Anticholesteremic Agents; Antioxidants; Carotenoids; Cholesterol; Cholesterol, LDL; Dietary Fats; Fruit; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Sitosterols; Vegetables

Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. They are absorbed only in trace amounts but inhibit the absorption of intestinal cholesterol including recirculating endogenous biliary cholesterol, a key step in cholesterol elimination. Natural dietary intake varies from about 167-437 mg/day. Attempts to measure biological effects in feeding studies have been impeded by limited solubility in both water and fat. Esterification of phytosterols with long-chain fatty acids increases fat solubility by 10-fold and allows delivery of several grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester reduces low density lipoprotein cholesterol by 10%, and little difference is observed between Delta(5)-sterols and 5alpha-reduced sterols (stanols). Phytosterols can also be dispersed in water after emulsification with lecithin and reduce cholesterol absorption when added to nonfat foods. In contrast to these supplementation studies, much less is known about the effect of low phytosterol levels in the natural diet. However, reduction of cholesterol absorption can be measured at a dose of only 150 mg during otherwise sterol-free test meals, suggesting that natural food phytosterols may be clinically important. Current literature suggests that phytosterols are safe when added to the diet, and measured absorption and plasma levels are very small. Increasing the aggregate amount of phytosterols consumed in a variety of foods may be an important way of reducing population cholesterol levels and preventing coronary heart disease.

Topics: Cholesterol; Dietary Supplements; Humans; Hypercholesterolemia; Intestinal Absorption; Phytosterols; Plants; Safety

Topics: Dietary Fiber; Dietary Supplements; Fish Oils; Food, Organic; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Probiotics; Soybean Proteins

Phytosterol-enriched margarines are a recent addition to the list of so-called 'functional foods'. The ingestion of phyto-sterols lowers the serum cholesterol by inhibiting intestinal uptake of the sterol. The phytosterols available in consumer products are comprised predominantly of beta-sitosterol and sitostanol. The esterified form of these phytosterols increases their solubility and enhances their residence time in the small intestine. Their ability to displace cholesterol from micelles in the small intestine underlies the mechanism that inhibits cholesterol absorption, leading to a 10% reduction in total serum cholesterol. Numerous well designed studies have documented the beneficial actions of these phytosterols on serum cholesterol.

Topics: Cholesterol; Humans; Hypercholesterolemia; Intestinal Absorption; Phytosterols

Although plant sterols (phytosterols) were chemically described in 1922, their biological role in human and animal health has been underestimated. Their ability to control cholesterol plasma levels in hypercholesterolimic patients was first described in 1983 when the structure of phytosterols implied that they could, by steric hindrance, inhibit the absorption of cholesterol from our diets. This has led to the development of functional foods containing high contents of these plant molecules or their esters as cholesterol controlling foods. Over the last 15 years, however, several reports have appeared in the literature indicating that phytosterols have some immunological activity as highlighted in animal models of inflammation or even in in-vitro and in-vivo models of cancer (colorectal and breast cancer). These findings were paralleled by epidemiological studies correlating the reduced risk of numerous diseases and the dietary intake of phytosterols. It is only in the last 10 years, however, that their direct immune modulatory activity on human lymphocytes has been proven and the mechanism of action in cancer cells has been elucidated. The use of phytosterols as supportive therapies in certain chronic conditions has been tested under clinical trial conditions. This review presents a summary of the in-vitro and in-vivo studies published to date.

Topics: Adjuvants, Immunologic; Animals; Cholesterol; Disease Models, Animal; HIV Infections; Humans; Hypercholesterolemia; Immune Tolerance; Intestinal Absorption; Neoplasms; Phytosterols; Phytotherapy; Sitosterols; Tuberculosis, Pulmonary; Tumor Cells, Cultured

The intake of one tub of margarine with added phytosterols per week has been shown to reduce plasma total and low density lipoprotein (LDL) cholesterol levels by 9 and 13% respectively, with no effect on high density lipoprotein (HDL) cholesterol or triglyceride levels. This reduction in cholesterol concentration may help to decrease the risk of coronary heart disease by 20 to 50%. No significant side effects have been reported. Phytosterols reduce cholesterol levels by inhibition of cholesterol absorption in the intestine. The margarines with added phytosterols are an example of functional foods (novel foods) which are designed to enhance health or contribute to reduction in a specific disease risk. In 1997, the European Union has introduced rules for the evaluation of novel foods, the Novel Food Regulatory Approval Procedure. Post-marketing surveillance of functional foods is obligatory to control long term safety and efficacy.

Topics: Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; European Union; Food, Fortified; Humans; Hypercholesterolemia; Phytosterols; Product Surveillance, Postmarketing; Triglycerides

Topics: Cholesterol; Diet, Fat-Restricted; Humans; Hypercholesterolemia; Hypolipidemic Agents; Margarine; Phytosterols; Sitosterols

Because atherosclerosis is a continuous process throughout life, expert panels have suggested guidelines to reduce the risk of cardiovascular disease, starting from childhood. The guidelines focus on population-based measures and on treating hypercholesterolaemia in individual children. Low-fat diets in children have been widely debated. There is little evidence that growth is stunted or that nutritional deficiencies arise if the energy that is lost by limiting fat intake is substituted with other nutrients. Dietary fibre, plant sterols and fish oils have been used to modify lipid levels in children; however, the efficacy of these dietary adjuncts is limited. Bile acid-binding resins are the only approved drugs to lower cholesterol levels in children and appear to be well tolerated. However, compliance with resins is low because of unpalatability, so low dosages are preferred and vitamin supplementation is prudent. Data on HMG CoA reductase inhibitors and fibrates are insufficient to recommend these drugs at present. Drug treatment should be restricted to children who are at exceptionally high risk of disease, usually those with genetic dyslipidaemias.

Topics: Anion Exchange Resins; Anticholesteremic Agents; Bile Acids and Salts; Binding Sites; Child; Child, Preschool; Cholesterol; Diet, Fat-Restricted; Dietary Fiber; Female; Fish Oils; Guidelines as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Infant; Male; Phytosterols; Risk Assessment

Topics: Diabetes Mellitus, Type 2; Humans; Hypercholesterolemia; Lipoproteins; Phytosterols; Sensitivity and Specificity; Structure-Activity Relationship

Topics: Animals; Arteriosclerosis; Diet, Atherogenic; Dietary Fats; Dietary Fiber; Dietary Proteins; Humans; Hypercholesterolemia; Phytosterols; Plant Proteins; Plants, Edible

Topics: Adult; Cholesterol; Female; Genes, Recessive; Humans; Hypercholesterolemia; Intestines; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Sitosterols; Sterols; Stigmasterol; Tendons; Xanthomatosis

Topics: Cacao; Cholesterol; Cholesterol, Dietary; Coronary Disease; Dietary Fats; Evaluation Studies as Topic; Fatty Acids; Fatty Acids, Essential; Fatty Acids, Unsaturated; Helianthus; Humans; Hydrogenation; Hypercholesterolemia; Male; Mathematics; Oils; Phytosterols; Seeds; Structure-Activity Relationship; Zea mays

Topics: Animals; Butter; Cholesterol; Cocos; Diet; Dietary Fats; Evaluation Studies as Topic; Fats; Fats, Unsaturated; Fatty Acids; Fatty Acids, Essential; Female; Glycine max; Humans; Hydrogenation; Hypercholesterolemia; Male; Margarine; Oils; Phytosterols; Seeds; Structure-Activity Relationship; Triglycerides; Zea mays

The consumption of 2 g/d plant sterols (PSs) reduces circulating LDL cholesterol by ≤10%. The degree of LDL cholesterol lowering was associated with specific apolipoprotein E [APOE, Reference SNP (rs)429358] and cholesterol 7α-hydroxylase (CYP7A1, rs3808607) genosets in previous post hoc analyses of randomized controlled trials. However, because post hoc analyses do not conform to the randomization model, there is a greater potential that the findings could be due to type I error, thus warranting validation through an a priori-designed intervention trial.. The GenePredict Plant Sterol study (GPS) was designed to validate associations of LDL cholesterol lowering with specific APOE and CYP7A1 genosets through a priori recruitment of individuals carrying prespecified genosets.. A 2-center, double-blind, placebo-controlled, randomized 2-period crossover dietary intervention with 2 g/d PS for 28 d with a minimum 28-d washout was undertaken from July 2017 to December 2019. A priori recruitment of individuals with slightly elevated LDL cholesterol was based on genosets of APOE isoforms and CYP7A1 rs3808607. Randomization was performed with stratification by sex and genoset.. The recruitment target of 64 participants with prespecified genosets could not be reached, despite the screening of 477 individuals; 42 participants completed the intervention trial. Reductions in LDL cholesterol were similar across all 3 genosets (-0.298 ± 0.164, -0.357 ± 0.115, -0.293 ± 0.109 mmol/L; P = 0.0002 overall; P = 0.9126 for treatment × genoset), providing evidence that the shortfall in recruitment might not have stopped the trial from meeting the objective.. APOE and CYP7A1 genotypes did not influence the efficacy of LDL cholesterol reductions upon dietary intervention with PSs. Findings of previous post hoc analyses could not be validated in a trial using a priori genotype-based recruitment. Obtaining adequate numbers of participants is challenging in trials using genoset-based recruitment, even for common variants.

Topics: Apolipoproteins E; Cholesterol 7-alpha-Hydroxylase; Cholesterol, LDL; Humans; Hypercholesterolemia; Phytosterols

To evaluate the effect of phytosterol capsule supplementation associated with the National Cholesterol Education Program (NCEP) Step 2 diet on LDL-C levels in children and adolescents with dyslipidemia.. The rate of change for LDL-C was not different between intervention and control groups (p=0.30). No significant reduction was also observed for TC (p=0.47), HDL-C (p=0.97), insulin (p=0.27), triglycerides (p=0.38), systolic blood pressure (p=0.11), and diastolic blood pressure (p=0.57) compared to control group. Although we observed a high adherence to the capsule intake (95.7% in phytosterol and 93.8% in the control group), the low adherence to the diet may have contributed to explaining the results.. Daily phytosterol capsules supplementation associated with the NCEP Step 2 diet did not reduce LDL-cholesterol concentrations in children and adolescents with dyslipidemia.

Topics: Adolescent; Child; Cholesterol; Cholesterol, HDL; Cross-Over Studies; Diet; Dietary Supplements; Double-Blind Method; Dyslipidemias; Humans; Hypercholesterolemia; Phytosterols

Most studies focused on the benefits of lycopene on serum lipids but no studies have been specifically designed to assess the role of a tomato sauce from vine-ripened tomatoes on patients affected by polygenic hypercholesterolemia. The aim of this study was to compare the lipid-lowering effect of a novel functional tomato sauce with a well-known functional food with a lipid-lowering effect, i.e. a sterol-enriched yogurt.. In this cross-over study, we evaluated a population of 108 ambulatory patients affected by polygenic hypercholesterolemia of both gender, who were allocated to a tomato sauce (namely OsteoCol) 150 ml/day or a sterol-enriched yogurt (containing sterols 1.6 g/die) treatment, for 6 weeks. Carotenoids content was 3.5 mg per gram of product. We measured serum lipids and creatinine and transaminases at basal and follow-up visit.. A total of 91 subjects completed the protocol. A significant difference in LDL-cholesterol change was found between participants taking yogurt, tomato sauce (high adherence) and tomato sauce (low adherence) (- 16; - 12; + 8 mg/dl respectively; p < 0.001). We found a greater LDL-cholesterol reduction in the participants with a basal LDL-cholesterol more than 152 mg/dl (15% for sterol-enriched yogurt and 12% for tomato sauce at high adherence).. A novel functional tomato sauce from vine-ripened tomatoes compares favourably with a commercialised sterol-enriched yogurt in term of absolute LDL-cholesterol change. Intake of a tomato sauce with a high carotenoid content may support treatment of patients affected by common hypercholesterolemia. The present study has various limitations. The presence of other dietary components, which may have influenced the results, cannot be ruled out. Of course, these results cannot be extrapolated to other populations. Furthermore, there was a low adherence rate in the tomato sauce group. Moreover, we did not report serum carotenoids data.. ID: 13244115 on the ISRCTN registry, retrospectively registered in 2019-5-14. URL: http://www.isrctn.com/ISRCTN13244115.

Topics: Cross-Over Studies; Humans; Hypercholesterolemia; Lipids; Phytosterols; Solanum lycopersicum

Phytosterols reduce intestinal cholesterol absorption and help to lower LDL-cholesterol. Many Chinese adults are lactose-intolerant and cannot tolerate bovine milk enriched with phytosterol. Soya-milk is a common beverage in Asia and it has beneficial effects on general health. We therefore conducted a randomized double-blind controlled trial to assess the effectiveness of a phytosterols-enriched soya drink in lowering serum LDL-cholesterol level (primary outcome) and other cardiovascular parameters (secondary outcomes).. One hundred and fifty-nine normocholesterolaemic participants (85 men and 74 women; aged 19-79) were randomized to daily intake of one serving of phytosterols-enriched soya drink (N = 82), equivalent to 2 g of phytosterol per day, or a matched soya drink without phytosterols (N = 77) for 3 weeks. Adverse events, withdrawal and compliance were documented.. Among the treatment group (N = 82), phytosterols-enriched soya drink significantly decreased LDL-cholesterol by 5.96% (SE 1.48, 95% CI - 8.91%, - 3.00%) with a median of 6.74% compared with baseline, resulting in a significant reduction of 4.70% (95% CI - 8.89%, - 0.51%; p = 0.028) with a median of 5.20% compared with placebo (N = 77). In contrast, there were no significant changes in other lipid parameters, blood glucose, blood pressure, body weight or waist circumference. Remarkably, 95% of the participants randomized to the fortified drink reported no adverse events at all.. Daily consumption of a phytosterols-enriched soya drink may be a simple and cost-neutral means of lowering LDL-cholesterol in individuals in China, with massive population and rising incidence of coronary heart disease (ClinicalTrials.gov identifier: NCT02881658; date of registration: 14 Aug 2016).

Topics: Adult; Animals; Asia; Cattle; China; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Male; Phytosterols

Fish oil (FO)-based lipid emulsions (LEs) have been reported to prevent hepatic dysfunction in patients treated with parenteral nutrition (PN). We studied patients with alterations of γ-glutamyl transferase (GGT) associated with the administration of PN containing olive/soybean (O/S)-based LE. The aim of this study was to determine whether the strategy of reducing the lipid dose by 50%, by changing to an FO-based LE, reduced plasma levels of phytosterols (PS) and GGT more effectively and safely, than the strategy of reducing lipid contribution by 50% while maintaining the same LE composition.. A randomized double-blind clinical trial was carried out in patients with normal initial GGT, who after a minimum of 1 wk of daily PN (0.8 g/kg of O/S-based LE) presented with GGT values twice the upper normal value. At the time of randomization 1:1, lipids were reduced to 0.4 g/kg daily. Group A maintained O/S LE and group B changed to FO LE. The primary endpoints were reduction of plasmatic PS and GGT on day 7 after randomization, performed in the study population per protocol by Student's t test and simple linear regression. Secondary outcomes included alkaline phosphatase (AP), alanine transaminase (ALT), and total bilirubin (BIL), and safety variables.. Nineteen patients were included. On day 7 after randomization, GGT and AP values were higher in the O/S group (n = 10; GGT: median [Med], 4.99; interquartile range [IQR], 4.09; AP: Med, 2.59 μkat/L; IQR 1.74) than in the FO group (n = 9; GGT: Med, 2.26 μkat/L; IQR, 1.07; AP: Med, 1.2 μkat/L; IQR 1.44). Although there were no differences in ALT and BIL values, the ALT decrease was larger and more statistically significant in the FO group than in the O/S group (P = 0.009). Total PS (Med, 21.10 μg/mL; IQR, 5.50) in the O/S group was higher than in the FO group (Med, 13.4 μg/mL; IQR, 10.65; P = 0.002). Significant decreases in PS and their fractions were observed, with the exception of campesterol and stigmasterol.. Plasma accumulation of PS and high values of GGT, AP, and ALT can be prevented with the exclusive administration of FO-based LE.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Bilirubin; Double-Blind Method; Fat Emulsions, Intravenous; Female; Fish Oils; gamma-Glutamyltransferase; Humans; Hypercholesterolemia; Intestinal Diseases; Linear Models; Lipid Metabolism, Inborn Errors; Liver; Liver Function Tests; Male; Middle Aged; Parenteral Nutrition; Phytosterols; Plant Oils; Prospective Studies; Treatment Outcome

Experimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 ± 12 years; LDL-c ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (

Topics: Adult; Aged; Apolipoproteins B; Atherosclerosis; Biomarkers; Brazil; C-Reactive Protein; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Endothelin-1; Female; Humans; Hypercholesterolemia; Inflammation; Lipids; Male; Middle Aged; Phytosterols; Plasma; Soy Milk; Sterols; Triglycerides

The primary and secondary objectives were to investigate the triglyceride (TG) and LDL-cholesterol (LDL-C) lowering effects of a spread with added plant sterols (PS) and fish oil as compared to a placebo spread.. This study had a randomized, double-blind, placebo-controlled, parallel group design with two intervention arms. Following a 2-week placebo run-in period, 260 healthy individuals with modestly elevated blood TG (≥ 1.4 mmol/L) and LDL-C (≥ 3.4 mmol/L) concentrations consumed either the placebo or intervention spread for 4 weeks. The intervention spread contained 2.0 g/day PS and 1.0 g/day eicosapentaenoic acid (EPA) + docosahexanoic acid (DHA) from fish oil. Fasting serum lipids and apolipoproteins (Apo) (exploratory) were measured at the end of the run-in and intervention phases.. Four-week consumption of the intervention spread resulted in significantly lower TG (- 10.6%, 95% CI - 16.0 to - 4.9%; P < 0.001) and LDL-C concentrations (- 5.2%; 95% CI - 7.8 to - 2.4%) as compared to placebo. Total cholesterol (- 3.9%; 95% CI - 6.1 to - 1.5%), non-HDL-C (- 5.4%; 95% CI - 8.1 to - 2.7%), remnant-cholesterol (- 8.1%; 95% CI - 3.4 to - 12.5%), ApoAII (- 2.9%; 95% CI - 5.5 to - 0.2%), ApoCIII (- 7.7%; 95% CI - 12.1 to - 3.1%) and ApoB (- 3.2%; 95% CI - 5.9 to - 0.4%) concentrations were also significantly lower, as compared to placebo. No significant treatment effects were found for HDL-cholesterol, ApoAI, ApoCII, Apo E or ApoB/ApoAI.. Four-week consumption of the intervention spread led to significant and clinically relevant decreases in serum TG, LDL-C and other blood lipid concentrations. The study was registered at clinicaltrials.gov (NCT02728583).

Topics: Adolescent; Adult; Aged; Cholesterol, LDL; Double-Blind Method; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Hypercholesterolemia; Hypertriglyceridemia; Male; Phytosterols; Triglycerides; Young Adult

We previously demonstrated that the combination of phytosterols (PS) and curcumin administered as dietary supplements significantly lowers LDL-cholesterol (LDL-C) more than either treatment alone. The aim of this study was to investigate the effects of this combination in a novel food (bread) on plasma lipid profiles in hypercholesterolaemic individuals. In a double-blinded, placebo-controlled, 2 × 2 factorial trial, participants were randomised to receive bread fortified with placebo (PL), 2.3 g PS (PS), 228 mg curcumin (CC) or a combination of 2.3 g PS and 228 mg CC (PS-CC) daily for four weeks. Primary outcomes were fasting plasma lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)] and secondary outcomes were plasma LDL-particle (LDL-P) profile: LDL-P number and LDL-P size. Cardiovascular disease (CVD) risk (Framingham Risk Algorithm) was also explored. There was no significant difference between PL and CC or PS and PS-CC on blood lipids or CVD risk; therefore, groups were pooled for final analysis: the PL and CC group (PL-C, n = 36) and the PS and PS-CC group (PS-C, n = 39). PS-C significantly lowered TC (-0.52 mmol L-1, p < 0.0001), LDL-C (-0.49 mmol L-1, p < 0.0001) and CVD risk (-1.1 absolute %, p = 0.0005) compared to the PL-C group. Reductions from baseline in the PS-C group compared to that in the PL-C group were 7.6% and 10.6% for TC and LDL-C, respectively, and statistically significant (p < 0.0001). CVD-risk in the PS-C group reduced significantly (-12.7%) compared to that in the PL-C group (p = 0.0005). HDL-C and TG remained unchanged. The LDL-P number significantly decreased in the PS-C group by 124.33 nmol L-1 compared to that in the PL-C group (p = 0.005) and both groups showed a significant decrease in LDL-P size (p < 0.01); however, the absolute nm change in LDL-P size did not differ between groups and the percent change in LDL-P size in the PS-C group was borderline significant (-0.89%, p = 0.05) compared to that in the PL-C group. Regular consumption of PS-enriched bread with or without curcumin lowers blood cholesterol; however, curcumin alone did not influence blood lipids. Bread may be a convenient means of delivering PS with greater compliance for reducing the blood cholesterol concentration.

Topics: Adolescent; Adult; Aged; Australia; Bread; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Female; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Phytosterols; Triglycerides; Young Adult

Evidence from healthcare professionals suggest that consumer compliance to healthy diet and lifestyle changes is often poor. The present study investigated the effect of advice provided by a physician or dietitian on consumer adherence to these measures combined with consuming foods with added plant sterols (PS) with the aim of lowering low-density lipoprotein cholesterol (LDL-C).. One hundred mildly-to-moderately hypercholesterolaemic individuals were enrolled into a parallel, randomised, placebo-controlled study. Dietitians (dietitian group; DG) advised 50 individuals in six weekly face-to-face behavioural therapy sessions, whereas the other 50 received standard advice from physicians (physician group, PG). Both groups consumed foods with added PS (three servings a day) for 6 weeks. Subsequently, all individuals were followed-up for another 6 weeks under real-life conditions. Blood lipids were measured at baseline and weeks 6 and 12 and 3-day diet diaries were taken at weeks 1, 6 and 12.. Individuals in the DG significantly improved their dietary habits, physical activity and increased PS intake compared to the PG. After 6 weeks, LDL-C decreased in both groups compared to baseline without any significant differences between groups. At week 12, LDL-C was further significantly improved only in the DG (P = 0.006) compared to week 6. Total cholesterol, LDL-C and triglycerides were significantly lower in the DG compared to the PG at week 12 after adjusting for levels at week 6 (P < 0.001, P < 0.001 and P = 0.009, respectively).. Although structured counselling by dietitians and common standard advice by physicians were equally effective with respect to improving blood cholesterol after 6 weeks, dietitians were more effective in the longer-term (i.e. 6 weeks after the end of the intervention period).

Topics: Adult; Behavior Therapy; Cholesterol, LDL; Consumer Behavior; Counseling; Diet; Diet Records; Dietetics; Exercise; Feeding Behavior; Female; Health Behavior; Humans; Hypercholesterolemia; Life Style; Male; Nutritionists; Patient Compliance; Patient Education as Topic; Physicians; Phytosterols; Triglycerides

Dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatory effects in preclinical studies, however, consistent findings in humans are lacking.. Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatory effects to optimise cardio-protection. The objective of this trial was to investigate the effects of dietary intervention with PS with or without curcumin on blood lipids (primary outcome) in hypercholesterolaemic individuals.. A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d-200 mg/d respectively) for four weeks. Primary outcomes included fasting total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fasting blood glucose concentrations.. Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC, LDL-cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC and LDL-cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC and LDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) and LDL-cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and TG concentrations remained unchanged across all groups. No adverse side effects were reported.. The addition of curcumin to phytosterol therapy provides a complementary cholesterol-lowering effect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhanced lipid-lowering and compliance in hypercholesterolaemic individuals. ANZCTR identifier: 1261500095650.

Topics: Anticholesteremic Agents; Cholesterol; Curcumin; Double-Blind Method; Drug Interactions; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Treatment Outcome; Triglycerides

The hypocholesterolemic effect and the modification of serum biomarkers of a dietary plant sterol (PS) intake, cholesterol precursors and cytokines after the consumption of milk-based fruit beverages with a milk fat globule membrane were evaluated by a randomized, double-blind, crossover, multiple dose bioavailability study. Postmenopausal women (n = 38) consumed daily 250 mL of a beverage with or without 2 g of PS added during 6 weeks in each of the study periods. With the intake of the PS-added beverage, significant decreases (mg dL-1) in serum total cholesterol (pre-treatment: 220.0 ± 27.8 vs. post-treatment: 212.9 ± 25.8; p < 0.05) and LDL-cholesterol (129.4 ± 28.5 vs. 121.7 ± 24.4; p < 0.05) were detected. The cholesterol precursor lathosterol (11.2%), markers of the dietary PS intake (campesterol 43.1% and β-sitosterol 32.5%), and anti-inflammatory IL-10 cytokine (22.5%) increased significantly, with a concomitant significant reduction in pro-inflammatory IL-1β (6.7%). No variations in HDL-cholesterol, other sterols (desmosterol and stigmasterol) or cytokines (IL-6, IL-8, IL-12p70 and TNF-α) were detected. These results indicated that this kind of PS-enriched milk-based fruit beverage is suitable during the period of clinical intervention, and its consumption may be an adequate way to improve PS functionality since a significant reduction in cholesterol levels has been observed. Therefore, the intake of this beverage could contribute to reduce the risk of cardiovascular disease also obtaining a beneficial effect on the serum inflammatory status in postmenopausal women.

Topics: Anticholesteremic Agents; Beverages; Cholesterol, HDL; Cholesterol, LDL; Cytokines; Double-Blind Method; Female; Glycolipids; Glycoproteins; Humans; Hypercholesterolemia; Lipid Droplets; Lipids; Middle Aged; Phytosterols; Postmenopause

To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE).. Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE.. EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE.. In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status.. ClinicalTrials.govNCT01584206.

Topics: Adolescent; Adult; Anticholesteremic Agents; Cholestanol; Cholestenones; Cholesterol; Ezetimibe; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Phytosterols; Sitosterols; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult

Phytosterols found naturally in plants are known to reduce cholesterol absorption in the gut. The traditional southern Chinese diet typically contains many vegetables and not much meat, and there is high prevalence of lactose intolerance in Chinese; we therefore aimed to test if phytosterols-enriched milk is effective in lowering serum LDL-cholesterol in Chinese. Two hundred and twenty-one participants (41 men and 180 women; age 24-79) without cholesterol-lowering drugs or diabetes mellitus were randomized to daily intake of phytosterols-enriched low-fat milk which contained 1.5 g phytosterols per day (N = 110) or a conventional low-fat milk (N = 111) for three weeks. Fasting bloods were taken before and at the end of the study for the measurement of lipid and glucose profile. Physical examination was also performed. Comparing treatment with control, treatment group had significant decrease in serum LDL-cholesterol level (9.5 ± 2.0%; p < 0.0001). Phytosterols intake also decreased total cholesterol (P < 0.0001) and diastolic blood pressure (P = 0.01). Consumption of a phytosterols-enriched low-fat milk led to a significant fall in LDL-cholesterol, total cholesterol, and diastolic blood pressure in Chinese. This can be recommended as part of a healthy diet for people. (ClinicalTrials.gov identifier: NCT02541201; Date of registration: 26 Aug 2015).

Topics: Adult; Aged; Animals; Anticholesteremic Agents; Asian People; Cholesterol; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Milk; Phytosterols; Young Adult

To study the effect of milk enriched with phytosterol ester on blood cholesterol.. Participants with hypercholesterolemia were recruited from community health center and randomly assigned to 3 groups: milk enriched with phytosterol ester group( PS group, n = 59), normal milk group( n = 58) and non-dairy group( n = 62). The intervention lasted for 2 months. At baseline, all subjects in the 3groups received health education on prevention and control of hypercholesterolemia. For PS and normal milk groups, subjects consumed 500 g milk per day, the intake ofphytosterol in PS group was 1. 58 g / d. For non-dairy group, subjects did not consume any dairy products during the trial. Subjects were assessed on their physical activity level and blood cholesterols were measured during monthly follow-up.. Finally 157 subjects completed the trial. By the end of the first month, the TC and LDL-C levels of PS group were significantly lower than that of normal milk group. After adjustment, there was no significant difference between baseline and 1-month TC levels in PS group. The levels of TG and HDL-C in PS group were significantly increased while the LDL-C level was significantly decreased after 1-month intervention. Compared with normal milk and nondairy groups, no differences were observed for these four indicators. After 2-month intervention, the TC and LDL-C levels of PS group were significantly lower than that of normal milk and non-dairy groups. The levels of TC and LDL-C in PS group were significantly reduced compared to baseline levels after adjustment. TG level was increased while HDL-C level was unchanged. Compared with normal milk and non-dairy groups, the levels of TC and LDL-C in PS group were significantly declined while no significant difference was observed for TG and HDL-C levels.. s Milk enriched with phytosterol ester has a notable effect on lowering TC and LDL-C levels in subjects with hypercholesterolemia.

Topics: Animals; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Humans; Hypercholesterolemia; Milk; Phytosterols

Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, the impact of cholesterol synthesis and absorption on changes in plasma PS is explored.. The study was a double-blind, randomized, placebo-controlled, parallel-group study with the main aim to investigate the effects of PS on vascular function (clinicaltrials.gov: NCT01803178). Hypercholesterolemic but otherwise healthy men and women (n = 240) consumed low-fat spreads without or with added PS (3 g/d) for 12 weeks after a 4-week run-in period. Blood sampling was performed at week 0, 4, 8 and 12. Basal cholesterol-standardized concentrations of lathosterol and sitosterol + campesterol were used as markers of cholesterol synthesis and absorption, respectively. In the PS group, plasma sitosterol and campesterol concentrations increased within the first 4 weeks of intervention by 69% (95%CI: 58; 82) starting at 7.2 μmol/L and by 28% (95%CI: 19; 39) starting at 11.4 μmol/L, respectively, and remained stable during the following 8 weeks. Placebo-corrected increases in plasma PS were not significantly different between high and low cholesterol synthesizers (P-values >0.05). Between high and low cholesterol absorbers, no significant differences were observed, except for the cholesterol-standardized sum of four major plasma PS (sitosterol, campesterol, brassicasterol and stigmasterol) showing larger increases in low absorbers (78.3% (95%CI: 51.7; 109.5)) compared to high absorbers (40.8% (95%CI: 19.9; 65.5)).. Increases in plasma PS stabilize within 4 weeks of PS intake and do not seem impacted by basal cholesterol synthesis or absorption efficiency. This study was registered at clinicaltrials.gov (NCT01803178).

Topics: Adult; Aged; Cholestadienols; Cholesterol; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Lipid Metabolism; Male; Middle Aged; Phytosterols; Prospective Studies; Sitosterols; Stigmasterol

Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE). Mild to moderate hyperlipidemic patients (n = 170) were recruited from different communities and treated with placebo soy milk powder or 3.4 g PS esters-enriched soy milk powder (2.0 g/d free PS in 30 g soy milk powder). The fasting serum lipid profiles at the baseline and after 3 and 6 months of intervention were measured. The ApoE genotype was also determined. After 3 months of PS intervention, the serum lipid profile was not changed significantly in either group. The serum total cholesterol, low-density lipoprotein cholesterol, and non- high-density lipoprotein cholesterol levels decreased by 9.3%, 11.4%, and 12.6%, respectively, in the PS group at the end of the intervention (6 months) compared with the control group, whereas the serum high-density lipoprotein cholesterol and triglyceride levels were not affected significantly. In the PS group, both the ApoE3 and ApoE4 carriers had a similar response to PS consumption. These findings suggested that PS-fortified soy milk powder was effective in lowering the serum cholesterol levels in older Chinese volunteers with mild to moderate hypercholesterolemia in both the ApoE3 and ApoE4 carriers.

Topics: Aged; Apolipoproteins E; China; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Esters; Female; Food, Fortified; Food, Preserved; Genotype; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Placebos; Soy Milk; Triglycerides

To assess if ezetimibe (EZE), a sterol-absorption inhibitor, improves platelet (PLT) count and size relative to its effect on plasma plant sterol (PS) in patients with sitosterolemia (STSL).. Patients with STSL (5 males, 3 females, 16-56 years of age) receiving EZE intervention as part of their routine care participated in this study. EZE was discontinued for 14 weeks (off) and then resumed for another 14 weeks (on). Hematology variables along with plasma and red blood cells (RBC) PS and total cholesterol (TC) levels were measured at the end of each phase.. EZE increased PLT count (23% ± 9%) and decreased mean PLT volume (MPV; 10% ± 3%, all P < .05). In patients off EZE, PLT counts inversely correlated (r = -0.96 and r = -0.91, all P < .01) with plasma and RBC PS to TC ratio (PS/TC), and MPV positively correlated (r = 0.91, P = .03 and r = 0.93, P = .02) with plasma and RBC PS/TC. EZE reduced plasma and RBC sitosterol (-35% ± 4% and -28% ± 3%), total PS (-37% ± 4% and -28% ± 3%, all P < .0001) levels, and PS/TC (-27% ± 4% and -28% ± 4%, P < .01).. EZE reduces plasma and RBC PS levels, while increasing PLT count and decreasing MPV, and thereby may reduce the risk for bleeding in STSL. Plasma PS levels and ABCG5/ABCG8 genes should be analyzed in patients with unexplained hematologic abnormalities.

Topics: Adolescent; Adult; Anticholesteremic Agents; Azetidines; Canada; Cholesterol; Erythrocyte Count; Ezetimibe; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Phytosterols; Pilot Projects; Platelet Count; Treatment Outcome; United States; Young Adult

The sterol profile of rapeseed oil differs from that of tall oil with higher contents of campesterol and brassicasterol. We previously found that margarines providing 2 g/day of sterols from rapeseed or tall oil resulted in similar reductions in LDL cholesterol of 8-9%. The aim of the present study was to investigate whether the consumption of these margarines affected markers of endothelial function, inflammation and hemostasis.. Blood samples were collected from 58 hypercholesterolemic volunteers who completed a double-blinded, randomized, crossover trial. Subjects consumed each of the two sterol margarines and a control non-sterol margarine for 4 weeks separated by one-week washout periods. All the margarines had the same fatty acid composition. Concentrations of vascular cell adhesion molecule-l (VCAM-1), E-selection, circulating tumor necrosis factor α (TNFα) and plasminogen activator inhibitor-1 (total, tPAI-1; active, PAI-1) were quantified.. Rapeseed-sterol margarine reduced E-selection concentrations compared to the control margarine (p = 0.012) while tall-sterol margarine had no effect. The rapeseed-sterol margarine also reduced tPAI-1 (p = 0.008) compared to the tall-sterol margarine. No significant changes were observed in TNFα and VCAM-1. No association was found between LDL reduction and changes in E-selection and tPAI-1.. Rapeseed-sterol margarine demonstrated favorable effects on vascular risk markers.

Topics: Adult; Aged; Biomarkers; Brassica rapa; Cholestadienols; Cholesterol, LDL; Cytokines; E-Selectin; Endothelium, Vascular; Female; Hemostasis; Humans; Hypercholesterolemia; Inflammation; Male; Margarine; Middle Aged; Phytosterols; Plant Oils; Vascular Cell Adhesion Molecule-1

Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with nonresponse to PS consumption; however, prospective studies that show this association have yet to be conducted.. The goal was to test whether the lathosterol-to-cholesterol ratio (L:C ratio), a surrogate marker of endogenous cholesterol synthesis, serves as an a priori predictor of cholesterol lowering in response to PS consumption.. Sixty-three mildly hypercholesterolemic adults who were preselected as possessing either high endogenous cholesterol synthesis [HS; n = 24; L:C = 2.03 ± 0.39 μmol/mmol (mean ± SD)] or low endogenous cholesterol synthesis (LS; n = 39; L:C = 0.99 ± 0.28 μmol/mmol) on the basis of baseline L:C consumed 2 g PS/d or a placebo for 28 d with the use of a dual-center, single-blind, randomized crossover design. Plasma lipid and noncholesterol sterol concentrations were measured at the end of each phase.. PS consumption lowered total cholesterol (TC; -0.25 ± 0.05 mmol/L; P < 0.0001) and LDL cholesterol (-0.17 ± 0.04 mmol/L; P < 0.0001) overall. Specifically, LS individuals responded to PS treatment with a reduction in TC (-0.40 ± 0.07 mmol/L; P < 0.0001) and LDL cholesterol (-0.29 ± 0.05 mmol/L; P = 0.0002), whereas HS individuals failed to show cholesterol lowering (TC: -0.09 ± 0.09 mmol/L; P = 0.2843; LDL cholesterol: -0.05 ± 0.07 mmol/L; P = 0.4917). The odds of LS participants responding to PS consumption with cholesterol lowering better than the mean cholesterol lowering in all participants were 4.25 (95% CI: 1.242, 14.556; P = 0.0211) for TC and 3.36 (95% CI: 1.112, 10.161; P = 0.0317) for LDL cholesterol, which was higher than for HS participants.. The L:C ratio predicts the extent of reduction in circulating TC and LDL cholesterol in response to PS consumption. Cholesterol synthesis assessment may thus have a use in identifying responders and nonresponders to PS therapy.

Topics: Adult; Aged; Algorithms; Anticholesteremic Agents; Biomarkers; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Down-Regulation; Female; Humans; Hypercholesterolemia; Male; Manitoba; Margarine; Maryland; Middle Aged; Phytosterols; Single-Blind Method

The benefits of dietary phytosterols (PhySs) and long-chain n-3 PUFA (ω3) have been linked to their effects as cholesterol- and triglyceride (TGL)-lowering agents. However, it remains unknown whether these compounds have further metabolic effects on LDL lipid composition. Here, we studied the effects of PhyS- or ω3-supplemented low-fat milk (milk) on the LDL-lipidome. Overweight and moderately hypercholesterolemic subjects (n = 32) were enrolled in a two-arm longitudinal crossover study. Milk (250 ml/day), enriched with either 1.57 g PhyS or 375 mg ω3 (EPA + DHA), was given to the participants during two sequential 28 day intervention periods. Compared with baseline, PhyS-milk induced a higher reduction in the LDL cholesterol (LDLc) level than ω3-milk. LDL resistance to oxidation was significantly increased after intervention with PhyS-milk. Changes in TGL and VLDL cholesterol were only evident after ω3-milk intake. Lipidomic analysis revealed a differential effect of the PhyS- and ω3-milk interventions on the LDL lipid metabolite pattern. Content in LDL-glycerophospholipids was reduced after PhyS-milk intake, with major changes in phosphatidylcholine (PC) and phosphatidylserine subclasses, whereas ω3-milk induced significant changes in the long-chain polyunsaturated cholesteryl esters and in the ratio PC36:5/lysoPC16:0, associated to a reduced inflammatory activity. In conclusion, daily intake of milk products containing PhyS or ω3 supplements induce changes in the LDL-lipidome that indicate reduced inflammatory and atherogenic effects, beyond their LDLc- and TGL-lowering effects.

Topics: Administration, Oral; Adult; Aged; Animals; Cholesterol; Cross-Over Studies; Double-Blind Method; Fatty Acids, Omega-3; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Lipoproteins, LDL; Male; Middle Aged; Milk; Overweight; Oxidation-Reduction; Particle Size; Phytosterols; Treatment Outcome

Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage.. This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD.. This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed.. In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: -0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: -0.40, -0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively.. The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.

Topics: Biomarkers; Brachial Artery; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Double-Blind Method; Endpoint Determination; Energy Intake; Female; Humans; Hypercholesterolemia; Life Style; Male; Middle Aged; Phytosterols; Pulse Wave Analysis; Sitosterols; Triglycerides

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with plant stanol esters did not affect serum PCSK9 concentration. Thus, plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal.

Topics: Biomarkers; Case-Control Studies; Cholesterol, LDL; Dietary Fats; Double-Blind Method; Female; Finland; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Plant Oils; Proprotein Convertase 9; Proprotein Convertases; Serine Endopeptidases; Severity of Illness Index; Time Factors; Treatment Outcome

Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects two blood lipid risk factors. Yet, their combined effects on TG and Chol in various lipoprotein subclasses have been investigated to a limited extent.. In a randomized, double-blind, placebo-controlled, parallel study, we determined TG and Chol in 13 LP subclasses in fasting serum of 282 hypercholesterolemic subjects, who consumed either a placebo spread or one of the four spreads containing PS (2.5 g/day) and EPA+DHA (0.0, 0.9, 1.3, and 1.8 g/day) for 4 weeks. After PS treatment, total LDL-Chol was reduced, which was not further changed by EPA+DHA. No shift in the LDL-Chol particle distribution was observed. The addition of EPA+DHA to PS dose-dependently reduced VLDL-Chol and VLDL-TG mainly in larger particles. Furthermore, the two highest doses of EPA+DHA increased Chol and TG in the larger HDL particles, while these concentrations were decreased in the smallest HDL particles.. The consumption of a low-fat spread enriched with both PS and EPA+DHA induced shifts in the lipoprotein distribution that may provide additional cardiovascular benefits over PS consumption alone.

Topics: Adult; Aged; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Computer Simulation; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Double-Blind Method; Eicosapentaenoic Acid; Fasting; Humans; Hypercholesterolemia; Lipoproteins; Middle Aged; Phytosterols; Triglycerides

To determine the effects of 40 mg of pravastatin, 2 g of phytosterols, and combination therapy on lipid profiles and to compare the reduction of LDL cholesterol between combination therapy and monotherapy.. Thirty-six HIV-infected patients treated with ARVs who had high LDL cholesterol levels but no current usage of any lipid-lowering agents were enrolled into the open-labelled, randomized, cross-over study. All patients were assigned randomly into one of four intervention groups: (1) pravastatin 40 mg cross-over to the combination of pravastatin 40 mg and phytosterols 2 g (combination group), (2) the combination group cross-over to pravastatin 40 mg, (3) phytosterols 2 g cross-over to the combination group, and (4) the combination group cross-over to phytosterols 2 g. Each active treatment lasted 4 weeks with a wash-out period of 4 weeks.. The baseline mean TC, TG, HDL-c, and LDL-c levels in 36 HIV patients were 248.09 ± 34.73, 172.36 ± 125.44, 54.92 ± 16.67, and 175.13 ± 29.00 mg/dl, respectively. Pravastatin, phytosterols, and combination therapy reduced TC and LDL-c but TG and HDL-c were not significantly different from the baselines. The mean LDL-c reductions in the pravastatin, phytosterols, and the combination groups were 28.76 ± 9.32, 9.12 ± 7.84, and 27.08 ± 15.58%, respectively. The LDL-c levels in the pravastatin and combination groups were reduced more than in the phytosterols group (p < 0.01). There was no difference in the LDL-c reduction between the combination and pravastatin monotherapy groups (-25.61 ± 10.43 vs. -28.12 ± 14.07%, p = 0.555).. Pravastatin had moderate potency on LDL-c lowering in HIV patients but could not bring LDL-c to goal. Adding phytosterols to pravastatin for a 4-week duration could not demonstrate any additional lipid-lowering effect. Thai Clinical Trial Registry: TCTR20150126002 date: January 23, 2015.

Topics: Adult; Anticholesteremic Agents; Cholesterol, LDL; Cross-Over Studies; Drug Therapy, Combination; Female; HIV Infections; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Pravastatin

The main guidelines for cardiovascular disease prevention suggest that nutraceuticals could be an efficacious tool to improve lipid pattern. Our aim was to carry out a clinical trial comparing the metabolic effects of a combined nutraceutical containing both red yeast rice and polyunsaturated fatty acids (PUFAs) and a phytosterol-based approach in a setting of clinical practice. This was a multicenter open study with parallel control. We consecutively enrolled 107 pharmacologically untreated subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome, assigned to 8-week treatment with a combined treatment with red yeast rice (Dif1Stat(®), including 5 mg monacolin K) and 610 mg PUFAs. A parallel group of 30 subjects with similar characteristics was treated with phytosterols 1600 mg/die. In the combined nutraceutical group, compared with the baseline level, we observed a significant decrease in total cholesterol (TC; -42.50 ± 18.1 mg/dL), low-density lipoprotein cholesterol (LDL-C; -37.6 ± 13.6 mg/dL), triglycerides (TG; -19.8 ± 25.1 mg/dL), and non-HDL-C (-43.1 ± 17.7 mg/dL) (all P < .001). In the phytosterol-treated group, compared to the baseline level, we observed a significant decrease in TC (-13.7 ± 4.3 mg/dL), LDL-C (-17.6 ± 8.5 mg/dL), and non-HDL-C (-14.1 ± 5.6 mg/dL) (all P < .001). When comparing the combined nutraceutical effect with that of phytosterols, we observed that the combined nutraceutical intake was associated with a significantly higher decrease in TC, LDL-C, TG, and non-HDL-C (all P < .001). In the short term, a combined nutraceutical containing red yeast rice and PUFAs is well tolerated and efficacious in reducing plasma lipid levels in subjects affected by primary polygenic hypercholesterolemia and metabolic syndrome.

Topics: Adult; Anticholesteremic Agents; Biological Products; Cholesterol; Cholesterol, LDL; Dietary Supplements; Fatty Acids, Unsaturated; Female; Humans; Hypercholesterolemia; Lipids; Lovastatin; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Treatment Outcome; Triglycerides

in the last few years, as the rate of childhood obesity has been rising, there has been a parallel increase in the incidence of dislipemia in the pediatric population, in which blood triglycerids might play an important role. Plant sterols have been shown to be useful in the tratment of hypercholesterolemia, but not of hypertrygliceridemia. Our study focusses on determining the efficacy of phytosterol-supplemented milk for the treatment of hypertriglyceridemia in children. Study Population and Method: we designed a double- blind, randomized, controlled clinical trial on 67 pediatric patients. The treatment group received low-fat, phytosterol-supplemented milk and the control group received low-fat conventional milk.. we observed differences in triglyceridemia between the phytosterol-supplemented group and the non-supplemented group. The effect attributable to the intake of milk supplemented with plant sterols was a reduction of triglyceridemia of 5.88 mg/dl compared with the control group.. we conclude that phytosterol-supplemented milk (2.24 gr of plant sterols daily) might be an adequate tool in the management of hypertriglyceridemia in pediatric patients.. Introducción: en estos últimos años, paralelamente a la epidemia de obesidad, se ha producido un aumento de las dislipemias en la población pediátrica. En estas dislipemias es posible que los triglicéridos sanguíneos también tengan un papel importante. Los esteroles vegetales se han mostrado eficaces en el tratamiento de la hipercolesterolemia, pero no de la hipertrigliceridemia. Nuestro objetivo en este estudio es determinar la eficacia de la leche enriquecida en fitoesteroles para la disminución de la hipertrigliceridemia en la población infantil. Población y método: se diseñó un ensayo clínico, controlado, aleatorizado, y doble ciego, con leche desnatada enriquecida con esteroles vegetales y leche desnatada no enriquecida. Se incluyeron 67 pacientes pediátricos. Resultados: tras la ingesta observamos diferencias en la trigliceridemia final entre la leche desnatada enriquecida con esteroles vegetales y la leche desnatada no enriquecida con esteroles. El efecto atribuible a la ingesta de la leche enriquecida con fitosteroles vegetales fue de una disminución de 5,88 mg/dl. Conclusión: concluimos que la leche enriquecida con esteroles vegetales (2,24 gr de esteroles vegetales al día) podría constituir una estrategia adecuada para el tratamiento de la hipertrigliceridemia en pacientes pediátricos.

Topics: Child; Child, Preschool; Cultured Milk Products; Diet, Fat-Restricted; Dietary Supplements; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Male; Phytosterols; Treatment Outcome; Triglycerides

Hypercholesterolemia, particularly high LDL-c and non-HDL-c levels, is a traditional risk for cardiovascular disease. Ingestion of diets containing phytosterols and inulin can reduce plasma LDL-c and triglyceride levels, respectively. Phytosterols and inulin-enriched soymilk may be an alternative for a supplemental diet to improve both LDL-c and non-HDL-c to reduce the risk of cardiovascular disease.. Two hundred and forty subjects who were 18 years old or older and had a baseline LDL-c of 130 mg/dl or higher were enrolled into the double-blinded randomized controlled trial study. Subjects were randomly assigned into the study group that received 2 g/day of phytosterols and 10 g/day of inulin-enriched soymilk or into the control group that received standard soymilk. The lipid profile was measured every 2 weeks for 8 weeks. Primary outcomes were 1) to determine the LDL-c reduction after consumption of phytosterols and inulin-enriched soymilk for 8 weeks and 2) to compare the difference of the LDL-c levels between the study and control groups. The secondary outcomes were to compare the difference of TC, TG and HDL-c between the study and control groups.. At the end of the study, the median LDL-c levels decreased significantly from 165 (132, 254) mg/dl to 150 (105, 263) mg/dl in the study group (p < 0.001) and from 165 (130, 243) mg/dl to 159 (89, 277) mg/dl in the control group (p = 0.014). The LDL-c reduction was significantly better in the study group (-10.03%, (-37.07, 36.00) vs -1.31% (-53.40, 89.73), p < 0.001). TC also reduced significantly by 6.60% in the study group while it reduced only by 1.76% in the control group (p < 0.001). There were no statistical differences in TG and HDL-c levels between both study groups. The adverse events in the study group and the control groups were not different (RR 1.33 [0.871-2.030, 95 % CI]).. Daily consumption of soymilk containing 2 g of phytosterols and 10 g of inulin reduced TC and LDL-c better than standard soymilk. It had no effect on TG and HDL-c levels compared to standard soymilk. Both soymilk products were comparably safe.. Thai Clinical Trial Registry: TCTR20150417001 date: April 17, 2015.

Topics: Adolescent; Adult; Aged; Cholesterol, LDL; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Inulin; Male; Middle Aged; Phytosterols; Soy Foods; Thailand; Young Adult

A well-controlled clinical trial previously demonstrated the efficacy of a novel softgel dietary supplement providing 1.8 g/day esterified plant sterols and stanols, as part of the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to improve the fasting lipid profile of men and women with primary hypercholesterolemia (fasting low-density lipoprotein [LDL] cholesterol ≥ 130 and <220 mg/dL [≥ 3.37 and <5.70 mmol/L]). The purpose of this randomized, double blind, placebo-controlled crossover study (conducted July 2011 to January 2012) was to support these previous findings in a similar, but independent, sample with a different lead investigator and research site. Repeated measures analysis of covariance was used to compare outcomes for sterol/stanol and placebo treatment conditions using the baseline value as a covariate. Forty-nine subjects were screened and 30 (8 men and 22 women) were randomized to treatment (all completed the trial). Baseline (mean ± standard error of the mean) plasma lipid concentrations were: total cholesterol 236.6 ± 4.2 mg/dL (6.11 ± 0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8 ± 3.0 mg/dL (1.47 ± 0.08 mmol/L), LDL cholesterol 151.6 ± 3.3 mg/dL (3.92 ± 0.09 mmol/L), non-HDL cholesterol 179.7 ± 4.6 mg/dL (4.64 ± 0.12 mmol/L), and triglycerides 144.5 ± 14.3 mg/dL (1.63 ± 0.16 mmol/L). Mean placebo-adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL cholesterol (-4.3%), non-HDL cholesterol (-4.1%), and total cholesterol (-3.5%), but not for triglycerides or HDL cholesterol. These results support the efficacy of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to augment reductions in atherogenic lipid levels in individuals with hypercholesterolemia.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Dietary Supplements; Double-Blind Method; Esterification; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Placebos; Sitosterols; Triglycerides

Small dense low density lipoprotein-cholesterol (sdLDL-C) molecules are more atherogenic compared with large buoyant ones. Phytosterols-enriched diets are effective in decreasing total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) concentrations in hyperlipidemic children without significant adverse effects. Limited data on the impact of such a diet on sdLDL-C levels is available in adults while there are no reports concerning children. The purpose of this study is to prospectively evaluate the effect of the daily consumption of 2 g of plant sterols on sdLDL-C levels in children with hypercholesterolemia.. Fifty-nine children, 25 with LDL-C ≥ 3.4 mmol/l (130 mg/dl) and 34 with LDL-C < 3.4 mmol/l, aged 4.5-15.9 years, were included in the study. A yogurt-drink enriched with 2 g of plant sterols was added to the daily diet of hypercholesterolemic children and 6-12 months later lipid profiles were reassessed. Direct quantitative methods were used to measure LDL-C and sdLDL-C levels.. The consumption of plant sterols reduced sdLDL-C significantly (p < 0.001), but levels remained higher compared with controls (p < 0.001). TC, LDL-C, non high density lipoprotein-cholesterol (NonHDL-C) and apolipoprotein B (ApoB) levels also decreased significantly (p < 0.05). The median reduction of sdLDL-C and LDL-C was 16.6% and 13%, respectively. These variables decreased >10% in sixteen children (64%), independently from baseline levels, sex, age and body mass index (BMI). High density lipoprotein-cholesterol (HDL-C), lipoprotein a [Lp(a)], and triglycerides (TGs) levels remained unaffected.. Plant sterols decrease sdLDL-C significantly and may be beneficial for children with hypercholesterolemia.

Topics: Adolescent; Biomarkers; Body Mass Index; Child; Child, Preschool; Cholesterol, LDL; Diet; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Male; Nephelometry and Turbidimetry; Phytosterols; Prospective Studies; Treatment Outcome

Post-menopausal women are at higher risk of cardiovascular disease and bone demineralization. Phytosterols (PS) may be used for hypercholesterolemia in some groups and β-cryptoxanthin (β-Cx) displays a unique anabolic effect on bone. Our aim was to assess the changes in cardiovascular and bone turnover markers from the oral intake of β-Cx and PS in post-menopausal women.. A randomized, double-blind, crossover study with β-Cx (0.75 mg/day) and PS (1.5 g/day), single and combined, was performed in 38 postmenopausal women. Diet was supplemented with 1 × 250 mL milk-based fruit drink/day for 4 weeks with a wash-out period of 4-weeks in between. Serum β-Cx and PS were determined by UPLC and CG-FID respectively. Outcome variables included markers of bone turnover and cardiovascular risk. Biological effect was assessed by paired t test and generalized estimating equations analysis that included the previous treatment, the order of intervention and the interactions. The intake of beverages containing β-Cx and PS brought about a significant increase in serum levels of β-Cx, β-sitosterol and campesterol. Intervention caused changes in almost all the markers while the order, previous treatment and the interaction did not reach statistical significance. Only the intake of the beverage containing β-Cx plus PS brought about significant decreases in total cholesterol, c-HDL, c-LDL and bone turnover markers.. β-Cx improves the cholesterol-lowering effect of PS when supplied simultaneously and this combination may also be beneficial in reducing risk of osteoporosis.. ClinicalTrials.gov number NCT01074723.

Topics: Administration, Oral; Aged; Bone and Bones; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Cryptoxanthins; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Healthy Volunteers; Humans; Hypercholesterolemia; Middle Aged; Phytosterols; Postmenopause; Risk Factors; Sitosterols; Treatment Outcome; Triglycerides

Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n-3 (ω-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA from fish oil (FO) in a single food format was expected to beneficially affect 2 blood lipid risk factors. The aim of this study was to investigate the dose-response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL-C were investigated. The study was designed as a randomized, double-blind, placebo-controlled parallel study. After a 4-wk run-in period, subjects were randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of 4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after the intervention, fasting blood samples were drawn for measuring serum lipids and EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and 247 women with a mean age of 57.9 y (range: 25-74 y) were included. Eighteen subjects dropped out during the study. At baseline, mean TG and LDL-C concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a significant dose-response relation for the TG-lowering effect of EPA+DHA [βln (TG) = -0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C group, TG concentrations were 9.3-16.2% lower in the different FO groups (P < 0.05 for all groups). LDL-C concentrations were 11.5-14.7% lower in the different PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in erythrocyte membranes were dose-dependently higher after FO intake than after the C spread, indicating good compliance. Consumption of a low-fat spread enriched with PSs and different low doses of n-3 fatty acids from FO decreased TG concentrations in a dose-dependent manner and decreased LDL-C concentrations. This trial was registered at clinicaltrials.gov as NCT01313988.

Topics: Adult; Aged; Cholesterol, HDL; Cholesterol, LDL; Diet; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Double-Blind Method; Eicosapentaenoic Acid; Erythrocyte Membrane; Fasting; Female; Fish Oils; Humans; Hypercholesterolemia; Life Style; Male; Middle Aged; Phytosterols; Triglycerides

To observe the impact of plant sterol esters (PSE) mixed in low fat milk powder (2.5 g of PSE/day) on plasma cholesterol levels in hypercholesterolemic subjects during a 6-week intervention period.. In this double-blind, randomized, placebo-controlled study, 59 subjects (19 males, mean age (60.28 ± 6.98) years) with primary hypercholesterolemia (fasting LDL cholesterol between 3.4-6.0 mmol/L) were randomly divided into two groups (treatment group, 2.5 g of plant sterol esters a day, n = 30) and placebo group (n = 29). Blood samples were collected at week 0, 3 and 6. The primary outcome was change in plasma LDL-cholesterol (LDL-C). Secondary outcomes were changes in total cholesterol (TC), HDL cholesterol (HDL-C), triglycerides (TG), anthropometry and blood biochemistry.. LDL-C significantly reduction from baseline (4.18 ± 0.54) mmol/L to (3.44 ± 0.61) mmol/L (-17.7%, P < 0.05) at week 3 and (3.35 ± 0.39) mmol/L (-19.9%, P < 0.05) at week 6 in the treatment group, whereas in placebo group from (4.11 ± 0.54) mmol/L at baseline to (3.47 ± 0.60) mmol/L (-15.57%, P < 0.05) and (3.61 ± 0.39) mmol/L (-12.17%, P < 0.05) at week 3 and week 6, respectively. TC was reduced from (6.30 ± 0.86) mmol/L at baseline to (5.92 ± 0.75) mmol/L (-6.03%, P > 0.05) at week 3 and (5.43 ± 0.77) mmol/L (-13.8%, P < 0.05) at week 6 in treatment group, from (6.20 ± 0.76) mmol/L at week 0 to (5.70 ± 0.76) mmol/L (-8.06%, P < 0.05) at week 3 and (5.84 ± 0.75) mmol/L (-5.81%, P < 0.05) at week 6 in placebo group. PSE-enriched milk did not affect plasma HDL-C level and TG level at both week 3 and week 6. After normalization to the placebo group, the treatment group showed significant reduction in LDL-C and total cholesteron after 6 weeks. The observed difference of reduction was 7.69% (-0.33 mmol/L, P < 0.05) for LDL-C and 8.00% (-0.51 mmol/L, P < 0.05) for TC between the two groups. There were no significant changes in safety parameters, including blood biochemistry tests during the study period.. Plant sterol ester enriched milk powder is effective in reducing LDL-C among Chinese hypercholesterolemic subjects at a dosage recommended by EFSA.

Topics: Animals; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; History, 18th Century; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Milk; Phytosterols; Triglycerides

Numerous studies have shown an inverse association between cholesterol´s concentration associated with High-Density Lipoprotein Cholesterol (HDL-C) and cardiovascular risk. The present study intends to investigate the possible relation between Apolipoprotein A (ApoA1) and HDL-C as a new strategy to reduce cardiovascular risk.. was determine the effect of ApoA1 in cholesterol ´s metabolism through its influence on HDL-C in young adult population.. One clinical trial, controlled, randomized, double-blind, providing a commercial milk, "Naturcol", with sterols for 3 weeks (n = 19) and placebo (n = 16). A questionnaire Ad Hoc was designed and a complete anthropometric study was made. SPSS 21.0 was used to analyse the data.. Significant differences were observed between sterol milk and placebo in a single marker, Low-Density Lipoprotein Cholesterol (LDL-C). A linear dispersion of data between HDL-C and ApoA1 was found, both at the beginning and end of the intervention (Person Correlation = 0.846 and 0.903, respectively). High dependency measures by linear regression (R2= 0.715 and 0.816, respectively) were observed.. A significant relation between HDL-C and ApoA1 was proven. Taking into account the importance that HDL-C levels seem to have on cardiovascular health, ApoA1 is presented as an important clinical marker to improve heart function as well as to reduce cardiovascular risk.. Antecedentes: Numerosos estudios han demostrado una asociación inversa entre la concentración de colesterol asociado a lipoproteínas de alta densidad de colesterol (HDL-c) y el riesgo cardiovascular. El presente estudio investigo la posible relación entre la apolipoproteína A (ApoA1) y el HDL-C como una nueva estrategia para reducir el riesgo cardiovascular. Objetivo: determinar el efecto de ApoA1 en el metabolismo del colesterol a través de su influencia sobre el HDL-c en la población adulta joven. Métodos: ensayo clínico, controlado, aleatorizado, doble ciego, proporcionando una leche comercial con esteroles, “Naturcol”, durante 3 semanas (n = 19) y placebo (n = 16). Se diseñó un cuestionario Ad Hoc y se realizó un estudio antropométrico completo. Se utilizó el programa SPSS 21.0 para analizar los datos estadísticos. Resultados: Se observaron diferencias significativas entre la leche de esterol y el placebo únicamente en un solo marcador, en las lipoproteínas de baja densidad del colesterol (LDL-c). Se encontró una dispersión lineal de datos entre HDL-C y ApoA1, tanto al principio y al final de la intervención (correlación de Person = 0,846 y 0,903, respectivamente). Se observó alta dependencia en la regresión lineal (R2 = 0,715 y 0,816, respectivamente). Conclusión: Una relación significativa entre el HDL-c y ApoA1 fue comprobada. Teniendo en cuenta la importancia que los niveles de HDL-c parecen tener en la salud cardiovascular, la ApoA1 se presenta como un importante marcador clínico para mejorar la función del corazón, así como para reducir el riesgo cardiovascular.

Topics: Adult; Anthropometry; Apolipoprotein A-I; Biomarkers; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipoproteins, HDL; Male; Phytosterols

Phytosterols are recommended in combination with diet therapy to reduce elevated LDL-cholesterol level. Meta-analyses indicate a 10% reduction in LDL-cholesterol from intake of approximately 2 g phytosterols/d incorporated into fat-based foods. However, the cholesterol lowering effect from capsules containing phytosterols is less documented. The pre-specified primary endpoint of the present study was to investigate the effect of capsules with phytosterols on circulating LDL-cholesterol in patients with mild to moderate hypercholesterolemia.. In a double-blinded, randomized, placebo-controlled crossover study, 41 men and women were randomized into two four-weeks intervention periods with softgel capsules containing either phytosterols (2.0 g/d) or sunflower oil. There was a three-weeks washout period between the intervention periods.. No significant difference in total- or LDL-cholesterol between the phytosterol and the placebo period were observed after four weeks intervention (0.0 mmol/L (95%CI: -0.3 to 0.2), P = 0.74 and -0.1 mmol/L (95%CI: -0.3 to 0.1), P = 0.32, respectively).. Daily intake of capsules containing 2 g phytosterols did not reduce total- or LDL-cholesterol significantly in a highly relevant target group for the use of phytosterol products. The present results may emphasize the importance of choosing a suitable dosage-delivery system in order to achieve optimal cholesterol lowering effect. The study was registered at www.clinicaltrials.gov, IDno:NCT00485095.

Topics: Administration, Oral; Aged; Anticholesteremic Agents; Biomarkers; Capsules; Chemistry, Pharmaceutical; Cholesterol, LDL; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Down-Regulation; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Norway; Phytosterols; Plant Oils; Severity of Illness Index; Sunflower Oil; Time Factors; Treatment Outcome

Many patients who refuse or cannot tolerate statin drugs choose alternative therapies for lipid lowering.. This study aimed to determine the lipid-lowering effects of phytosterol tablets and lifestyle change (LC) on top of red yeast rice (RYR) therapy in patients with a history of statin refusal or statin-associated myalgias.. A total of 187 participants (mean low-density lipoprotein cholesterol [LDL-C], 154 mg/dL) took RYR 1800 mg twice daily and were randomized to phytosterol tablets 900 mg twice daily or placebo. Participants were also randomized to a 12-week LC program or usual care (UC). Primary end point was change in LDL-C at 12, 24, and 52 weeks. Secondary end points were effect on other lipoproteins, high-sensitivity C-reactive protein, weight, and development of myalgia.. Phytosterols did not significantly improve LDL-C at weeks 12 (P = .54), 24 (P = .67), or 52 (P = .76) compared with placebo. Compared with the UC group, the LC group had greater reductions in LDL-C at weeks 12 (-51 vs -42 mg/dL, P = .006) and 24 (-48 vs -40 mg/dL, P = .034) and was 2.3 times more likely to achieve an LDL-C <100 mg/dL (P = .004). The LC group lost more weight for 1 year (-2.3 vs -0.3 kg, P < .001). All participants took RYR and had significant decreases in LDL-C, total cholesterol, triglycerides, high-sensitivity C-reactive protein, and an increase in high-density lipoprotein cholesterol for 1 year when compared with baseline (P < .001). Four participants stopped supplements because of myalgia.. The addition of phytosterol tablets to RYR did not result in further lowering of LDL-C levels. Participants in an LC program lost significantly more weight and were more likely to achieve an LDL-C <100 mg/dL compared with UC.

Topics: Adult; Aged; Aged, 80 and over; Biological Products; Dietary Supplements; Double-Blind Method; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Life Style; Lipids; Male; Middle Aged; Phytosterols; Treatment Outcome; Young Adult

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a softgel capsule dietary supplement, providing esterified plant sterols/stanols 1.8 g/d, in 28 participants (≈ 75% women) with primary hypercholesterolemia (fasting low-density lipoprotein cholesterol [LDL-C] levels ≥ 130 and <220 mg/dL), a mean age of 58.4 y, and a mean body mass index of 27.9 kg/m(2).. After a 5-wk National Cholesterol Education Program (NCEP) Therapeutic Lifestyle Changes (TLC) diet and a single-blinded placebo lead-in, subjects received double-blinded placebo or sterol/stanol softgel capsules for 6 wk and then crossed over to the opposite product for 6 wk while continuing the TLC diet. Fasting lipids were assessed in duplicate at the end of the diet lead-in (baseline) and the end of each treatment.. The mean baseline lipid concentrations (milligrams per deciliter) were 223 for total cholesterol (TC), 179 for non-high-density lipoprotein cholesterol (non-HDL-C), 154 for low-density lipoprotein cholesterol, 44 for HDL-C, 125 for triacylglycerols, and 5.2 for TC/HDL-C. Differences from the control responses (plant sterol/stanol minus control) in the per-protocol sample were significant (P < 0.05) for LDL-C (-9.2%), non-HDL-C (-9.0%), TC (-7.4%), TC/HDL-C (-5.4%), and triacylglycerols (-9.1%). The HDL-C responses were not significantly different between treatments.. The incorporation of softgel capsules providing esterified plant sterols/stanols 1.8 g/d into the NCEP TLC diet produced favorable changes in atherogenic lipoprotein cholesterol levels in these subjects with hypercholesterolemia.

Topics: Capsules; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Supplements; Female; Gels; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Phytotherapy; Single-Blind Method; Triglycerides

Hypolipidemic and/or hypocholesterolemic effects are presumed for dietary milk phospholipid (PL) as well as plant sterol (PSt) supplementation. The aim was to induce changes in plasma lipid profile by giving different doses of milk PL and a combination of milk PL with PSt to healthy volunteers.. In an open-label intervention study, 14 women received dairy products enriched with moderate (3 g PL/day) or high (6 g PL/day) dose of milk PL or a high dose of milk PL combined with PSt (6 g PL/day + 2 g PSt/day) during 3 periods each lasting 10 days.. Total cholesterol concentration and HDL cholesterol concentration were reduced following supplementation with 3 g PL/day. No significant change in LDL cholesterol concentration was found compared with baseline. High PL dose resulted in an increase of LDL cholesterol and unchanged HDL cholesterol compared with moderate PL dose. The LDL/HDL ratio and triglyceride concentration remained constant within the study. Except for increased phosphatidyl ethanolamine concentrations, plasma PL concentrations were not altered during exclusive PL supplementations. A combined high-dose PL and PSt supplementation led to decreased plasma LDL cholesterol concentration, decreased PL excretion, increased plasma sphingomyelin/phosphatidyl choline ratio, and significant changes in plasma fatty acid distribution compared with exclusive high-dose PL supplementation.. Milk PL supplementations influence plasma cholesterol concentrations, but without changes of LDL/HDL ratio. A combined high-dose milk PL and PSt supplementation decreases plasma LDL cholesterol concentration, but it probably enforces absorption of fatty acids or fatty acid-containing hydrolysis products that originated during lipid digestion.

Topics: Adult; Algorithms; Animals; Beverages; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dairy Products; Fatty Acids; Feces; Female; Food, Formulated; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Lipids; Milk; Phospholipids; Phytosterols

Plant sterols are naturally occurring cholesterol-lowering compounds which are industrially incorporated in various foods. A novel food carrier is rye bread, the intake of which can be monitored in trials utilizing newly defined plasma biomarkers. Our aim was to determine the effects of plant sterols incorporated into high-fiber rye bread on serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios and lipophilic (pro)vitamins in healthy free-living normocholesterolemic individuals.. In this double-blind, dietary intervention trial the subjects (n=68) were randomized to receive a rye bread (9.3g/d fiber) with added plant sterols (2g/d) (active) or without (control). In the second phase of the study the amount of rye bread was doubled providing 18.6g/d fiber and in the active group 4g/d plant sterols. Compliance was monitored utilizing 3-day food diaries and a novel rye fiber-derived biomarker in plasma. Intake of rye bread enriched with 2g/d of plant sterols during two weeks reduced significantly serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios by 5.1%, 8.1%, 8.3% and 7.2%, respectively, compared to controls. Correspondingly, the following two-week treatment with 4g/d of plant sterols resulted in 6.5%, 10.4%, 5.5% and 3.7% difference compared to controls, being most pronounced for LDL (0.33 mmol/L). The treatments did not affect lipophilic (pro)vitamin levels.. Rye bread enriched with 2-4g/d of nonesterified plant sterols beneficially modifies cardiovascular lipid risk factors in normocholesterolemic subjects compared to controls.

Topics: Adult; Apolipoproteins; Bread; Carotenoids; Cholesterol, HDL; Cholesterol, LDL; Dietary Fiber; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Risk Factors; Secale; Tocopherols; Vitamins; Young Adult

The mechanisms implicated in the LDL-cholesterol (LDL-C)-lowering effects of the Mediterranean-type diet (MedDiet) are unknown. The present study assessed the impact of the MedDiet consumed under controlled feeding conditions, with and without weight loss, on surrogate markers of cholesterol absorption, synthesis and clearance using plasma phytosterols, lathosterol and proprotein convertase subtilisin/kexin-9 (PCSK9) concentrations, respectively, in men with the metabolic syndrome. The subjects' diet (n 19, 24-62 years) was first standardised to a baseline North American control diet (5 weeks) followed by a MedDiet (5 weeks), both under weight-maintaining isoenergetic feeding conditions. The participants then underwent a 20-week free-living energy restriction period (10 (sd 3) % reduction in body weight, P < 0·01), followed by the consumption of the MedDiet (5 weeks) under controlled isoenergetic feeding conditions. The LDL-C-lowering effect of the MedDiet in the absence of weight loss ( - 9·9 %) was accompanied by significant reductions in plasma PCSK9 concentrations ( - 11·7 %, P < 0·01) and in the phytosterol:cholesterol ratio ( - 9·7 %, P < 0·01) compared with the control diet. The addition of weight loss to the MedDiet had no further impact on plasma LDL-C concentrations and on these surrogate markers of LDL clearance and cholesterol absorption. The present results suggest that the MedDiet reduces plasma LDL-C concentrations primarily by increasing LDL clearance and reducing cholesterol absorption, with no synergistic effect of body weight loss in this process.

Topics: Adolescent; Adult; Aged; Biomarkers; Body Mass Index; Cholesterol; Cholesterol, LDL; Diet, Mediterranean; Diet, Reducing; Humans; Hypercholesterolemia; Isomerism; Male; Metabolic Syndrome; Middle Aged; Overweight; Phytosterols; Proprotein Convertase 9; Proprotein Convertases; Quebec; Serine Endopeptidases; Weight Loss; Young Adult

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

Topics: Adult; Animals; Anticholesteremic Agents; Cholesterol, LDL; Cross-Over Studies; Dietary Fats; Dietary Supplements; Esters; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Milk; Phytosterols; Phytotherapy; Plant Extracts; Plant Oils; Sterols

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol - control) were significant (p < 0.05) for LDL-C ( - 4.9%), non-HDL-C ( - 3.6%) and TC ( - 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia.

Topics: Cholesterol; Cross-Over Studies; Dietary Supplements; Female; Humans; Hypercholesterolemia; Life Style; Male; Middle Aged; Phytosterols; Phytotherapy; Plant Extracts; Triglycerides

Plant sterol (PS) supplementation is increasingly accepted as a dietary strategy to lower plasma cholesterol concentrations. However, information is scarce about the effect of increased PS intake in potentially vulnerable groups, such as phytosterolemia heterozygotes (HET).. This study assessed the responsiveness of circulating PS and lipid concentrations and cholesterol kinetics (absorption and synthesis) to daily PS supplementation in HET (ABCG8 S107X mutation) compared with a healthy control cohort.. A double-blind, randomized, crossover, placebo-controlled study was conducted in 10 HET and 15 control subjects. The participants had a mean (±SEM) age of 34 ± 2 y and a BMI (in kg/m²) of 29.9 ± 1.1 and consumed ∼1.6 g PS or placebo capsules daily with supper for 4 wk. Cholesterol absorption and synthesis were assessed by using [¹³C]cholesterol and deuterium oxide, respectively.. Plasma LDL-cholesterol concentrations decreased (P = 0.006) in both groups after PS supplementation (HET: 2.73 ± 0.19 mmol/L; control: 3.11 ± 0.19 mmol/L) compared with placebo (HET: 3.12 ± 0.20 mmol/L; control: 3.50 ± 0.21 mmol/L), whereas PS concentrations (campesterol+β-sitosterol) increased (P = 0.03) in both groups after PS supplementation (HET: 39.72 ± 6.05 μmol/L; control: 24.03 ± 1.65 μmol/L) compared with placebo (HET: 27.32 ± 3.80 μmol/L; control: 21.12 ± 2.05 μmol/L). Cholesterol absorption efficiency decreased (P = 0.010) by ∼22% and ∼17% and synthesis rates increased (P = 0.040) by ∼20% and ∼24% in the HET and control groups, respectively, in response to PS consumption compared with placebo.. These data suggest that heterozygosity for the ABCG8 S107X mutation does not influence the action of dietary PS on circulating cholesterol concentrations but may affect sterol absorption.

Topics: Adolescent; Adult; Aged; Amino Acid Substitution; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Cholesterol; Cohort Studies; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Female; Heterozygote; Humans; Hypercholesterolemia; Intestinal Absorption; Intestinal Diseases; Kinetics; Lipid Metabolism, Inborn Errors; Lipids; Male; Middle Aged; Mutant Proteins; Phytosterols; Young Adult

Lifestyle intervention is recommended as the primary treatment for mild hypertension and hypercholesterolemia. We studied the effects of a spread containing bioactive milk peptides IPP and VPP, as well as plant sterols, on cardiovascular risk factors in 104 hypertensive, hypercholesterolemic subjects in a randomised, placebo-controlled double-blind intervention. Middle-aged subjects consumed 20 g day⁻¹ of a spread containing 4.2 mg of IPP and VPP as well as 2 g of plant sterols for 10 weeks after a 2 week run-in period. Blood pressure was measured at home 3 times a week. Office blood pressure and 24 h ambulatory blood pressure measurements were performed at the end of the run-in and intervention periods. Blood samples were analysed for serum lipids, plasma glucose and inflammation markers. A significant decrease (-4.1 mmHg vs. -0.5 mmHg, p = 0.007) in systolic blood pressure was seen in the active group, compared to placebo at home measurements. Office blood pressure and 24 h nighttime or daytime ambulatory systolic or diastolic pressure did not differ between the groups. Total (-0.16 vs. 0.25 mmol l⁻¹, p = 0.005) and LDL cholesterol (-0.16 vs. 0.18 mmol l⁻¹, p = 0.006) decreased significantly in the active group compared to the placebo. No significant differences between groups were seen for plasma glucose or inflammation markers. The results thus suggest that milk peptides IPP and VPP and plant sterols, in a low-fat spread matrix, produce a clinically significant reduction in systolic blood pressure as well as serum total and LDL cholesterol without adverse effects. Functional foods that affect 2 major risk factors offer a safe and convenient way to reduce the risk of cardiovascular disease by supporting lifestyle intervention.

Topics: Adult; Aged; Animals; Anticholesteremic Agents; Antihypertensive Agents; Blood Glucose; Blood Pressure; Cattle; Cholesterol, LDL; Double-Blind Method; Female; Fermentation; Humans; Hypercholesterolemia; Hypertension; Lactobacillus helveticus; Male; Margarine; Middle Aged; Milk; Peptides; Phytosterols

Elevated low-density lipoprotein (LDL) cholesterol is a significant risk factor for cardiovascular disease. It is estimated that 42% of females and 34% of males in the USA have elevated total cholesterol. The current mainstay of lipid-lowering therapy utilizes 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (i.e., statin) medications that lower total cholesterol and LDL cholesterol by an average of 20% and 28%, respectively. However, due to the significant side effects of statin medications, many patients seek alternative therapies to help manage their hypercholesterolemia. Red yeast rice (Monascus purpureus) has been used as a food and as an herbal medication in China for centuries. Phytosterols are foods that are similar in structure and function to animal cholesterol. Both of these compounds have been shown in clinical studies to significantly lower LDL cholesterol. We report on a case series of 18 patients with hypercholesterolemia despite therapeutic lifestyle change through diet and exercise who took a proprietary product combining red yeast rice and phytosterols as a powdered shake in an effort to improve their cholesterol indices. Statistically significant reduction (p < .05) in the following mean variables was seen: total cholesterol 19% (46 mg/dL) and LDL 33% (53 mg/dL) after 6 weeks using the blend. There was no significant difference in body mass index (BMI), triglyceride, high-density lipoprotein (HDL) cholesterol levels, or systolic and diastolic blood pressure over the same period. This magnitude of reduction in LDL cholesterol is significantly greater than the 28% reduction observed in the 1999 Journal of the American Medical Association (JAMA) meta-analysis on the average effectiveness of statin medications in lowering cholesterol levels. None of the participants in our study reported any muscle pains, and no abnormal liver function tests were seen while taking the product. Though this case series is limited by small sample size, study duration, and lack of control group, the product's significant reduction in LDL cholesterol without severe side effects indicates that this product may be a clinically effective and well tolerated alternative treatment to using statin medications to treat hypercholesterolemia.

Topics: Anticholesteremic Agents; Biological Products; Cholesterol; Cholesterol, LDL; Drug Combinations; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Monascus; Phytosterols; Phytotherapy

Non-cholesterol sterols reflect cholesterol metabolism. Statins reduce cholesterol synthesis usually with a rise in cholesterol absorption. Common hyperlipemias have shown different patterns of cholesterol metabolism. We evaluated whether cholesterol absorption and synthesis may differ after statin therapy in primary hyperlipemias.. We determined lipid profile, apoprotein B and serum sterols (lathosterol, sitosterol, campesterol by gas chromatography/mass spectrometry) before and after statins in 80 untreated hyperlipemic patients, 40 with polygenic hypercholesterolemia (PH) and 40 with familial combined hyperlipemia (FCH).. At baseline in FCH lathosterol was significantly higher while campesterol and sitosterol were significantly lower than in PH. After statins, the reduction in LDL-C did not significantly differ between the two groups; in PH there was a significant decrease of lathosterol from 96.1 to 52.6 102 μmol/mmol cholesterol (p=0.0001) with no significant modifications in campesterol and sitosterol; on the opposite, in FCH lathosterol decreased from 117 to 43 102 μmol/mmol cholesterol (p=0.0001) and campesterol and sitosterol significantly increased from 38 to 48 102 μmol/mmol cholesterol (p=0.0001), and from 75 to 86 102 μmol/mmol cholesterol, (p=0.022), respectively. After statin therapy only in FCH Δ-LDL-C showed a significant inverse correlation with Δ-sitosterol and with Δ-campesterol.. Primary hyperlipemias show different patterns of response to statins: in PH LDL reduction appears completely "synthesis inhibition" dependent, while in FCH LDL decrease appears to be synthesis dependent, partially limited by absorption increase. Studying cholesterol metabolism before and after hypolipemic therapy might be useful in identifying the best tailored treatment.

Topics: Adult; Aged; Atorvastatin; Cholesterol; Cholesterol, LDL; Female; Gas Chromatography-Mass Spectrometry; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemia, Familial Combined; Hyperlipidemias; Lipids; Male; Middle Aged; Phytosterols; Pyrroles; Simvastatin; Sitosterols

The percentage of hypercholesterolemic individuals not reaching their LDL-cholesterol (LDL-C) goal remains high and additional therapeutic strategies should be evaluated. The objective of this study was to evaluate the cholesterol-lowering efficacy and mechanism of action of bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 capsules in hypercholesterolemic adults.. A total of 127 subjects completed a randomized, double-blind, placebo-controlled, parallel-arm, multicenter study. Subjects were randomized to consume L. reuteri NCIMB 30242 capsules or placebo capsules over a 9-week intervention period. The primary outcome was LDL-C relative to placebo at the study end point.. L. reuteri NCIMB 30242 capsules reduced LDL-C by 11.64% (P<0.001), total cholesterol by 9.14%, (P<0.001), non-HDL-cholesterol (non-HDL-C) by 11.30% (P < 0.001) and apoB-100 by 8.41% (P = 0.002) relative to placebo. The ratios of LDL-C/HDL-cholesterol (HDL-C) and apoB-100/apoA-1 were reduced by 13.39% (P = 0.006) and 9.00% (P = 0.026), respectively, relative to placebo. Triglycerides and HDL-C were unchanged. High-sensitivity C-reactive protein and fibrinogen were reduced by 1.05 mg/l (P = 0.005) and 14.25% (P = 0.004) relative to placebo, respectively. Mean plasma deconjugated bile acids were increased by 1.00 nmol/l (P=0.025) relative to placebo, whereas plasma campesterol, sitosterol and stigmasterol were decreased by 41.5%, 34.2% and 40.7%, respectively.. The present results suggest that the deconjugation of intraluminal bile acids results in reduced absorption of non-cholesterol sterols and indicate that L. reuteri NCIMB 30242 capsules may be useful as an adjunctive therapy for treating hypercholesterolemia.

Topics: Adult; Apolipoprotein A-I; Apolipoprotein B-100; Bile Acids and Salts; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Fibrinogen; Humans; Hypercholesterolemia; Intestinal Absorption; Limosilactobacillus reuteri; Male; Middle Aged; Phytosterols; Sitosterols; Stigmasterol

The importance of both low-density lipoprotein cholesterol (LDLc) size and the apolipoprotein E (Apo E) in the atherogenic process is known, but there is little information with regard to the effect of phytosterols (PS) on these parameters. The aim of this study was to evaluate the influence of PS on lipid profile and LDLc size according to Apo E genotype.. This was a randomized parallel trial employing 75 mild-hypercholesterolemic subjects and consisting of two 3-month intervention phases. After 3 months of receiving a standard healthy diet, subjects were divided into two intervention groups: a diet group (n=34) and a diet+PS group (n=41) that received 2 g/day of PS. Total cholesterol (TC), triacylglycerols, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, Apo A-I and B-100, LDLc size and Apo E genotype were determined.. Patients receiving PS exhibited a significant decrease in TC (5.1%), LDLc (8.1%), non-HDLc (7.4%) and Apo B-100/Apo A-I ratio (7.7%), but these effects did not depend on Apo E genotype. No significant changes were found in lipid profile according to Apo E genotype when patients following dietary recommendations were considered as a whole population or separately. No variations in LDLc size were observed in any of the intervention groups.. The results of this study show that Apo E genotype does not have an impact on the lipid response to PS as a cholesterol-lowering agent in mild-hypercholesterolemic patients. Furthermore, the evidence obtained confirms that LDLc particle size is not modified when PS are added to a standard healthy diet.

Topics: Animals; Apolipoproteins E; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Food, Fortified; Genotype; Humans; Hypercholesterolemia; Lipids; Lipoproteins, LDL; Male; Middle Aged; Milk; Particle Size; Phytosterols; Polymorphism, Genetic; Treatment Outcome; Triglycerides

As sitosterolemic patients have an increased cardiovascular risk, there is concern that reducing serum LDL-cholesterol concentrations by plant sterols enriched functional foods might adversely affect vascular function. Whether increased concentrations of plant sterols truly affect vascular function and whether these effects are exclusive to the larger vessels remains unknown. We compared the effects of long-term plant sterol and -stanol consumption on changes in retinal vessels diameter which reflex alterations in the microcirculation. Three randomized groups were studied at baseline and after 85-weeks. Group one (N=11) consumed plant sterol enriched margarine (2.5g/day), the second (N=8) plant stanol enriched margarine (2.5g/day), and the control group (N=11) non-enriched margarine (2.5g/day). Serum cholesterol-standardized campesterol and sitosterol concentrations increased by 354.84±168.22·102μmol/mmol and 84.36±48.26·102μmol/mmol (p<0.001), respectively in the sterol group, while decreasing non-significantly in the plant stanol group. Serum LDL-cholesterol concentrations decreased significantly in both the plant sterol (-0.33±0.33mmol/L, p=0.016) and -stanol groups (-0.38±0.34mmol/L, p=0.018) compared to the increase in the controls (0.29±0.34mmol/L). The mean change in venular diameters for the plant sterol group (2.3±3.1μm), plant stanol groups (-0.8±3.4μm) and control group (-0.8±5.1μm) did not reach significance but the change in cholesterol-standardized campesterol concentrations correlated positively with the change in venular diameter independent of changes in serum LDL-cholesterol concentrations (r=0.39, N=30, p=0.033). Increased serum campesterol concentration correlated positively with increased retinal venular diameter, independent from changes in serum LDL-cholesterol concentrations. This may constitute an explanation for the suggested effects of plant sterols on vascular function. However, this novel finding needs confirmation and further study.

Topics: Adolescent; Adult; Aged; Arterioles; Cholesterol; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Phytosterols; Plant Extracts; Retinal Vessels; Sitosterols; Sterols; Venules

To establish the effectiveness of a new phytosterol-containing spread derived from rice bran oil (RBO), a randomised, double-blind, cross-over human clinical trial was conducted over 12 weeks. A total of eighty mildly hypercholesterolaemic (total blood cholesterol level ≥ 5 and ≤ 7·5 mmol/l with a serum TAG level of ≤ 4·5 mmol/l) individuals were randomised into two groups (n 40). Group 1 consumed spread only daily for 4 weeks. They were randomised to consume 20 g RBO spread (RBOS), 20 g standard spread (SS) or 20 g phytosterol-enriched spread (PS). After a 4-week period, individuals changed to the next randomised treatment until all three treatments had been consumed. Group 2 consumed spread plus oil daily for 4 weeks. They consumed 20 g RBOS plus 30 ml RBO, 20 g SS plus 30 ml sunflower oil or 20 g RBOS. Blood samples were collected for the analysis of lipid parameters, and 3 d diet records were collected. Compared with SS, RBOS significantly reduced total cholesterol by 2·2 % (P = 0·045), total cholesterol:HDL by 4·1 % (P = 0·005) and LDL-cholesterol by 3·5 % (P = 0·016), but was not as effective overall as PS, which reduced total cholesterol by 4·4 % (P = 0·001), total cholesterol:HDL by 3·4 % (P = 0·014) and LDL-cholesterol by 5·6 % (P = 0·001). In group 2, the addition of RBO to the RBOS produced no differences in cholesterol levels. These results confirm that RBOS is effective in lowering serum cholesterol when consumed as part of a normal diet.

Topics: Adult; Analysis of Variance; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diet Records; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Plant Oils; Rice Bran Oil

Phytosterols (PS) lower LDLc, but their effect on metabolic syndrome (MetS) remains unknown. We evaluated whether low-fat milk enriched with PS improves cardiovascular risk factors in these patients.. A randomised parallel trial employing 24 moderate-hypercholesterolaemic MetS patients and consisting of two 3-month intervention phases. After a 3-month healthy diet, patients were divided into two intervention groups: diet (n = 10) and diet + PS (n = 14) (2 g/day). A control group of 24 moderate-hypercholesterolaemic patients without MetS (matched in age and BMI) underwent the same procedure.. Neither dietary intervention nor enrichment of PS induced any improvement in the serum lipoprotein profile of MetS patients. By contrast, in the non-MetS population, a healthy diet effectively reduced TC, LDLc, non-HDLc and Apo B-100, with further decreases in TC (6.9%), LDLc (10.5%), non-HDLc (10.3%), Apo B-100 (6.2%) and Apo B-100/ApoA-I ratio (11.6%) being observed when PS were administered. No differences in LDL diameter, hsCRP or homocysteine were detected in any of the groups after consuming PS. This supplementation produced a significant increase in PS levels only in the non-MetS population.. PS therapy appears to be of little value to MetS patients, likely due to its reduced intestinal cholesterol absorption. The efficacy of PS as hypocholesterolaemic agents is thus limited.

Topics: Adult; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Cholesterol, Dietary; Dietary Supplements; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Intestinal Absorption; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Risk Factors; Severity of Illness Index; Sitosterols; Spain

Oat bran shows cholesterol-lowering properties, but its effects on other cardiovascular risk markers are less frequently investigated. This study examined the effects of oat bran on blood lipids, hemostatic factors and energy utilization.. A double-blind, randomized crossover study in 24 adults (age 25.2±2.7 years; body mass index: 24.9±2.9 kg/m2), who completed two 2-week dietary intervention periods: low-fiber diet (control) or an oat bran (control +102 g oat bran/day) diet. Fasting blood samples were drawn before and after each period, and 3-day fecal samples were collected during the last week of each period.. Total cholesterol decreased by 14% during the oat bran period compared with 4% during the control period (P<0.001). Non-high-density lipoprotein (HDL) cholesterol decreased by 16% in the oat bran period compared with 3% in the control period (P<0.01), as did total triacylglycerol (21 vs 10%, P<0.05) and very-low-density lipoprotein triacylglycerol 33 vs 9%, P<0.01). Plasminogen activator inhibitor-1 (PAI-1) and factor VII (fVII) levels decreased more during consumption of oat bran compared with the control period (PAI-1: 30 vs 2.3%, P<0.01; fVII: 15 vs 7.6%, <0.001). Fecal volume and dry matter were greater when consuming the oat bran diet compared with the control (P<0.001), and energy excretion was increased by 37% (1014 vs 638 kJ/day, P<0.001); however, changes in body weight did not differ (oat bran:-0.3±0.5 kg; control: 0.0±0.7 kg).. Addition of oat bran (6 g soluble fiber/day) to a low-fiber diet lowered total and non-HDL cholesterol, as well as hemostatic factors, and may affect energy balance through reduced energy utilization.

Topics: Adult; Avena; Cardiovascular Diseases; Cholesterol, HDL; Cross-Over Studies; Diet; Dietary Fiber; Double-Blind Method; Edible Grain; Female; Hemostatics; Humans; Hypercholesterolemia; Lipoproteins, VLDL; Male; Phytosterols; Plasminogen Activator Inhibitor 1; Risk Factors; Triglycerides; Young Adult

The relationship between plant sterol (PS) absorption and circulatory concentrations with cholesterol absorption and biosynthesis during PS consumption has yet to be clearly elucidated in humans. It is therefore essential to examine campesterol, β-sitosterol, and cholesterol absorption and cholesterol fractional synthesis rate (FSR) following PS consumption in individuals with high versus low basal circulatory PS concentrations.. A randomized, crossover trial was conducted in 82 hypercholesterolemic men consuming spreads with or without 2 g/d of PS for two 4-week periods, each separated by a 4-week washout. Endpoint tracer enrichments after ingestion of (2)H-labeled campesterol or β-sitosterol and (13)C-labeled cholesterol were determined by isotope ratio mass spectrometry.. For both phases of dietary intervention, the endpoint cholesterol absorption index was positively correlated with campesterol (r = 0.5864, p < 0.0001) and β-sitosterol (r = 0.4676, p < 0.0001) absorption indices; inversely, endpoint cholesterol FSR correlated negatively with the absorption indices of campesterol (r = -0.5004, p < 0.0009), β-sitosterol (r = -0.4154, p < 0.05), and cholesterol (r = -0.4056, p < 0.0001). PS intervention reduced absorption indices of campesterol, β-sitosterol, and cholesterol by 36.5% ± 2.7%, 39.3% ± 2.9%, and 34.3% ± 1.9%, respectively, but increased cholesterol FSR by 33.0% ± 3.3% relative to control. Endpoint circulatory PS levels (cholesterol adjusted) were positively associated with endpoint absorption indices of campesterol (r = 0.5586, p < 0.0001, for placebo; r = 0.6530, p < 0.0001, for PS intake) and cholesterol (r = 0.3683, p < 0.001 for placebo; r = 0.3469, p < 0.002, for PS intake) and were negatively associated with cholesterol FSR (r = -0.3551, p < 0.002, for placebo; r = -0.3643, p < 0.001, for PS intake). The cholesterol-lowering effect of PS was most pronounced among individuals falling within the 50th-75th percentiles of basal PS concentrations.. These data suggest that basal PS concentrations indicate not only sterol absorption efficiency but also the extent of PS-induced cholesterol reduction and thus might be clinically useful to predict the extent of cholesterol response to PS intervention within a given individual.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Endpoint Determination; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols; Triglycerides

Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism.. Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both P<0.0001). Fecal cholesterol excretion was significantly greater (P<0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; (P<0.0001 relative to control).. The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00863265.

Topics: Adult; Aged; Anticholesteremic Agents; Azetidines; Cholesterol, Dietary; Cholesterol, LDL; Combined Modality Therapy; Drug Synergism; Ezetimibe; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Phytosterols; Young Adult

It has been demonstrated that statins can increase intestinal sterol absorption. Augments in phytosterolemia seems related to cardiovascular disease.. We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.. In an open label, randomized, parallel-design study with blinded endpoints, subjects with primary hypercholesterolemia (n = 116) were assigned to receive during 12 weeks, a daily dose of 25 g of fiber (corresponding to 6 g of soluble fibers) plus rosuvastatin 40 mg (n = 28), rosuvastatin 40 mg alone (n = 30), sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber (n = 28), or sinvastatin 40 mg plus ezetimibe 10 mg (n = 30) alone.. The four assigned therapies produced similar changes in total cholesterol, LDL-cholesterol, and triglycerides (p < 0.001 vs. baseline) and did not change HDL-cholesterol. Fiber intake decreased plasma campesterol (p < 0.001 vs. baseline), particularly among those patients receiving ezetimibe (p < 0.05 vs. other groups), and β-sitosterol (p = 0.03 vs. baseline), with a trend for lower levels in the group receiving fiber plus ezetimibe (p = 0.07). Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol (p = 0.003 vs. other groups). Compared to non-fiber supplemented individuals, those treated with fibers had weight loss (p = 0.04), reduced body mass index (p = 0.002) and blood glucose (p = 0.047).. Among subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia. Additional benefits include improvement in blood glucose and anthropometric parameters.

Topics: Azetidines; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fiber; Ezetimibe; Female; Fluorobenzenes; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Phytosterols; Pyrimidines; Rosuvastatin Calcium; Sitosterols; Sulfonamides; Triglycerides

Studies have been conducted on supplementing the daily diet with plant sterol ester-enriched milk derivatives in order to reduce LDL-cholesterol levels and, consequently, cardiovascular risk. However, clinical practice guidelines on hypercholesterolaemia state that there is not sufficient evidence to recommend their use in subjects with hypercholesterolaemia. The main objective of this study is to determine the efficacy of the intake of 2 g of plant sterol esters a day in lowering LDL-cholesterol levels in patients diagnosed with hypercholesterolaemia. The specific objectives are: 1) to quantify the efficacy of the daily intake of plant sterol esters in lowering LDL-cholesterol, total cholesterol and cardiovascular risk in patients with hypercholesterolaemia; 2) to evaluate the occurrence of adverse effects of the daily intake of plant sterol esters; 3) to identify the factors that determine a greater reduction in lipid levels in subjects receiving plant sterol ester supplements.. Randomised, double-blind, placebo controlled experimental trial carried out at family doctors' surgeries at three health centres in the Health Area of Albacete (Spain). The study subjects will be adults diagnosed with "limit" or "defined" hypercholesterolaemia and who have LDL cholesterol levels of 130 mg/dl or over. A dairy product in the form of liquid yoghurt containing 2 g of plant sterol ester per container will be administered daily after the main meal, for a period of 24 months. The control group will receive a daily unit of yogurt not supplemented with plant sterol esters that has a similar appearance to the enriched yoghurt. The primary variable is the change in lipid profile at 1, 3, 6, 12, 18 and 24 months. The secondary variables are: change in cardiovascular risk, adherence to the dairy product, adverse effects, adherence to dietary recommendations, frequency of food consumption, basic physical examination data, health problems, lipid-lowering medication, physical activity, smoking habits and socio-demographic variables.. If plant sterol ester supplements were effective a sounder recommendation for the consumption of plant sterols in subjects with hypercholesterolaemia could be made.

Topics: Adolescent; Adult; Anticholesteremic Agents; Cholesterol; Clinical Protocols; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Phytosterols; Spain; Young Adult

Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored.. We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols.. In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption.. When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 microg/dL, staest: 37 +/- 2 microg/dL, serum campestanol during intervention, controls: 0.5 +/- 0 microg/dL, staest: 9 +/- 1 microg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks.. Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.

Topics: Adult; Aged; Anticholesteremic Agents; Biomarkers; Cholesterol; Double-Blind Method; Esters; Female; Follow-Up Studies; Food, Formulated; Humans; Hypercholesterolemia; Intestinal Absorption; Lipids; Lipoproteins; Male; Middle Aged; Phytosterols; Phytotherapy; Sitosterols; Time Factors

A healthy diet and plant sterols (PS) are recommended for reducing low-density lipoprotein (LDL) cholesterol and, subsequently, the risk of premature cardiovascular disease. PS mediate a decrease in fat-soluble vitamin concentration, which can lead to a general impairment of antioxidative defenses and an increase in oxidative stress. Thus, we evaluated the effects of a healthy diet, including PS-enriched low-fat milk, on cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects. This was a randomized parallel trial employing 40 subjects and consisting of two 3-month intervention phases. After 3 months on a standard healthy diet, subjects were divided into two intervention groups: a diet group and a diet+PS group (2 g/day). Lipid profile, apolipoproteins, high-sensitivity C-reactive protein and oxidative stress parameters were analyzed. Diet significantly reduced total and LDL cholesterol (4.0% and 4.7%, respectively), produced an increase in the level of beta-carotene (23%) and improved the antioxidant capacity of LDL cholesterol particles (4.6%). PS induced a significant decrease in total cholesterol (6.4%), LDL (9.9%) and the apolipoprotein B100/apolipoprotein A1 ratio (4.9%), but led to a decrease in cryptoxanthin level (29%) without any change being observed in the antioxidant capacity of LDL cholesterol particles, total antioxidant status or lipid peroxidation. After 3 months, we observed the positive effect of including a PS supplement in dietary measures, as the lipoprotein-mediated risk of cardiovascular disease was reduced. Despite a decrease in the concentration of cryptoxanthin, no evidence of a global impairment of antioxidative defenses or an enhancement of oxidative stress parameters was found.

Topics: Adult; Aged; Animals; Cardiovascular Diseases; Humans; Hypercholesterolemia; Middle Aged; Milk; Oxidative Stress; Phytosterols

Phytosterols (PS) are recommended to reduce LDL-cholesterol. However, the influence of cholesterol and fat intake on the lipid-lowering effect of PS in mildly hypercholesterolaemia is unclear. Thus, the aim of the present study was to evaluate whether the efficacy of PS is related to the composition of saturated fat and dietary cholesterol intake. Additionally, serum carotenoid content was analysed to evaluate to what extent it was undermined by PS. This was a 3-month randomised, parallel trial with a three-arm design. Patients were divided into three groups: healthy diet (n 24), healthy diet+PS (n 31) and free diet+PS (n 29), receiving 2 g/d of PS. Healthy and free diets were characterised by a daily ingestion of 6.8 % of saturated fat and 194.4 mg of cholesterol and 12.7 % of saturated fat and 268.1 mg of cholesterol, respectively. After PS therapy, patients receiving the healthy diet+PS or a free diet+PS exhibited a similar reduction in total cholesterol (6.7 and 5.5 %), LDL-cholesterol (9.6 and 7.0 %), non-HDL-cholesterol (12.2 and 8.9 %) and apo B-100/apo A-I ratio (11.5 and 11.6 %), respectively. In patients following the healthy diet, (β-carotene concentration rose by 26.9 %, whereas the β-carotene and lycopene levels dropped by 21.0 and 22.8 % in the group receiving the free diet+PS, respectively. No change was observed in carotenoid levels in healthy diet+PS group. In conclusion, the efficacy of PS in relation to lipoprotein profile is not influenced by saturated fat or dietary cholesterol intake, which confirms the positive effect of healthy diet therapy in improving the negative effects that PS exert on carotenoid levels.

Topics: Adolescent; Adult; Aged; Animals; Apolipoproteins; beta Carotene; Cholesterol; Cholesterol, Dietary; Dietary Fats; Fatty Acids; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Milk; Phytosterols; Phytotherapy; Plant Extracts; Young Adult

The aim of the current study was to evaluate the therapeutic effects of omega-3 plant sterol esters (n-3-PSE) on lipid profile and other coronary heart disease risk factors in subjects with mixed hyperlipidemia.. Ninety-one patients with mixed hyperlipidemia were randomized in a double blind fashion to receive either placebo (corn oil) or n-3-PSE. Twenty four patients dropped out or were excluded from the efficacy analysis due to protocol violation. The primary efficacy endpoint was mean change in plasma low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment. Other efficacy measures included plasma lipids, lipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels. Participants who completed the double-blind study were given the option to continue into an open-label, 12-weeks follow up phase.. n-3-PSE treatment did not result in a significant change in LDL-C levels. Triglyceride levels were reduced significantly by 19% (51 mg/dL, p < 0.0001) in the n-3-PSE group in comparison with the placebo group (p = 0.025). Diastolic blood pressure and hsCRP were reduced by 7% (5.9 mmHg) and 7.8% (0.6 mg/L), respectively, and were significantly different from the placebo group (p = 0.036 and p = 0.018, respectively).. In patients with mixed hyperlipidemia, n-3-PSE treatment may offer a safe and effective therapy for triglyceride level reduction while avoiding the typical increase in LDL-C levels associated with n-3 fatty acid treatment. The observed reduction in blood pressure and inflammation markers warrants further evaluation. The positive effect of n-3-PSE treatment was preserved at the end of the follow up phase.

Topics: Blood Pressure; C-Reactive Protein; Cholesterol, LDL; Double-Blind Method; Esters; Fatty Acids, Omega-3; Female; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Male; Middle Aged; Phytosterols; Placebos; Triglycerides

To date, there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus (T2DM). In this study, we recruited patients for hypercholesterolemic groups with T2DM (n = 42; men/women = 24/18; HbA1c = 6.7 ± 5.4%) and without T2DM (n = 21; men/women = 7/14; HbA1c = 5.3 ± 0.4%). Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study. At baseline and after 12 weeks of treatment, several lipid parameters, including serum low-density-lipoprotein cholesterol (LDL-C), non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and cholesterol synthesis/absorption-related markers, were measured. Compared with those at the baseline, the levels of LDL-C, non-HDL-C, campesterol, and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups. After adjusting for confounding factors, such as age, gender, smoking, and BMI, the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM (-25.1 ± 13.6% in LDL-C, -20.5 ± 11.2% in non-HDL-C) than those without T2DM (-20.5 ± 7.8% in LDL-C, P < 0.05; -17.4 ± 7.6% in non-HDL-C, P < 0.05). The reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM. Taken together, these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM.

Topics: Aged; Azetidines; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholestanol; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Ezetimibe; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipids; Male; Middle Aged; Phytosterols; Sitosterols

Plant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant beta-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved.. The effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated in a multicenter, randomized double blind study. Hypercholesterolemic patients consumed a FM daily for 6 weeks. Subjects were randomized to receive either 1.6g of plant sterol-enriched FM (n=60) or control FM product (n=56). After 6 weeks of plant sterol-enriched FM consumption, LDL cholesterol was reduced from 166.2+/-2.0 to 147.4+/-2.8 mg/dL (p=0.01). A significant reduction was observed for total cholesterol (from 263.5+/-2.6 to 231.0+/-3.2mg/dL, p=0.01). There was greater LDL cholesterol lowering among hypercholesterolemic patients with higher LDL cholesterol at baseline. We found a reduction of plasma 8-isoprostane in patients taking plant sterol-enriched FM (from 43.07+/-1.78 to 38.04+/-1.14 pg/ml, p=0.018) but not in patients taking the control product (from 42.56+/-2.12 to 43.19+/-2.0 pg/ml, p=NS). Campesterol and beta-sitosterol levels were not influenced by phytosterol consumption.. Daily consumption of low-fat plant sterol dairy product favourably changes lipid profile by reducing LDL-cholesterol, and may also have an anti-oxidative effect through a reduction of plasma isoprostanes.

Topics: Anticholesteremic Agents; Antioxidants; Cholesterol; Cultured Milk Products; Dinoprost; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Italy; Male; Middle Aged; Oxidative Stress; Phytosterols; Sterols; Time Factors; Treatment Outcome

Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce plasma cholesterol levels due to reduced intestinal absorption. The aim of this study was to investigate the effect of phytosterol-enriched yogurt consumption on the major serum lipid parameters, low density lipoprotein (LDL) receptor activity, LDL-receptor affinity, and CD36 expression in hypercholesterolemic subjects. Fifteen patients affected by polygenic hypercholesterolemia were evaluated in a single-blind randomized crossover study after a 4 weeks treatment with a phytosterol-enriched yogurt containing 1.6 g esterefied phytosterols (equivalent to 1.0 g free phytosterol). Lipid parameters were compared with a phytosterol-free placebo-controlled diet. The effect of the two treatments on each variable, measured as percentage change, was compared by paired samples t test and covariance analysis. The treatment induced a modest but significant decrease in LDL-cholesterol levels (4.3%, P = 0.03) and a significant increase in high density lipoprotein (HDL) 3-cholesterol (17.1%, P = 0.01). Phytosterol consumption had no effect on LDL-receptor activity whereas patient LDL-receptor affinity significantly increased (9.7%, P = 0.01) and CD36 expression showed a marked significant decrease (18.2%, P = 0.01) in the phytosterol-enriched yoghurt patients. Our data show that the oral administration of a phytosterol-enriched yogurt has modest but significant effects on commonly measured lipid parameters. The improvement of LDL-receptor affinity and the reduction in CD36 expression may reflect an important antiatherogenic effect.

Topics: CD36 Antigens; Cholesterol, LDL; Cross-Over Studies; Female; Humans; Hypercholesterolemia; Lipoproteins, LDL; Lymphocytes; Male; Middle Aged; Phytosterols; Receptors, LDL; Yogurt

Polymorphisms of the ABCG5 and ABCG8 genes interfere with cholesterol absorption and synthesis. We determined whether common polymorphisms of these genes regulate the responses of serum cholesterol and vascular function during long-term inhibition of cholesterol absorption. Mildly to moderately hypercholesterolaemic subjects (n 282) completed a 1-year study consuming plant stanol or sterol ester (2 g stanol or sterol) or control spread. Serum cholesterol and non-cholesterol sterols, markers of cholesterol absorption and synthesis, and variables of vascular function and structure were analysed in relation to common polymorphisms of ABCG5 and ABCG8. At baseline, subjects with the 54K allele of ABCG8 had higher brachial endothelial-dependent flow-mediated dilatation than those without it (5.79 (se 0.31) v. 4.46 (se 0.44) %; P = 0.049), and subjects with the 632V allele of ABCG8 had larger brachial artery diameter than those without it. Polymorphisms of ABCG5 and ABCG8 were neither associated with serum cholesterol reduction nor changes in cholesterol metabolism or in vascular function. However, in subjects with the 400K allele of ABCG8, intima media thickness (IMT) was increased in all groups more than in those without it (P < 0.05). In conclusion, serum cholesterol lowering with absorption inhibition was not associated with polymorphic sites of ABCG5 and ABCG8. However, regulation of baseline cholesterol metabolism and vascular function and structure, and IMT progression during 1 year seemed to share some of the common polymorphic sites of these genes, suggesting a gene-regulated interaction between cholesterol metabolism and vascular function and structure.

Topics: Adult; Aged; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Brachial Artery; Carotid Arteries; Cholesterol; Double-Blind Method; Female; Food, Fortified; Gene Expression Regulation; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Phytosterols; Polymorphism, Genetic; Sitosterols; Tunica Intima; Tunica Media; Vasodilation

The present study was designed to evaluate the independent and interactive effects of a once-a-day yoghurt drink providing 2 g plant sterols/d and capsules providing 2 g fish oil n-3 long-chain (LC) PUFA/d on plasma lipids, apolipoproteins and LDL particle size. Following a 2-week run-in period, 200 mildly hypercholesterolaemic Indian adults aged 35-55 years were randomised into one of four groups of a 2 x 2 factorial, double-blind controlled trial. The 4-week treatments consisted of (1) control yoghurt drink and control capsules, (2) control yoghurt drink and fish oil capsules, (3) plant sterol-enriched yoghurt drink and control capsules, or (4) plant sterol-enriched yoghurt drink and fish oil capsules. Blood was drawn before and after the 4-week intervention. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The main effects of plant sterols were a 4.5 % reduction in LDL-cholesterol and a 15 % reduction in TAG without a significant change in HDL-cholesterol. Overall, fish oil n-3 LC-PUFA did not significantly affect cholesterol concentrations but reduced TAG by 15 % and increased HDL-cholesterol by 5.4 %. The combination significantly lowered TAG by 15 % v. control. No significant interaction between plant sterols and n-3 LC-PUFA was observed on plasma cholesterol concentrations. In conclusion, once-a-day intake of 2 g plant sterols/d in a yoghurt drink, 2 g fish oil n-3 LC-PUFA/d in capsules, and their combination had beneficial effects on the lipid profile of mildly hypercholesterolaemic Indian adults. The potent hypotriacylglycerolaemic effect of plant sterols observed in the present study and this population warrants additional investigation.

Topics: Adult; Age Factors; Apolipoproteins; Capsules; Energy Intake; Fatty Acids, Omega-3; Feeding Behavior; Female; Fish Oils; Humans; Hypercholesterolemia; Hyperlipidemias; India; Life Style; Lipids; Lipoproteins, LDL; Male; Middle Aged; Patient Compliance; Phytosterols; Reproducibility of Results

Recent animal and human studies have shown that plant sterols and stanols, which are used as functional food ingredients to lower increased LDL cholesterol concentrations, pass the blood-brain barrier. Whether this affects neurocognitive functioning and mental well-being in humans has, to our knowledge, never been investigated. The aim of the present study was therefore to examine the effects of long-term plant sterol or stanol consumption on neurocognitive functioning and mood in a randomized, double-blind, placebo-controlled dietary intervention trial. To this end, hypercholesterolemic individuals, aged 43-69 y, receiving stable statin treatment were randomly assigned to an 85-wk supplementation with margarines enriched with plant sterol esters (2.5 g/d), plant stanol esters (2.5 g/d), or placebo. At baseline and at the end of the intervention period, all participants underwent a cognitive assessment. In addition, subjective cognitive functioning and mood were assessed by means of questionnaires (Cognitive Failure Questionnaire and depression subscale of the Symptom Checklist 90, respectively). Long-term supplementation with plant sterol or stanol esters did not affect cognitive performance (memory, simple information processing speed, complex information processing speed, Letter-Digit Substitution test performance), subjective cognitive functioning, or mood. In conclusion, the present results indicate that long-term use of plant sterols or stanols at recommended intakes of 2.5 g/d does not affect neurocognitive functioning or mood in hypercholesterolemic individuals receiving statin treatment.

Topics: Adolescent; Adult; Affect; Aged; Blood Pressure; Cognition; Diet; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Learning; Male; Margarine; Memory; Middle Aged; Phytosterols; Placebos; Sitosterols; Thinking; Young Adult

Studies in our laboratory have previously demonstrated in hamsters a superior cholesterol-lowering ability of plant sterol (PS) esters enriched in stearate compared with linoleate. We therefore conducted a randomized, double-blind, 2-group parallel, placebo-controlled study to test the cholesterol-lowering properties of stearate-enriched PS esters in normo- and hypercholesterolemic adults. Thirty-two adults, 16 per group with equal number of males and females in each group, participated in the 4-wk study. Participants consumed 3 g/d (1 g three times per day with meals) of either PS esters or placebo delivered in capsules. Serum LDL cholesterol concentration significantly decreased 0.42 mmol/L (11%) and the LDL:HDL cholesterol ratio decreased 10% with PS ester supplementation, whereas LDL particle size and lipoprotein subclass particle concentrations (as measured by NMR) were not affected. The percent change in LDL cholesterol was positively correlated with baseline lathosterol concentration (r = 0.729; P = 0.0014), indicating an association between the magnitude of LDL change and the rate of whole-body cholesterol synthesis. Serum campesterol (but not sitosterol) concentration significantly increased in the PS ester group. Serum tocopherol, retinol, and beta-carotene concentrations were not affected by PS ester supplementation. Thus, our findings demonstrate the usefulness of a novel stearate-enriched PS ester compound in decreasing LDL cholesterol in both normo- and hypercholesterolemic adults. The extent to which PS ester fatty acid composition affects intestinal micelle formation and cholesterol absorption in humans requires further study.

Topics: Adult; Aged; Anticholesteremic Agents; Cellulose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Stearates

Although consumption of various plant sterol (PS)-enriched beverages is effective in lowering plasma cholesterol, the lipid-lowering potential of PS in a soymilk format has not been investigated thoroughly. Therefore, to evaluate the efficacy of PS-enriched soy beverages on plasma lipids and cholesterol kinetics, we conducted two separate 28 d dietary controlled cross-over studies. In study 1, the cholesterol-lowering efficacy of a low-fat (2 g/serving) PS enriched soy beverage was examined in 33 normal cholesterolemic subjects in comparison with 1% dairy milk. In study 2, we investigated the efficacy of a moderate-fat (3.5 g/serving) PS-enriched soy beverage on plasma cholesterol concentrations and cholesterol kinetic responses in 23 hypercholesterolemic subjects compared with 1% dairy milk. Both the low and moderate-fat PS-enriched soymilk varieties provided 1.95 g PS/d. Endpoint plasma variables were analyzed by repeated-measures ANOVA using baseline values as covariates for plasma lipid measurements.. In comparison with the 1% dairy milk control, the low-fat soy beverage reduced (P < 0.05) total and LDL-cholesterol by 10 and 13%, respectively. Consumption of the moderate-fat PS-enriched soy beverage reduced (P < 0.05) plasma total and LDL-cholesterol by 12 and 15% respectively. Fasting triglycerides were reduced by 9.4% following consumption of the moderate-fat soy beverage in comparison with the 1% dairy milk. Both low and moderate-fat PS-enriched soy varieties reduced (P < 0.05) LDL:HDL and TC:HDL ratios compared with the 1% dairy milk control. Consumption of the moderate-fat PS-enriched soymilk reduced (P < 0.05) cholesterol absorption by 27%, but did not alter cholesterol synthesis in comparison with 1% dairy milk.. We conclude that, compared to 1% dairy milk, consumption of low and moderate-fat PS-enriched soy beverages represents an effective dietary strategy to reduce circulating lipid concentrations in normal to hypercholesterolemic individuals by reducing intestinal cholesterol absorption. TRIAL REGISTRATION (CLINICALTRIALS.GOV): NCT00923403 (Study 1), NCT00924391 (Study 2).

Topics: Cholesterol; Cholesterol, LDL; Cross-Over Studies; Dietary Fats; Humans; Hypercholesterolemia; Kinetics; Lipids; Phytosterols; Soy Milk

To assess safety during a diet based on low-fat foods enriched with nonesterified wood-derived plant sterols and mineral nutrients related to serum phytosterol, sex hormone and fat-soluble vitamin metabolism.. Seventy-one study participants (52 women, 19 men) with mild-to-moderate hypercholesterolemia completed the double-blind, placebo-controlled feeding trial lasting for 15 weeks. The subjects were randomly allocated to the sterol group receiving food items enriched with mineral nutrients as well as with a total of 1.25, 2.5 and 5.0 g per day of plant sterols during the first, second and third 5-week periods, respectively, or to the placebo group receiving similar food items without plant sterols. This outpatient clinical trial with free-living subjects was carried out at two hospital clinics.. Two significant findings were observed. Serum sitosterol concentrations increased from 2.84 to 5.35 mg l(-1) (P<0.004 vs placebo) but those of serum total plant sterols did not because of compensatory changes in other phytosterols. The highest plant sterol levels did not exceed 0.6% of total serum sterols. Serum alpha-tocopherol concentrations decreased in the sterol group by 10% (P<0.0002), but the between-group difference disappeared after adjusting for the change in the carrier (LDL cholesterol).. Fifteen-week consumption of natural nonesterified plant sterol-enriched food does not cause any serious adverse effects during such a period. However, serum alpha-tocopherol levels were somewhat reduced in the sterol group suggesting that long-term effects of plant sterols on serum fat-soluble vitamin concentrations should be further explored, especially in relation to very low-fat diets.

Topics: Adult; Aged; alpha-Tocopherol; Cholesterol, LDL; Diet; Double-Blind Method; Female; Finland; Food, Fortified; Gonadal Steroid Hormones; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Phytosterols; Sitosterols; Vitamins

Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects.. In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents) or without plant sterols (control) for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C). Secondary measurements were changes in total cholesterol (TC), non-HDL cholesterol (non-HDL-C), HDL cholesterol (HDL-C) and triglycerides.. Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p < 0.05). TC and non-HDL-C concentrations decreased by 0.26 mmol/l and 0.31 mmol/l (each p < 0.05), respectively. Mean reductions in total, LDL and non-HDL cholesterol were significantly greater than in the placebo group (p < 0.05). HDL-C and triglycerides were not affected. Compliance was very high (>96%), and products were well tolerated.. Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Double-Blind Method; Female; France; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Soy Milk

Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3-7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n 18) or plant stanol (n 19) (2.5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0.28 mmol/l (or 8.7 %; P = 0.08) and 0.42 mmol/l (13.1 %; P = 0.006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7 alpha-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.

Topics: Analysis of Variance; Anticholesteremic Agents; Biomarkers; Cholestenones; Cholesterol; Cholesterol, LDL; Double-Blind Method; Esters; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipid Metabolism; Lipoproteins; Male; Margarine; Middle Aged; Phytosterols; Sitosterols; Stigmasterol

This study examined the effect of plant sterols added, together with an emulsifying agent, to a low-fat yoghurt on the serum lipid and plant sterol values in moderately hypercholesterolaemic volunteers. Study I was a randomized double-blind, cross-over trial. For 4 weeks, 15 volunteers consumed yoghurt containing 1 g plant sterols or a placebo yoghurt. Study II was a randomized, double-blind, parallel-group study. For 8 weeks, the sterol group (n = 12) ingested daily two yoghurts (2 g/day plant sterols) and the placebo group (n = 14) ingested two yoghurts without plant sterols. Study I: compared with the placebo, the sterol yoghurt reduced serum total cholesterol by 0.15 mmol/l (2.2%, P=0.235) and low-density lipoprotein (LDL) cholesterol by 0.19 mmol/l (4.3%, P=0.082), and increased serum campesterol by 0.26 mg/100 ml (P=0.006) and sitosterol by 0.11 mg/100 ml (P=0.015). Study II: compared with the placebo, the sterol yoghurt reduced serum total cholesterol by 0.41 mmol/l (6.3%, P=0.167) and LDL cholesterol by 0.28 mmol/l (6.4%, P=0.306), and increased serum campesterol by 0.28 mg/100 ml (P=0.016) and sitosterol by 0.40 mg/100 ml (P=0.206). Meta-analysis: the pooled treatment difference was -0.34 mmol/l (5.2%, P=0.173) in total cholesterol and was -0.26 mmol/l (-5.8%, P=0.261) in LDL cholesterol, when the sterol yoghurt was compared with the placebo. A low-fat yoghurt enriched with 1-2 g/day plant sterols reduced serum cholesterol levels in moderately hypercholesterolaemic subjects. Campesterol and sitosterol serum levels increased, but their concentration remained in the range of normal values.

Topics: Adult; Analysis of Variance; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Sitosterols; Yogurt

To test the dose-response effect on low-density lipoprotein cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat spread.. Dose responses of soybean oil (BO), tall oil (TO) and a mix of tall oil and rapeseed oil (TO/RP) as fatty acid esters were tested in a parallel design in free-living subjects recruited from the general community who had elevated cholesterol concentrations. Subjects received either control for 6 weeks or 1.6 g PS per day for 3 weeks, then 3.0 g/day for 3 weeks.. LDL-c was lowered significantly by consumption of 1.6 g/day of PS (-10.4%, range -7.3 to -11.4%). Increasing the dose to 3.0 g/day modestly reduced LDL-c concentrations further to -14.7%. TO, containing 78% sitosterol, produced an increase in serum sitosterol of 6.5 nmol/ml, while BO, containing only 27% campesterol, produced an increase in serum campesterol of 9.5 nmol/ml in 6 weeks. After PS withdrawal, serum sterols declined by 50% within 2 weeks.. Different PS sources were equally effective in lowering serum LDL-c concentrations. The decrease in absolute concentrations of LDL-c was dependent on the baseline concentrations.

Topics: Adult; Aged; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Sitosterols; Triglycerides; Young Adult

Dietary therapy using phytosterols can reinforce statin treatment; however the value of a low-dose combination of those agents remains to be investigated. Plant sterols (PS), dissolved in diacylglycerol (DAG) oil, (PS/DAG) can be effective at a relatively low dose. The objective of the present study was to examine the effect of PS/DAG oil on blood cholesterol concentrations in hypercholesterolemic outpatients on low-dose pravastatin (10 mg/day).. The patients (n=61) were randomly assigned to one of three groups, who consumed TAG (control), DAG or PS/DAG oil. The average intake of PS from the PS/DAG oil during the test period was significantly higher than that for TAG and DAG oils (502 vs. 49 and 38 mg/day, P<0.05). Significant cholesterol-lowering effects from the baseline were observed in the case of the PS/DAG oil treatment alone. Changes in low-density lipoprotein (LDL) cholesterol were inversely correlated with baseline serum campesterol concentrations (r=-0.560, P<0.05), but not baseline LDL cholesterol concentrations. In addition, serum apolipoprotein B concentrations were reduced to a greater extent in subjects with high versus low levels of baseline campesterol (-13.2 mg/dL vs. -3.1 mg/dL, P<0.05). Furthermore, there was a mild, but significant reduction in serum lipoprotein (a) concentration from the baseline (-5.9 mg/dL), which was correlated with the reduction in serum apolipoprotein B concentration (r=0.596, P<0.05).. A low-dose combination of PS/DAG oil and pravastatin may be a useful strategy for further ameliorating blood cholesterol and lipoprotein (a) concentrations for hypercholesterolemic patients with a low response to pravastatin.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Diglycerides; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Female; Humans; Hypercholesterolemia; Lipoprotein(a); Male; Middle Aged; Phytosterols; Pravastatin; Solubility; Treatment Outcome; Triglycerides

Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and ratios of these sterols to total cholesterol (TC) are reported to correlate with efficiency of intestinal cholesterol absorption, whereas levels of certain cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios to TC correlate with cholesterol biosynthesis. However, there is a paucity of published data concerning the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) on these parameters.. To characterize the effects of ezetimibe co-administered with statins, compared with each treatment alone, on cholesterol precursor sterols and plasma phytosterol levels.. A post-hoc analysis was performed to determine the effects of treatment with ezetimibe 10 mg, simvastatin (10-80 mg), and atorvastatin (10-80 mg), alone or in combination, on these non-cholesterol sterols using plasma samples from two randomized controlled trials involving patients with primary hypercholesterolemia (low-density lipo protein [LDL-C] = 145-250 mg/dL; triglycerides < or = 350 mg/dL; N = 975) but without a recent (< or = 6-month) history of coronary heart disease (CHD) or either uncontrolled or newly diagnosed diabetes mellitus.. Ezetimibe monotherapy significantly reduced plasma sitosterol and campesterol concentrations from baseline compared with placebo (both p < 0.001), whereas statins significantly lowered desmo sterol and lathosterol levels (p < 0.001 vs. placebo). Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these sterols (p < 0.001).. The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe-statin) doses and circulating non-cholesterol levels.

Topics: Aged; Anticholesteremic Agents; Azetidines; Cholesterol; Double-Blind Method; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Placebos; Simvastatin; Sitosterols; Sterols

In a placebo-controlled double-blind study, we examined the effects of dressing containing plant sterol (PS) on blood lipids and the safety in Japanese borderline or mildly hypercholesterolemic subjects. Fifty-nine subjects [total cholesterol (TC) concentration > or = 200 mg/dL] were randomly divided into two groups and were given daily 15 g of dressing containing 800 mg of PS [PS(+)-group] or without PS [PS(-)-group] for 12 weeks. Every 4 weeks, fasting blood was examined and subjective symptoms were analyzed. Serum TC, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) concentrations did not change in the PS(-)-group, while TC and ApoB significantly decreased in the PS(+)-group at 8 and 12 weeks and LDL-C at 4, 8 and 12 weeks. Moreover, serum TC, LDL-C and ApoB concentrations were significantly lower than those of PS(-)-group at 8 and 12 weeks. Other laboratory tests were all in normal ranges and no adverse events were observed. The results indicated that PS-containing dressing decreased serum TC, LDL-C and ApoB concentrations in borderline or mildly hypercholesterolemic subjects. It is therefore proved that the dressing containing PS is helpful in maintaining blood cholesterol level normal and hence, the health of Japanese.

Topics: Adult; Apolipoproteins B; Asian People; Cholesterol, LDL; Fasting; Female; Food Additives; Humans; Hypercholesterolemia; Japan; Male; Middle Aged; Phytosterols

The number of hypercholesterolemic individuals who do not meet their cholesterol recommended targets is inappropriately high. The use of plant sterol-enriched foods could help in this clinical setting.. To evaluate the efficacy and side effects of plant sterol-enriched fermented milk in reducing LDL-cholesterol and increasing the number of patients who attain their therapeutic targets.. This was a multicentre, randomised, double-blind, placebo-controlled, parallel clinical trial. Eighty-three hypercholesterolemic patients that were not at therapeutic goals were studied. The patients received one 100 ml serving of either plain (control) low-fat or phytosterol enriched (1.6 g of free sterol equivalents) drinkable yogurt per day along with the main meal for 42 days. The principal variables were variation on LDL cholesterol (LDL-C) concentration and the number of patients achieving therapeutic goals after intervention.. Patients on phytosterols attained an average LDL-C reduction of more than 10% (12.2% after 3 weeks; 10.6% after 6 weeks) (P = 0.001; 95% CI: 4.03-19.00) regardless of statin therapy compared to the control group. About 50% of the subjects on phytosterols, as compared to 20% of controls, attained their LDL-C target values (<3.3 or <2.6 mmol/l for primary and secondary prevention, respectively) at the end of the study (P < 0.001). HDL-cholesterol (HDL-C) did not change and triglycerides (TG) were decreased by 14% (P < 0.018). The plasma sterols/total cholesterol ratio increased.. Plant sterol-enriched fermented milk significantly reduced LDL-C and increased the number of moderately hypercholesterolemic patients achieving therapeutic targets.

Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Cholesterol, LDL; Cultured Milk Products; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Treatment Outcome; Yogurt

Plant sterols (PSs) reduce plasma total and low-density lipoprotein cholesterol (LDL-C) levels by reducing cholesterol absorption; however, it is not known whether the level of dietary cholesterol intake has an impact on the efficacy of PSs on blood lipids. The purpose of this study was to determine the effect of high vs low dietary cholesterol levels on the lipid-lowering efficacy of free PSs. The study was a semirandomized, double-blind, crossover trial consisting of four 28-day feeding phases each separated by a 4-week washout period. Otherwise healthy hypercholesterolemic subjects (n = 22) consumed each of (a) low-cholesterol control (C(-)S(-)), (b) high-cholesterol control (C(+)S(-)), (c) 22 mg PSs per kilogram of body weight with a low-cholesterol diet (C(-)S(+)), and (d) 22 mg PSs per kilogram of body weight with a high-cholesterol diet (C(+)S(+)). Blood was drawn on the first and last 2 days of each phase to measure plasma total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triacylglycerols as well as plasma campesterol and beta-sitosterol concentrations. Dietary cholesterol had no effect on PS efficacy as a cholesterol-lowering agent because no interaction was found between the 2 factors. However, dietary cholesterol and PS intake had significant independent effects on plasma total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels. beta-Sitosterol levels in plasma increased (P < .0001) as a result of PS supplementation. Data from the present study indicate that, although PSs and dietary cholesterol exert independent effects on plasma cholesterol, PS efficacy is not affected by varying levels of cholesterol intake.

Topics: Aged; Aged, 80 and over; Body Weight; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diet; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Patient Compliance; Patient Dropouts; Phytosterols; Triglycerides

Plant sterols combined with exercise beneficially alter lipid profiles in hypercholesterolemic adults. Although the mechanism by which plant sterols favorably modulate lipid levels is well established, no trial to date has examined the effect of exercise, alone or combined with plant sterols, on cholesterol kinetics. Thus, the current objective was to examine the effects of exercise, plant sterols, and the combination of exercise and plant sterols on cholesterol absorption and synthesis. In an 8-week, parallel-arm trial, 84 subjects were randomized to 1 of 4 interventions: plant sterols combined with exercise, plant sterols, exercise, or control. Diets were not controlled. Total cholesterol and triglyceride levels decreased (P<0.01) by 7.7% and 11.8%, respectively, whereas high-density lipoprotein (HDL) cholesterol levels increased (P<0.01) by 7.5% in the combination group. Mean posttreatment low-density lipoprotein (LDL) cholesterol levels decreased (P<0.01) by 0.30 mmol/L in the combination group. Cholesterol absorption was 16% lower (P<0.01) in the combination group and 18% lower (P<0.01) in the plant sterol group, when compared with control. Exercise had no effect on cholesterol absorption. Nonsignificant increases in cholesterol synthesis rates of 63% (0.084+/-0.014 pools/day), 59% (0.075+/-0.013 pools/day), and 57% (0.072+/-0.011 pools/day) were observed in the combination, exercise, and plant sterol groups, respectively, relative to the control group (0.031+/-0.019 pools/day). LDL cholesterol levels correlated with cholesterol absorption, as represented by the area under the deuterium enrichment curve (r=0.23, P=0.05), and with percent absorption relative to control (r=0.25, P=0.03). These findings suggest that exercise does not modulate lipid levels by altering to cholesterol absorption or synthesis, whereas plant sterols favorably alter levels of LDL cholesterol by suppressing intestinal absorption.

Topics: Body Composition; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Exercise; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Phytosterols; Single-Blind Method

Intake of food products rich in water-soluble fiber beta-glucan and products enriched with plant stanol esters lower serum cholesterol. Combining 2 functional food ingredients into one food product may achieve additional reductions of serum cholesterol. Our objective was to investigate the effects of a simultaneous intake of beta-glucan plus plant stanol esters on lipid metabolism in mildly hypercholesterolemic volunteers. In a randomized, controlled, 3-period crossover study, 40 mildly hypercholesterolemic men and women received muesli in random order twice a day for 4 wk, which provided, in total, 5 g control fiber from wheat (control muesli), 5 g oat beta-glucan (beta-glucan muesli), or 5 g oat beta-glucan plus 1.5 g plant stanols (combination muesli). beta-Glucan muesli decreased serum LDL cholesterol by 5.0% compared with control muesli (P = 0.013). Combination muesli reduced LDL cholesterol by 9.6% compared with control muesli (P < 0.001), and by 4.4% compared with beta-glucan muesli (P = 0.036). Serum HDL cholesterol and triacylglycerol concentrations did not differ after the 3 treatments. Compared with control muesli, beta-glucan muesli increased bile acid synthesis (P = 0.043) and decreased cholesterol absorption (P = 0.011). Addition of plant stanols did not influence bile acid synthesis but decreased cholesterol absorption (P < 0.001) and raised cholesterol synthesis (P = 0.016) compared with control muesli, and the plant stanols decreased cholesterol absorption compared with beta-glucan muesli (P = 0.004). The combination muesli decreased serum concentrations of sitostanol compared with control muesli (P = 0.010). Plasma concentrations of lipid-soluble antioxidants did not differ after the 3 treatments. beta-Glucan muesli effectively lowered serum LDL cholesterol concentrations. The addition of plant stanol esters to beta-glucan-enriched muesli further lowered serum LDL cholesterol, although effects were slightly less than predicted.

Topics: Adolescent; Adult; Aged; Antioxidants; beta-Glucans; Bile Acids and Salts; Cholesterol; Cross-Over Studies; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Lipids; Lipoproteins; Male; Middle Aged; Phytosterols

We previously demonstrated that a diet therapy involving consumption of 7.28 g psyllium (PSY) and 2 g of plant sterols (PS) per day reduced LDL cholesterol from 3.6 +/- 0.7 to 3.1 +/- 0.8 mmol/L (P < 0.01) and decreased the number of intermediate density lipoprotein particles and the smaller LDL and HDL subfractions in hypercholesterolemic individuals (n = 33). The study design was a randomized double blind crossover. Subjects consumed either 2 test cookies containing PSY+PS or 2 placebo cookies for 1 mo with a 3-wk wash out between treatments. To explore mechanisms of the lipid-lowering effects of combined PSY+PS, we present data related to intravascular and molecular regulation. Intake of PSY+PS decreased the cholesterol concentration in LDL-1 from 2.46 +/- 0.66 to 2.26 +/- 0.46 mmol/L and in LDL-2 from 0.63 +/- 0.24 to 0.54 +/- 0.27 mmol/L (P < 0.05) in the test compared with the placebo period. An increase in LDL peak size from 27.3 +/- 0.8 to 27.5 +/- 0.6 nm (P < 0.05) and a decrease in the prevalence of LDL pattern B from 27 to 18% (P < 0.05) also occurred during the PSY+PS period. Cholesteryl ester transfer protein activity was 11% lower (P < 0.05) during the test period. Notably, the abundance of the LDL receptor in circulating mononuclear cells as measured by real time PCR was 26% higher during the test compared with the placebo period (P < 0.03). These results indicate that the hypocholesterolemic action of PSY and PS can be explained in part by modifications in the intravascular processing of lipoproteins and by increases in LDL receptor-mediated uptake.

Topics: Adult; Aged; Cholesterol; Cholesterol Ester Transfer Proteins; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipoproteins; Lipoproteins, LDL; Male; Middle Aged; Monocytes; Osmolar Concentration; Oxidation-Reduction; Particle Size; Phosphatidylcholine-Sterol O-Acyltransferase; Phytosterols; Psyllium; Receptors, LDL; RNA, Messenger; Time Factors; Tissue Distribution

Plant sterols (PS) and MUFA are well-documented cholesterol lowering agents. We aimed to determine the effect of PS esterified to olive oil fatty acids (PS-OO) on blood lipid profile and lipid peroxidation in hypercholesterolaemic subjects. Twenty-one moderately overweight, hypercholesterolaemic subjects consumed three consecutive treatment diets, each lasting 28 d and separated by 4-week washout periods, using a randomized crossover design. Diets contained 30 % energy as fat, 70 % of which was provided by olive oil (OO), and differed only in the treatment oils: OO, PS esterified to sunflower oil fatty acids (PS-SO), and PS-OO. Both PS-SO and PS-OO treatments provided 1.7 g PS /d. PS-OO and PS-SO consumption resulted in a decrease (P = 0.0483) in LDL-cholesterol (LDL-C) concentrations compared with the OO diet. Although total cholesterol and apo B-100 levels were not significantly affected, PS-SO and, to some extent, PS-OO reduced the total:HDL-cholesterol (HDL-C) ratio (P = 0.0142) and the apo B-100:apo A-I ratio (P = 0.0168) compared with the OO diet. There were no differences across diets in lipoprotein(a) (Lp(a)) and lipid peroxidation levels. However, following consumption of OO and PS-SO, Lp(a) concentrations increased (P = 0.0050 and 0.0421, respectively), while PS-OO treatment did not affect Lp(a) levels. Furthermore, there was a decrease (P = 0.0097) in lipid peroxidation levels with PS-OO treatment during the supplementation phase. Our results suggest that supplementing an OO-rich diet with PS-OO favourably alters the plasma lipid profile and may decrease the susceptibility of LDL-C to lipid peroxidation in hypercholesterolaemic subjects.

Topics: Apolipoproteins; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Dietary Fats, Unsaturated; Diglycerides; Double-Blind Method; Fatty Acids; Female; Humans; Hypercholesterolemia; Lipid Peroxidation; Male; Olive Oil; Oxidative Stress; Phytosterols; Plant Oils; Sunflower Oil; Thiobarbituric Acid Reactive Substances

The cholesterol-lowering effects of plant sterols in a format suitable for use in China have not previously been investigated. We conducted the study to quantify in adult Chinese the effects on blood lipid concentrations of a plant sterol-enriched milk tea powder. The study was a double-blind, randomised trial in which 309 participants were randomised to receive daily 2.3 or 1.5 g plant sterol supplementation or placebo for 5 weeks. The milk tea was consumed with the two fattiest meals of the day with half the assigned daily dose taken on each occasion. Fasting venous blood samples were collected before commencement and upon completion of randomised treatment. The mean age of study participants was 44 years, 62% were female and 62% had a history of hypercholesterolaemia. Baseline mean total cholesterol was 5.5 mmol/l and LDL-cholesterol was 3.2 mmol/l. Compared with placebo, the 2.3 g/d plant sterol dose reduced total cholesterol by 0.25 (95% CI 0.07, 0.43) mmol/l (P = 0.01) and the 1.5 g/d dose by 0.23 (95% CI 0.06, 0.41) mmol/l (P = 0.01). For LDL-cholesterol the corresponding reductions were 0.17 (95% CI 0.00, 0.35) mmol/l (P = 0.06) and 0.15 (95% CI -0.02, 0.32) mmol/l (P = 0.08). For neither outcome was there evidence of differences between the effects of the two doses (both P values >0.4). In conclusion, the consumption of plant sterol-enriched milk tea decreased cholesterol concentrations although to a lesser extent than was anticipated. The reason for reduced efficacy is unclear but may be attributable to the novel food format used or the Chinese population studied.

Topics: Adolescent; Adult; Aged; Animals; Cholesterol; Double-Blind Method; Female; Follow-Up Studies; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Milk; Patient Compliance; Phytosterols; Tea; Treatment Outcome; Triglycerides

As opposed to traditional food based delivery we examined the efficacy of ingesting encapsulated phytosterol esters on indices of lipid health in hypercholesterolemic adults.. We performed a randomized, double-blinded, parallel-group, placebo-controlled, clinical intervention examining 54 men and women (20-70 y of age) with a low-density lipoprotein cholesterol (LDL-C) level > or =3.33 mmol/L. Participants were not taking cholesterol-lowering medications. Treatment consisted of ingesting 2.6 g of encapsulated phytosterol esters (n = 25) or a matching placebo (n = 29) for 12 wk.. Total cholesterol (TC) levels at baseline (mean +/- SD) were 6.29 +/- 0.7 mmol/L in the phytosterol group and 6.00 +/- 0.7 mmol/L in the placebo group. Baseline LDL-C levels were 4.27 +/- 0.7 mmol/L in the treatment group and 4.00 +/- 0.8 mmol/L in the placebo group. Analysis of variance and Tukey's least significant difference post hoc analyses revealed a significant within-group reduction in TC (-0.23 +/- 0.4 mmol/L, P < 0.05) and LDL-C (-0.22 +/- 0.5 mmol/L, P < 0.05) for the phytosterol treatment group. Mean reductions in TC and LDL-C were greater than placebo (P < 0.05). Percentages of change from baseline for TC were -3.52% (95% confidence interval -6.44 to -0.40) for phytosterol treatment and 2.64% (95% confidence interval 0.30-5.60) for placebo. Those for LDL-C were -5.00% (95% confidence interval -9.92 to -0.08) for phytosterol and 4.89 (95% confidence interval 0.24-9.5) for placebo. No other significant effects were observed.. Encapsulated phytosterol ester ingestion appears to positively modulate LDL-C. Given that the reduction in LDL-C was not as extensive as in food-based trials, future investigations should examine potential timing and dose issues relative to encapsulated delivery.

Topics: Adult; Aged; Analysis of Variance; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols

The effect of diet v. statins on LDL particle size as a risk factor for CVD has not been examined. We compared, in the same subjects, the impact of a dietary portfolio of cholesterol-lowering foods and a statin on LDL size electrophoretic characteristics. Thirty-four hyperlipidaemic subjects completed three 1-month treatments as outpatients in random order: a very-low saturated fat diet (control); the same diet with 20 mg lovastatin; a dietary portfolio high in plant sterols (1 g/4200 kJ), soya proteins (21.4 g/4200 kJ), soluble fibres (9.8 g/4200 kJ) and almonds (14 g/4200 kJ). LDL electrophoretic characteristics were measured by non-denaturing polyacrylamide gradient gel electrophoresis of fasting plasma at 0, 2 and 4 weeks of each treatment. The reductions in plasma LDL-cholesterol levels with the dietary portfolio and with statins were comparable and were largely attributable to reductions in the estimated concentration of cholesterol within the smallest subclass of LDL (portfolio - 0.69 (se 0.10) mmol/l, statin - 0.99 (se 0.10) mmol/l). These were significantly greater (P < 0.01) than changes observed after the control diet ( - 0.17 (se 0.08) mmol/l). Finally, baseline C-reactive protein levels were a significant predictor of the LDL size responsiveness to the dietary portfolio but not to the other treatments. The dietary portfolio, like the statin treatment, had only minor effects on several features of the LDL size phenotype, but the pronounced reduction in cholesterol levels within the small LDL fraction may provide additional cardiovascular benefit over the traditional low-fat diet of National Cholesterol Education Program Step II.

Topics: Aged; Analysis of Variance; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Cross-Over Studies; Diet, Fat-Restricted; Dietary Fats; Dietary Fiber; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Lovastatin; Male; Middle Aged; Particle Size; Phytosterols; Risk

The purpose of this study was to evaluate the effect of low-fat products enriched with plant sterols in addition to a National Cholesterol Education Program step 1 diet on serum lipids and lipoproteins.. This study was a double-blind, randomised, placebo-controlled cross-over design with a run-in period and 2 intervention periods, each lasting 4 weeks. A total of 46 mildly hypercholesterolemic subjects (age 50.6+/-9.8) completed the trial. The study products consisted of 20 g low-fat margarine (35% fat) and 250 ml low-fat milk (0.7% fat), in total delivering 2.3g plant sterols/d.. Serum total and low-density lipoprotein cholesterol were significantly reduced by 5.5% (p<0.001, 95% CI: 2.5; 8.3) and 7.7% (p=0.001, 95% CI: 3.4; 11.9), respectively, by plant sterol-enriched products compared to placebo. Serum apolipoprotein B was significantly reduced by 4.6% (p<0.05, 95% CI: 1.7; 7.5), and apolipoprotein B/apolipoprotein A-I by 3.4% (p<0.05, 95% CI: 0.1; 6.6) after plant sterol intake compared to the placebo supplement.. A combination of low-fat margarine and milk enriched with plant sterols significantly reduced low-density lipoprotein cholesterol, apolipoprotein B and the ratio of apolipoprotein B to apolipoprotein A-I in mildly hypercholesterolemic subjects, but had no effect on C-reactive protein and lipoprotein (a) concentrations.. Unilever Denmark A/S.

Topics: Adult; Aged; Animals; Anticholesteremic Agents; Apolipoprotein A-I; Apolipoproteins B; Cholesterol, LDL; Cross-Over Studies; Diet, Fat-Restricted; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Margarine; Middle Aged; Milk; Phytosterols; Phytotherapy

Plant sterol (PS)-enriched foods have been shown to reduce plasma LDL-cholesterol concentrations. In most studies, however, PSs were incorporated into food products of high fat content.. We examined the effect of daily consumption of PS-supplemented low-fat fermented milk (FM) on the plasma lipid profile and on systemic oxidative stress in hypercholesterolemic subjects.. Hypercholesterolemic subjects (LDL-cholesterol concentrations >or=130 and

Topics: Animals; C-Reactive Protein; Carotenoids; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Fermentation; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Milk; Oxidative Stress; Patient Compliance; Phytosterols; Sitosterols; Treatment Outcome; Triglycerides

Consumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption of cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources such as olive oil (OO) or omega-3 FA from fish oil (FO), known to exert potent hypotriglyceridemic effects. Our objective was to compare the actions of different FA esterified to PS on blood lipids, carotenoid bioavailability as well as inflammatory and coagulation markers.. Twenty-one moderately overweight, hypercholesterolemic subjects consumed experimental isoenergetic diets enriched with OO (70% of fat), each lasting 28-day and separated by 4-week washout periods, using a randomized crossover design. Diets were supplemented with three PS esters preparations, PS-FO, PS-SO, or PS-OO. All PS treatments contained an equivalent of 1.7 PS g/d, and the PS-FO provided a total of 5.4 g/d FO FA (eicosapentaenoic and docosahexaenoic acids).. There were no differences between PS-containing diet effects on total cholesterol, LDL-cholesterol, or high-density lipoprotein (HDL)-cholesterol levels. However, PS-FO consumption resulted in markedly lower (P < 0.0001) fasting and postprandial triglyceride concentrations compared with PS-SO and PS-OO. These treatments affected plasma beta-carotene (P = 0.0169) and retinol (P = 0.0244), but not tocopherol (P = 0.2108) concentrations. Consumption of PS-FO resulted in higher beta-carotene (P = 0.0139) and retinol (P = 0.0425) levels than PS-SO and PS-OO, respectively. Plasma TNF-alpha, IL-6, C-reactive protein, prostate specific antigen, and fibrinogen concentrations were unaffected by the PS-interventions. In contrast, plasminogen activator inhibitor 1 (PAI-1) concentrations were lower (P = 0.0282) in the PS-FO-fed than the PS-SO, but not the PS-OO (P = 0.7487) groups.. Our findings suggest that, in hypercholesterolemic subjects consuming an OO-based diet, PS-FO results in lowered blood triglyceride and PAI-1 concentrations, and higher fat-soluble vitamin levels in comparison to the vegetable oil FA esters of PS (PS-SO and PS-OO). Thus, PS-FO may offer hyperlipidemic subjects a more comprehensive lipid lowering approach while reducing the potential risk of decreased plasma carotenoid concentrations.

Topics: Adipose Tissue; Adult; Aged; Biological Availability; Biomarkers; Blood Coagulation; Carotenoids; Esters; Fasting; Female; Fish Oils; Humans; Hypercholesterolemia; Inflammation; Male; Middle Aged; Phytosterols; Plant Oils; Plasminogen Activator Inhibitor 1; Solubility; Triglycerides; Vitamins

To determine the impact of intake occasion (with or without a meal), and product fat level on the cholesterol-lowering efficacy of a plant sterol (PS)-enriched (3 g/day) single-dose yoghurt drink.. Double-blind, randomized, placebo-controlled, parallel study with a 4 weeks run-in and 4 weeks intervention period.. Subjects recruited from the general community.. A total of 184 moderate hypercholesterolaemic subjects (81 men and 103 women) (age 57+/-2 years) completed the study.. The study product was a 100-g single-dose yoghurt drink with or without added PS in the form of PS esters. The subjects were randomly assigned to one of five 4-week treatments: (i) drink A (0.1% dairy fat, 2.2% total fat) with a meal, (ii) drink A without a meal, (iii) drink B (1.5% dairy fat, 3.3% total fat) with a meal, (iv) drink B without a meal and (v) placebo drink with a meal.. LDL-cholesterol (LDL-C) was significantly lowered when the single-dose drink was taken with a meal independent of its fat content (drink A: -9.5% (P<0.001, 95% CI: -13.8 to -5.2); drink B: -9.3% (P<0.001, 95% CI: -13.7 to -4.9)) as compared to placebo. When consumed without a meal, LDL-C was also significantly decreased (drink A: -5.1% (P<0.05, 95% CI: -9.4 to -0.8); drink B: -6.9% (P<0.01, 95% CI: -11.3 to -2.5) as compared to placebo, however the effect was significantly smaller as compared to the intake with a meal.. These results indicate that a PS-ester-enriched single-dose yoghurt drink effectively reduces LDL-C irrespective of the fat content of the product. A substantially larger decrease in serum cholesterol concentration was achieved when the single-dose drink was consumed with a meal emphasizing the importance of the intake occasion for optimal cholesterol-lowering efficacy.. Unilever Research and Development, Vlaardingen, The Netherlands.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Diet; Dietary Fats; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Treatment Outcome; Yogurt

The purpose of this study was to determine whether supplements of plant sterols and/or glucomannan improve lipid profile and cholesterol biosynthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments.. A randomized, crossover study consisting of four phases of 21 days, with each phase separated by a 28-day washout.. The Mary Emily Clinical Nutrition Research Unit of McGill University.. Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38-74 years.. Subjects were supplemented with plant sterols (1.8 g/day), glucomannan (10 g/day), a combination of glucomannan and plant sterols, and a placebo, provided in the form of bars.. Overall plasma cholesterol concentrations were lowered (P<0.05) after combination treatment (4.72+/-0.20 mmol/l) compared to control (5.47+/-0.18 mmol/l). Plasma low-density lipoprotein (LDL) cholesterol concentrations were decreased (P<0.05) after glucomannan (3.16+/-0.14 mmol/l) and combination treatments (2.95+/-0.16 mmol/l) compared to control (3.60+/-0.16 mmol/l). The results of lipid profiles did not differ between subject groups. Overall plasma lathosterol concentrations, an index of cholesterol biosynthesis, were lowered (P<0.05) after the combination treatment compared to the plant sterol treatment.. The results suggest that glucomannan and a combination of glucomannan and plant sterols substantially improves plasma LDL cholesterol concentrations.. Forbes Medi-Tech Inc., Vancouver, British Columbia, Canada.

Topics: Adult; Aged; Cathartics; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Mannans; Middle Aged; Phytosterols

The aim of this study was to investigate whether a plant sterol mixture would reduce serum cholesterol when added to low fat dairy products in subjects with hypercholesterolaemia, and to examine the effects of the mixture on the serum plant sterol and fat-soluble vitamin levels.. A parallel, double-blind study.. The study was performed in three different locations in Finland.. In total, 164 mildly or moderately hypercholesterolaemic subjects participated in the study.. The subjects were randomly divided into two groups: a plant sterol group and a control group. The subjects consumed the products for 6 weeks after a 3-week run-in period. The targeted plant sterol intake was 2 g/day in the sterol group.. During the treatment period, there was a 6.5% reduction in serum total cholesterol in the sterol group while no change was observed in the control group (P<0.0005). Serum low-density lipoprotein (LDL) cholesterol was reduced by 10.4% in the sterol group and by 0.6% in the control group (P<0.00005). There was no change during the trial in serum high-density lipoprotein (HDL) cholesterol or triacylglycerol concentrations. The HDL/LDL cholesterol ratio increased by 16.1% in the sterol group and by 4.3% in the control group (P=0.0001). Serum plant sterol levels increased significantly (P=0.0001) in the sterol group. None of the fat-soluble vitamin levels decreased significantly when changes in serum total cholesterol were taken into account. The hypocholesterolaemic effect of sterol administration was not influenced by apolipoprotein E phenotype.. Yoghurt, low-fat hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced serum cholesterol in hypercholesterolaemic subjects and no adverse effects were noted in the dietary control of hypercholesterolaemia.

Topics: Anticholesteremic Agents; Apolipoproteins E; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dairy Products; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Phenotype; Phytosterols; Safety; Triglycerides; Vitamin A; Vitamin D; Vitamin K; Vitamins

The objective of this study was to investigate the effective dose of plant sterol ester (PSE)-enriched diacylglycerol (DAG) oil for healthy subjects with mild hypercholesterolemia.. A randomized, placebo-controlled, double-blind, parallel study was performed in patients with mild hypercholesterolemia; 0.0, 0.3, 0.4, and 0.5 g of PSE was dissolved in 15 g of a DAG-containing mayonnaise-type product; and 15 g/d of the product was administered 4 wk.. Total serum cholesterol levels were significantly decreased as a result of the ingestion of at least 0.4 g/d of PSE, and serum low-density lipoprotein cholesterol levels were significantly decreased by the ingestion of at least 0.3 g/d of PSE.. Daily ingestion of 15 g of DAG plus mayonnaise containing at least 0.4 g/d of PSE for 4 wk may significantly decrease cholesterol.

Topics: Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diglycerides; Dose-Response Relationship, Drug; Double-Blind Method; Esters; Humans; Hypercholesterolemia; Male; Phytosterols; Treatment Outcome

To assess the effects of plant sterol or stanol ester consumption on their incorporation into erythrocytes and their effects on osmotic fragility of red blood cells.. Double-blind, randomized, placebo-controlled intervention trial.. Forty-one subjects on stable statin treatment - who already have increased serum plant sterol and stanol concentrations - first received for 4 weeks a control margarine. For the next 16 weeks, subjects were randomly assigned to one of three possible interventions. Eleven subjects continued with control margarine, 15 subjects with plant sterol ester enriched and 15 subjects with plant stanol ester-enriched margarine. Daily plant sterol or stanol intake was 2.5 g. Erythrocyte haemolysis was measured spectrophotometrically at five different saline concentrations.. Despite significant (P = 0.004) increases of, respectively, 42 and 59% in cholesterol-standardized serum sitosterol and campesterol concentrations in the plant sterol group as compared to the control group, campesterol levels in the red blood cells did not change (P = 0.196). Osmotic fragility did not change significantly (P = 0.757) in the plant sterol and plant stanol groups as compared to the control group.. We conclude that plant sterol and stanol ester consumption for 16 weeks does not change osmotic fragility of erythrocytes in statin-treated patients.. Netherlands Organisation for Health Research and Development (Program Nutrition: Health, Safety and Sustainability, Grant 014-12-010).

Topics: Anticholesteremic Agents; Cholesterol; Double-Blind Method; Erythrocytes; Esters; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Margarine; Middle Aged; Osmolar Concentration; Phytosterols; Sitosterols

Recommendations for decreasing the risk of developing cardiovascular disease include increasing the intake of plant sterols and fish oil. The cholesterol-lowering action of plant sterols, when provided in a fish-oil fatty acids vehicle, remains to be investigated in humans. A randomized, crossover-feeding, single-blind trial was conducted in 30 subjects with mild-to-moderate hypercholesterolemia to study the effects on plasma lipids of 2 novel forms of plant sterols: those combined with, or esterified to, fish-oil fatty acids. The treatments were margarine (control), free plant sterols, plant sterols esterified to fatty acids from sunflower oil, plant sterols esterified to very long-chained fatty acids from fish oil, and plant sterols combined with the same amount of very long-chained fatty acids from fish oil. Each sterol-containing food (1.0-1.8 g plant sterols/d) was consumed for 29 d as a single dose with breakfast under staff supervision. Compared with the control treatment, none of the plant sterol preparations reduced plasma total cholesterol or LDL cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, lipoprotein (a), or C-reactive protein concentration. Relative to the control phase, all plant sterols treatment increased the plasma HDL cholesterol concentration (P < 0.05) by approximately 8%. In conclusion, because standard forms of plant sterols did not reduce plasma cholesterol concentrations, the efficacy of the new formulation of plant sterols cannot be confirmed from the present study design, where plant sterols were given as a single morning dose.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diet; Esterification; Fatty Acids; Female; Fish Oils; Humans; Hypercholesterolemia; Lipids; Lipoprotein(a); Male; Middle Aged; Phytosterols; Plant Oils; Sunflower Oil

Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, beta-carotene, and alpha-tocopherol levels using a threefold excess of the effective dose obtained in our previous study.. A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control.. There were no subjective adverse effects or changes in serum retinol, alpha-tocopherol, and beta-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values.. Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise.

Topics: Adult; alpha-Tocopherol; Anticholesteremic Agents; beta Carotene; Diglycerides; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Phytosterols; Treatment Outcome; Vitamin A; Vitamins

Plant sterols have been reported to decrease plasma concentrations of cholesterol without any side effects. To evaluate the effects on plasma cholesterol concentrations and the hemorheological parameters, we performed a study with hypercholesterolemic patients (n = 19) treated with phytosterol-enriched milk (2 g/day). Hypercholesterolemic patients (n = 15) of matched age drinking equal type of milk but without phytosterols were used as control group. Concentrations of total cholesterol, HDL-C, LDL-C and hemorheological parameters were measured in the beginning, after 15 and 30 days of milk intake. After 15 days of beverage intake, hypercholesterolemic subjects treated with phytosterol-enriched milk showed a significant decrease in plasma concentrations of total cholesterol and LDL-C by 9.62% (p < 0.05) and 12.20% (p < 0.05), respectively. After 30 days, a little increase in the total cholesterol and LDL-C concentrations were observed. In the hypercholesterolemic control group there were nonsignificant changes between plasma concentrations of total cholesterol, HDL-C and LDL-C during the study. The evaluation of plasma viscosity and erythrocyte aggregation shows no changes statistically significant during the study for both groups studied. The results obtained during the study show a positive effect with the phytosterol-enriched milk as plasma cholesterol-lowering as combined treatment for hypercholesterolemia.

Topics: Adult; Animals; Blood Viscosity; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Erythrocyte Aggregation; Hemorheology; Humans; Hypercholesterolemia; Lipid Metabolism; Middle Aged; Milk; Phytosterols

We conducted a randomized, double blind, crossover, placebo-controlled study to determine the effects of a combination therapy including plant sterols (PS) and psyllium (PSY), provided via cookies, on plasma lipids and on the size and subfraction distribution of VLDL, LDL, and HDL. Thirty-three healthy free-living individuals (11 males and 22 females), aged 35-65 y, with a BMI between 25 and 35 kg/m(2) and initial plasma LDL cholesterol (LDL-C) concentrations between 2.6 and 4.1 mmol/L (100 and 160 mg/dL), were randomly assigned to receive treatment cookies (7.68 g/d PSY and 2.6 g/d PS) or placebo cookies (0 g PSY+PS) for 4 wk. After a 3-wk washout period, subjects received the other cookies for an additional 4 wk. Plasma total cholesterol concentrations were significantly reduced for all subjects, from 5.65 +/- 0.72 mmol/L after the placebo period to 5.28 +/- 0.76 mmol/L after the PSY+PS cookie period (P < 0.01). These reductions were primarily in LDL-C, which decreased from 3.48 +/- 0.70 to 3.14 +/- 0.78 mmol/L after PSY+PS cookie consumption (P < 0.01). Intake of the PSY+PS cookie decreased the number of intermediate density lipoprotein (IDL), LDL, and HDL particles (P < 0.05) and plasma apo B concentrations (P < 0.01). The decreases in LDL and HDL particles were in the small subfractions. Because smaller LDL particles are associated with an increased risk of heart disease and because smaller HDL particles are indicative of diminished reverse cholesterol transport, we conclude that the combination therapy resulted in a less atherogenic lipoprotein profile. In addition, the evaluation of lipoprotein subfractions resulting from the action of the fiber and plant sterols in the intestinal lumen provides an insight on the secondary mechanisms of plasma LDL-C lowering.

Topics: Adult; Aged; Apolipoproteins B; Blood Glucose; Cholesterol, LDL; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipoproteins; Lipoproteins, HDL; Lipoproteins, IDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Middle Aged; Particle Size; Phytosterols; Phytotherapy; Placebos; Postmenopause; Premenopause; Psyllium

Dietary intervention studies incorporating phytosterol-enriched margarine spreads have reported significant decreases in total and low-density lipoprotein (LDL) cholesterol in populations with both normal lipid levels and those with hypercholesterolemia. There is emerging support for more diverse and lower-fat phytosterol-enriched matrixes. Controversy exists, however, over whether phytosterol-enriched foods affect serum fat-soluble vitamins.. We investigated whether a flavanol-rich cocoa snack food containing phytosterols would decrease total and LDL cholesterol levels in subjects with hypercholesterolemia and significantly affect serum fat-soluble vitamins and carotenoids.. A randomized, double-blind parallel arm study design was used. Subjects were randomized to one of two dietary treatments: a cocoa flavanol-enriched snack bar containing 1.5 g phytosterol (n=32), or a control product containing no phytosterols (n=35). Subjects consumed two servings per day.. Consumption of the phytosterol-enriched snack bars but not control bars for 6 weeks was associated with significant reductions in plasma total (4.7%; P<0.01) and LDL cholesterol (6%; P<0.01), and the ratio of total to high-density lipoprotein cholesterol (7.4%; P<0.001). There were no changes in high-density lipoprotein cholesterol, triglycerides, or lipid-adjusted lycopene, beta-cryptoxanthin, lutein/zeaxanthin, alpha-carotene levels, or levels of serum vitamins A or E. A significant reduction in lipid-adjusted serum beta-carotene was observed in the phytosterol but not the no-phytosterol-added group (P<0.05).. This study supports the use of a novel phytosterol-enriched snack bar to effectively reduce plasma total and LDL cholesterol levels in a population with hypercholesterolemia. The data suggest that the incorporation of this snack food into a balanced diet represents a practical dietary strategy in the management of serum cholesterol levels.

Topics: Cacao; Carotenoids; Catechin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Flavonols; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Triglycerides; Vitamin A; Vitamin E

Fish-oil fatty acid esters of plant sterols (FO-PS) were shown to have hypotriglyceridemic and hypocholesterolemic properties in animal models.. The objective of the study was to evaluate the hypolipidemic effects of FO-PS supplementation in healthy hypercholesterolemic persons fed an olive oil (OO)-based diet.. Twenty-one moderately overweight, hyperlipidemic subjects participated in a semi-randomized, single-blind, 4-period crossover study including 4 experimental isoenergetic diets of 4 wk each and 4-wk intervening washout periods. Diets contained 30% of energy as fat, of which 70% was from extra-virgin OO, and differed only in the supplement oil: OO, fish oil, FO-PS, or sunflower oil esters of plant sterols (SU-PS). Both fish oil and FO-PS provided 5.4 g total eicosapentaenoic and docosahexaenoic acids/d. FO-PS, SU-PS, and OO provided the equivalent of 1.7, 1.7, and 0.02 g free plant sterols/d, respectively.. Fish oil and FO-PS resulted in fasting and postprandial plasma triacylglycerol concentrations that were markedly lower than those observed with OO and SU-PS (P = 0.0001), but to a different extent. LDL cholesterol was significantly lower after supplementation with FO-PS and SU-PS than at the end of the control OO diet (P = 0.0031 and 0.0407, respectively). HDL cholesterol was not affected. FO-PS and SU-PS resulted in a lower ratio of total to HDL cholesterol and lower apolipoprotein (apo) B concentrations than did OO and fish oil. The ratio of apoB to apoA was significantly lower after SU-PS consumption than after consumption of OO (P = 0.0126) and fish oil (P = 0.0292). FO-PS and SU-PS resulted in similar ratios of apoB to apoA. HDL2 and the ratio of HDL2 to HDL3 were significantly higher at the end of the FO-PS treatment than at the end of the OO (P = 0.0006), fish oil (P = 0.0036), and SU-PS (P = 0.0016) treatments.. Supplementation of an OO-based diet with FO-PS may reduce cardiovascular disease risk more than does supplementation with fish oil or SU-PS.

Topics: Adult; Aged; Anticholesteremic Agents; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Fats, Unsaturated; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Esters; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Hypercholesterolemia; Male; Middle Aged; Olive Oil; Phytosterols; Plant Oils; Sunflower Oil; Triglycerides

The cholesterol-lowering efficacy of plant sterol esters (PSteE) or stanol esters (PStaE) in regular- and low-fat spreads has been consistently demonstrated, while their effectiveness in a low-fat, aqueous food carrier such as milk and yoghurt is less well established.. Two studies were carried out to assess the cholesterol-lowering effect of PSteE-enriched low-fat milk and PSteE- and PStaE-enriched low-fat yoghurt in modestly hypercholesterolemic subjects (total cholesterol between 5-7.5 mmol/l).. Study one was a single blind crossover design with 4 phases of 3-week interventions. Subjects consumed 300 ml/d of placebo or PSteE-milk (2.0 g plant sterols/d) alone or combined with 25 g/d of placebo or PSteE-spread. Study two was a fully randomised, double blind crossover design with 3 phases of 3-week interventions. Subjects consumed 2 portions (150 g tubs each) of placebo, PSteE-yoghurt (1.8 g plant sterols/d) or PStaE-yoghurt (1.7 g plant stanols/d). In study one 39 subjects (21 men and 18 women) and in study two 40 subjects (17 men and 23 women) completed the dietary intervention.. In study one, PSteE-milk and PSteE-spread were equally efficacious in lowering total and LDL-cholesterol as compared to placebo by 6-8% and 8-10%, respectively. No significant additional cholesterol-lowering was observed with the combination of PSteE-milk and PSteE-spread (4 g plant sterols/d). PSteE-enriched milk and the combination of PSteE-enriched milk plus spread both lowered lipid-adjusted serum beta-carotene concentrations by 10-14% (P < 0.02),while the PSteE-rich spread alone did not significantly alter serum beta-carotene levels. In study two, the PSteE- and PStaE-enriched yoghurts reduced LDL-cholesterol significantly compared to placebo by 0.27 +/- 0.05 mmol/l (6%) and 0.23 +/- 0.05 mmol/l (5%), respectively. In both studies, there was no effect on HDL-cholesterol and triacylglycerol concentrations.. Plant sterols in the form of their esters when provided in lowfat milk and yoghurt are effective in lowering total and LDL-cholesterol.

Topics: Adult; Aged; Animals; Carotenoids; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet Records; Diet, Fat-Restricted; Esters; Female; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Milk; Phytosterols; Sitosterols; Surveys and Questionnaires; Yogurt

To determine the effectiveness of prescribing 2 g plant sterols/stanols per day as an addition to standard practice in a dietary outpatient clinic.. A randomized parallel design of comparative 12-week interventions.. Patients referred by a general practitioner to a dietary outpatient clinic for the management of hyperlipidemia were eligible. Twenty-five patients (15 women and 10 men) completed the study.. Counseling regarding diet for hyperlipidemia was based on the National Cholesterol Education Program guidelines. The intervention group was instructed to incorporate approximately 25 g/day of margarine, containing plant sterols/stanols, which delivered approximately 2 g plant sterols/stanols.. Changes in diet, body weight, and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured.. Changes in dietary and biochemical outcomes were assessed using Student's t test. For nonnormally distributed data, Wilcoxon signed rank test was used, and Mann-Whitney U tests were conducted to determine the proportion of subjects reaching defined goals. The number needed to treat index was used to report effectiveness of the intervention.. Five of 14 subjects in the intervention group compared with 0 of 11 in the control group achieved a reduction in serum cholesterol of >/=15% ( P <.05). Using the number needed to treat index, for each 2.8 patients counseled with routine prescription of plant sterols/stanols, one additional patient would obtain a reduction in cholesterol by >/=15% compared with conventional management. This was achieved without any detrimental effects on the dietary fatty acid profile.. Routine prescription of margarine containing plant sterol/stanol is an effective strategy in the management of hypercholesterolemic patients in the clinical setting.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Treatment Outcome; Triglycerides

Plant sterols and exercise favourably alter lipid profiles in a way that protect against future coronary heart disease (CHD). However, their effects on other indicators of CHD risk, such as LDL particle size, still need further clarification.. This study examined the effect of plant sterols, exercise, and the combination of plant sterols and exercise, on LDL particle size and distribution in previously sedentary, hypercholesterolemic adults.. In an 8-week, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomized to one of four intervention groups: (1) combination of sterols and exercise, (2) exercise, (3) sterol, or (4) control.. Exercise significantly (P < 0.05) reduced post-treatment LDL peak particle size from 255 to 253 A. Additionally, exercise significantly (P < 0.05) decreased the proportion of large LDL particles within plasma. Sterol supplementation significantly (P < 0.05) decreased the estimated cholesterol concentrations within small, medium, and large LDL particles by 13.4, 13.5, and 14.4%, respectively, yet had no effect on the distribution of cholesterol among various LDL particle sizes. Furthermore, decreased body weight post-training was associated with increased cholesterol in small LDL particles (r = -0.52, P < 0.0001). Decrease in body fat percent (BF%) post-training was associated with increased cholesterol concentrations in small LDL particles (r = -0.29, P < 0.01).. On the basis of modulating LDL electrophoretic characteristics, the present study demonstrates that plant sterols have no effect on CHD risk, while short-term exercise may potentially increase CHD risk by decreasing LDL peak particle size.. This study was sponsored by The Heart and Stroke Foundation of Canada.

Topics: Adult; Aged; Analysis of Variance; Body Composition; Body Weight; Cholesterol, LDL; Exercise; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Particle Size; Phytosterols; Single-Blind Method

To examine the impact of nonfat and low-fat phytosterol-enriched beverages on low-density lipoprotein (LDL) electrophoretic characteristics.. Double-blind, randomized, crossover, placebo-controlled dietary trial.. Diets were prepared and consumed at the Mary Emily Clinical Nutrition Research Unit of McGill University. Analyses were performed at the Institute on Nutraceuticals and Functional Foods of Laval University.. In total, 15 moderately hypercholesterolemic persons consumed each of three experimental diets that each comprised a different beverage: nonfat placebo (NF control), nonfat with phytosterols (NFPS) or low-fat with phytosterols (LFPS). Participants consumed three beverages daily at meal time for a total of 1.8 g of phytosterols per day. Nondenaturing 2-16% polyacrylamide gradient gel electrophoreses were used to characterize LDL size characteristics.. The NFPS and LFPS beverage induced no significant changes in several features of the LDL size phenotype compared to the control diet.. The consumption of phytosterol-supplemented nonfat and low-fat beverages is not associated with clinically meaningful changes in the LDL particle size phenotype.

Topics: Adult; Aged; Beverages; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Fats; Double-Blind Method; Female; Food, Organic; Humans; Hypercholesterolemia; Male; Middle Aged; Particle Size; Phenotype; Phytosterols; Triglycerides

Plant sterols, soy proteins, viscous fibers, and nuts are advised for cholesterol reduction, but their combined effect on plant sterol absorption has never been tested. We assessed their combined action on serum sterols in hyperlipidemic subjects who were following low-saturated fat diets before starting the study and who returned to these diets post-test. The 1-mon test (combination) diet was high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), viscous fiber (9 g/1,000 kcal), and almonds (14 g/1000 kcal). Fasting blood was obtained for serum lipids and sterols, and erythrocytes were obtained for fragility prior to and at 2-wk intervals during the study. The combination diet raised serum campesterol concentrations by 50% and beta-sitosterol by 27%, although these changes were not significant after Bonferroni correction; near-maximal rises were found by the end of the first week, but no change was found in red cell fragility despite a 29% reduction in the LDL cholesterol level. No significant associations were observed between changes in red cell fragility and blood lipids or sterols. We conclude that plant sterols had a minimal impact on serum sterol concentrations or red cell fragility in hyperlipidemic subjects on diets that greatly reduced their serum lipids.

Topics: Adult; Aged; Aged, 80 and over; Cholesterol; Demography; Diet; Dietary Fiber; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Osmotic Fragility; Phytosterols; Plant Proteins, Dietary; Risk Factors

Because of hyperglycemia and hyperinsulinemia, diabetic persons have higher cholesterol synthesis and lower cholesterol absorption rates than do nondiabetic persons. Differences in plant sterol efficacy between diabetic and nondiabetic persons have not been examined.. The objective was to compare the degree of response of plasma lipid concentrations and glycemic control to plant sterol consumption in a controlled diet between hypercholesterolemic type 2 diabetic and nondiabetic subjects.. Fifteen nondiabetic subjects and 14 diabetic subjects participated in a double-blinded, randomized, crossover, placebo-controlled feeding trial. The diet included 1.8 g/d of either plant sterols or cornstarch placebo over 21 d, separated by a 28-d washout period.. Plant sterol consumption significantly reduced (P < 0.05) LDL-cholesterol concentrations from baseline in both nondiabetic and diabetic subjects by 15.1% and 26.8%, respectively. The diabetic subjects had significantly (P < 0.05) lower absolute concentrations of total cholesterol after treatment than did the nondiabetic subjects; however, there was no significant difference in the percentage change from the beginning to the end of the trial. There was also a significant decrease (P < 0.05) in absolute non-HDL-cholesterol concentrations after treatment in both groups.. The results showed that plant sterols are efficacious in lowering LDL cholesterol and non-HDL cholesterol in both diabetic and nondiabetic persons. Plant sterol consumption may exist as a dietary management strategy for hypercholesterolemia in persons with type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Erythrocytes; Fatty Acids; Female; Glycated Hemoglobin; Humans; Hypercholesterolemia; Insulin; Male; Middle Aged; Phytosterols; Phytotherapy; Treatment Outcome

Clinical trials have shown that an intake of 2 to 3 g/day of esterified plant stanol--when incorporated in margarines or spreads--significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations without affecting serum high-density lipoprotein cholesterol or triglyceride levels. There is also a growing interest in incorporating cholesterol-lowering ingredients into low-fat foods. Esterification of stanols with long-chain fatty acids increases fat solubility by 10-fold and enables the incorporation of plant stanols into different food products, even low-fat foods. It provides a means of introducing an adequate daily amount of stanol for optimal reduction of cholesterol absorption, while maintaining a high-quality food product. Recent clinical trials show that esterified plant stanols effectively reduce serum total and LDL cholesterol levels, even when used in food vehicles with a low-fat content.

Topics: Adult; Aged; Cholesterol, LDL; Clinical Trials as Topic; Diet, Fat-Restricted; Dietary Fats; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Phytosterols; Sitosterols

Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle.. Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up.. The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin.. High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.

Topics: Adult; Age Factors; Aged; Atorvastatin; Biopsy; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Citrate (si)-Synthase; Dose-Response Relationship, Drug; Double-Blind Method; Electron Transport; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Muscles; Patient Selection; Phytosterols; Pyrroles; Sex Factors; Simvastatin; Sitosterols; Succinate Cytochrome c Oxidoreductase; Time Factors; Ubiquinone

Plant sterol/stanol margarines are recommended as a lipid-lowering dietary supplement in the treatment of hypercholesterolemia. Parameters predicting the individual cholesterol-lowering effect have not been elucidated so far. Therefore, we investigated the responsiveness to sitostanol-supplemented margarine in a specially selected population.. From a total number of 137 male subjects with hypercholesterolemia, eight subjects with the lowest and eight subjects with the highest ratios of lathosterol to campesterol in serum were included in the study. They received 1 g sitostanol-supplemented margarine b.i.d. for four weeks. Serum lipoproteins, the cholesterol precursor lathosterol, the plant sterols campesterol and sitosterol were measured. Subjects with a low ratio of lathosterol to campesterol had a significant decrease of serum total cholesterol (-14.2%; p < 0.01) and LDL cholesterol (-13.8%; p < 0.01; responder). In subjects with a high ratio there was no significant change in total cholesterol and LDL cholesterol (2.2 and 4.3%; non-responder).. The ratio of serum lathosterol to campesterol predicts the reduction of total cholesterol and LDL cholesterol during administration of sitostanol-supplemented margarine in patients with mild hypercholesterolemia.

Topics: Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Patient Selection; Phytosterols; Predictive Value of Tests; Sitosterols; Triglycerides

Hypercholesterolemia is a major risk factor for coronary artery disease. Therapeutic lifestyle changes include dietary modifications such as inclusion of phytosterols, which effectively lowers low-density lipoprotein (LDL) cholesterol in margarines and other fats. Their effectiveness in nonfat moieties is not yet established. The aim of this study was to examine if phytosterols alter the plasma lipoprotein profile when incorporated into nonfat orange juice.. After a 2-week run-in phase with orange juice, 72 mildly hypercholesterolemic healthy subjects were randomized to receive either placebo orange juice (placebo OJ) or plant sterol-fortified orange juice (sterol OJ) (2g/d) for 8 weeks. Fasting blood was obtained at baseline, after 2 weeks of OJ, and after 8 weeks of placebo/sterol-OJ supplementation. Sterol OJ supplementation significantly decreased total (7.2%), LDL (12.4%), and non-high-density lipoprotein (HDL) cholesterol (7.8%) compared with baseline and compared with placebo OJ (P<0.01). Apolipoprotein B levels were significantly decreased (9.5%) with sterol OJ. There were no significant changes in HDL cholesterol or triglycerides with the sterol OJ. While folate and B12 levels significantly increased, homocysteine levels were unchanged.. Orange juice fortified with plant sterols are effective in reducing LDL cholesterol and could easily be incorporated into the therapeutic lifestyle changes dietary regimen.

Topics: Adult; Aged; Apolipoproteins B; Beverages; Cholesterol; Cholesterol, LDL; Citrus; Double-Blind Method; Female; Folic Acid; Food, Fortified; Homocysteine; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols; Stigmasterol; Treatment Outcome; Vitamin B 12

To measure the relative effects of each of four phytosterol ester-enriched low-fat foods (bread, breakfast cereal, milk and yoghurt) on serum lipids, plasma phytosterols and carotenoids.. : Three research centres undertook a randomised, incomplete crossover, single-blind study consisting of four treatment periods of 3 weeks each, one of which was a control period. Each sterol-enriched test food provided 1.6 g/day of phytosterols as sterol esters.. General Community.. In all 58, free-living men and women with mean age (s.d.) 54 (8) y, moderately elevated plasma total cholesterol 6.2 (0.7) mmol/l and body mass index 26.2 (3.0) kg/m(2).. Serum lipids, plasma phytosterols and carotenoids.. Serum total and LDL cholesterol levels were significantly lowered by consumption of phytosterol-enriched foods: milk (8.7 and 15.9%) and yoghurt (5.6 and 8.6%). Serum LDL cholesterol levels fell significantly by 6.5% with bread and 5.4% with cereal. They were both significantly less efficacious than sterol-enriched milk (P<0.001). Plasma sitosterol increased by 17-23% and campesterol by 48-52% with phytosterol-enriched milk and bread. Lipid-adjusted beta-carotene was lowered by 5-10% by sterols in bread and milk, respectively.. This is the first study to demonstrate that cholesterol-lowering effects of plant sterol esters may differ according to the food matrix. Plant sterols in low-fat milk was almost three times more effective than in bread and cereal. Despite phytosterol-enriched cereal products resulting in lower serum cholesterol reductions compared to sterol-enriched milk, the detection of similar changes in plasma phytosterols demonstrated that such products still delivered and released phytosterols to the gut.

Topics: Adult; Aged; Animals; Anticholesteremic Agents; Bread; Carotenoids; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Edible Grain; Esters; Female; Food Analysis; Humans; Hypercholesterolemia; Lipid Metabolism; Lipids; Male; Middle Aged; Milk; Phytosterols; Phytotherapy; Single-Blind Method; Yogurt

To determine the effect of nonesterified, nonhydrogenated plant sterols solubilized in a partly vegetable oil-filled low-fat milk on serum low-density lipoprotein cholesterol (LDL) in mildly hypercholesterolemic patients.. Double-blind, randomized, placebo-controlled three-arm crossover study.. Outpatient clinical trial.. A total of 138 patients were screened, providing 81 patients for randomization; 71 patients completed the study.. The study product was a 500 ml milk blend with or without nonesterified, nonhydrogenated sterols. The daily consumption of sterols in the three groups was 0 g/day, control group (C); 1.2 g/day, (Lo); or 1.6 g/day, (Hi), respectively. The patients were randomly assigned to one of three different treatment sequences. Each intervention period was 4 weeks. The total study duration was 12 weeks.. The milk product was well tolerated. The placebo-adjusted mean reduction in LDL was 7.13+/-12.31 and 9.59+/-12.44% (mean+/-s.d.) for Lo and Hi groups, respectively (P<0.0001); there was no statistically significant difference in LDL lowering for the Lo and Hi groups. There were no significant changes in serum vitamin E or carotenoid concentrations after standardization with LDL cholesterol during the study period.. The present study shows for the first time a substantial reduction in LDL cholesterol with a new, partly vegetable oil-filled 1.2% low-fat milk product, containing nonesterified plant sterols from soybean oil, in a randomized, placebo-controlled trial. This result encourages further development of novel low-fat dairy products containing free plant sterols for future use in cholesterol-lowering initiatives.

Topics: Aged; Animals; Antioxidants; Carotenoids; Cholesterol, LDL; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Milk; Phytosterols; Vitamin E

Plant sterol supplementation was shown to reduce total and LDL-cholesterol concentrations, whereas endurance training was shown to increase HDL-cholesterol concentrations and decrease triacylglycerol concentrations.. The objective was to examine the effect of plant sterols, endurance training, and the combination of plant sterols and endurance training on plasma lipid and lipoprotein cholesterol concentrations, sterol concentrations, and cholesterol precursor concentrations in previously sedentary hypercholesterolemic adults.. In an 8-wk, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomly assigned to receive 1 of 4 interventions: 1) combination of sterols and exercise, 2) exercise, 3) sterols, or 4) control treatment.. Sterol supplementation significantly (P < 0.01) decreased total cholesterol concentrations by 8.2% from baseline. In addition, sterols significantly (P < 0.01) lowered absolute LDL-cholesterol concentrations after treatment but had no effect on the percentage change from the beginning to the end of the trial. Exercise significantly (P < 0.01) increased HDL-cholesterol concentrations by 7.5% and decreased triacylglycerol concentrations by 13.3% from baseline. Moreover, sterol supplementation significantly (P < 0.05) increased lathosterol, campesterol, and beta-sitosterol concentrations after treatment. Exercise significantly (P < 0.01) decreased percentage of body fat by 3.9% from the beginning to the end of the trial.. In comparison with plant sterols or exercise alone, the combination of plant sterols and exercise yields the most beneficial alterations in lipid profiles. Implementation of such a combination therapy could improve lipid profiles in those at risk of coronary artery disease.

Topics: Adult; Analysis of Variance; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Exercise; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Single-Blind Method

The purpose of the study was to investigate the effect of non-esterified plant sterol-enriched and mineral-enriched low-fat and low-salted meat products compared with control meat products, on serum total and lipoprotein lipids and blood pressure in subjects with mildly to moderately elevated serum cholesterol concentration. A randomised, placebo-controlled, single-blind, repeated measure design was used. Altogether 21 volunteers completed the study. The study began with a pre-trial period of 1-2 weeks, which was followed by three different test periods in the following order: meat products enriched with plant sterols (1.2 g/day), potassium, calcium and magnesium (MP1); meat products with no added plant sterols and minerals (control); and meat products with plant sterols (2.1 g/day), potassium, calcium and magnesium (MP2). Each test period lasted for 3 weeks. During the MP2 period, the serum total and low-density lipoprotein cholesterol concentration decreased 4.9+/-7.5% (P<0.05) and 4.6+/-11.3% (not significant), respectively, compared with the control period. No differences in the high-density lipoprotein cholesterol and total triglyceride concentrations or in systolic blood pressure and diastolic blood pressure were found among the test periods. In conclusion, the present study showed that frankfurters and cold cuts enriched with plant sterols from tall oil, potassium, calcium and magnesium, as part of habitual Finnish diet reduced the serum total cholesterol concentration in hypercholesterolemic subjects when the intake of sitosterols was 2.1 g/day, but not with the lower dose.

Topics: Adult; Aged; Blood Pressure; Diet; Energy Intake; Female; Food, Fortified; Humans; Hypercholesterolemia; Lipids; Male; Meat Products; Middle Aged; Minerals; Phytosterols; Single-Blind Method

Regular intake of plant sterol (phytosterol)-enriched foods enhances the cholesterol lowering effect of diets. One side effect associated with plant sterol consumption is a modest reduction in plasma carotenoid concentrations. This study investigated the effect of consuming a low-fat National Cholesterol Education Programme (NCEP) Step 1 diet, including a low-fat plant sterol ester (PSE)-enriched spread on cholesterol metabolism to determine if specific dietary advice to increase daily fruit and vegetable intake could prevent reduced plasma carotenoid concentrations.. In this randomised, crossover double-blind trial, 48 hypercholesterolaemic men received 21 g day(-1) of a low-fat PSE-enriched spread or placebo for 3 weeks, interrupted by 3 weeks washout. Individuals also adhered to a NCEP Step 1 diet and repeated 3-day food diaries monitored adherence. Specific advice was provided to increase dietary fruit and vegetable intakes. Fasting blood samples were collected at pre- and post-intervention for lipoprotein and carotenoid analysis.. Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly (P <0.05) reduced, by 4.6 and 7.1%, respectively, after the PSE-enriched low-fat spread. Plasma apo B concentrations were significantly (P <0.0005) lower after the PSE spread. PSE consumption was also associated with significantly (P <0.05) lower total plasma beta-carotene concentrations, but this change was not significant after lipid standardisation. PSE consumption had no effect on retinol, alpha-carotene, gamma-tocopherol, alpha-tocopherol, lutein, zeaxanthin, beta-crypyoxanthin or lycopene concentrations.. Dietary advice to increase daily fruit and vegetable consumption may be effective in preventing a reduction in plasma carotenoid concentrations previously associated with PSE consumption. Further, PSE incorporated in a low-fat spread and consumed as part of a NCEP Step 1 diet are effective in reducing total and LDL cholesterol.

Topics: Adult; Antioxidants; Carotenoids; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diet, Fat-Restricted; Double-Blind Method; Female; Fruit; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Treatment Outcome; Vegetables

To determine the effect of a plant sterol-enriched spread on plasma cholesterol concentrations when replacing butter or a standard polyunsaturated spread in a diet containing 30% of energy fat.. Parallel butter phase followed by double-blind, randomized, cross-over polyunsaturated spread phases.. General community.. Volunteer sample of 50 free-living men and women with mean age (s.d.) 46.7 y (10.5), moderately elevated plasma total cholesterol 5.95 mmol/l (0.78), and body mass index 26.0 (3.9) kg/m(2).. Participants ate a moderately low-fat diet (30% of energy) for the 11-week intervention. During the first 3 weeks the diet included 20 g per day of butter. Participants were then randomized to replace the butter with 25 g of polyunsaturated spread with or without 2 g of plant sterols for 4 weeks, crossing over in the last 4 weeks to the alternate spread.. Plasma cholesterol and fatty acids.. Replacing butter with a standard polyunsaturated fat spread reduced mean plasma total cholesterol concentrations by 4.6% (from 6.09 (0.82) to 5.81 (0.77) mmol/l, P<0.01) and low-density lipoprotein cholesterol by 5.5% (from 3.98 (0.76) to 3.76 (0.74) mmol/l, P<0.05). Replacing butter with a polyunsaturated spread containing plant sterols reduced plasma total cholesterol by 8.9% (from 6.09 (0.82) to 5.55 (0.76) mmol/l, P<0.01) and low density lipoprotein cholesterol by 12.3% (from 3.98 (0.76) to 3.49 (0.72) mmol/l, P<0.01). Plasma high density lipoprotein cholesterol concentration was the same on the three diets.. In people with moderately raised plasma cholesterol concentrations consuming reduced-fat diets the reduction in plasma total and low-density lipoprotein cholesterol concentrations achieved by replacing butter with a polyunsaturated spread is enhanced by addition of plant sterols.

Topics: Body Mass Index; Butter; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diet, Fat-Restricted; Dietary Fats, Unsaturated; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Treatment Outcome

This randomized, double-blind, controlled trial evaluated the influence of low fat, low saturated fat food products that contained free tall oil-based phytosterols (TOP) and oat beta-glucan (from whole oats and bran concentrate) on serum lipid concentrations in adults with mild-to-moderate hypercholesterolemia. After a 5-wk National Cholesterol Education Program Step I diet lead-in period, 112 subjects incorporated one of two treatments into their diets for 6 wk: food products (cereal, snack bar and beverage) that provided 1.8 g TOP and 2.8 g beta-glucan/d and contained < or =3.0 g total fat and < or =1.0 g saturated fat (TOP/beta-glucan treatment) or similar control foods. The serum LDL cholesterol response from baseline to the end of study was significantly larger in the TOP/beta-glucan treated group than in the control group, in which there was no change (-3.7 vs. 0.4%; P = 0.013). Likewise, total cholesterol decreased in the TOP/beta-glucan treatment group and did not change significantly in the controls (-2.3 vs. 0.8%; P = 0.043). Serum HDL cholesterol and triglyceride responses did not differ between the groups. The results of this trial suggest that consumption of a group of low fat, TOP and beta-glucan- containing foods is a useful adjunct in the dietary management of hypercholesterolemia.

Topics: Adult; Aged; Avena; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet; Diet Records; Dietary Fats; Dietary Fiber; Double-Blind Method; Female; Glucans; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Triglycerides

To show whether the ratios of squalene and cholesterol precursor sterols to cholesterol and cholestanol and plant sterols to cholesterol change differently in plasma and especially in the red cells of hypercholesterolemic children during consumption of plant stanol and sterol ester spreads.. In a randomized, double-blind, crossover study, hypercholesterolemic children (n = 23) consumed low-fat plant stanol and sterol ester spreads for 5-week periods separated by a 5-week washout period. Plasma and red cell lipids, squalene, and noncholesterol sterols were measured before and at the end of each period.. The plant stanol and sterol ester spreads lowered plasma total (-9% and -6%, respectively) and low-density lipoprotein (-12% and -9%) cholesterol but had no effect on red cell cholesterol, high-density lipoprotein cholesterol, or plasma triglycerides. The ratios of plasma and red cell sitosterol and campesterol to cholesterol decreased by 32% to 36% (P <.001) with the plant stanol ester and increased by 40% to 52% (P <.001) with the sterol ester spread.. Consumption of plant sterols increases and consumption of plant stanols decreases the ratios of plant sterols to cholesterol in red cells of hypercholesterolemic children proportionately to the respective changes in plasma.

Topics: Child; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Double-Blind Method; Erythrocytes; Female; Humans; Hypercholesterolemia; Male; Margarine; Phytosterols; Sitosterols; Time Factors; Triglycerides

The cholesterol absorption inhibiting properties of plant sterols in milks are unknown. The milk fat globule membrane components may enhance the absorption of cholesterol and could make plant sterols less efficient in this complex matrix.. To evaluate in hypercholesterolemic men the cholesterol absorption inhibiting properties of verified properly solubilized, non-esterified plant sterols in partly vegetable oil containing milks.. The plant sterols in milk were determined to be properly solubilized, and to have effective in vitro functionality. Sixteen hypercholesterolemic adult men (initial total cholesterol 5.8-8.6 mM) then consumed milk containing sterols (1.8 g of non-esterified pure plant sterols/d) and control milk, alternatively, during two 6-day periods in a double blind cross over design. During the trial, cholesterol absorption was evaluated from the ratio of plasma isotopic enrichment of [26, 26, 26, 27, 27, 27-(2)H(6)]cholesterol from oral intake (35.6 +/- 0.2 micromol, +/- SEM) over enrichment of [23, 24, 25, 26, 27-(13)C(5)]cholesterol from intravenous injection (77.9 +/- 0.5 micromol).. Plant sterols in low fat milks contained very few crystals > 11 microm in the presence and absence of bile salts and lysophospholipids, and inhibited cholesterol uptake in Caco-2 cell. This assured that the sterols were properly solubilized prior to the clinical trial. In the clinical study, compliance of volunteers was excellent. After tracer injections (72 h), the plasma [(2)H] and [(13)C] isotopic enrichments changed from 0.024 +/- 0.001 and 0.072 +/- 0.003 MPE (control) to 0.015 +/- 0.001 and 0.074 +/- 0.002 MPE during sterol treatment, respectively. Cholesterol absorption was reduced from 70.1 +/- 4.2 % with control to 41.1 +/- 4.0 % with milks containing plant sterol (P < 0.001).. These results demonstrate that properly solubilized non-esterified plant sterols in milks significantly inhibit cholesterol absorption in mildly hypercholesterolemic men.

Topics: Adult; Animals; Caco-2 Cells; Cholesterol; Cholesterol, Dietary; Cross-Over Studies; Deuterium; Double-Blind Method; Emulsions; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Milk; Particle Size; Phytosterols; Solubility; Treatment Outcome

It has been reported that phytosterol esters reduce cholesterol absorption and lower serum cholesterol concentration. There have been very few studies published on the effect of dose of phytosterol esters less than 1.0 g/day on plasma cholesterol levels in healthy subjects using commonly consumed foods. In this study, we evaluated the effect of 0.45 g/day (as free sterol) phytosterol ester-enriched dissolved in vegetable oil on plasma lipoproteins in sixty healthy males with slightly elevated total cholesterol concentration. This study was conducted in a randomized, double-blind, placebo-controlled, and arm parallel study. A total of 14 g/day of phytosterol ester-enriched vegetable oil containing 0.45 g phytosterol (as the major free sterol) was compared with a control vegetable oil containing 0.04 g phytosterol (as the major free sterol). All subjects did not change their usual dietary habit and consumed foods that included about 360 mg/day cholesterol for 12 weeks. In subjects with higher total cholesterol concentrations (>200mg/dL), the phytosterol enriched-vegetable oil significantly reduced total cholesterol (10.3%, P<0.05), very low density (VLDL) lipoprotein cholesterol (22.5%, P<0.05), and remnant-like lipoprotein (RLP) cholesterol (24.7%, P<0.01) compared with the control vegetable oil. A reduction in low density lipoprotein (LDL) cholesterol concentration was also observed. In particular, the improvement in serum lipoprotein was more pronounced in subjects with higher total cholesterol concentrations. Triglycerides and high density lipoprotein (HDL) cholesterol did not change significantly. Plasma concentration of fat-soluble vitamins (tocopherol and retinol) and beta-carotene were not statistically significantly affected by phytosterol ester-enriched vegetable oil. These findings indicate that a daily consumption of phytosterol ester as low as 0.45 g/day (as free sterol) is effective in lowering blood total cholesterol concentration and RLP cholesterol concentration. Lower total cholesterol, VLDL cholesterol and RLP cholesterol due to consumption of the phytosterol ester-enriched vegetable oil may be helpful in reducing the risk of CHD in the population.

Topics: Adult; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Esters; Humans; Hypercholesterolemia; Lipoproteins; Male; Phytosterols; Plant Oils; Triglycerides

Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.

Topics: Adult; Aged; Aged, 80 and over; Cholesterol; Cholesterol, Dietary; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Erythrocyte Deformability; Female; Food Preferences; Homocysteine; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Middle Aged; Phytosterols; Prunus; Risk Factors; Satiety Response; Soybean Proteins

This study aimed at relating the pattern of response to dietary plant sterol ester (PSE) treatment of plasma lipids concentrations and apo E polymorphisms.. Patients (20-60y old: 50 women; 10 men) with primary moderate hypercholesterolemia were fed margarine (20g/d), received no treatment (placebo), and were fed PSE (2.8g/d = 1.68 phytosterols), during 3 periods of 4 weeks each, in a crossover, double-blind study. DNA was extracted from white blood cells for the apo E polymorphisms.. PSE treatment significantly lowered TC and LDL-C 10% and 12%, respectively, in relation to the baseline, and 6% and 8% in relation to the placebo phase, but HDL-C and TG levels were not modified. In regard to the apo E genotyping, no significant difference occurred between apo E 3/3 and apo E (3/4).. Dietary plant sterol ester (PSE) treatment reduced cholesterolemia, and the reduction of LDL-C in absolute values was more pronounced when the initial LDL - C concentration were elevated.

Topics: Adult; Apolipoproteins E; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Double-Blind Method; Esters; Female; Genotype; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Phytotherapy; Polymorphism, Genetic; Triglycerides

The objective of this study was to evaluate whether plant sterol-ester margarine has an additive or interactive effect on low-density lipoprotein (LDL) cholesterol reduction when ingested in combination with a statin drug. This was a multicenter, randomized, double-blind study with 4 parallel treatment arms in a balanced 2 x 2 factorial design. The 4 daily treatment options were: (1) placebo plus regular margarine 25 g (n = 38); (2) placebo plus sterol-ester margarine 25 g (2 g of plant sterol) (n = 39); (3) cerivastatin 400 microg plus regular margarine 25 g (n = 38); and (4) cerivastatin 400 microg plus sterol-ester margarine 25 g (n = 37). The study was conducted in men and women with primary hypercholesterolemia with baseline LDL cholesterol >/=97 mg/dl (mean 206). The primary efficacy parameter was the percent change in LDL cholesterol between baseline and at the end of 4 weeks' treatment. Cerivastatin (vs placebo) reduced LDL cholesterol by 32% (95% confidence intervals 28% to 36%, p <0.0001) and sterol-ester margarine (vs regular margarine) by 8% (95% confidence interval 4% to 12%, p <0.0001). The effect of sterol-ester margarine and cerivastatin together was additive (39% reduction in LDL cholesterol), but there was no significant interactive effect between sterol-ester margarine and cerivastatin (p = 0.29). The treatments were generally well tolerated with no major differences in adverse events between groups. In subjects with primary hypercholesterolemia, statin and sterol-ester margarine used together produce a purely additive effect on LDL cholesterol reduction. The addition of sterol-ester margarine to statin therapy offers LDL cholesterol reduction equivalent to doubling the dose of statin.

Topics: Apolipoproteins; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Fat-Restricted; Dietary Fats; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Margarine; Middle Aged; New South Wales; Phytosterols; Pyridines; Queensland; Treatment Outcome; Triglycerides

In a randomized, double-blind, placebo-controlled trial we evaluated the effect of dietary chocolates enriched with a wood-based phytosterol-phytostanol mixture, containing 18 % (w/w) sitostanol, compared with placebo dietary chocolates in seventy subjects with primary hypercholesterolaemia (total cholesterol levels below 8 mmol/l). For 4 weeks, participants consumed three servings of the phytosterol-enriched chocolate/d that provided 1.8 g unesterified phytosterols/d or a placebo chocolate in conjunction with a low-fat, low-cholesterol diet. Plasma total and LDL-cholesterol levels were statistically significantly reduced by 6.4 % (-0.44 mmol/l) and 10.3 % (-0.49 mmol/l), respectively, after 4 weeks of phytosterol-enriched-chocolate treatment. Plasma HDL-cholesterol and triacylglycerol levels were not affected. Consumption of phytosterol-enriched chocolates significantly increased plasma lathosterol concentration (+20.7 %), reflecting an increased endogenous cholesterol synthesis in response to phytosterol-induced decreased intestinal cholesterol absorption. Furthermore, the chocolates enriched with phytosterols significantly increased both plasma sitosterol (+95.8 %) and campesterol (+64.1 %) levels, compared with the placebo chocolate group. However, the absolute values of plasma sitosterol and campesterol remained within the normal range, that is, below 10 mg/l. The chocolates with phytosterols were palatable and induced no clinical or biochemical side effects. These findings indicate that dietary chocolate enriched with tall oil-derived phytosterols (1.8 g/d) is effective in lowering blood total and LDL-cholesterol levels in subjects with mild hypercholesterolaemia and thus may be helpful in reducing the risk of CHD in these individuals.

Topics: Adult; Apolipoproteins B; Cacao; Chi-Square Distribution; Cholesterol; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Plant Oils; Sitosterols; Statistics, Nonparametric

Plant sterols, in various forms, have been shown to reduce total and LDL-cholesterol concentrations. Particularly controversial at present is the effect of the degree of hydrogenation of the plant sterols on cholesterol-lowering efficacy and the responsible mechanisms.. Our goal was to examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentrations and cholesterol absorption, synthesis, and turnover.. Fifteen otherwise healthy hypercholesterolemic subjects consumed each of 4 dietary treatments in a randomized crossover design. Unesterified sterols and stanols were blended into the butter component of the diet at a dosage of 1.8 g/d. The diets contained plant sterols (NS), plant stanols (SS), a 50:50 mixture of sterols and stanols (NSS), or cornstarch (control).. Plasma total cholesterol concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS, and NSS groups, respectively, than in the control group. LDL-cholesterol concentrations were 11.3%, 13.4%, and 16.0% lower (P < 0.03) in the NS, SS, and NSS groups, respectively, than in the control group. Plasma triacylglycerols and HDL-cholesterol concentrations did not differ significantly across diets. Cholesterol absorption efficiency was 56.0%, 34.4%, and 48.9% lower (P < 0.001) in the NS, SS, and NSS groups, respectively, than in the control group. The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group. Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group.. These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption.

Topics: Adult; Butter; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diet; Double-Blind Method; Female; Humans; Hypercholesterolemia; Kinetics; Lipids; Male; Middle Aged; Phytosterols; Phytotherapy; Sitosterols

Plant-sterol-enriched spreads lower LDL cholesterol but may also lower lipid-standardized carotenoids.. Our objective was to assess whether advice to consume specific daily amounts of foods high in carotenoids prevents a reduction in plasma carotenoid concentrations in subjects who consume plant sterol or stanol esters.. Forty-six hypercholesterolemic free-living subjects completed a 3-way, double-blind, randomized crossover comparison. Subjects consumed each of the following 3 spreads (25 g/d) for 3 wk: control-1 (sterol-free), sterol ester-1 (2.3 g plant sterol esters), and stanol ester-1 (2.5 g plant stanol esters). During the 3-wk interventions, subjects were advised to eat > or =5 servings of vegetables and fruit/d, of which > or =1 serving was to be carrots, sweet potatoes, pumpkins, tomatoes, apricots, spinach, or broccoli.. The dietary advice resulted in a 13% increase in plasma beta-carotene in subjects who consumed control-1 (P = 0.04). The plasma beta-carotene concentrations of subjects who consumed control-1 did not differ significantly from those of subjects who consumed stanol ester-1 or sterol ester-1. This result was achieved by an increase of one daily serving of high-carotenoid vegetables or fruit. LDL cholesterol decreased 7.7% and 9.5% after consumption of sterol ester-1 and stanol ester-1, respectively (P < 0.001 for both), and differences between the LDL-cholesterol values obtained were not significant.. Dietary advice to consume an additional daily serving of a high-carotenoid vegetable or fruit when consuming spreads containing sterol or stanol esters maintains plasma carotenoid concentrations while lowering LDL-cholesterol concentrations significantly.

Topics: Analysis of Variance; Antioxidants; Body Mass Index; Carotenoids; Cholesterol, LDL; Cross-Over Studies; Diet; Dietary Fats; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols

Dietary phytosterols have been reported to lower total and low-density lipoprotein (LDL) cholesterol. However, less is known about the influence of cholesterol and fat intake on the cholesterol-lowering effect of esterified phytosterols in mild to moderate hypercholesterolemia. Sixty-three healthy subjects (38 women, 25 men, 42 +/- 11 years, LDL cholesterol > 130 mg/dL) were investigated in a randomized, double-blind, placebo-controlled, cross-over study. A total of 20 g/d of a phytosterol ester-enriched margarine (1.82 g/d of phytosterols) was compared with a control margarine (0.06 g/d of phytosterols). After 3 weeks of intake, participants crossed over to the other margarine. A 3-day dietary recall was performed at the beginning and at the end of the study to assess cholesterol, fat, and energy intake. Phytosterol ester-enriched margarine significantly changed total cholesterol (-3.4%, P <.005), LDL cholesterol (-5.4%, P <.001, 144 +/- 28 v 154 +/- 26 mg/dL), high-density lipoprotein (HDL) cholesterol (+3.4%, P <.05), apolipoprotein B (-4.0%, P <.005), and LDL/HDL cholesterol ratio (-7.8%, P <.001) compared with the control margarine. In the tertiles with the highest dietary intake of cholesterol, energy, total fat, and saturated fatty acids, and with the highest baseline proportion of campesterol to cholesterol, LDL cholesterol reduction was 11.6% (P <.001), 9.5% (P =.001), 9.4% (P =.001), 8.4% (P =.005), and 6.2% (P =.014), respectively. Triglycerides, plasma viscosity, and fibrinogen concentration did not change significantly. The improvements of LDL, HDL, total cholesterol, apolipoprotein B concentrations, and LDL/HDL cholesterol ratio during the daily consumption of a phytosterol ester-enriched margarine were most marked in those subjects with a high dietary intake of cholesterol, energy, total fat, and saturated fatty acids and with high baseline cholesterol absorption.

Topics: Adult; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Fats; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipoproteins; Male; Margarine; Middle Aged; Phytosterols; Placebos

The ability of plant sterol esters (PSE) in salad dressing to modify plasma lipids and carotenoids was determined in 26 men and 27 women fed controlled, weight-maintaining, isocaloric diets. Diets contained typical American foods that provided 32% of energy from fat. Dressings contained 8 g (ranch) or 4 g (Italian) of fat per serving. PSE (3.6 g/d) were provided in two servings/d of one of the dressings. Diets with ranch or Italian dressing without and with PSE were fed for 3 wk/diet and crossed over randomly within dressings. Diets were adjusted to similar fat and fatty acid concentrations. Type of salad dressing did not affect plasma lipids, lipoproteins, carotenoids, or fat-soluble vitamins (P > 0.05). Switching from a self-selected baseline diet to the control diet resulted in reduction in low density lipoprotein (LDL) cholesterol of 7.9%, a decrease in high density lipoprotein (HDL) cholesterol of 3.1%, and a decrease in triglycerides (TG) of 9.3%. Consumption of 3.6 g of PSE resulted in further decreases in LDL cholesterol (9.7%) and TG (7.3%) but no additional change in HDL cholesterol. Total plasma carotenoids decreased 9.6% with PSE. An automated stepwise procedure was developed to produce candidate mixed models relating plasma carotenoid response to PSE. These models adjusted for preintervention plasma carotenoid levels and effects of diets on blood lipids. There were significant decreases in beta-carotene, alpha-carotene, and beta-cryptoxanthin (females only) not associated with changes in plasma lipids. Plasma carotenoids on all diets remained within normal ranges. We conclude that low-fat foods, such as salad dressings, are effective carriers for PSE.

Topics: Adult; Apolipoproteins; Carotenoids; Cholesterol; Diet; Dietary Fats, Unsaturated; Female; Food Analysis; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Male; Middle Aged; Phytosterols

Spreads enriched with plant sterol and stanol esters have been shown to possess similar cholesterol-lowering properties; however, their comparative capacity to alter circulating levels of other fat-soluble compounds has not been fully assessed. To compare actions of sterol and stanol ester consumption on serum fat-soluble vitamin and carotenoid concentrations, 15 hypercholesterolemic subjects were fed each of 3 fixed foods treatment diets over 21 days using a randomized crossover controlled design. Diets contained either (1) margarine (M), (2) margarine with sterol esters (MSE; 1.92 g/d), or (3) margarine with stanol esters (MSA; 1.76 g/d). No significant differences were found in initial or final serum fat-soluble vitamin and carotenoid concentrations among the 3 phases. Serum retinol and alpha- and gamma-tocopherol concentrations at baseline and endpoint and percentage changes relative to baseline for MSE and MSA were not significantly different from those of the M diet. After adjusting for total cholesterol reduction, no changes for alpha- and gamma-tocopherol were found. Serum vitamins D and K, lycopene, and lutein concentrations and percentage changes did not differ across diets. Serum concentrations at baseline and endpoint and percentage changes for alpha- and beta-cryptoxanthin and alpha- and gamma-carotene were not different among the diets, nor did serum alpha- and gamma-carotene concentrations to total cholesterol ratios differ. Serum lutein, beta-cryptoxanthin, and alpha-carotene concentrations increased over time. In conclusion, our results show no effect of consumption of esterified plant sterols or stanols on serum fat-soluble vitamin or carotenoid concentrations compared with a control diet.

Topics: Adult; alpha-Tocopherol; beta Carotene; Carotenoids; Cross-Over Studies; Cryptoxanthins; Diet; Double-Blind Method; gamma-Tocopherol; Humans; Hypercholesterolemia; Lutein; Male; Margarine; Middle Aged; Patient Compliance; Phytosterols; Placebos; Sitosterols; Solubility; Vitamin A; Vitamin K; Vitamins; Xanthophylls

In this randomized double-blind placebo-controlled cross-over study the effects of spreads enriched with plant sterols were determined on serum lipids, lipoprotein and apolipoprotein concentrations in a Belgian population.. Fourty-two healthy adult volunteers (22 men and 20 women) with an average age of 55 (SD 9) years and with serum total cholesterol concentrations below 300 mg/dl, consumed during two consecutive periods of 4 weeks two different low-fat spreads. Both the plant sterol rich and control spreads contained 35% of fat and had an almost equal fat composition. The sterol content of the enriched spread was 8.3%. Intake of the spreads was 25 g/day.. Serum total and LDL-cholesterol concentrations lowered by 7% (18 mg/dl) and 10% (16 mg/dl), respectively, with the plant sterol-enriched compared to the control spread. Serum HDL-cholesterol concentration did not significantly differ between the two spreads. Apolipoprotein B concentrations lowered by 8% (0.08 g/l) with the plant sterol-enriched spread, while concentrations of apolipoprotein A-I did not change.. These findings indicate that a daily intake of 25 gram low-fat spread containing 2 gram plant sterol per day is effective in lowering blood total and LDL cholesterol, and apolipoprotein B concentrations. This lowering may help to reduce the risk of heart disease in the population.

Topics: Adult; Aged; Apolipoprotein A-I; Apolipoproteins B; Belgium; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipoproteins; Male; Middle Aged; Phytosterols; Reference Values; Severity of Illness Index; Treatment Outcome; Triglycerides

Although supplementing the diet with large quantities of phytosterols reduces cholesterol absorption and LDL-cholesterol concentrations, very little is known about the smaller amounts of phytosterols present naturally in food. Vegetable oils are the richest dietary source of phytosterols; corn oil contains 0.77% phytosterols by weight.. We tested the hypothesis that removing phytosterols from corn oil would increase cholesterol absorption when measured in single-meal tests containing corn oil as a source of fat.. Free and esterified phytosterols were removed from corn oil on a kilogram scale by a new technique of competitive saturation adsorption to silica. Healthy subjects with a mean (+/-SEM) serum cholesterol concentration of 5.10 +/- 0.18 mmol/L received an otherwise sterol-free test breakfast on 2 occasions 2 wk apart that contained 35 mg hexadeuterated cholesterol and 30-35 g of a corn oil preparation. The plasma enrichment of tracer was measured by negative ion mass spectrometry.. Cholesterol absorption was 38.0 +/- 10.2% higher after consumption of the sterol-free corn oil than after consumption of commercial corn oil with an identical fatty acid content (P = 0.005; n = 10). When corn oil phytosterols were added back to sterol-free corn oil at a concentration of 150 mg/test meal, cholesterol absorption was reduced by 12.1 +/- 3.7% (P = 0.03; n = 5) and by 27.9 +/- 9.1% (P = 0.01; n = 10) after inclusion of 300 mg phytosterols.. Phytosterols comprising < 1% of commercial corn oil substantially reduced cholesterol absorption and may account for part of the cholesterol-lowering activity of corn oil previously attributed solely to unsaturated fatty acids.

Topics: Absorption; Adult; Cholesterol; Cholesterol, LDL; Corn Oil; Cross-Over Studies; Deuterium; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Mass Spectrometry; Phytosterols

Consumption of phytosterol-supplemented margarine lowers total plasma cholesterol (TC) and LDL-cholesterol concentrations in older middle-aged hypercholesterolemic individuals. The effects of incorporating phytosterols into lower-fat foods on the plasma lipids of young men at increased risk of developing cardiovascular disease have not been studied.. We tested the hypothesis that a single daily dose of soybean phytosterols added to ground beef will lower plasma TC and LDL-cholesterol concentrations in mildly hypercholesterolemic young men.. In a triple-blind, 4-wk study, 34 male college students with elevated plasma TC (5.85 +/- 0.70 mmol/L), LDL cholesterol (4.02 +/- 0.60 mmol/L), and TC:HDL cholesterol (5.5 +/- 1.2) were randomly assigned to the control (ground beef alone) or treatment (ground beef with 2.7 g of phytosterols) group. The phytosterol mixture was two-thirds esterified and one-third nonesterified and consisted of beta-sitosterol (48%), campesterol (27%), and stigmasterol (21%).. Consumption of phytosterol-supplemented ground beef lowered plasma TC and LDL-cholesterol concentrations and TC:HDL cholesterol from baseline by 9.3%, 14.6%, and 9.1%, respectively (P < 0.001). The LDL particle size did not change, suggesting that the decrease was primarily of particle number. The decreases were similar in subjects with (n = 8) and without (n = 9) a family history of premature cardiovascular disease. No significant changes were found in the control group.. Phytosterol-supplemented ground beef effectively lowers plasma TC and LDL cholesterol and has the potential to become a functional food to help reduce the risk of cardiovascular disease.

Topics: Adult; Animals; Cattle; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Food, Fortified; Glycine max; Humans; Hypercholesterolemia; Male; Meat Products; Phytosterols; Sitosterols; Stigmasterol

BACKGROUND Numerous studies have shown that dietary plant sterols (phytosterols and phytostanols) and their esters can decrease cholesterol absorption. However, few researchers have examined the effects of plant sterols on cholesterol absorption and synthesis using stable isotope tracers, instead of relying on endogenous pathway precursors. Further, we have worked with non-esterified lecithin-solubilized stanols as opposed to the more frequently studied esterified sterols and stanols. The vehicle was an oil-in-water liquid emulsion rather than the more common spread vehicle typically employed.. To determine the effects of relatively low doses of lecithin-solubilized non-esterified stanols in liquid emulsions on cholesterol absorption and synthesis in mildly hypercholesterolemic subjects.. In a randomized, double blind crossover design, 12 mildly hypercholesterolemic men received either a free phytostanol supplement (3 g/d in 3 servings) or a control treatment for 3 days. Cholesterol endogenous synthesis rate was determined using the rate of incorporation of deuterium from body water into newly formed cholesterol molecules. Cholesterol absorption at the intestinal level was determined using the dual isotope method using 13C cholesterol injected intravenously and 180 cholesterol given orally.. Cholesterol absorption was 55.7 +/- 6.5 % for the control and 33.5 +/- 5.3% for the phytostanol treatment. This massive reduction of the cholesterol absorption did not induce, on average, a difference in cholesterol endogenous synthesis which was measured at 0.074 +/- 0.0015 pool/d for plant sterols and 0.0736 +/- 0.0015 pool/d for controls (p > 0.05).. The results demonstrated that lecithin-solubilized stanols administrated during a short period of time (3 days) in an oil-in-water emulsion can dramatically decrease cholesterol absorption, without a consistent, concomitant increase in synthesis, which is highly suggestive of effective LDL cholesterol lowering. The effects of synthesis should be verified in a longer study with more subjects.

Topics: Adult; Carbon Isotopes; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Deuterium; Dietary Supplements; Double-Blind Method; Emulsions; Humans; Hypercholesterolemia; Intestinal Absorption; Kinetics; Male; Middle Aged; Oxygen Isotopes; Phytosterols; Phytotherapy

Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet.. This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia.. Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group).. Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control).. A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Topics: Adult; Aged; Carotenoids; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet, Fat-Restricted; Double-Blind Method; Esters; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Margarine; Middle Aged; Patient Compliance; Phytosterols; Vitamins

This study was performed to investigate the difference in the serum-cholesterol- and triglyceride-lowering activities between phytosterols dissolved in diacylglycerol (PS/DG) and dispersed in triacylglycerol (PS/TG). The effects of the solvent on the concentrations of serum beta-sitosterol and campesterol were examined.. The study had a randomised crossover design.. Twelve healthy normocholesterolemic or moderately hypercholesterolemic men aged 29-50 y participated in this study.. For 2 weeks before the test period (designated as the control period), all subjects consumed control mayonnaise (PS free) daily with supper and were randomly assigned to two groups for the 2 week test period; one group was given mayonnaise containing PS (500 mg/day) dissolved in DG (10 g/day), and the other mayonnaise containing PS (500 mg/day) dispersed in TG (10 g/day). After a wash out period consuming control PS-free mayonnaise for 4 weeks, the groups were reversed for 2 weeks.. PS/TG feeding had no effect on the serum cholesterol level. In contrast, PS/DG feeding significantly reduced the total and LDL cholesterol levels from the initial value of 5.57 to 5.31 mmol/l (4.7%; P<0.05) and from 3.69 to 3.39 mmol/l (7.6%; P<0.05), respectively. Moreover, the degree of total cholesterol reduction induced by PS/DG feeding in the test period was significantly greater than that induced by PS/TG feeding (P<0.05). In addition, the serum beta-sitosterol and campesterol concentrations did not change during the PS/TG or PS/DG feeding periods.. Dissolution of PS in DG had a better serum cholesterol lowering effect than dissolution in TG.. Kao Corporation.

Topics: Adult; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diglycerides; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols; Solubility; Triglycerides

The objective of the present study was to assess the effect of consumption of a yoghurt-based drink enriched with 1-2 g plant sterols/d on serum lipids, transaminases, vitamins and hormone status in patients with primary moderate hypercholesterolaemia. Thirty patients were randomly assigned to one of two treatment groups: a low-fat low-lactose yoghurt-based drink enriched with 1 g plant sterol extracted from soyabean/d v. a low-fat low-lactose yoghurt, for a period of 4 weeks. After a 2-week wash-out period, patients were crossed over for an additional 4-week period. Second, after a 4-week wash-out period, eleven patients were treated with 2 g plant sterols/d in a second open part of the study for a period of 8 weeks. The yoghurt enriched with plant sterols significantly reduced, in a dose-dependent manner, serum total cholesterol and LDL-cholesterol levels and LDL-cholesterol:HDL-cholesterol (P<0.001), whereas no changes were observed in HDL-cholesterol and triacylglycerol levels, either in the first or the second part of the study. There were only slight, not statistically significant, differences in serum transaminase, vitamin and hormone levels. To conclude, a low-fat yoghurt-based drink moderately enriched with plant sterols may lower total cholesterol and LDL-cholesterol effectively in patients with primary moderate hypercholesterolaemia.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Double-Blind Method; Female; Gonadal Steroid Hormones; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Transaminases; Vitamins; Yogurt

Plant sterols have been shown to reduce serum lipid concentrations. The effectiveness is highly dependent on the physical state of the plant sterols. By means of a new crystallizing method, plant sterols can be added into dietary fats and oils homogeneously. In this fat ingredient, plant sterols are in a microcrystalline form.. We investigated the cholesterol-lowering effect and possible side effects of vegetable oil-based spreads fortified with two different doses of microcrystalline plant sterols.. This double-blind randomized, placebo-controlled study consisted of a 6-wk run-in and a 6-month experimental period. During the run-in period, all 155 hypercholesterolemic subjects received rapeseed oil-based control spread. In the beginning of the experimental period subjects were randomly assigned into one of three experimental groups. The control group continued to use control spread, and the two test groups used spreads with added plant sterols of either 1.5 g/d or 3.0 g/d. The subjects consumed test spreads as a part of their normal diet without any restrictions in lifestyle and diet.. Plasma total- and LDL-cholesterol concentrations were significantly reduced by 7.5-11.6% (0.46-0.62 mmol/1) in groups consuming margarine enriched with free plant sterols, compared with the control group. The effects were similar between the two groups consuming either 1.5g or 3.0 g plant sterols per day. No effect on HDL-cholesterol or triacylglycerol concentrations occurred. The test spreads did not induce any adverse effects in blood clinical chemistry, hematology or decreases in serum concentrations of lipid soluble vitamins.. Microcrystalline plant sterols are effective in lowering serum total- and LDL-cholesterol concentrations without obvious side effects. The daily dose of 1.5 g plant sterols is enough to reach the maximum effect.

Topics: Adult; Carotenoids; Cellulose; Cholesterol; Cholesterol, LDL; Double-Blind Method; Excipients; Female; Food, Fortified; Humans; Hypercholesterolemia; Intestinal Absorption; Kinetics; Longitudinal Studies; Male; Margarine; Middle Aged; Oxidation-Reduction; Phytosterols; Vitamins

Plant sterols have been incorporated into nutritional fats to achieve cholesterol lowering, but studies using enrichment of low-fat foods with plant sterols have not been reported. Our study was aimed at determining the effect of dietary intake of low-fat foods containing natural nonesterified plant sterols together with recommended doses of calcium, magnesium, and potassium on serum cholesterol and low-density lipoprotein (LDL) cholesterol-lowering in persons with mild to moderate hypercholesterolemia. This was a randomized, double-blind, placebo-controlled feeding trial lasting 15 weeks and performed in 2 university hospital centers. Seventy-eight subjects aged 25 to 75 years with serum cholesterol concentrations varying between 6 mmol/L (232 mg/dl) and 8 mmol/L (310 mg/dl) were randomly allocated to active treatment consisting of intake of bread, meat products, and jam enriched with 1.25 to 5.0 g/day of plant sterols and the slightly elevated concentrations of mineral nutrients, or the corresponding placebo food items. Serum lipid, high-density lipoprotein cholesterol and calculated LDL cholesterol concentrations were determined. Seventy-one persons completed the trial. Reduction in serum total cholesterol was 8% in the active treatment group and 3% in the placebo group (p = 0.0071) and that of LDL cholesterol was 13% in the active treatment group and 5% in the placebo group (p = 0.0070). In conclusion, natural nonesterified plant sterols contained in low-fat food items and ingested in moderate doses reduced serum total and LDL cholesterol concentrations to the same extent as reported previously for esterified plant sterol derivatives added to nutritional fats. The presence of mineral nutrients in doses recommended for blood pressure-lowering did not interfere with the cholesterol-lowering efficacy of the sterols, providing a promising approach to dietary prevention of cardiovascular diseases.

Topics: Adult; Aged; Analysis of Variance; Cholesterol, LDL; Dietary Fats; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Phytosterols; Trace Elements

To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine.. Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g)-containing foods were eaten during 4 week test periods of cross-over design following a 4 week control food period. In Study 2, in a random order cross-over design, a 50% dairy fat spread with or without 2.4 g sterol esters daily was tested.. Hypercholesterolaemic subjects; 22 in study 1 and 15 in study 2.. Plasma lipids, plasma sterols, plasma carotenoids and tocopherols.. Study 1-median LDL cholesterol was reduced by the sterol esters (-13.6%; P<0.001 by ANOVA on ranks; P<0.05 by pairwise comparison) and by stanols (-8.3%; P=0.003, ANOVA and <0.05 pairwise comparison). With sterol esters plasma plant sterol levels rose (35% for sitosterol, 51% for campesterol; P<0.001); plasma lathosterol rose 20% (P=0.03), indicating compensatory increased cholesterol synthesis. With stanols, plasma sitosterol fell 22% (P=0.004), indicating less cholesterol absorption. None of the four carotenoids measured in plasma changed significantly. In study 2, median LDL cholesterol rose 6.5% with dairy spread and fell 12.2% with the sitosterol ester fortified spread (P=0.03 ANOVA and <5% pairwise comparison).. 1. Plant sterol esters and non-esterified stanols, two-thirds of which were incorporated into low-fat foods, contributed effectively to LDL cholesterol lowering, extending the range of potential foods. 2. The LDL cholesterol-raising effect of butter fat could be countered by including sterol esters. 3. Plasma carotenoids and tocopherols were not reduced in this study.. Meadow Lea Foods, Australia.

Topics: Adult; Aged; Anticholesteremic Agents; Antioxidants; Butter; Carotenoids; Cholesterol; Cross-Over Studies; Diet, Fat-Restricted; Esters; Female; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Phytotherapy; Single-Blind Method; Treatment Outcome; Vitamin E

The effect of plant stanol ester on serum cholesterol is dose-dependent. However, it is not clear what the dose is beyond which no additional benefit can be obtained. Therefore, we determined the dose-response relationship for serum cholesterol with different doses of plant stanol ester in hypercholesterolemic subjects. In a single-blind design each of 22 men or women consumed five different doses of plant stanol [target (actual) intake 0 (0), 0.8 (0.8), 1.6 (1.6), 2.4 (2.3), 3.2 (3.0) g/d] added as plant stanol esters to margarine for 4 wk. The order of dose periods was randomly determined. Serum total cholesterol concentration decreased (calculated in reference to control) by 2.8% (P = 0.384), 6.8% (P < 0.001), 10.3% (P < 0.001) and 11.3% (P < 0.001) by doses from 0.8 to 3.2 g. The respective decreases for LDL cholesterol were 1.7% (P = 0. 892), 5.6% (P < 0.05), 9.7% (P < 0.001) and 10.4% (P < 0.001). Although the decreases were numerically greater with 2.4 and 3.2 g doses than with the 1.6 g dose, these differences were not significant (P = 0.054-0.516). Serum plant stanols rose slightly, but significantly with the dose (P < 0.001). Apolipoprotein B concentration was decreased significantly already at the dose of 0.8 g (8.7%, P < 0.001). Apolipoprotein E genotype did not affect the lipid responses. We conclude that significant reduction of serum total and LDL cholesterol concentrations is reached with the 1.6-g stanol dose, and increasing the dose from 2.4 to 3.2 g does not provide clinically important additional effect.

Topics: Adult; Aged; Anticholesteremic Agents; Carotenoids; Child, Preschool; Cholesterol; Dose-Response Relationship, Drug; Esters; Female; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Male; Margarine; Middle Aged; Osmolar Concentration; Phytosterols; Single-Blind Method; Sitosterols; Vitamins

It has been suggested that phytosterol and phytostanol esters possess similar cholesterol-lowering properties, however, whether mechanisms responsible are identical has not been addressed. To address this question, cholesterol plasma levels, absorption, biosynthesis, and turnover were measured in 15 hypercholesterolemic subjects consuming prepared diets each over 21 d using a cross-over design. Diets contained either i) margarine (M), ii) margarine with phytosterol esters (MSE) (1.84 g/d), or iii) margarine with phytostanol esters (MSA) (1.84 g/d). Cholesterol absorption was measured using the ratio of [(13)C]cholesterol(oral):D(7)-cholesterol(IV); biosynthesis using D incorporation from D(2)O and turnover by D(7)-cholesterol(IV) decay rates. Plasma total cholesterol level at d 21/22 was lower (P < 0. 05) for MSE (13.4%) but not MSA (10.2%) versus M (6.0%) diets. Plasma low density lipoprotein-cholesterol (LDL-C) mean reductions at d 21/22 were larger (P < 0.05) for MSE (12.9%) and MSA (7.9%) compared with M (3.9%). Plasma TG and high density lipoprotein-cholesterol (HDL-C) levels did not differ across diets. Cholesterol absorption was reduced (P < 0.05) 36.2 and 25.9% at d 21 for MSE and MSA versus M, while cholesterol biosynthesis was reciprocally increased (P < 0.05) 53.3 and 37.8% for MSE and MSA versus M, respectively. Cholesterol turnover was not influenced by diet. These data indicate that plant sterol and stanol esters differentially lower circulating total and LDL cholesterol levels by suppression of cholesterol absorption in hypercholesterolemic subjects.

Topics: Absorption; Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Double-Blind Method; Humans; Hypercholesterolemia; Kinetics; Lipids; Male; Margarine; Middle Aged; Phytosterols

To investigate cholesterol-lowering effects of stanol ester (STAEST) and sterol ester (STEEST)-enriched margarines as part of a low-fat diet.. According to a Latin square model randomized double-blind repeated measures design with three test margarines and three periods.. Outpatient clinical trial with free-living subjects.. Thirty-four hypercholesterolaemic subjects completed the study.. Subjects consumed three rapeseed oil-based test margarines (STAEST, STEEST and control (no added stanols or sterols)) as part of a low-fat diet each for 4 weeks.. Mean daily intake of total plant sterols plus stanols was 2.01-2.04 g during the two test margarine periods. In reference to control, serum total cholesterol was reduced by 9.2 and 7.3% with the STAEST and STEEST margarine, respectively (P<0.001 for both). The respective reductions for low-density lipoprotein (LDL) cholesterol were 12.7 and 10.4% (P<0. 001). The cholesterol-lowering effects of the test margarines did not differ significantly. The presence of apolipoprotein E4 allele had a significant effect on LDL cholesterol response during the STAEST margarine only. Serum sitosterol and campesterol increased by 0.83 and 2.77 mg/l with the STEEST (P<0.001), respectively and decreased by 1.18 and 2.60 mg/l with the STAEST margarine (P<0.001). Increases of serum sitostanol and campestanol were 0.11 and 0.19 mg/l with the STAEST margarine (P<0.001), repsectively. No significant changes were found in serum fat-soluble vitamin and carotenoid concentrations when related to serum total cholesterol.. STAEST and STEEST margarines reduced significantly and equally serum total and LDL cholesterol concentrations as part of a low-fat diet.. Grant to the University of Kuopio by Raisio Benecol Ltd, Raisio, Finland.

Topics: Adult; Aged; Anticholesteremic Agents; Antioxidants; Carotenoids; Cholesterol; Diet, Fat-Restricted; Double-Blind Method; Esters; Female; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Plant Oils; Sitosterols; Vitamin E

To investigate the potential effects of high-dose 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor on plasma phytosterol, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), hypercholesterolemic subjects received 40 or 80 mg/d simvastatin in a 24-week prospective clinical trial. Plasma lipid levels were analyzed enzymatically, and plasma phytosterol concentrations were determined using gas-liquid chromatography. The change in the plasma phytosterol-campesterol level was used as an indicator of cholesterol absorption in humans. Simvastatin treatment reduced plasma campesterol (-24%, P = .017) but did not affect circulating stigmasterol and sitosterol levels. A dose of 80 mg/d simvastatin produced a larger decrease (P = .050) in plasma campesterol (0.1680 mmol/L) than 40 mg/d (0.0237 mmol/L) versus baseline. There was a positive correlation between plasma campesterol and TC both before (r = .54, P = .027) and after (r = .63, P = .009) treatment. Plasma TC and TG levels did not differ between groups receiving 40 or 80 mg/d simvastatin. Simvastatin treatment reduced circulating TC, LDL-C, and TG by 40%, 50%, and 33% (P<.007), respectively. There was no significant effect of simvastatin on plasma HDL-C, but the HDL-C/LDL-C ratio increased 1.3-fold (P<.0001). In conclusion, this HMG-CoA reductase inhibitor reduces the plasma campesterol level, a marker of cholesterol absorption, which may contribute to the mechanism by which simvastatin decreases circulating cholesterol levels.

Topics: Adult; Aged; Cholesterol; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Lipids; Male; Middle Aged; Phytosterols; Simvastatin

We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas-liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5-39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10- 46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0. 001) and serum plant sterol proportions by 8-13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.

Topics: Anticholesteremic Agents; Body Mass Index; Cholestanol; Cholesterol; Dietary Fats, Unsaturated; Esters; Fatty Acids, Monounsaturated; Humans; Hypercholesterolemia; Kinetics; Margarine; Phytosterols; Rapeseed Oil; Sitosterols; Sterols

To investigate the dose-response relationship between cholesterol lowering and three different, relatively low intake levels of plant sterols (0.83, 1.61, 3.24 g/d) from spreads. To investigate the effects on lipid-soluble (pro)vitamins.. A randomized double-blind placebo controlled balanced incomplete Latin square design using five spreads and four periods. The five study spreads included butter, a commercially available spread and three experimental spreads fortified with three different concentrations of plant sterols.. One hundred apparently healthy normocholesterolaemic and mildly hypercholesterolaemic volunteers participated.. Each subject consumed four spreads, each for a period of 3.5 week.. Compared to the control spread, total cholesterol decreased by 0.26 (CI: 0.15-0.36), 0.31 (CI: 0.20-0.41) and 0.35 (CI: 0.25-0.46) mmol/L, for daily consumption of 0.83, 1.61 and 3.24 g plant sterols, respectively. For LDL-cholesterol these decreases were 0.20 (CI: 0.10-0.31), 0.26 (CI: 0.15-0.36) and 0.30 (CI: 0.20-0.41). Decreases in the LDL/HDL ratio were 0.13 (CI: 0.04-0.22), 0.16 (CI: 0.07-0.24) and 0.16 (CI: 0.07-0.24) units, respectively. Differences in cholesterol reductions between the plant sterol doses consumed were not statistically significant. Plasma vitamin K1 and 25-OH-vitamin D and lipid standardized plasma lycopene and alpha-tocopherol were not affected by consumption of plant sterol enriched spreads, but lipid standardized plasma (alpha + beta)-carotene concentrations were decreased by about 11 and 19% by daily consumption of 0.83 and 3.24 g plant sterols in spread, respectively.. The three relatively low dosages of plant sterols had a significant cholesterol lowering effect ranging from 4.9-6.8%, 6.7-9.9% and 6.5-7.9%, for total, LDL-cholesterol and the LDL/HDL cholesterol ratio, respectively, without substantially affecting lipid soluble (pro)vitamins. No significant differences in cholesterol lowering effect between the three dosages of plant sterols could be detected. This study would support that consumption of about 1.6 g of plant sterols per day will beneficially affect plasma cholesterol concentrations without seriously affecting plasma carotenoid concentrations.

Topics: Adult; Antioxidants; Butter; Carotenoids; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lycopene; Male; Margarine; Middle Aged; Phytosterols; Surveys and Questionnaires; Vitamin D; Vitamin E; Vitamin K

To determine the efficacy of stanol esters in lowering cholesterol in a US population.. After a run-in phase, 318 subjects were randomized to receive one of the following margarine-like spreads containing stanol ester or placebo for 8 weeks: EU 3 G: 1 g of stanol (ester form) per 8-g serving of a European formula 3 times a day; US 3 G: 1 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; US 2 G: 0.67 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; or placebo spread.. Mean +/- SD baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 233+/-20 and 153+21 mg+/-dL, respectively. In the US 3 G group, 3 g daily of stanol esters lowered TC and LDL-C levels by 6.4% and 10.1%, respectively. There was a dose-dependent response compared with 2 g daily (US 2 G). Triglyceride and high-density lipoprotein cholesterol levels were unchanged. The incidence of adverse effects was not different from placebo. Serum vitamin A and 25-hydroxyvitamin D levels were not affected.. Stanol esters lowered TC and LDL-C levels in a mildly hypercholesterolemic US population without evidence of adverse effects. It may be a useful dietary adjunct to lower cholesterol.

Topics: Adult; Anticholesteremic Agents; beta Carotene; Cholestanols; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Dose-Response Relationship, Drug; Double-Blind Method; Esters; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols; Treatment Outcome; Triglycerides; United States; Vitamin A; Vitamin D

To investigate the effects of low-fat stanol ester margarines on concentrations of serum carotenoids.. A randomized parallel double-blind study design consisting of a 4-week run-in (high-fat diet) and an 8-week experimental (low-fat, low-cholesterol diet) period. During the experimental diet period subjects consumed low-fat wood stanol ester (WSEM), vegetable oil stanol ester (VOSEM) or control (no stanol esters) margarine daily. The daily mean total stanol intake was 2.31 and 2.16 g in the WSEM and VOSEM groups, respectively.. Outpatient clinical trial with free-living subjects.. Altogether, 60 hypercholesterolaemic subjects were selected for the study out of 91 originally screened. The study was completed by 55 subjects.. Serum alpha- and beta-carotene and lycopene determined by the HPLC.. Serum alpha-carotene concentration did not change significantly in either of the experimental groups, whereas beta-carotene concentration decreased significantly in the WSEM and VOSEM groups (P<0.01), and the change differed significantly (P<0.05 and P <0.01, respectively) from that of the control group. Decrease in alpha+beta-carotene concentration was significantly greater (P <0.05) in both experimental groups than in the control group. However, the change in alpha-, beta- or alpha+beta-carotene/total cholesterol ratio did not differ significantly among the groups. No significant changes were found in serum lycopene or lycopene/total cholesterol ratio in both experimental groups.. Low-fat stanol ester margarines appeared to have little effect on serum concentrations of alpha-, beta- or alpha + beta-carotene, or lycopene.. Grant to the University of Kuopio by Raisio Benecol Ltd, Raisio, Finland.

Topics: Adult; Anticholesteremic Agents; beta Carotene; Carotenoids; Cholesterol; Dietary Fats; Double-Blind Method; Esters; Female; Humans; Hypercholesterolemia; Lycopene; Male; Margarine; Phytosterols

To compare effects on plasma total-, LDL-, and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester.. A randomized double-blind placebo-controlled balanced incomplete Latin square design with five treatments and four periods of 3.5 weeks. Margarines enriched with sterols from soybean, sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine. Sterol intake was between 1.5-3.3 g/d. Two thirds of the soybean oil sterols were esterified to fatty acids.. Unilever Research Laboratory, Vlaardingen, The Netherlands.. One hundred healthy non-obese normocholesterolaemic and mildly hypercholesterolaemic volunteers aged 45+/-12.8 y, with plasma total cholesterol levels below 8 mmol/L at entry.. Plasma lipid, carotenoid and sterol concentrations, blood clinical chemistry and haematology, fatty acid composition of plasma cholesterylesters and food intake.. Ninety-five volunteers completed the study. None of the margarines induced adverse changes in blood clinical chemistry, serum total bile acids or haematology. Plasma total- and LDL-cholesterol concentrations were significantly reduced by 8-13% (0.37-0.44 mmol/L) compared to control for margarines enriched in soybean oil sterol-esters or sitostanol-ester. No effect on HDL-cholesterol concentrations occurred. The LDL- to HDL-cholesterol ratio was reduced by 0.37 and 0.33 units for these margarines, respectively. Effects on blood lipids did not differ between normocholesterolaemic and mildly hypercholesterolaemic subjects. Plasma sitosterol and campesterol levels were significantly higher for the soybean oil sterol margarine and significantly lower for the sitostanol-ester margarine compared to control. Dietary intake was very similar across treatments. The fatty acid composition of plasma cholesterylesters confirmed the good compliance to the treatment. All sterol enriched margarines reduced lipid-standardized plasma alpha- plus beta-carotene levels. Plasma lycopene levels were also reduced but this effect was not significant for all products.. A margarine with sterol-esters from soybean oil, mainly esters from sitosterol, campesterol and stigmasterol, is as effective as a margarine with sitostanol-ester in lowering blood total- and LDL-cholesterol levels without affecting HDL-cholesterol concentrations. Incorporation in edible fat containing products of such substances may substantially reduce the risk of cardiovascular disease in the population.

Topics: Adult; Carotenoids; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats, Unsaturated; Double-Blind Method; Humans; Hypercholesterolemia; Margarine; Middle Aged; Phytosterols; Placebos; Plant Oils; Sitosterols; Soybean Oil

Dietary fibre has been suggested to interfere with endogenous cholesterol synthesis in the liver. Therefore the effects of oat bran on the proportions of cholesterol synthesis precursors (squalene, delta(8-) cholesterol, desmosterol and lathosterol), cholestanol and plant sterols (campesterol and beta-sitosterol) to cholesterol were analysed in serum of 36 hypercholesterolaemic subjects.. A randomized study of eight weeks duration when beta-glucan-rich oat bran (n = 20, subjects) or wheat bran (n = 16) was used as a part of a cholesterol lowering diet. Plant sterols and cholesterol synthesis precursors were analysed from frozen samples afterward.. In the oat-bran group, but not in the wheat bran group, serum total cholesterol declined transiently. The proportions of plant sterols and cholesterol in serum, which reflect cholesterol absorption efficiency were unchanged. However, the proportions of squalene appeared to be transiently increased during the study. Subjects with apolipoprotein E 4 allele had higher serum campesterol and sitosterol levels (suggestive of efficient cholesterol absorption) than those with homozygous apolipoprotein E 3 allele.. Since the cholesterol precursors in serum reflecting endogenous cholesterol synthesis remained almost unchanged the reduction in the serum cholesterol level by oat bran treatment can not be ascribed to an inhibition of the endogenous cholesterol synthesis.

Topics: Adult; Alleles; Apolipoprotein E4; Apolipoproteins E; Avena; Cholesterol; Dietary Fiber; Female; Glucans; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols; Squalene

Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble preparation. We tested the tolerability and cholesterol-lowering effect of margarine containing sitostanol ester in a population with mild hypercholesterolemia.. We conducted a one-year, randomized, double-blind study in 153 randomly selected subjects with mild hypercholesterolemia. Fifty-one consumed margarine without sitostanol ester (the control group), and 102 consumed margarine containing sitostanol ester (1.8 or 2.6 g of sitostanol per day).. The margarine containing sitostanol ester was well tolerated. The mean one-year reduction in serum cholesterol was 10.2 percent in the sitostanol group, as compared with an increase of 0.1 percent in the control group. The difference in the change in serum cholesterol concentration between the two groups was -24 mg per deciliter (95 percent confidence interval, -17 to -32; P < 0.001). The respective reductions in low-density lipoprotein (LDL) cholesterol were 14.1 percent in the sitostanol group and 1.1 percent in the control group. The difference in the change in LDL cholesterol concentration between the two groups was -21 mg per deciliter (95 percent confidence interval, -14 to -29; P < 0.001). Neither serum triglyceride nor high-density lipoprotein cholesterol concentrations were affected by sitostanol. Serum campesterol, a dietary plant sterol whose levels reflect cholesterol absorption, was decreased by 36 percent in the sitostanol group, and the reduction was directly correlated with the reduction in total cholesterol (r = 0.57, P < 0.001).. Substituting sitostanol-ester margarine for part of the daily fat intake in subjects with mild hypercholesterolemia was effective in lowering serum total cholesterol and LDL cholesterol.

Topics: Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Sitosterols; Triglycerides

A randomized double-blind study was made in 67 modestly hypercholesterolemic subjects by replacing 50 g of daily dietary fat by the same amount of a rapeseed oil preparation without and with fat-soluble sitostanol esters. The diet became relatively rich in dietary fat (37%) especially in subjects with a low basal calorie intake. The esters were prepared by transesterification of sitostanol with rapeseed oil fatty acids. The effects of sitostanol esters were studied on serum cholesterol and cholesterol synthesis (measuring cholesterol precursors in serum) and absorption (measuring serum plant sterols). The results were related to different apoE phenotypes. A 6-week regimen of about 3.4 g/day of sitostanol lowered total and low density lipoprotein (LDL) cholesterol levels by 7.5% and 10%, respectively, over that due to rapeseed oil alone. High density lipoprotein (HDL) cholesterol and triglyceride concentrations were unchanged. Thus, the HDL/LDL cholesterol ratio was significantly increased. The decrease in LDL cholesterol level was more consistent in subjects with the epsilon 4 allele than in those with homozygous epsilon 3 alleles. Sitostanol markedly decreased serum campesterol (-46%) and sitosterol (-30%), especially in subjects with the epsilon 4 alleles known to have high cholesterol absorption . The decreases of LDL cholesterol and plant sterols were interrelated, suggesting that reduced cholesterol absorption contributed to the lowering of LDL cholesterol. Serum sitostanol was unchanged, while the serum cholesterol precursors, delta 8-cholestenol, desmosterol, and lathosterol, were compensatorily increased by 10% (P < 0.05), most consistently in the subjects with epsilon 4 alleles, indicating an increase in cholesterol synthesis. The study demonstrates that sitostanol esters dissolved in dietary fat can be recommended for treatment of modest primary hypercholesterolemia and are apparently practical and suitable for cholesterol lowering in a general population.

Topics: Adult; Apolipoproteins; Apolipoproteins E; Brassica; Cholesterol; Dietary Fats; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Plant Oils; Sitosterols; Squalene

Topics: Absorption; Animals; Arteriosclerosis; Cholesterol; Cholesterol, Dietary; Cholestyramine Resin; Clinical Trials as Topic; Food; Humans; Hypercholesterolemia; Phytosterols; Risk; Sitosterols

Increases in serum total and low-density lipoprotein (LDL) cholesterol are known as hypercholesterolemia, and it is a significant risk factor for the emergence of cardiovascular illnesses. Any action strategy for lowering serum cholesterol is supported by lifestyle changes. Phytosterols are organic substances from the triterpene family. Phytosterols can lower serum LDL cholesterol levels because of their structural resemblance to cholesterol. Phytosterols are used to enrich or fortify a broad spectrum of food products. Phytosterols are quickly oxidized, just like cholesterol and unsaturated fatty acids. The utilization of free phytosterols for the manufacture of functional meals is highlighted in this chapter, which also focuses on the therapeutic effects of phytosterols and their technological concerns in the industrial field.

Topics: Cholesterol; Cholesterol, LDL; Food Industry; Humans; Hypercholesterolemia; Phytosterols

Serum phytosterol profiles are essential for the diagnosis and management of sitosterolemia. However, pediatric reference interval (RI) studies are scarce and various mass spectrometry (MS) approaches for phytosterol analysis still face multiple limitations. Therefore, an optimized gas chromatography (GC)-MS assay and age-related RIs in children are both required.. Cholesterol and phytosterols (sitosterol, campesterol, cholestanol, stigmasterol, and sitostanol) were simultaneously determined by optimized GC-MS and performance was verified by the lower limit of quantification (LLOQ), linearity, precision, recovery, matrix effects, and method comparison. Healthy children (247 males and 263 females) were recruited, sex and age dependence were assessed using quantile regression (2.5th percentile and 97.5th percentile), and RIs were established according to Clinical and Laboratory Standards Association guideline C28-A3. These RIs were validated in 19 patients with sitosterolemia and 23 patients with hypercholesterolemia.. The optimized method shortened the sample processing time by approximately 60 min. Among the five phytosterols, all precision, recoveries (ranging from 89.97% to 104.94%), and relative matrix effects (%CV: ranging from 0.08% to 13.88%) met the specifications. GC-MS showed good agreement with lower cholesterol concentrations compared to conventional enzymatic methods. No significant differences between males and females were observed for all phytosterols, but age dependency was found and age-related RIs were established accordingly. Five phytosterols were significantly higher than RIs in patients with sitosterolemia.. We established age-related RIs for five phytosterols in children based on an optimized GC-MS assay, providing a screening tool for the diagnosis of sitosterolemia in children.

Topics: Child; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Male; Phytosterols; Sitosterols

Phytosterols (PSs) have been proposed as dietary means to lower plasma LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit. Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of cholesterol and non-cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than cholesterol to offset their cholesterol reduction benefit. Based on their LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.

Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Phytosterols; Risk Factors

Topics: Cardiovascular Diseases; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Whistleblowing

Sitosterolemia is a rare autosomal recessive hereditary disease caused by loss-of-function genetic mutations in either ATP-binding cassette subfamily G member 5 or member 8 (ABCG5 or ABCG8). Here, we investigate novel variants in ABCG5 and ABCG8 that are associated with the sitosterolemia phenotype. We describe a 32-year-old woman with hypercholesterolemia, tendon and hip xanthomas, autoimmune hemolytic anemia and macrothrombocytopenia from early life, which make us highly suspicious of the possibility of sitosterolemia. A novel homozygous variant in ABCG5 (c.1769C>A, p.S590X) was identified by genomic sequencing. We also examined the lipid profile, especially plant sterols levels, using gas chromatography-mass spectrometry. Functional studies, including western blotting and immunofluorescence staining, showed that the nonsense mutation ABCG5 1769C>A hinders the formation of ABCG5 and ABCG8 heterodimers and the function of transporting sterols. Our study expands the knowledge of variants in sitosterolemia and provides diagnosis and treatment recommendations.

Topics: Adult; ATP Binding Cassette Transporter, Subfamily G, Member 5; Female; Humans; Hypercholesterolemia; Lipid Metabolism, Inborn Errors; Lipoproteins; Mutation; Phytosterols; Thrombocytopenia

The high blood level of low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for cardiovascular disease. Plant sterols, known as phytosterols (PSs), can reduce LDL-C in a range of 8-14%. The extent of LDL-C reduction depends on its formulation. Encapsulation into liposomes is one formulation strategy to enhance the efficiency of PSs. PSs (campesterol, stigmasterol, and β-sitosterol) have frequently been assessed alone or in combination for their LDL-C-lowering ability. However, one naturally abundant PS, brassicasterol, has not yet been tested for its efficacy. We have previously developed a novel liposomal formulation containing the PS mixture present naturally in canola that is composed of brassicasterol, campesterol, and β-sitosterol. In this work, the efficacy of our novel liposomal PS formulation that includes brassicasterol was assessed in a hamster model. Animals were divided into five groups: (i) liposomal PS in orange juice, (ii) liposomal PS in water, (iii) marketed PS in orange juice, (iv) control orange juice, and (v) control water. The animals were fed a high-fat, cholesterol-supplemented (0.5%) diet to induce hypercholesterolemia. The treatment was administered orally once daily for 4 weeks. Fasting blood samples were collected at baseline, week 2, and week 4. The extent of the reduction of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides was compared among the groups. Liposomal PSs in both orange juice and water significantly reduced LDL-C compared to their controls. Furthermore, the liposomal PS was as effective as a marketed PS-containing product in reducing LDL-C. Liposomal PSs in both orange juice and water showed similar efficacy in LDL-C reduction, highlighting that these vehicles/food matrices do not affect the efficacy of PSs. The liposomal formulation of a natural PS mixture extracted from canola oil, with brassicasterol as a major component, exhibited a significant LDL-C reduction in a hamster model.

Topics: Animals; Cholesterol; Cholesterol, LDL; Diet; Hypercholesterolemia; Hyperlipidemias; Liposomes; Phytosterols

Sitosterolemia, also known as phytosterolemia, results from increased intestinal absorption of plant sterols and decreased intestinal and biliary excretion of sterols, resulting in increased levels of plant sterols in the plasma. The most common symptoms include xanthomas, premature atherosclerosis, hemolytic anemia and macrothrombocytopenia, however delayed diagnosis or misdiagnosis also occur.. Clinical exome sequencing was performed on a 10-year-old boy whom we followed up with signs of pancytopenia accompanied by macrothrombocytopenia and stomatocytosis. In addition, the blood sterol levels of the patient and his family were studied.. A novel homozygous c.904 + 5G > C intronic variant was detected in ABCG5 gene in index case. The mother and father were identified as carriers. The blood plant sterol levels of the patient and his family were studied, and the levels in the patient confirmed Sitosterolemia. Sitosterol levels decreased dramatically with restricted diet and ezetimibe treatment.. In children, signs of Sitosterolemia may be subtle and the only symptom may be hematological. Therefore, Sitosterolemia should be kept in mind in children with stomatocytosis and macrothrombocytopenia.

Topics: Adolescent; Child; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Pancytopenia; Phytosterols; Sitosterols

Clinical manifestations and genetic backgrounds of Japanese patients with sitosterolemia have been unclear.. We searched PubMed for studies using the keywords "sitosterolemia" or "phytosterolemia" and "Japan". Moreover, we added information from the members of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare (MHLW) of Japan.. We identified 36 patients with sitosterolemia caused by biallelic pathogenic mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) or ATP-binding cassette subfamily G member 8 (ABCG8) from 31 families in Japan. The diagnosed age ranged from 0 to 64 years (median 13 years). The median sitosterol and LDL cholesterol levels were 100 μg/ml (IQR: 50-183), and 193 mg/dl (IQR: 108-295), respectively. All the patients exhibited cutaneous and/or tendon xanthomas, up to 9 (25%) patients exhibited premature coronary artery disease, 5 (16%) patients exhibited arthritis, and 8 (22%) patients exhibited blood abnormalities. Ezetimibe was administered to all the patients, including infantile cases, while statins, colestimide, evolocumab, probucol, and LDL apheresis were also used.. We are providing a demographic overview of the clinical and genetic backgrounds of Japanese patients with sitosterolemia.

Topics: Adenosine Triphosphate; Adolescent; Adult; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Child; Child, Preschool; Humans; Hypercholesterolemia; Infant; Infant, Newborn; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Middle Aged; Phytosterols; Young Adult

Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in. From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the. Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.

Topics: Adolescent; Adult; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Phytosterols; Young Adult

Topics: Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Pregnancy

Plant sterol intake is widely recommended for patients with cardiovascular risk factors based on the inhibitory effect on intestinal cholesterol absorption. Although plant sterols, once absorbed, can promote atherosclerosis, their intake is believed to be safe because of poor absorption, except in rare hyperabsorbers with homozygous ABCG5/8 mutations. We report a case of new-onset type 1 diabetes accompanied by hypercholesterolemia. At the initial presentation with diabetic ketoacidosis, the patient showed marked hypercholesterolemia. Whole-exome sequencing revealed a heterozygous pathogenic variant in ABCG5 (p.R419H). The initial serum plant sterol levels were markedly high (sitosterol 32.5 μg/mL, campesterol 66.0 μg/mL), close to the range observed in patients with homozygous ABCG5/8 mutations, which were largely reduced by insulin treatment without ezetimibe. The addition of ezetimibe normalized plant sterol levels. These findings provide the first evidence that uncontrolled diabetes plays a causal role in the pathogenesis of phytosterolemia.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; Diabetes Mellitus; Ezetimibe; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols

We report a noteworthy case of a 10-year-old girl who presented with papular and nodular lesions on the skin that were clinically and histologically mistaken for progressive nodular histiocytosis. During the clinical management of the patient, the high lipid levels raised the suspicion of lipid metabolism disease and helped us to make the correct diagnosis of sitosterolemia. In sitosterolemia, proper management such as restriction of plant sterol intake and administration of cholesterol absorption inhibitor can improve prognosis.

Topics: Child; Cholesterol; Female; Histiocytosis; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Sitosterols; Skin Diseases; Xanthomatosis

Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in the ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in the selective excretion of plant sterols from the liver and intestine, leading to a failure to excrete plant sterols. Sitosterolemia, which is currently considered a rare genetic disorder, has been described as a phenocopy of homozygous familial hypercholesterolemia (FH). Typical phenotypes of sitosterolemia, including elevated low-density lipoprotein (LDL) cholesterol, tendon xanthomas, and premature coronary artery disease, overlap those of homozygous FH; however, there are substantial differences between these two diseases in terms of treatments and prognoses. Moreover, it is of note that sitosterolemia appears to be quite underdiagnosed, although accurate diagnosis and appropriate interventions will likely to lead to better prognoses compared with homozygous FH. Unlike cases of homozygous FH, dietary counseling is quite effective in reducing the LDL cholesterol as well as sitosterol of patients with sitosterolemia. In this chapter, we summarize the current understandings of this disease and provide useful tips for the diagnosis as well as better treatment of patients with sitosterolemia.

Topics: Adenosine Triphosphate; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cholesterol; Cholesterol, LDL; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Sitosterols

Sitosterolemia (STSL) is an extremely rare genetic disease. Xanthomas as the first symptom are frequently misinterpreted as familial hypercholesterolemia (FH) in children. Inappropriate treatment may deteriorate the condition of STSL.. To present the clinical and laboratory characteristics of xanthomatous children diagnosed with sitosterolemia in comparison with childhood FH with xanthomas.. We summarized and compared the clinical characteristics of STSL and FH patients with xanthomas as the first manifestations and investigated the different indicators between the STSL and FH groups, as well as their diagnostic values for STSL.. Two tertiary pediatric endocrinology departments contributed ten STSL cases. Five of the STSL patients (50%) experienced mild anemia, whereas two (20%) had vascular complications. The xanthomas of the STSL group displayed morphologies comparable to those of the FH group. There were ten cases of homozygous FH (HoFH) with xanthomas as the predominant symptom of the control group who had no anemia. The serum cholesterol (Chol) levels of the STSL and FH groups were 12.57 (9.55 ~ 14.62) mmol/L and 17.45 (16.04 ~ 21.47) mmol/L, respectively (p value 0.002). The serum low-density lipoprotein cholesterol (LDL-c) levels of the STSL and FH groups were 9.26 ± 2.71 mmol/L and 14.58 ± 4.08 mmol/L, respectively (p value 0.003). Meanwhile, the mean platelet volume (MPV) levels of the STSL and FH groups were 11.00 (9.79 ~ 12.53) fl. and 8.95 (8.88 ~ 12.28) fl., respectively (p value 0.009). The anemia proportions of the STSL and FH groups were 50% and 0%, respectively (p value 0.033). The AUC values of Chol, LDL-c, MPV, hemoglobin (Hb) for the diagnosis of STSL were 0.910, 0.886, 0.869, 0.879, respectively. Chol ≤ 15.41 mmol/L, LDL-c ≤ 13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L were the best thresholds for diagnosing STSL with childhood xanthomas.. The xanthoma morphology of STSL patients resembles that of FH patients. Xanthomas as the initial symptom of a child with Chol ≤ 15.41 mmol/L, LDL-c≤13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L, he was most likely to have STSL.

Topics: Child; Cholesterol; Cholesterol, LDL; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols; Xanthomatosis

Obstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity.. Our results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.

Topics: Chromatography, Liquid; Humans; Hypercholesterolemia; Obesity; Phytosterols; Severity of Illness Index; Sleep Apnea, Obstructive; Tandem Mass Spectrometry

Sitosterolemia is a rare inherited condition in which plant sterols are stored and deposited in the tissues. Described in 1974 by Battacharyya and Connor, it is characterized by tendon and tuberous xanthomas and a propensity to premature coronary atherosclerosis. We present the first reported case of the disease being manifest in the periorbital region. A 44-year-old man presented with a six-month history of swelling below the left eyebrow overlying the orbital rim, but without displacement of the globe. Magnetic resonance imaging identified a soft tissue mass within the orbit, with subsequent biopsy confirming a xanthogranulomatous process consistent with the diagnosis of sitosterolemia. Management of sitosterolemia aims to reduce plasma plant sterol concentrations which subsequently lowers serum cholesterol reducing the xanthomas and atherosclerotic cardiovascular diseases. This report highlights a rare, under-recognised condition (and indeed the first reporting periocular disease), and the potential dangers if misdiagnosed as hypercholesterolemia.

Topics: Adult; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols

Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Blockade of phytosterol absorption either by therapeutic inhibition or by genetic inactivation of NPC1L1 prevented the induction of inflammation and arrhythmogenesis. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These comorbidities provide insight into the underlying pathophysiological mechanism for phytosterolemia-associated risk of sudden cardiac death.

Topics: Animals; Arrhythmias, Cardiac; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cytokines; Death, Sudden, Cardiac; Fibrosis; Heart Failure; Hypercholesterolemia; Inflammation; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols

谷固醇血症是一种罕见的常染色体隐性遗传脂质代谢异常疾病，其特征为血浆和组织中谷固醇的含量增高、蓄积。现报道1例以血小板减少和肝功能异常就诊，通过相关检查发现ABCG5基因突变确诊为谷固醇血症患儿，同时分析患儿的临床特征。.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; Child; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Liver; Mutation; Phytosterols; Thrombocytopenia

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Blood Platelet Disorders; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mice; Phytosterols

Topics: Cholesterol; Coronary Artery Disease; Humans; Hypercholesterolemia; Lipoproteins; Phytosterols

Coronary heart disease (CHD) is one of the leading causes of mortality in many low-income and middle-income countries, including Indonesia, with elevated blood cholesterol level being one of significant risk factors for this condition. The problem should be addressed by combining healthy lifestyle and diet, where functional foods having a cholesterol-lowering activity could play a significant role. A group of compounds that had been proven to show cholesterol-lowering ability are plant sterols. To develop more suitable functional foods that could substantially contribute to hypercholesterolemia prevention in Indonesian population, up-to-date data about plant sterols dietary intake are required, and were not available until this research was done. This study aimed to estimate daily plant sterols intake and to determine the consumption pattern of foods containing plant sterols in rural and urban area of Bogor, West Java, Indonesia. The research was conducted with a cross-sectional design, with 200 respondents. The study revealed that the level of plant sterols intake in Bogor reached on average 229.76 mg/day and was not significantly different between urban and rural area. Cereals, vegetables, and fruit products were the main food sources of plant sterols in both areas. In addition, a list of several surveyed food items possible to be enriched with plant sterols was developed within the study. These results provide baseline data to develop functional foods fortified with plant sterols suitable for the Indonesian needs and taste. However, further studies are needed to confirm efficacy and safety of introducing such phytosterol-enriched products into a habitual diet, especially considering possible long-term side effects of plant sterol treatment.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Coronary Disease; Cross-Sectional Studies; Diet; Diet Surveys; Eating; Feeding Behavior; Female; Food Ingredients; Food, Fortified; Functional Food; Humans; Hypercholesterolemia; Indonesia; Male; Middle Aged; Phytosterols

Hyperlipidemia is described as an increase in serum and/or plasma levels of triglycerides, cholesterol, or both. This disturbance can be primary in some cases, or combined with other comorbidities such as endocrinopathies, liver diseases, or specific drug use. Among the various ways to control dyslipidemia are specific diets, omega-3 fatty acid supplementation, or hypolipemiant treatment. Herbal medicine has been used in the human clinical routine to reduce cholesterol circulation. With an aim to expand its application in veterinary medicine, we analyzed the use of phytosterols in dogs as a potential alternative to control hypercholesterolemia. We performed lipidogram analysis in healthy dogs to examine the possible adverse effects during the treatment. Eight Beagle dogs received orally two 650 mg capsules of phytosterols (Collestra, Aché), for 15 consecutive d, along with the 2 usual meals. All animals remained clinically stable during the trial. There were significant alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels during the trial. LDL was reduced (86.8 ± 29.89 mg/dL [D0], 74.45 ± 31.58 mg/dL [D8], and 58.91 ± 18.65 mg/dL [D15]; P = 0.0442) and HDL was elevated (83.40 ± 12.05 mg/dL [D0], 86.46 ± 13.05 mg/dL [D8], and 101.5 ± 10.52 [D15]; P = 0.0141), while total cholesterol and triglyceride concentrations remained constant and within the normal range for canine species. Thus, a 1300 mg dose of phytosterols, administrated orally and fractionated along with the 2 usual meals, was capable of reducing LDL and increasing HDL concentration in healthy nondyslipidemic dogs, which makes them candidates to be included on the list of hypolipemiant drugs for clinical use in dogs with hypercholesterolemia.

Topics: Animals; Cholesterol; Cholesterol, LDL; Dog Diseases; Dogs; Hypercholesterolemia; Phytosterols; Triglycerides

Phytostanols are naturally occurring compounds that reduce blood cholesterol levels significantly. However, their aqueous insolubility poses formulation challenges.. To formulate and characterize solid lipid nanoparticle carriers for phytostanol esters to enhance the bioavailability of phytostanols.. Phytostanol ester solid lipid nanoparticles were formulated by the microemulsion method. They were characterized for particle size distribution, polydispersity index, shape, surface charge, entrapment efficiency, stability, chemical structure, and thermal properties. The uptake of the formulation by cell lines, HepG2 and HT-29, and its effect on cell viability were evaluated.. The formulation of solid lipid nanoparticles was successfully optimised by varying the type of lipids and their concentration relative to that of surfactants in the present study. The optimised formulation had an average diameter of (171 ± 9) nm, a negative surface charge of (-23.0 ± 0.8) mV and was generally spherical in shape. We report high levels of drug entrapment at (89 ± 5)% in amorphous form, drug loading of (9.1 ± 0.5)%, nanoparticle yield of (67 ± 4)% and drug excipient compatibility. The biological safety and uptake of the formulations were demonstrated on hepatic and intestinal cell lines.. Phytostanol ester solid lipid nanoparticles were successfully formulated and characterized. The formulation has the potential to provide an innovative drug delivery system for phytostanols which reduce cholesterol and have a potentially ideal safety profile. This can contribute to better management of one of the main risk factors of cardiovascular diseases.

Topics: Cell Death; Drug Compounding; Emulsions; Endocytosis; Esters; Flow Cytometry; Hep G2 Cells; HT29 Cells; Humans; Hypercholesterolemia; Lipids; Nanoparticles; Particle Size; Phytosterols; Powders; Spectroscopy, Fourier Transform Infrared; Static Electricity; Temperature

Topics: Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols

Topics: Blood Platelets; Child; Erythrocytes, Abnormal; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols; Thrombocytopenia

报道1例以鼻衄、脾大起病，后因肝功能异常而最终诊断为谷固醇血症的病案。文中患者的诊治过程曲折，期间经历了两次肝脏穿刺组织学检查、脾脏切除手术，但病因一直未能明确。最终，通过基因检测等检查确诊并予以治疗，此后患者肝功能改善、未再出现鼻衄。该例病案提醒临床医生，遇到反复肝功能异常的患者，若经常规实验室、影像学及组织学检查后仍未明确病因，则应重视遗传代谢性肝病相关基因的筛查，利于及时诊断、尽早治疗。.

Topics: Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Liver; Phytosterols

The present study was conducted to establish a practical method for measuring non-cholesterol sterols and reference intervals of serum levels.. Healthy subjects (109 men and 151 women), four patients with sitosterolemia, and 10 heterozygous mutation carriers of ABCG5/ABCG8 genes were investigated. Then, three non-cholesterol sterols (sitosterol, campesterol, and lathosterol) of fasting serum samples were measured via a practical and highly sensitive gas chromatography (GC) method with 0.2 µg/mL as the lower limit of quantification. The coefficient of variation (CV) values for within-run reproducibility were 3.06%, 1.89%, and 1.77% for lathosterol, campesterol, and sitosterol, respectively. The CV values for between-run reproducibility were 2.81%, 2.06%, and 2.10% for lathosterol, campesterol, and sitosterol, respectively.. The serum levels of sitosterol and campesterol were significantly higher in women than in men, whereas the serum levels of lathosterol were significantly higher in men than in women. Because of these gender difference, the determination of reference intervals of the three sterol values was performed by considering gender. The reference intervals of sitosterol, campesterol, and lathosterol were 0.99-3.88, 2.14-7.43, and 0.77-3.60 µg/mL in men and 1.03-4.45, 2.19-8.34, and 0.64-2.78 µg/mL in women, respectively. The serum levels of sitosterol and campesterol were higher in patients with sitosterolemia (94.3±47.3 and 66.3±36.6 µg/mL, respectively) than in healthy subjects.. These results demonstrate a practical and highly sensitive GC method to measure non-cholesterol sterol levels and gender-segregated reference intervals of sitosterol, campesterol, and lathosterol in Japanese healthy subjects.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cholesterol; Cholesterol, Dietary; Chromatography, Gas; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Phytosterols; Reference Values; Reproducibility of Results; Sex Factors; Sitosterols

HepG2 cells were incubated with a 16.5:1.7:1 ratio of cholesterol:sitosterol:campesterol (CSC), a ratio of the major sterols observed in the plasma of phytosterolemia patients, or with cholesterol alone in combination with [

Topics: Carbon Radioisotopes; Cholesterol; Cholesterol Esters; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation; Hep G2 Cells; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Models, Biological; Phytosterols; Receptors, LDL; Sitosterols

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) μg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) μg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) μg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

Topics: Adult; Cholesterol; Fat Emulsions, Intravenous; Female; Fish Oils; Humans; Hypercholesterolemia; Inpatients; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Parenteral Nutrition; Parenteral Nutrition Solutions; Phytosterols; Plant Oils; Prospective Studies; Stigmasterol; Vegetables

Sitosterolemia is a rare lipid metabolism disease with heterogeneous manifestations. Atherosclerosis can occur in children, and therefore, early detection, diagnosis, and treatment of this disease are important. We studied 18 pediatric patients with sitosterolemia who showed a significant increase in plasma lipid levels and analyzed their clinical, biochemical, and genetic characteristics. We recorded the initial serum lipid results and clinical manifestations of the patients. Lipid and plant sterol levels were measured after homozygous or compound heterozygous mutations of ABCG5 or ABCG8 were identified by genetic testing. Plasma plant sterol levels were analyzed by gas chromatography. Fourteen cases of sitosterolemia were examined by ultrasound and echocardiography. The initial total cholesterol and low-density lipoprotein levels of the children were significantly increased, but then markedly decreased after diet control or drug treatment, and even reached normal levels. Carotid atherosclerosis and aortic valve regurgitation were present in three of 14 patients. Serum lipid levels of children with sitosterolemia and xanthomas were notably higher than those without xanthomas. There were no significant differences in clinical manifestations between patients with different genotypes. In conclusion, sitosterolemia should be considered in children with hyperlipidemia who do not present with xanthomas, especially with a significant increase in total cholesterol and low-density lipoprotein levels. There does not appear to be a correlation between clinical phenotype and genotype.

Topics: Child; Child, Preschool; Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols

Sitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention.. We evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio-whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved.. We identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965-1G>A, c.323-1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes.. Our findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.

Topics: Asian People; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Child; Child, Preschool; Exome Sequencing; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation; Phenotype; Phytosterols

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cardiometabolic Risk Factors; Cholesterol, Dietary; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Intestinal Absorption; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Patient Care Management; Phytosterols

Sitosterolemia is caused by homozygous or compound heterozygous gene mutations in either ATP-binding cassette subfamily G member 5 (ABCG5) or 8 (ABCG8). Since ABCG5 and ABCG8 play pivotal roles in the excretion of neutral sterols into feces and bile, patients with sitosterolemia present elevated levels of serum plant sterols and in some cases also hypercholesterolemia. A 48-year-old woman was referred to our hospital for hypercholesterolemia. She had been misdiagnosed with familial hypercholesterolemia at the age of 20 and her serum low-density lipoprotein cholesterol (LDL-C) levels had remained about 200-300 mg/dL at the former clinic. Although the treatment of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors was ineffective, her serum LDL-C levels were normalized by ezetimibe, a cholesterol transporter inhibitor. We noticed that her serum sitosterol and campesterol levels were relatively high. Targeted analysis sequencing identified a novel heterozygous ABCG5 variant (c.203A>T; p.Ile68Asn) in the patient, whereas no mutations were found in low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), or Niemann-Pick C1-like intracellular cholesterol transporter 1 (NPC1L1). While sitosterolemia is a rare disease, a recent study has reported that the incidence of loss-of-function mutation in the ABCG5 or ABCG8 gene is higher than we thought at 1 in 220 individuals. The present case suggests that serum plant sterol levels should be examined and ezetimibe treatment should be considered in patients with hypercholesterolemia who are resistant to HMG-CoA reductase inhibitors.

Topics: Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; Cholesterol; Cholesterol, LDL; Diagnostic Errors; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Loss of Function Mutation; Middle Aged; Phytosterols; Sitosterols; Treatment Failure

We herein report a rare case presenting with severe hypercholesterolemia, massive Achilles tendon xanthomas, and multi-vessel coronary artery disease. Initially, the patient was misdiagnosed with familial hypercholesterolemia. However, a genetic analysis using our custom sequencing panel covering genes associated with Mendelian lipid disorders revealed him to have a genetic basis of sitosterolemia with compound heterozygous mutations in the adenosine triphosphate binding cassette subfamily G5 (ABCG5) gene. A comprehensive genetic analysis can be particularly useful for diagnosing cases with severe phenotypes, leading to appropriate and medical therapies. Our patient was refractory to statins, whereas ezetimibe and PCSK9 inhibitor with a low-plant-sterol diet successfully reduced his serum levels of low-density lipoprotein cholesterol.

Topics: Achilles Tendon; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; Cholesterol, LDL; Ezetimibe; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Mutation; Phytosterols; Treatment Outcome; Xanthomatosis

Sitosterolemia is an inherited lipid disorder which presents with elevated serum sitosterol and can result in an increased risk of premature cardiovascular disease. However, sitosterol cannot be accurately measured by routine diagnostic assays, meaning that sitosterolemia diagnosis can often be difficult, especially with many clinical features overlapping with familial hypercholesterolemia. With such complications resulting in increasing reports of misdiagnosis, the prevalence of sitosterolemia is predicted to be much higher than previously reported.. Gas chromatography-mass spectrometry was utilized to measure sitosterol levels of normocholesterolemic and hypercholesterolemic children. Subsequently, an epidemiologically determined cutoff level of sitosterol was calculated and applied to estimate the prevalence of children with increased sitosterol and identify potential sitosterolemia patients. Massively parallel sequencing was used to confirm the diagnosis in suspected patients.. Samples from 109 normocholesterolemic and 220 hypercholesterolemic were tested for phytosterols. Sitosterol and campesterol levels were significantly increased in hypercholesterolemic children (mean 22.0±45.9 μmol/L for sitosterol and 26.0±32.8 μmol/L for campesterol) compared to normocholesterolemic children (mean 12.1±4.9 μmol/L for sistosterol and 14.8±6.7 μmol/L for campesterol). Via application of a cutoff of 35.9 μmol/L, the prevalence rates for increased and overtly increased sitosterol in hypercholesterolemic children were 6.4% and 1.4% respectively. Furthermore, 3 suspected sitosterolemia patients were identified, with 2 patients receiving molecular confirmation for sitosterolemia diagnosis.. Our findings reaffirm that the prevalence of sitosterolemia is probably much higher than previously reported, which also indicates the significant risk of misdiagnosis of sitosterolemia with familial hypercholesterolemia. Special lipid testing including sitosterol, especially in children with uncontrolled hypercholesterolemia, is recommended in children in order to identify potential sitosterolemia patients that would otherwise be neglected.

Topics: Adolescent; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Child; Child, Preschool; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Pedigree; Phytosterols; Prevalence; Sitosterols

The heterodimeric ATP-binding cassette (ABC) sterol transporter, ABCG5/G8, is responsible for the biliary and transintestinal secretion of cholesterol and dietary plant sterols. Missense mutations of ABCG5/G8 can cause sitosterolemia, a loss-of-function disorder characterized by plant sterol accumulation and premature atherosclerosis. A new molecular framework was recently established by a crystal structure of human ABCG5/G8 and reveals a network of polar and charged amino acids in the core of the transmembrane domains, namely, a polar relay. In this study, we utilize genetic variants to dissect the mechanistic role of this transmembrane polar relay in controlling ABCG5/G8 function. We demonstrated a sterol-coupled ATPase activity of ABCG5/G8 by cholesteryl hemisuccinate (CHS), a relatively water-soluble cholesterol memetic, and characterized CHS-coupled ATPase activity of three loss-of-function missense variants, R543S, E146Q, and A540F, which are respectively within, in contact with, and distant from the polar relay. The results established an in vitro phenotype of the loss-of-function and missense mutations of ABCG5/G8, showing significantly impaired ATPase activity and loss of energy sufficient to weaken the signal transmission from the transmembrane domains. Our data provide a biochemical evidence underlying the importance of the polar relay and its network in regulating the catalytic activity of ABCG5/G8 sterol transporter.

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Allosteric Regulation; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Binding Sites; Biological Transport; Cholesterol; Cholesterol Esters; Cholic Acid; Gene Expression; Humans; Hypercholesterolemia; Intestinal Diseases; Kinetics; Lipid Metabolism, Inborn Errors; Lipoproteins; Models, Molecular; Mutation; Phytosterols; Pichia; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Recombinant Proteins; Thermodynamics

Sea buckthorn seed oil (SBSO) has been used as a functional food in the prevention of heart diseases. The present study investigates the effects of SBSO on blood cholesterol and the gut microbiota in hypercholesterolemia hamsters. Four groups of hamsters (n = 8 each) were given one of four diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD) containing 0.1% cholesterol, and an HCD diet with sea buckthorn seed oil replacing 50% lard (SL) or replacing 100% lard (SH). Feeding SL and SH diets could reduce blood total cholesterol by 20-22%. This was accompanied by the down-regulation of the gene expression of acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporter8 (ABCG8). SBSO supplementation also increased the production of intestinal short-chain fatty acids and fecal outputs of neutral sterols. Metagenomic analysis demonstrated that feeding SL and SH diets could favorably modulate the relative abundance of Bacteroidales_S24-7_group, Ruminococcaceae, and Eubacteriaceae. It was therefore concluded that SBSO was effective in reducing blood cholesterol in hypercholesterolemic hamsters via increasing intestinal cholesterol excretion and promoting the growth of SCFA-producing bacteria.

Topics: Animals; Anticholesteremic Agents; ATP-Binding Cassette Transporters; Bacteria; Cholesterol; Cricetinae; Fatty Acids; Fatty Acids, Volatile; Gastrointestinal Microbiome; Hippophae; Humans; Hypercholesterolemia; Male; Mesocricetus; Phytosterols; Plant Oils; Seeds; Sterol O-Acyltransferase; Triglycerides

Cardiovascular disease is expected to remain the leading cause of death worldwide despite the introduction of proprotein convertase subtilisin/kexin type 9 inhibitors that effectively control cholesterol. Identifying residual risk factors for cardiovascular disease remains an important step for preventing and clinically managing the disease. Here we report cardiac injury and increased mortality occurring despite a 50% reduction in plasma cholesterol in a mouse model of phytosterolemia, a disease characterized by elevated levels of dietary plant sterols in the blood. Our studies show accumulation of stigmasterol, one of phytosterol species, leads to left ventricle dysfunction, cardiac interstitial fibrosis and macrophage infiltration without atherosclerosis, and increased mortality. A pharmacological inhibitor of sterol absorption prevents cardiac fibrogenesis. We propose that the pathological mechanism linking clinical sitosterolemia to the cardiovascular outcomes primarily involves phytosterols-induced cardiac fibrosis rather than cholesterol-driven atherosclerosis. Our studies suggest stigmasterol is a potent and independent risk factor for cardiovascular disease.

Topics: Animals; Atherosclerosis; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cell Survival; Dietary Supplements; Fibrosis; Human Umbilical Vein Endothelial Cells; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Phytosterols; Stigmasterol; Ventricular Dysfunction, Left

Topics: Adolescent; Anemia, Hemolytic, Congenital; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Blood Platelets; Child; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation, Missense; Phytosterols; Thrombocytopenia

Topics: Cholestanol; Cholesterol; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Intestinal Diseases; Limit of Detection; Lipid Metabolism, Inborn Errors; Phytosterols; Reference Standards; Sitosterols; Xanthomatosis, Cerebrotendinous

Health benefits of soybean germ oil have not yet been fully explored. The present study examined the blood cholesterol-lowering activity of soybean germ oil and the underlying mechanisms in hypercholesterolemic hamsters. Forty hamsters were randomly assigned into five groups and fed a non-cholesterol diet, a high cholesterol diet and one of three high cholesterol diets containing 0.50% cholestyramine, 4.75% soybean germ oil, and 9.50% soybean germ oil, respectively, for 6 weeks. The result showed that soybean germ oil significantly decreased plasma cholesterol by 18.5-31.5%, which was accompanied by 28.3-62.7% increase in excretion of fecal neutral sterols and bile acids. The effect was mediated by down-regulation of intestinal Niemann-Pick C1-like 1 protein (NPC1L1) and up-regulation of liver cholesterol-7α-hydroxylase (CYP7A1). We concluded that soybean germ oil favorably modulated the blood cholesterol concentration by inhibiting cholesterol absorption through inhibiting gene expression of NPC1L1 and by enhancing bile acid excretion via promoting gene expression of CYP7A1.

Topics: Animals; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cricetinae; Humans; Hypercholesterolemia; Intestinal Mucosa; Male; Phytosterols; Soybean Oil

Topics: Adult; ATP Binding Cassette Transporter, Subfamily G, Member 5; Genetic Diseases, Inborn; Heterozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation; Phytosterols

Topics: Animals; Animals, Newborn; Apolipoproteins E; Cytokines; Dietary Supplements; Female; Gene Expression Regulation; Hypercholesterolemia; Liver; Male; Maternal Nutritional Physiological Phenomena; Mice, Mutant Strains; Oxysterols; Phytosterols; Plaque, Atherosclerotic; Pregnancy; Weaning

Phytosterolemia is a rare genetic disease caused by mutation of the ABCG5/8 gene. Our aim was to elucidate the natural history and homeostasis of phytosterolemia.. We analyzed a Hutterite kindred consisting of 21 homozygotes with phytosterolemia assembled over a period of two decades, all of whom carried the ABCG8 S107X mutation and were treated with ezetimibe.. Most of these subjects were asymptomatic and devoid of clinical stigmata, and this, since they were ascertained primarily by a process of cascade testing, suggests that, relative to its true prevalence, phytosterolemia is a condition of low morbidity. All subjects have responded well to treatment with ezetimibe. Initial (pre-treatment) and post-ezetimibe levels of cholesterol and sitosterol were measured and percentage changes on ezetimibe were calculated. We found initial levels to be inversely related to subjects' ages as were percentage responses to ezetimibe therapy. There was also a direct correlation between initial levels and percentage responses to ezetimibe. Hence on-treatment levels were very uniform.. This evidence of a link with age leads us to propose that an age-related change in cholesterol and sterol homeostasis occurs at puberty in phytosterolemia and that the change is due to high sterol and/or stanol levels causing feedback inhibition of sterol regulatory element-binding protein (SREBP-2) processing. This would explain the well-documented phenomenon of depressed cholesterol synthesis in phytosterolemia. It is also well-known that LDL-receptor activity is increased, and this feasibly explains reduced LDL levels and consequent reduction of plasma cholesterol and sitosterol levels. Downregulated SREBP-2 processing would be expected to also lower proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and this would explain high LDL-receptor activity. The above state could be termed disrupted homeostasis and the alternative, seen mostly in children and characterized by hypercholesterolemia and hypersterolemia, simple homeostasis.

Topics: Adolescent; Adult; Age Factors; Anticholesteremic Agents; Asymptomatic Diseases; ATP Binding Cassette Transporter, Subfamily G, Member 8; Biomarkers; Canada; Child; Child, Preschool; Cholesterol; Ezetimibe; Female; Genetic Predisposition to Disease; Homeostasis; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Mutation; Phenotype; Phytosterols; Prevalence; Puberty; Rare Diseases; Risk Factors; Sitosterols; Time Factors; Treatment Outcome; United States; Young Adult

Sitosterolemia is an extremely rare, autosomal recessive disease characterized by high plasma cholesterols and plant sterols because of increased absorption of dietary cholesterols and sterols from the intestine, and decreased excretion from biliary tract. Previous study indicated that sitosterolemic patients might be vulnerable to post-prandial hyperlipidemia, including high remnant-like lipoprotein particles (RLP) level. Here we evaluate whether a loading dietary fat increases a post-prandial RLP cholesterol level in sitosterolemic patients compared to heterozygous familial hypercholesterolemic patients (FH).. We recruit total of 20 patients: 5 patients with homozygous sitosterolemia, 5 patients with heterozygous sitosterolemia, and 10 patients with heterozygous FH as controls from May 2015 to March 2018 at Kanazawa University Hospital, Japan. All patients receive Oral Fat Tolerance Test (OFTT) cream (50 g/body surface area square meter, orally only once, and the cream includes 34% of fat, 74 mg of cholesterol, and rich in palmitic and oleic acids. The primary endpoint is the change of a RLP cholesterol level after OFTT cream loading between sitosterolemia and FH. We measure them at baseline, and 2, 4, and 6 hours after the oral fat loading.. This is the first study to evaluate whether sitosterolemia patients have a higher post-prandial RLP cholesterol level compared to heterozygous FH patients.. The result may become an additional evidence to restrict dietary cholesterols for sitosterolemia. This study is registered at University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000020330).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cholesterol; Dietary Fats; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Phytosterols; Postprandial Period; Prognosis; Triglycerides; Young Adult

We aimed to clarify post-prandial accumulation of remnant-like particles (RLP) in patients with sitosterolemia.. After oral fat load, there was no significant difference of the iAUC of LDL-C between sitosterolemia and heterozygous FH, whereas the iAUC of apoB48 was significantly larger in the sitosterolemic subjects compared with that of heterozygous FH (2.9 µg/mL×h vs. 1.3 µg/mL×h, p＜0.05). Under these conditions, the iAUCs of RLP-C and RLP-TG levels were significantly larger in the sitosterolemic subject compared with those of heterozygous FH (9.5 mg/dL×h vs. 5.7 mg/dL×h, p＜0.05; 149 mg/dL×h vs. 40 mg/dL×h, p＜0.05, respectively), whereas those of heterozygous carriers were comparable with those with heterozygous FH.. Post-prandial lipoprotein metabolism in sitosterolemia appeared to be impaired, leading to their elevation in serum sterol levels. (UMIN Clinical Trials Registry number, UMIN000020330).

Topics: Adolescent; Adult; Biomarkers; Cholesterol; Female; Follow-Up Studies; Heterozygote; Humans; Hypercholesterolemia; Incidence; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Phytosterols; Postprandial Period; Prognosis; Triglycerides

Topics: Atherosclerosis; Diet, High-Fat; Humans; Hypercholesterolemia; Male; Phytosterols; Risk Factors; Severity of Illness Index; Young Adult

Topics: Animals; Coturnix; Follow-Up Studies; Gonadal Steroid Hormones; Humans; Hypercholesterolemia; Mice; Phytosterols; Rats; Sexual Behavior; Testosterone

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 8; Child, Preschool; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Mutation; Phytosterols; Xanthomatosis

Topics: Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Sterols

Topics: Atherosclerosis; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols

Topics: Biomarkers; Cholesterol; Humans; Hypercholesterolemia; Hyperlipidemias; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Postprandial Period; Prognosis; Risk Factors; Triglycerides

Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported.. Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis.. EZE reduced (p < 0.05) total sterols (-12.5 ± 4.1%) and LDL-sterol (-22.7 ± 5.7%) and its sterol mass of large VLDL (-24.4 ± 4.5%), VLDL remnants (-21.1 ± 7.9%) and large IDL (-22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (-21.8± 5.0%), total sterols/HDL (-28.2 ± 5.5%) and TG/HDL (-27.4 ± 6.5%, all p < 0.01).. EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

Topics: Adolescent; Adult; Anticholesteremic Agents; Cholesterol, HDL; Electrophoresis, Polyacrylamide Gel; Ezetimibe; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins, HDL; Lipoproteins, IDL; Lipoproteins, VLDL; Male; Middle Aged; Phytosterols; Treatment Outcome; Young Adult

Topics: Ezetimibe; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins, HDL; Phytosterols

Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene, leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8.. We aimed to perform the molecular characterization of two children with severe primary hypercholesterolemia.. Case #1 was a 2 year-old girl with high LDL-cholesterol (690 mg/dl) and tuberous and intertriginous xanthomas. Case #2 was a 7 year-old boy with elevated LDL-C (432 mg/dl) but no xanthomas. In both cases, at least one parent had elevated LDL-cholesterol levels. For the molecular diagnosis, we applied targeted next generation sequencing (NGS), which unexpectedly revealed that both patients were compound heterozygous for nonsense mutations: Case #1 in ABCG5 gene [p.(Gln251*)/p.(Arg446*)] and Case #2 in ABCG8 gene [p.(Ser107*)/p.(Trp361*)]. Both children had extremely high serum sitosterol and campesterol levels, thus confirming the diagnosis of sisterolemia. A low-fat/low-sterol diet was promptly adopted with and without the addition of ezetimibe for Case #1 and Case #2, respectively. In both patients, serum total and LDL-cholesterol decreased dramatically in two months and progressively normalized.. Targeted NGS allows the rapid diagnosis of sitosterolemia in children with severe hypercholesterolemia, even though their family history does not unequivocally suggest a recessive transmission of hypercholesterolemia. A timely diagnosis is crucial to avoid delays in treatment.

Topics: Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Biomarkers; Child; Child, Preschool; Cholesterol, LDL; Codon, Nonsense; Diet, Fat-Restricted; DNA Mutational Analysis; Ezetimibe; Female; Genetic Predisposition to Disease; Heterozygote; High-Throughput Nucleotide Sequencing; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Phenotype; Phytosterols; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome; Up-Regulation

Sitosterol is the most abundant plant sterol found in our diet. Sitosterolemia (OMIM 210250), also known as phytosterolaemia, is a rare autosomal recessive disease caused by the inability to efficiently excrete plant sterol, and is characterized by cutaneous xanthomas and accelerated atherosclerosis. Sitosterolaemia is caused by homozygous or compound heterozygous mutations in either ABCG5 or ABCG8 (both on chromosome 2p21), which encode the sterol efflux transporter ABCG5 (sterolin-1) and ABCG8 (sterolin-2), respectively. To investigate a Tunisian family with several members who manifested with generalized cutaneous xanthomas, whereas others had only isolated xanthelasmas. Genetic analysis was performed based on exome sequencing of DNA obtained from five affected individuals and one unaffected individual from a Tunisian family.. A novel mutation in the ABCG8 gene, designated c.965-1G>C, was identified by exome sequencing in the members of this family. The homozygous form was associated with generalized cutaneous xanthomatosis while the heterozygous form was linked to isolated xanthelasmas. Our results indicate a gene dosage effect of ABCG8 and suggest that individuals at risk should be followed closely.

Topics: Adult; ATP Binding Cassette Transporter, Subfamily G, Member 8; Female; Heterozygote; Homozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Mutation; Pedigree; Phytosterols; Skin Diseases; Tunisia; Xanthomatosis

Sitosterolemia is a rare lipid metabolism disorder that involves storage of plant sterols. This disease is associated with atherosclerosis, but detailed vascular endothelial assessment is difficult.. We report a 5-year-old girl with sitosterolemia who presented with xanthomas at 23 months of age. Her total cholesterol was 868 mg/dL, and her plasma sitosterol level was 9.48 mg/dL. Direct sequencing detected a homozygous mutation in gene ABCG5 (p.Arg389His). Echocardiographic examination revealed that the carotid artery intima media thickness (cIMT) was 0.4 mm with heterogenous hyperechogenicity inside the arterial wall. She was treated using dietary therapy and ezetimibe, which effectively lowered her sitosterol levels. After 3 years of treatment, her cIMT was stable in diameter and arterial wall echogenicity had improved.. Sitosterolemia is a unique disorder in which it is difficult to avoid premature atherosclerosis because of high sitosterol levels. cIMT measurement with arterial wall assessment may improve management.

Topics: Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; Carotid Arteries; Carotid Intima-Media Thickness; Child, Preschool; Cholesterol, LDL; Echocardiography; Ezetimibe; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Mutation; Phytosterols

The aim of this study was to develop a method for neutral fecal sterols determination in subjects receiving a normal diet with or without a plant sterols-enriched beverage using gas chromatography-mass spectrometry (GC/MS). Sample preparation conditions (homogenization of lyophilized feces with water) were evaluated. Sterol determination required direct hot saponification, unsaponifiable extraction with hexane, and the formation of trimethylsilyl (TMS) ether derivatives. The method allows the quantification of cholesterol, plant sterols and their metabolites (coprostanol, coprostanone, cholestanol, cholestanone, methylcoprostanol, methylcoprostanone, ethylcoprostenol, stigmastenol, ethylcoprostanol and ethylcoprostanone). Good linearity was obtained (r > 0.96) and interference was only observed for coprostanone, where the standard addition method proved necessary for quantification. The limits of detection (LOD) ranged from 0.10 to 3.88 µg/g dry feces and the limits of quantitation (LOQ) from 0.34 to 12.94 µg/g dry feces. Intra- and inter-assay precision (RSD %) were 0.9-9.2 and 2.1-11.3, respectively. Accuracy, expressed as percentage recovery (80-119%) was obtained for all determined sterols.

Topics: Beverages; Cholesterol; Feces; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Limit of Detection; Phytosterols; Sterols

Topics: Adolescent; Blood Component Removal; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Phytosterols; Treatment Outcome

An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation.. Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol-supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p < 0.05) expression of the primary intestinal cholesterol transport protein (Niemann-Pick C1-like 1) and the rate-limiting enzyme in hepatic cholesterol synthesis (HMG-CoAr), suggestive of a compensatory response to restore cholesterol balance. Furthermore, pups from PS-supplemented mothers exhibited a coordinated downregulation (p < 0.05) of several genes regulating fatty acid synthesis including PGC1β, SREBP1c, FAS, and ACC compared with the CH group. These results suggest that maternal PS supplementation during hypercholesterolemic pregnancies protects against aberrant lipid responses in newly-weaned offspring and results in differential regulation of cholesterol and lipid regulatory targets within the enterohepatic loop.

Topics: Animals; Apolipoproteins E; Cholesterol; Dietary Supplements; Disease Models, Animal; Down-Regulation; Female; Gene Expression Regulation; Hypercholesterolemia; Intestinal Mucosa; Liver; Membrane Transport Proteins; Mice; Mice, Knockout; Phytosterols; Pregnancy; Prenatal Exposure Delayed Effects

Topics: Adolescent; Adult; Child; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols; Young Adult

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Genetic Testing; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Mutation; Phytosterols

To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

Topics: Acyl Coenzyme A; Animals; Anticholesteremic Agents; Antioxidants; Bile Acids and Salts; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Dietary Fats; Dietary Supplements; Drug Synergism; Hypercholesterolemia; Intestinal Absorption; Liver; Male; Obesity; Phytosterols; Proprotein Convertase 9; Rats, Zucker; RNA, Messenger; Serine Endopeptidases; Thioctic Acid

The dynamics of cholesterol homeostasis and the development of cardiovascular disease (CVD) are complex and multifactorial, to which adds individual variability in the proportion of cholesterol from exogenous versus endogenous sources. The aim of this study was to undertake the first characterization of cholesterol absorption and synthesis profiles in Portuguese hypercholesterolemic adults through the quantification of surrogate markers, and the analysis of the predictive value of age and sex on the cholesterol homeostasis biomarkers.. Serum samples for the measurement of lipid profiles and cholesterol homeostasis markers were obtained for 100 men and 112 women, aged 30-65, with TC ≥ 5.2 mmol/L (~200mg/dL) and/or LDL-C ≥ 2.6 mmol/L (~100mg/dL), none of whom were on any lipid-lowering therapy.. Overall, sex-specific significant differences were observed in the cholesterol homeostasis markers and lipid profiles; women had lower cholesterol synthesis marker concentrations (P<0.01 for lathosterol) and lipid parameters (except for HDL-C concentrations). Age-related significant differences were also found, including higher concentrations of cholesterol absorption markers in association with increasing age.. In our study, the predictors of higher levels of cholesterol absorption markers were higher age and female gender.

Topics: Adult; Age Factors; Aged; Biomarkers; Cholestanol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Desmosterol; Diet; Female; Homeostasis; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Portugal; Sex Factors; Sitosterols; Triglycerides

Whole-exome sequencing allows for an unbiased and comprehensive mutation screening. Although successfully used to facilitate the diagnosis of single-gene disorders, the genetic cause(s) of a substantial proportion of presumed monogenic diseases remain to be identified. We used whole-exome sequencing to examine offspring from a consanguineous marriage featuring a novel combination of congenital hypothyroidism, hypomagnesemia and hypercholesterolemia. Rather than identifying one causative variant, we report the first instance in which three independent autosomal-recessive single-gene disorders were identified in one patient. Together, the causal variants give rise to a blended and seemingly novel phenotype: we experimentally characterized a novel splice variant in the thyroglobulin gene (c.638+5G>A), resulting in skipping of exon 5, and detected a pathogenic splice variant in the magnesium transporter gene TRPM6 (c.2667+1G>A), causing familial hypomagnesemia. Based on the third variant, a stop variant in ABCG5 (p.(Arg446*)), we established a diagnosis of sitosterolemia, confirmed by elevated blood plant sterol levels and successfully initiated targeted lipid-lowering treatment. We propose that blended phenotypes resulting from several concomitant single-gene disorders in the same patient likely account for a proportion of presumed monogenic disorders of currently unknown cause and contribute to variable genotype-phenotype correlations.

Topics: Adolescent; ATP Binding Cassette Transporter, Subfamily G, Member 5; Consanguinity; Female; Humans; Hypercholesterolemia; Hypothyroidism; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Magnesium Deficiency; Male; Mutation; Pedigree; Phenotype; Phytosterols; RNA Splicing; Thyroglobulin; TRPM Cation Channels; Young Adult

Topics: Biomarkers; Blood Platelets; Child; Erythrocytes, Abnormal; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipids; Male; Phytosterols

Phytosterols (P) and fish-oil (F) efficacy on high-oleic-sunflower oil (HOSO) diets were assessed in hypercholesterolemic growing rats. Controls (C) received a standard diet for 8 weeks; experimental rats were fed an atherogenic diet (AT) for 3 weeks, thereafter were divided into four groups fed for 5 weeks a monounsaturated fatty acid diet (MUFA) containing either: extra virgin olive oil (OO), HOSO or HOSO supplemented with P or F. The diets did not alter body weight or growth. HOSO-P and HOSO-F rats showed reduced total cholesterol (T-chol), non-high-density lipoprotein-cholesterol (non-HDL-chol) and triglycerides and increased HDL-chol levels, comparably to the OO rats. Total body fat (%) was similar among all rats; but HOSO-F showed the lowest intestinal, epididymal and perirenal fat. However, bone mineral content and density, and bone yield stress and modulus of elasticity were unchanged. Growing hypercholesterolemic rats fed HOSO with P or F improved serum lipids and fat distribution, but did not influence material bone quality.

Topics: Animals; Anticholesteremic Agents; Butter; Cholesterol; Cholesterol, HDL; Diet, Atherogenic; Diet, High-Fat; Dietary Fats, Unsaturated; Dietary Supplements; Fish Oils; Hypercholesterolemia; Male; Oleic Acid; Olive Oil; Phytosterols; Plant Oils; Random Allocation; Rats, Wistar; Sunflower Oil; Triglycerides; Weaning

ATP binding cassette (ABC) transporters play critical roles in maintaining sterol balance in higher eukaryotes. The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines. Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis. Here we use crystallization in lipid bilayers to determine the X-ray structure of human G5G8 in a nucleotide-free state at 3.9 Å resolution, generating the first atomic model of an ABC sterol transporter. The structure reveals a new transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide-binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. The G5G8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolaemia.

Topics: Adenosine Triphosphatases; Amino Acid Sequence; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Binding Sites; Biocatalysis; Crystallography, X-Ray; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Bilayers; Lipid Metabolism, Inborn Errors; Lipoproteins; Models, Molecular; Molecular Sequence Data; Nucleotides; Phytosterols; Protein Folding; Protein Multimerization; Protein Structure, Tertiary; Sterols

Whole exome sequencing (WES) technologies have accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. We encountered a 13-year-old Japanese female initially diagnosed with familial hypercholesterolemia on the basis of clinical manifestations of severe hypercholesterolemia (initial LDL cholesterol=609 mg/dl at the age of one) and systemic intertriginous xanthomas with histories of recurrent self-limiting episodes of fever and arthritis. Both her phenotypes seemed to co-segregate in a recessive manner. We performed WES on this patient, who was considered a proband. Among 206,430 variants found in this individual, we found 18,220 nonsense, missense, or splice site variants, of which 3,087 were rare (minor allele frequency ≤ 0.01 or not reported) in 1000 Genome (Asian population). Filtering by assuming a recessive pattern of inheritance with the use of an in silico annotation prediction tool, we successfully narrowed down the candidates to the compound heterozygous mutations in the ABCG5 gene (c.1256G＞A or p.Arg419His/c.1763-1G＞A [splice acceptor site]) and to the double-compound heterozygous mutations in the MEFV gene (c.329T＞C/C or p.Leu110Pro/c.442G＞C/C or p.Glu148Val). The patient was genetically diagnosed with sitosterolemia and familial Mediterranean fever using WES for the first time. Such a comprehensive approach is useful for identifying causative mutations for multiple unrelated inheritable diseases.

Topics: Adolescent; ATP Binding Cassette Transporter, Subfamily G, Member 5; Cholesterol, LDL; Computational Biology; Exome; Familial Mediterranean Fever; Female; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Polymerase Chain Reaction; Polymorphism, Single Nucleotide

Although there is a normal physiological rise in maternal lipids during pregnancy, excessive maternal hyperlipidemia during pregnancy increases cardiovascular disease risk for both the mother and offspring. There are limited safe lipid-lowering treatment options for use during pregnancy, therefore, we evaluated the influence of maternal phytosterol (PS) supplementation on lipid and lipoprotein metabolism in mothers and progeny.. Female Syrian golden hamsters were randomly assigned to three diets throughout prepregnancy, gestation, and lactation (n = 6/group): (i) Chow (Chow), (ii) chow with 0.5% cholesterol (CH), and (iii) chow with 0.5% CH and 2% PS (CH/PS). Compared with newly weaned pups from Chow dams, pups from dams fed the CH-enriched diet demonstrated increases (p < 0.05) in total-C, LDL-C, HDL-C, and total LDL and VLDL particle number. Pups from CH-fed mothers also exhibited higher hepatic CH concentration and differential mRNA expression pattern of CH regulatory genes. Pups from PS-supplemented dams demonstrated reductions (p < 0.05) in serum total-C, non-HDL-C, and LDL-C but also increased triglycerides compared with pups from CH-fed dams. Maternal PS supplementation reduced (p < 0.05) hepatic CH and increased the abundance of HMG-CoAr and LDLr protein in newly weaned pups compared with the CH group.. Results suggest that maternal PS supplementation is largely effective in normalizing CH in pups born to mothers with hypercholesterolemia, however, the cause and long-term influence of increased triglyceride is not known.

Topics: Animals; Animals, Newborn; Body Weight; Cholesterol; Dyslipidemias; Female; Hypercholesterolemia; Lactation; Lipid Metabolism; Liver; Male; Maternal Nutritional Physiological Phenomena; Mesocricetus; Phytosterols; Pregnancy; Sterol Regulatory Element Binding Protein 2; Triglycerides

A young girl, age 8.5 years, presented with profound hypercholesterolemia and early xanthomatosis, suggesting homozygous familial (or type II) hypercholesterolemia. The patient's low density lipoprotein (LDL) receptor function and parental lipoprotein profiles were determined to be normal, prompting revision of the initial diagnosis to pseudohomozygous familial hypercholesterolemia. When she subsequently presented with giant platelets, the case was presented to colleagues on an electronic mailing list. It was recommended that plasma and sterol analysis be performed, which led to a diagnosis of sitosterolemia. The presentation of profound hypercholesterolomia in childhood that ultimately is not attributed as due to homozygous or compound heterozygous defects in the LDL receptor gene has been termed pseudohomozygous familial (or type II) hypercholesterolemia (PHT2HC). Patients diagnosed with PHT2HC subsequently confirmed to have sitosterolemia have been previously reported only rarely. The challenge of achieving accurate specific diagnosis and appropriate workup for these conditions in children is discussed in the context of this rare case and review of the historical literature concerning these conditions.

Topics: Blood Platelets; Child; Diagnosis, Differential; Female; Homozygote; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Receptors, LDL; Sterols; Treatment Outcome; Xanthomatosis

The aim of the present study was to evaluate in vivo the potential anti-ischemic and antiatheromatic activity of Chios Mastic gum, the resin of the trunk and branches of "Pistacia lentiscus var. chia", used since antiquity in traditional Greek medicine. The main compounds of mastic are triterpenes, possessing phytosterol-like structures. This led to the hypothesis that mastic and particularly its neutral fraction, enriched in phytosterol-like compounds, possess antiatheromatic activities.. Total Mastic Extract without Polymer (TMEWP) and the neutral mastic fraction (NMF) were administered orally for 6 weeks to normal fed and to cholesterol fed rabbits in the form of sunflower oil solution. All the animals were randomly divided into 6 groups, anesthetized and subjected to 30min ischemia of the heart, followed by 3h reperfusion: At the end of the experiment the area at risk and the infarct zone were determined with the aid of fluorescent particles and triphenyl tetrazolium chloride staining, and small segments of the ascending and descending aorta and the heart were taken for histologic examination. Blood samples were collected at different time points of ischemia and reperfusion, for malondialdehyde (MDA) evaluation as an index of lipid peroxidation, for total and LDL cholesterol determination and for evaluation of oxidized LDL.. In the normal fed animals the NMF and the TMEWP reduced significantly the infarct size, while in the hypercholesterolemic rabbits both treatments were ineffective. Atherosclerosis was detected in all the animals fed cholesterol enriched diet in the form of subintimal accumulation of lipids and foamy macrophages. There was no detection of atherosclerosis in Groups treated with TMEWP and NMF, which both reduced the total cholesterol levels by 47 and 88% respectively, whilst had not effect on LDL oxidation. TMEWP and NMF reduced the MDA concentration in normal fed rabbits, but had no effect on MDA levels in cholesterol fed animals. TMEWP and NMPF reduce the infarct size in normal animals and possess significant antiatheromatic and hypolipidemic activities in rabbits fed cholesterol enriched diet.

Topics: Animal Feed; Animals; Anticholesteremic Agents; Greece; Hypercholesterolemia; Male; Mastic Resin; Myocardial Ischemia; Phytosterols; Pistacia; Plant Extracts; Rabbits; Resins, Plant; Triterpenes

Sitosterolemia is a very rare autosomal recessive lipoprotein metabolic disorder caused by homozygous or compound heterozygous mutations in one of the two adenosine triphosphate-binding cassette transporter genes, ABCG5 and ABCG8. Sitosterolemia is clinically characterized by xanthomas and atherosclerosis, arthritis, fever, hemolysis and macrothrombocytopenia even in early childhood. We described a 16-month-old girl, who had numerous yellowish-brown intertriginous xanthomas along the skin creases on the extremities with severe hypercholesterolemia and elevated plant sterol levels. Histopathologically, xanthoma showed aggregation of foam cells in the dermis with a zone of mucin deposits in the dermal papilla. Electron microscopy showed numerous membrane-bound lipid droplets and multivesicular lipid bodies in the foam cells, a round cell containing lipid droplets in the basal cell layer and abundant mucin deposits just beneath the basal lamina. Diagnosis of sitosterolemia was confirmed by DNA sequencing showing compound heterozygosity for previously reported missense mutations in exon 9 of ABCG5. Infants presenting with multiple xanthomas should be investigated for sitosterolemia, if there is no family history of dyslipidemia.

Topics: Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Skin; Xanthomatosis

Data on the characteristics of consumers of phytosterol-enriched products and modalities of consumption are rare. An observational study evaluating the lifestyle characteristics and cardiovascular risk (CVR) profile of phytosterol-enriched yogurt consumers was performed in France.. Subjects were recruited from general practitioners via electronic medical records. Data were obtained from 358 consumers and 422 nonconsumers with 519 subject questionnaires (243 consumers, 276 nonconsumers; 67% response).. Consumers had more cardiovascular risk factors than nonconsumers (2.0 ± 1.5 versus 1.6 ± 1.4; P < 0.001) and a higher 10-year SCORE cardiovascular risk (1.8 ± 2.0% versus 1.6 ± 2.2%; P = 0.008); they were older (P = 0.030) and had a higher incidence of hypercholesterolaemia (P < 0.001) and family or personal history of heart disease (P = 0.023/P = 0.026, respectively). Among consumers not on cholesterol-lowering medication, 99% were eligible for lifestyle interventions and 56% were eligible for lipid-lowering drug according to European guidelines. Consumers had a healthier lifestyle, with a higher (fruit/vegetable - saturated fatty acid) score than nonconsumers (P = 0.035), focused more on low-intensity leisure activity (P = 0.023), spent more time travelling by foot or bicycle (P = 0.012) and were more likely to act to reduce CVR. Phytosterol-enriched yogurt intake conformed to recommendations in two-thirds of consumers and was mainly consumed because of concerns over cholesterol levels and CVR.. The higher cardiovascular disease risk profile of phytosterol-enriched yogurt consumers corresponds to a population for whom European guidelines recommend lifestyle changes to manage cholesterol. The coherence of the data in terms of risk factors, adherence to lifestyle recommendations and the consumption of phytosterol-enriched yogurt conforming to recommendations reflects a health-conscious consumer population.

Topics: Adolescent; Adult; Cardiovascular Diseases; Feeding Behavior; Female; Food, Fortified; France; Humans; Hypercholesterolemia; Life Style; Male; Middle Aged; Phytosterols; Risk Factors; Surveys and Questionnaires; Yogurt; Young Adult

Topics: Abdominal Pain; Amish; Anticholesteremic Agents; Azetidines; Biopsy; Diagnosis, Differential; Ezetimibe; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Predictive Value of Tests; Retroperitoneal Fibrosis; Retroperitoneal Space; Tomography, X-Ray Computed; Treatment Outcome; Xanthomatosis; Young Adult

Topics: Child, Preschool; Female; Hematologic Diseases; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Xanthomatosis

The consumption of plant sterols is associated with a decrease in LDL cholesterol. However, it is also associated with an increase in plasma plant-sterol (sitosterol, campesterol) levels that may be detrimental. Indeed, the genetic disease sitosterolaemia, which is characterized by elevated plasma levels of plant sterol, is associated with premature atherosclerosis. Yet, although plasma plant-sterol levels are recognized markers of cholesterol absorption, the relationship between such levels and atherosclerosis is not clear. Several studies have analysed the association between plasma plant-sterol levels and cardiovascular disease (CVD), but have found conflicting results. Although the largest prospective trials and genome-wide association studies suggest that high plasma levels of plant sterols are associated with increased CV risk, other studies have reported no such association and even an inverse relationship. Thus, the available data cannot confirm an increased CV risk with plant sterols, but cannot rule it out either. Only a prospective interventional trial to analyse the effects of plant-sterol-enriched food on the occurrence of CV events can exclude a potential CV risk linked with their consumption.

Topics: Animals; Cardiovascular Diseases; Epidemiologic Studies; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Mice; Phytosterols; Plaque, Atherosclerotic; Risk Factors

Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Humans; Hypercholesterolemia; Jejunum; Leukocytes; Lipoproteins; Liver; Low Density Lipoprotein Receptor-Related Protein-5; Macrophages; Mice; Mice, Inbred C57BL; Monocytes; Phytosterols; RNA Interference; RNA, Messenger; RNA, Small Interfering; Spleen; Wnt Signaling Pathway

Topics: Atorvastatin; Drug Substitution; Electromyography; Fasciculation; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Leg; Middle Aged; Muscle Cramp; Phytosterols; Quinolines; Rosuvastatin Calcium; Toes

In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. Because lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers.. This study used the hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) mouse model to test the hypothesis that mothers supplemented with phytosterols during gestation and lactation would produce offspring with a more favorable lipid profile than offspring from unsupplemented mothers, despite having a genetic predisposition toward hypercholesterolemia.. Sixteen female apoE(-/-) mice were randomly assigned to 2 diets fed throughout the gestation and lactation periods: a cholesterol-enriched diet (CH) (0.15%) or the cholesterol-enriched diet supplemented with phytosterols (CH/PS) (2%). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively, and liver cholesterol was analyzed by GC.. Compared with the CH-fed dams at the end of lactation, phytosterol-supplemented dams displayed lower (P < 0.05) serum total cholesterol (-55%), non-HDL cholesterol (-56%), and LDL cholesterol (-47%), but no change (P > 0.05) in HDL cholesterol and triacylglycerol (TG) concentrations. Pups from phytosterol-fed dams demonstrated lower (P < 0.05) total cholesterol (-25%), non-HDL cholesterol (-25%), LDL cholesterol (-47%), and TGs (-41%), without any change (P > 0.05) in HDL cholesterol compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from phytosterol-supplemented dams displayed a lower (P < 0.05) number of total LDL particles (-34%), VLDL particles (-31%), and HDL particles (-30%).. Our results in apoE(-/-) mice suggest that even under strong genetic predisposition to hypercholesterolemia, pups born to mothers supplemented with phytosterols during gestation and lactation exhibit favorable liver and serum lipid responses compared with pups from unsupplemented mothers.

Topics: Animals; Apolipoproteins E; Dietary Supplements; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Hypercholesterolemia; Lactation; Lipid Metabolism; Lipoproteins; Maternal Nutritional Physiological Phenomena; Mice; Mice, Knockout; Phytosterols; Pregnancy

Topics: Adult; Blood Cell Count; Erythrocytes, Abnormal; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Leukocytes, Mononuclear; Lipid Metabolism, Inborn Errors; Phytosterols

Sitosterolemia (phytosterolemia) is a rare inherited sterol storage disorder, characterized by significantly elevated plasma levels of plant sterols. The clinical features of sitosterolemia are xanthomas, premature atherosclerosis, arthritis, and, occasionally, liver function impair and hematologic abnormalities. This disorder is caused by mutations of ABCG5/ABCG8 genes. We report here the clinical, laboratory, and molecular genetic features of 13 patients with sitosterolemia from eight unrelated families who had specific hematologic problems of macrothrombocytopenia, hemolytic anemia, and splenomegaly besides the major clinical manifestations. The peripheral blood films showed some unique features: large platelets surrounded by a circle of vacuoles, and various abnormal erythrocyte shapes, especially stomatocyte. According to these distinct changes of blood cell morphology, we identified two sitosterolemia patients who lacked the classical clinical phenomena. All the patients had been misdiagnosed with immune thrombocytopenia (ITP), Evans syndrome, or secondary ITP with delay being 28.8 years between symptom onset and correct diagnosis. These results indicate that sitosterolemia is certainly not as rare as originally thought. The phenomena of macrothrombocytopenia/hemolysis might represent a new platelet disorder. Plasma plant sterols and ABCG5/ABCG8 genes should be analyzed when such hematologic abnormalities are unexplained.

Topics: Adult; Anemia, Hemolytic, Congenital; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Blood Platelets; Cell Shape; Cholesterol; Delayed Diagnosis; Diagnostic Errors; DNA Mutational Analysis; Erythrocytes, Abnormal; Exons; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Osmotic Fragility; Pedigree; Phenotype; Phytosterols; Prevalence; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Splenomegaly; Thrombocytopenia; Vacuoles; Xanthomatosis

Assess the evolution of cardiovascular lifestyle behaviors in hypercholesterolemic patients concomitantly with changes in their daily intake of phytosterol-supplemented yoghurt (Phyto-SY).. Nationwide prospective observational study conducted in general practices across France and Spain. Each practitioner suggested lifestyle changes to five consecutive patients with hypercholesterolemia (whether or not they were taking hypocholesterolemic drugs) and recommended daily consumption of Phyto-SY. The study design involved an inclusion visit, a patient's self-monitoring assessment after 1 month, and a final visit after 4 months. Primary evaluation criterion: changes in dietary habits assessed by a standardized Nutritional Lifestyle score. Secondary criteria: changes in lipid profile, anthropometry (waist circumference) and lifestyle behavior.. A total of 2376 hypercholesterolemic patients (of whom 54.8% were women) were included. The average age was 56.2 years old. The Nutritional Lifestyle score improved from 15.4 ± 5.4 to 8.7 ± 4.0 (p < 0.0001). Total cholesterol decreased by 10.6% (<0.0001), HDL-C increased by 8.0% (<0.0001), and LDL-C fell by 12.7% (<0.0001). Similar results were observed in patients treated with statins and those who were not. Frequency of walking (>30 min) increased from 59.3% to 78.3% (p < 0.0001). The overweight rate decreased from 22.8% to 17.5% (p < 0.0001) and waist circumference from 94.6 ± 13.3 cm to 93.0 ± 12.8 cm (p < 0.0001). Nutritional Lifestyles and other lifestyle markers' improvement were parallel to adherence to Phyto-SY adherence.. Improvements in Nutritional Lifestyle scores, which included regular consumption of Phyto-SY over 4 months, was significantly linked to healthier lifestyles and to beneficial modifications in atherogenic lipid profiles, which reflected patient empowerment in a 'real life' context.

Topics: Adult; Aged; Biomarkers; Cholesterol; Combined Modality Therapy; Dietary Supplements; Directive Counseling; Feeding Behavior; Female; Follow-Up Studies; France; Functional Food; Health Behavior; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Life Style; Male; Middle Aged; Phytosterols; Prospective Studies; Spain; Treatment Outcome; Yogurt

Phytosterolemia is a rare autosomal recessive sterol storage disease caused by mutations in ABCG5 and ABCG8 genes. A 9-year-old Turkish boy who was presented with exclusively hematologic abnormalities had elevated plant sterol levels. Sequencing of ABCG5 and ABCG8 genes revealed a novel homozygous IVS10-1 G>T mutation in ABCG5 gene. Four of the 13 family members had xanthoma but they had neither hematologic abnormalities nor IVS10-1 G>T mutation. Ezetimibe therapy reduced plant sterol levels in association with marked clinical improvement. Plant sterol levels and ABCG5/ABCG8 genes should be analysed in patients with unexplained hemolytic anemia and macrothrombocytopenia.

Topics: Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Azetidines; Child; Ezetimibe; Hematologic Diseases; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Phytosterols; Point Mutation

Phytosterolemia is a rare autosomal recessive disorder characterized by dramatically elevated circulating levels of plant sterols (PS). Phytosterolemia is believed to be responsible for severe premature atherosclerosis. The clinical, biological and molecular genetic features of 5 patients with phytosterolemia and transient severe hypercholesterolemia challenge this hypothesis.. Our patients were referred for suspected homozygous familial hypercholesterolemia. Despite the phenotype, this diagnosis was invalidated and phytosterolemia was confirmed by the identification of mutations in the ABCG5/ABCG8 transporter complex. Plasma PS were analyzed with a mass spectrometric-gas chromatographic procedure. Vascular status was assessed with carotid ultrasonography and completed (for 4 of the 5 patients) with femoral ultrasonography; additional examinations of cardiovascular status included a stress test, determination of coronary calcium score, echocardiography, non-invasive assessment of endothelium-dependent dilatation and coronarography.. The 5 patients displayed markedly elevated levels of both β-sitosterol and campesterol (15-30 fold higher than normal values). However, none displayed significant signs of infraclinical premature atherosclerosis (respectively at the ages of 32, 27, 29, 11 and 11 years). All patients were characterized by very high levels of total (>450 mg/dl) and LDL-cholesterol (>350 mg/dl) at diagnosis which decreased markedly on dietary intervention alone. Treatment with cholestyramine or Ezetimibe ± atorvastatin normalized cholesterol levels, although plasma PS concentrations remained elevated.. The clinical and biological characteristics of our patients, considered together with reports of cases which equally lack CVD, support the contention that the premature atherosclerosis associated with phytosterolemia in some patients may be due at least in part to mechanisms independent of elevated circulating phytosterol levels.

Topics: Adolescent; Adult; Age Factors; Atherosclerosis; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Retrospective Studies; Severity of Illness Index; Young Adult

The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols.. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method.. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker.. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved.. Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117].

Topics: Adult; Aged; Cholestanol; Cholesterol; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Phytosterols; Randomized Controlled Trials as Topic; Sitosterols; Sterols; Young Adult

Sitosterolaemia is caused by mutations in either ABCG5 or ABCG8. Chinese and Japanese individuals usually have mutations in ABCG5. We herein report a known and a novel mutation in ABCG8 and their potential interaction with NPC1L1 polymorphisms in a Chinese family with sitosterolaemia. We sequenced ABCG5 and ABCG8 and measured the levels of plasma plant sterols in a 15-year-old Chinese girl with clinical sitosterolaemia (xanthomas with elevated low-density lipoprotein cholesterol (LDL-C) and plant sterols) and her apparently healthy family members. NPC1L1 was sequenced in the genetically affected sibling and other family members. A known mutation, c.490C＞T (p. Arg164(＊)), in exon 4 and a novel mutation, c.1949T＞G (p.Leu650Arg), in exon 13 of ABCG8 were detected in the proband and her sister, who had elevated sterols but low LDL-C levels and no xanthomas. The genetically affected sister, but not the proband, carried two additional heterozygous changes in NPC1L1 (rs2072183 C＞G, rs2301935 A＞C), which were inherited from the mother, who also had a low LDL-C level. In this study, we detected a known and a novel mutation in ABCG8 in a Chinese patient with sitosterolaemia. The same mutations were found in her clinically normal sister, suggesting that the contrasting features with the proband may be related to different variants in NPC1L1 and/or some other undetermined lipid-related genetic factors.

Topics: Adolescent; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; China; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Membrane Proteins; Membrane Transport Proteins; Mutation; Pedigree; Phytosterols; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; Sitosterols

A high-fat, high-energy (HFE) diet may be deleterious to the cardiovascular system and mental health. We previously reported that serum cholesterol levels and escape latency were significantly increased in mice by feeding them an HFE diet from gestation onward. In this study, we examined whether an HFE diet supplemented with phytosterols fed to pregnant C57BL/6j dams and their offspring would protect the HFE-diet-induced compromise of the offspring's learning capability. We measured serum cholesterol levels, brain N-methyl-D-aspartate receptor (NMDAR1) mRNA and protein expression and liver sterol 27-hydroxylase (Cyp27a1) mRNA expression, as well as a Morris water maze performance. The results showed that, compared to mice consuming the HFE diet alone, those also consuming phytosterols (the HFE + PS diet) significantly decreased mean serum low-density lipoprotein cholesterol levels and altered brain NMDAR1 mRNA and protein expression and liver Cyp27a1 mRNA expression. The Morris water maze experiments indicated that dietary phytosterol supplementation slightly decreased the escape latency (p = 0.07). Collectively, these observations suggest that consumption of phytosterols from early in life may help alleviate the detrimental effects of HFE diets in mice.

Topics: Animals; Anticholesteremic Agents; Behavior, Animal; Cholesterol, LDL; Cognition Disorders; Diet, High-Fat; Dietary Supplements; Energy Intake; Female; Hypercholesterolemia; Lactation; Learning Disabilities; Male; Maternal Nutritional Physiological Phenomena; Maze Learning; Memory Disorders; Mice; Mice, Inbred C57BL; Phytosterols; Pregnancy; Random Allocation; Weaning

With a view to investigate the ameliorative effects of sitosterol esters against degenerative effects of hypercholesterolemia brain antioxidant enzyme assays, brain lipid profile, brain phospholipid compositional change and brain neurotransmitter concentrates (glutamic acid, asparctic acid, glycine) were measured in hypercholesterolemic rats. The results indicated that phytosterol esters have a role in countering hypercholesterolemia-related changes in the brain by decreasing the cholesterol levels, increasing the phospholipid levels and increasing the level of antioxidant enzymes. The results suggest that phytosterol esters may be of therapeutic significance and may offer new and effective options for the treatment of hypercholesterolemia-induced changes in the brain.

Topics: alpha-Linolenic Acid; Amino Acids; Animals; Antioxidants; Brain; Chromatography; Docosahexaenoic Acids; Eicosapentaenoic Acid; Esters; Fish Oils; Glutathione; Hypercholesterolemia; Male; Neurotransmitter Agents; Phytosterols; Rats; Rats, Wistar; Sitosterols

Sitosterolemia is a rare, autosomal recessive disease caused by mutations in the adenosine triphosphate-binding cassette transporter genes ABCG5 or ABCG8 that result in accumulation of xenosterols in the body. Clinical manifestations include tendon xanthomas, premature coronary artery disease, hemolytic anemia, macrothrombocytopenia, and bleeding. Although the effect of sterol accumulation on the predisposition for atherosclerosis is evident, how xenosterol accumulation leads to defects in platelet physiology is unknown. Sitosterolemia induced in Abcg5- and Abcg8-deficient mice fed a high plant sterol diet resulted in accumulation of free sterols in platelet plasma membranes, leading to hyperactivatable platelets characterized by constitutive binding of fibrinogen to its αIIbβ3 integrin receptor, internalization of the αIIbβ3 complex, generation of platelet-derived microparticles, and changes in the quantity and subcellular localization of filamin. The latter was associated with macrothrombocytopenia, shedding of GPIbα, impaired platelet adhesion to von Willebrand factor, and inability to form stable thrombi. Plasma levels of soluble GPIbα were strongly correlated with plasma sitosterol levels in samples from human sitosterolemic patients, implicating a similar mechanism of sterol-induced platelet passivation in the human disease. Intercalation of plant sterols into the plasma membrane therefore results in dysregulation of multiple platelet activation pathways, leading to macrothrombocytopenia and bleeding.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Blood Platelets; Disease Models, Animal; Fibrinogen; Filamins; Hemorrhage; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Phytosterols; Platelet Activation; Platelet Glycoprotein GPIIb-IIIa Complex

Cholesterol and diet-derived oxidized cholesterol are absorbed in the small intestine and eliminated by bile acids. We determined whether ezetimibe, a selective cholesterol absorption inhibitor, changes serum oxidized cholesterol levels.. We measured levels of plant sterols, cholesterol precursors, and oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics and 32 controls. Twenty-four hypercholesterolemics received 10 mg ezetimibe/day for 4 weeks.. Plant sterols were 30-42% higher in hypercholesterolemics than in controls and positively correlated with low-density lipoprotein-cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53%, but did not change bile acid synthesis markers. 7β-hydroxycholesterol, a marker for non-enzymatic oxidation of cholesterol, was 66% higher in hypercholesterolemics than controls. Ezetimibe decreased 7β-hydroxycholesterol levels by 15% regardless of LDL-C reduction.. Ezetimibe decreases serum oxidized cholesterol generated by non-enzymatic reactions without impairing bile acid synthesis. Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet-derived oxidative burden.

Topics: Absorption; Aged; Anthropometry; Anticholesteremic Agents; Azetidines; Bile Acids and Salts; Body Mass Index; Case-Control Studies; Cholesterol; Diet; Ezetimibe; Female; Gas Chromatography-Mass Spectrometry; Humans; Hydroxycholesterols; Hypercholesterolemia; Intestine, Small; Japan; Life Style; Male; Middle Aged; Oxygen; Phytosterols; Sterols; Triglycerides

Foods incorporating plant sterols (PS) consistently decrease serum low-density lipoprotein cholesterol (LDL-C), although results vary depending on the PS form and food matrix. The objective was to study the effect of a novel triglyceride-recrystallized phystosterol (TRP) incorporated into fat-free milk on markers of cardiovascular risk compared to unmodified free sterols alone in the same fat-free milk.. Hypercholesterolemic men and women (n = 13 males/7 females; 56 ± 10 years; body mass index 27.3 ± 5.9 kg/m(2)) participated in 3 sequential 4-week phases of 480 mL milk consumption. During phase 1 (control) all subjects consumed 2% milk containing no PS, followed by phase 2 with fat-free milk containing free PS (2 g/d fPS) and phase 3 with fat-free milk with TRP (2 g/d). After each phase, determinations of lipoprotein cholesterol distribution, particle concentration via nuclear magnetic resonance (NMR), apolipoproteins, inflammatory markers, and fat-soluble dietary antioxidants were made.. Body mass, body composition, dietary energy and macronutrients, and physical activity were unaffected throughout the study. Compared to the control 2% milk, LDL-C was significantly (p < 0.05) decreased by fPS (-9.1%) and was further decreased by TRP (-15.4%); reductions with TRP were significantly greater. Total LDL particle concentration was decreased to a greater extent after TRP (-8.8%) than fPS (-4.8%; p < 0.05). Only TRP significantly decreased serum levels of apolipoprotein B (apoB; -6%), interleukin-8 (IL-8; -11%) and monocyte chemotactic protein-1 (MCP-1; -19%). Plasma α- and γ-tocopherols and carotenoids, normalized to cholesterol, remained unchanged throughout the study with the exception that β-carotene was lowered by 18%.. In summary, TRP in fat-free milk may provide cardiovascular benefits beyond that of fPS by inducing more substantial decreases in LDL cholesterol and particle concentration, associated with declines in markers of vascular inflammation.

Topics: Adult; Aged; Animals; Apolipoproteins B; Cardiovascular Diseases; Carotenoids; Chemokine CCL2; Cholesterol, LDL; Dietary Fats; Female; Food Handling; Humans; Hypercholesterolemia; Interleukin-8; Male; Middle Aged; Milk; Phytosterols; Risk Factors; Tocopherols; Triglycerides

Topics: Animals; Blood Platelets; Hemorrhage; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Platelet Activation

The aim of the present study is to evaluate the effect of eicosapentaenoic acid-docosahexaenoic acid (EPA-DHA) rich sterol ester and A-linolenic Acid (ALA) rich sterol ester on the atherogenic disturbances in hypercholesterolemic atherogenic animals. Six groups of male Wistar rats were employed in this study, wherein five groups were fed with a high cholesterol diet (stock diet supplemented with 1% cholesterol) for 30 days, among which, two groups of rats were also treated with EPA-DHA rich sterol ester in two doses (25 and 50 mg/rat/day, oral gavage) and two groups were treated with ALA rich sterol ester also in two doses (25 and 50 mg/rat/day, oral gavage). The remaining one group served as control. Abnormal increases in the levels of malondialdehyde, as well as depressed antioxidants status, were observed in hepatic tissue of hypercholesterolemic control group. Hypercholesterolemia induced abnormal elevation in the activities of marker enzymes in liver (aspartate transaminase, alanine transaminase and alkaline phosphatase) and was accompanied by increased hepatic cholesterol level and altered fatty changes in the histology of liver. These changes were restored partially in the groups administered with lower doses (25 mg/rat/day) of sterol esters. However, the higher doses (50 mg/rat/day) of sterol esters almost ameliorated the hypercholesterolemic-oxidative changes in the hypercholesterolemic rats. The results of this study present oxidative injury induced by hypercholesterolemic diet and administration of the treatment with higher doses of sterol esters afforded sound protection against lipemic-oxidative injury.

Topics: Acyl Coenzyme A; Animals; Antioxidants; Esters; Fatty Acids; Hypercholesterolemia; Lipid Metabolism; Liver; Liver Diseases; Liver Function Tests; Male; Malondialdehyde; Mevalonic Acid; Oxidative Stress; Phytosterols; Rats; Rats, Wistar

The present paper focuses on clinical issues concerning the psychopharmacological treatment of severe forms of post-traumatic stress disorder (PTSD).Using a case study, we discuss problems in this field against the background of psychodynamic and psychotraumatological theories. We also present strategies for the appropriate use of psychotropic drugs in the psychotherapy of PTSD.

Topics: Adoption; Adult; Child; Child Abuse; Child Abuse, Sexual; Child, Abandoned; Combined Modality Therapy; Countertransference; Drug Substitution; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Phytosterols; Projection; Psychoanalytic Theory; Psychotherapy, Psychodynamic; Psychotropic Drugs; Somatoform Disorders; Stress Disorders, Post-Traumatic

Probiotic bacteria and phytosterols are natural hypocholesterolemic agents with potential cardiovascular benefits. Accordingly, the present study was conducted to evaluate the effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats. Mixed probiotics treatment consisted of 8 probiotic strains: 2 strains of each of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus reuteri. The rats were fed for 8 wk with the given treatments in addition to a high-fat-high-cholesterol basal diet to induce hypercholesterolemia. Results showed that supplementation significantly reduced serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol, and triglycerides compared with the controls. The symbiotic treatment was more effective in lowering LDL-C, whereas mixed probiotics treatment more effectively lowered serum total cholesterol and LDL-C than the phytosterol-containing treatment. The phytosterol-containing treatments induced the increased activity of thyroid glands, as evident by elevated levels of serum total thyroxine, total triiodothyronine, and free triiodothyronine. In conclusion, the lipid profile can effectively be reduced to lower the incidence of cardiovascular disease using combinations of Lactobacillus-based probiotics and phytosterols in functional foods.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Dietary Supplements; Drug Therapy, Combination; Hypercholesterolemia; Lactobacillus; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Liver; Male; Phytosterols; Probiotics; Rats; Rats, Sprague-Dawley; Thyroid Hormones; Thyroxine; Triglycerides; Triiodothyronine

To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis.. In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the ABCG8 G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%-37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (P<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age- and sex-adjusted P=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association.. Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amish; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Biomarkers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Pennsylvania; Phenotype; Phytosterols; Risk Assessment; Risk Factors; Up-Regulation; Young Adult

Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance and antioxidant defenses reduction. Obesity-mediated oxidative stress plays an important role in the pathogenesis of dyslipidemia, vascular disease, and nonalcoholic hepatic steatosis. The antidyslipidemic activity of pigeon pea were evaluated by high-fat diet (HFD) hamsters model, in which the level of high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and total triglyceride (TG) were examined. We found that pigeon pea administration promoted cholesterol converting to bile acid in HFD-induced hamsters, thereby exerting hypolipidemic activity. In the statistical results, pigeon pea significantly increased hepatic carnitine palmitoyltransferase-1 (CPT-1), LDL receptor, and cholesterol 7α-hydroxylase (also known as cytochrome P450 7A1, CYP7A1) expression to attenuate dyslipidemia in HFD-fed hamsters; and markedly elevated antioxidant enzymes in the liver of HFD-induced hamsters, further alleviating lipid peroxidation. These effects may attribute to pigeon pea contained large of unsaturated fatty acids (UFA; C18:2) and phytosterol (β-sitosterol, campesterol, and stigmasterol). Moreover, the effects of pigeon pea on dyslipidemia were greater than β-sitosterol administration (4%), suggesting that phytosterone in pigeon pea could prevent metabolic syndrome.

Topics: Animals; Antioxidants; Cajanus; Carnitine O-Palmitoyltransferase; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Cricetinae; Diet, High-Fat; Disease Models, Animal; Hypercholesterolemia; Lipid Peroxidation; Liver; Male; Obesity; Oxidative Stress; Phytosterols; Receptors, LDL; Sitosterols; Stigmasterol; Triglycerides

Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine.. Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16.. The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, β-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05).. Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents.. Current Controlled Trials ISRCTN89549017.

Topics: Adolescent; Apolipoprotein A-I; beta Carotene; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Cholesterol, LDL; Fatty Acids, Omega-3; Female; Fish Oils; gamma-Tocopherol; Humans; Hypercholesterolemia; Male; Phytosterols; Pilot Projects; Risk Factors; Triglycerides; Vitamin B Complex; Young Adult

We investigated the behaviour of non-cholesterol sterols, surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol), in primary hyperlipemias.. We studied 53 patients with polygenic hypercholesterolemia (PH), 38 patients with familial combined hyperlipemia (FCH), and 19 age- and sex-matched healthy control subjects. In all participants, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled to mass spectrometry. To correct for the effect of plasma lipid levels, non-cholesterol sterol concentrations were adjusted for plasma cholesterol (10² μmol/mmol cholesterol). Patients with FCH were more frequently men, and had higher body mass index (BMI), fasting glucose, insulin and HOMA-IR. Lathosterol was higher in FCH than in pH or controls (p < 0.05). Campesterol was significantly lower in FCH (p < 0.05), while no differences were found between pH and controls. Sitosterol displayed higher values in pH compared to FCH (p < 0.001) and controls (p < 0.05). Spearman's rank correlations showed positive correlations of lathosterol with BMI, waist circumference, HOMA-IR, triglycerides, apoprotein B, and a negative one with HDL-cholesterol. Sitosterol had a negative correlation with BMI, waist circumference, HOMA-IR, triglycerides, and a positive one with HDL-cholesterol and apoprotein AI. Multivariate regression analyses showed that cholesterol absorption markers predicted higher HDL-cholesterol levels, while HOMA-IR was a negative predictor of sitosterol and BMI a positive predictor of lathosterol.. Our findings suggest the occurrence of an increased cholesterol synthesis in FCH, and an increased cholesterol absorption in pH. Markers of cholesterol synthesis cluster with clinical and laboratory markers of obesity and insulin resistance.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Hyperlipidemia, Familial Combined; Intestinal Absorption; Italy; Linear Models; Male; Middle Aged; Multifactorial Inheritance; Multivariate Analysis; Phytosterols; Risk Assessment; Risk Factors; Sitosterols; Sterols; Young Adult

Phytosterolemia is a rare autosomal recessive disease of plant sterol metabolism, the pathophysiological features of which are high plasma levels of plant sterols and xanthomatosis caused by mutations of ABCG5 and ABCG8 genes, and the combination of hemolysis and macrothrombocytopenia is an unusual clinical manifestation. All the patients of the 3 unrelated phytosterolemia first presented with prominent macrothrombocytopenia and stomatocytosis. They were either homozygous or compound heterozygous for ABCG5/ABCG8 gene mutations and had significantly elevated serum plant sterols levels quantified using high-performance liquid chromatography. The in vitro study demonstrated that sitosterol can cause changes in shape and osmotic fragility of red blood cells. These findings suggest that macrothrombocytopenia and stomatocytosis could be initial and main features in some patients with phytosterolemia and that serum phytosterols and relevant genes should be analyzed in patients whose macrothrombocytopenia and/or stomatocytosis are unexplained, especially whose parents are of consanguineous marriage.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Erythrocytes, Abnormal; Female; Heterozygote; Homozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation; Osmotic Fragility; Pedigree; Phytosterols; Sitosterols; Xanthomatosis

Topics: Anticholesteremic Agents; Azetidines; Cholesterol, Dietary; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Phytosterols

The effect of feeding a mixture of high molecular weight alcohols derived from sugarcane (SCA), both alone and in combination with phytosterols (PS), on changes in plasma lipids, organ cholesterol accumulation, and antioxidant status of Wistar rats was undertaken. Three separate experiments were conducted and each experiment had 3 subsets. In experiment 1, rats were fed on an AIN-76, semi-synthetic diet supplemented with 0%, 0.5%, and 5% SCA w/w. The second experiment consisted of feeding rats an atherogenic diet (AIN-76+0.5% cholesterol) containing 0%, 0.5%, and 5% SCA w/w. The third experiment consisted of feeding rats an atherogenic diet that contained 2% PS in combination with 0%, 0.5%, and 5% SCA. Rats fed the atherogenic diet exhibited significant elevations in total and low-density lipoprotein cholesterol, and significant reductions in the high-density lipoprotein/total cholesterol ratio, regardless of the presence of 0.5% or 5% SCA mixture. Serum cholesterol increased 29% to 35% in these animals compared with animals fed the nonatherogenic diets. In contrast, animals fed atherogenic diets that contained 2% PS exhibited no difference in serum lipids compared with counterparts fed nonatherogenic diets. The combined presence of SCA with PS had no effect on further lowering plasma cholesterol. No changes in C-reactive protein were observed, but plasma oxygen radical scavenging capacity values significantly (p < 0.05) decreased when rats were fed the atherogenic diets that contained the combination of PS and SCA. This result corresponded to an apparent greater (p < 0.05) susceptibility of red blood cells to oxidative stress.

Topics: Animals; Anticholesteremic Agents; C-Reactive Protein; Diet, Atherogenic; Dietary Supplements; Erythrocytes; Fatty Alcohols; Free Radical Scavengers; Hypercholesterolemia; Lipids; Male; Molecular Weight; Oxidants; Oxidative Stress; Phytosterols; Plant Stems; Rats; Rats, Wistar; Saccharum; Waxes

Cholesterol precursors and plant sterols have considerable potential as plasma biomarkers in several disorders of sterol metabolism and intestinal sterol absorption. Oxysterols are associated with atherogenesis, neurodegeneration, and inflammation. We developed a GC-MS method for the simultaneous analysis of these species in human plasma, including 24-, 25-, 27-hydroxycholesterol; 7-ketocholesterol; lanosterol; lathosterol; 7-dehydrocholesterol; desmosterol; stigmasterol; sitosterol; and campesterol.. Sterols were hydrolyzed with ethanolic potassium hydroxide solution, extracted by liquid/liquid extraction with n-hexane, and derivatized with N-methyl-N-trimethylsilyl-trifluoracetamide. Positive chemical ionization with ammonia, as reagent gas, was applied to generate high abundant precursor ions.. The definition of highly sensitive precursor/product ion transitions, especially for coeluting substances, allowed fast gas chromatography run times of under 8.5 min. Using the multiple reaction monitoring mode, detection limits in the picogram per milliliter range could be achieved for most compounds. The method was validated for precision and recovery. Intraassay and interassay CVs were mostly <15% for serum and plasma samples. The recoveries of supplemented plasma samples in different concentrations were 88%-117%. The method was applied to stratification of patients with disorders in cholesterol biosynthesis and/or cholesterol absorption in hypercholesterolemia. The method revealed associations of sterol species with thyroid dysfunction and type 2 diabetes.. This method allows high-throughput sterol profiling in various diseases.

Topics: Cholesterol; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Hyperthyroidism; Hypothyroidism; Niemann-Pick Disease, Type C; Phytosterols; Plasma; Sterols; Tandem Mass Spectrometry; Tangier Disease; Xanthomatosis, Cerebrotendinous

Abundant evidence over past decades shows that foods with added plant sterols and plant stanols lower serum LDL cholesterol concentrations. However, despite the overwhelming data, numerous scientific questions still remain. The objective of this paper is to summarize the considerations of 60 academic and industrial experts who participated in the scientific meeting in Maastricht, the Netherlands, on issues related to the health effects of plant sterols and plant stanols. The meeting participants discussed issues including efficacy profiling, heterogeneity in responsiveness, effects beyond LDL-C lowering, and food formulation aspects of plant sterol and stanol consumption. Furthermore, aspects related to the potential atherogenicity of elevated circulatory plant sterol concentrations were discussed. Until the potential atherogenicity of plant sterols is resolved, based on the results >200 clinical trials, the risk to benefit of plant sterol use is favorable. Evidence on these topics in plant sterol and plant stanol research was presented and used to reach consensus where possible. It was concluded that endpoint studies looking at plant sterol and plant stanol efficacy are needed, however, there was no clear opinion on the best marker and best design for such a study. Based on the current scientific evidence, plant sterols and plant stanols are recommended for use as dietary options to lower serum cholesterol.

Topics: Animals; Anticholesteremic Agents; Atherosclerosis; Biomarkers; Chemistry, Pharmaceutical; Cholesterol; Diet; Dietary Supplements; Humans; Hypercholesterolemia; Nutrition Policy; Phytosterols; Risk Assessment; Risk Factors; Sitosterols; Treatment Outcome; Triglycerides

Topics: Acid-Base Imbalance; Anemia, Hemolytic, Congenital; Erythrocytes, Abnormal; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Metabolism, Inborn Errors; Middle Aged; Phytosterols; Thrombocytopenia

We investigated whether the fat and protein fractions of freshwater clam (Corbicula fluminea) extract (FCE) could ameliorate hypercholesterolaemia in rats fed a high-cholesterol diet. We also explored the mechanism and the components that exert the hypocholesterolaemic effect of FCE. The doses of the fat and protein fractions were equivalent to those in 30 % FCE. The fat and protein fractions of FCE, two major components of FCE, significantly reduced the serum and hepatic cholesterol levels. The fat fraction more strongly reduced serum cholesterol levels than the same level of total FCE. The excretion of faecal neutral sterols increased in rats fed the total the FCE and the fat fraction of FCE. On the other hand, faecal bile acid levels were greater in rats fed the total FCE and the fat and protein fractions of FCE than in control animals. The hepatic gene expression of ATP-binding cassette transporter G5 and cholesterol 7α-hydroxylase was up-regulated by the administration of the total FCE and both the fat and protein fractions of FCE. These results showed that the fat and protein fractions of FCE had hypocholesterolaemic properties, and that these effects were greater with the fat fraction than with the protein fraction. The present study indicates that FCE exerts its hypocholesterolaemic effects through at least two different mechanisms, including enhanced excretion of neutral sterols and up-regulated biosynthesis of bile acids.

Topics: Animal Nutrition Sciences; Animals; Bile Acids and Salts; Bivalvia; Cholesterol; Disease Models, Animal; Fats; Feces; Hypercholesterolemia; Male; Phytosterols; Proteins; Rats; Rats, Wistar; Sterols

Phytosterolemia is an inherited disorder characterized by hypercholesterolemia and premature atherosclerosis, together with increased inflammatory states in some cases. The underlying mechanisms of atherogenesis in phytosterolemia, however, have not been completely elucidated. In this study, we investigated whether phytosterols would affect inflammatory reactions in macrophages and macrophage cell lines.. We incubated RAW264.7 cells (RAW) and mouse peritoneal macrophages (MPMs) with sitosterol (Sito), campesterol (Camp) or cholesterol (Chol) at low (8 µM, 16 µM) or high (160 µM) concentrations, and investigated their effects on LPS-induced secretion of IL-6 and TNF-α. We also analyzed their effects on endoplasmic reticulum (ER) stress in both cells, and on the cell proliferation of RAW.. At low sterol concentrations, only Chol resulted in a tendency toward the increased secretion of TNF-α from MPMs. At high concentrations, Chol induced a significant increase in TNF-α secretions from both cells; however, Sito resulted in a non-significant increase in TNF-α secretion. The effects on IL-6 secretions of Sito were also significantly less than those of Chol. Camp increased the secretions of both cytokines from MPMs; however, the extent of these increases was less pronounced than that of Chol. Augmentation of ER stress was greatest with Chol among the sterols, and the proliferation of RAW cells was inhibited only with Chol.. The lesser degree of inflammatory reactions and toxicity in macrophages with phytosterols than with cholesterol suggests that plant sterols themselves might not be primarily responsible for atherogenesis in phytosterolemia.

Topics: Alternative Splicing; Animals; Cell Proliferation; Cells, Cultured; Cholesterol; DNA-Binding Proteins; Endoplasmic Reticulum; Hypercholesterolemia; Interleukin-6; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Phytosterols; Regulatory Factor X Transcription Factors; Transcription Factors; Tumor Necrosis Factor-alpha

The present study describes the consumption of foods enriched with plant sterols (PS) and supplements containing PS, and evaluates PS intakes via the current consumption and for specific consumption scenarios. A market inventory was performed to collate different PS-enriched food items and supplements available in Belgium. An FFQ was developed to investigate the consumption of PS-enriched foods and supplements. A total of 139 pre-school children (2·5-7 years old) and 569 adults (308 women and 261 men) living in Flanders (the northern, Dutch-speaking part of Belgium) participated in the study. Of these, 21 % (Flemish pre-school children) and 28·5 % (Flemish adults) consume PS-enriched food products, leading to a mean PS intake in the consumer group of 0·70 (sd 0·61) g/d for pre-school children and 1·51 (sd 1·42) g/d for adults. Of the adult PS consumers, 23·2 % did not suffer from elevated blood cholesterol levels; 50 % of them had a PS intake less than or equal to 1 g/d and 16·4 % had a PS intake above 3 g/d and 7·8 % even had an intake above 4 g/d. Scenario studies assessed the intake when all Belgian adults would consume PS-enriched margarines without (scenario 1) or with (scenario 2) a daily consumption of a PS-enriched yoghurt drink. This resulted in an intake above 3 g/d in 17 % (women) and 29 % (men) for scenario 1 and 40 % (women) and 53 % (men) for scenario 2. The results indicate that PS-enriched food products are also consumed by the non-target group. Efficient communication tools are needed to inform consumers better about the target group of PS-enriched products, the advised dose per day and alternative dietary strategies to lower the blood cholesterol level.

Topics: Adolescent; Adult; Belgium; Child; Child, Preschool; Cholesterol; Diet; Diet Surveys; Humans; Hypercholesterolemia; Phytosterols; Surveys and Questionnaires; Young Adult

To assess the effectiveness (extent to which an intervention works in daily medical practice) of the use of phytosterol/phytostanol-enriched margarines to lower total and non-HDL cholesterol levels in users and non-users of statins.. Retrospective cohort study.. Data were obtained from questionnaires on health and food intake from a population-based longitudinal cohort linked to pharmacy-dispensing records.. The analysis included 3829 men and women (aged 31-71 years) who were examined during 1998-2002 and re-examined at 5-year follow-up during 2003-2007.. Recommended doses of margarines were consumed by only 9 % of the subjects. Serum total cholesterol decreased by respectively -0·16 (95 % CI -0·26, -0·05) mmol/l, -1·40 (95 % CI -1·51, -1·30) mmol/l and -1·64 (95 % CI -1·91, -1·37) mmol/l in subjects who started to use phytosterols/phytostanols only, statins only or a combination of both compounds at some point in time between examination and re-examination, compared with subjects who did not start using phytosterols/phytostanols or statins. Cholesterol-lowering effects of the phytosterols/phytostanols were similar in statin users and statin non-users and increased with increasing intake of enriched margarine (no intake, 0; low intake, -0·017 (95 % CI -0·16, 0·13) mmol/l; medium intake, -0·089 (95 % CI -0·22, 0·038) mmol/l; high intake, -0·32 (95 % CI -0·50, -0·14) mmol/l).. Although recommended intake levels of the enriched margarines were not reached by all persons, these data show that under customary conditions of use phytosterols/phytostanols are effective in lowering cholesterol levels in both statin users and non-users.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Female; Follow-Up Studies; Food-Drug Interactions; Food, Fortified; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Linear Models; Longitudinal Studies; Male; Margarine; Middle Aged; Multivariate Analysis; Phytosterols; Retrospective Studies; Surveys and Questionnaires

The present study was conducted to investigate the efficacy of synthesized plant steryl and stanyl laurate in lowering the cholesterol level and to further examine the cholesterol-lowering potential of the free plant sterols and stanols dissolved in liquid emulsion on serum and liver lipids in mice by oral administration. Experimental results showed that both plant steryl and stanyl laurate could significantly decrease the serum levels of TC, LDL-C, LDL-C/HDL-C, and liver cholesterol contents and markedly increase fecal cholesterol concentrations but have no effect on serum TAG level, indicating that the produced plant steryl and stanyl laurate retained the cholesterol-lowering potential of natural plant sterols and stanols. However, no statistical difference in cholesterol-lowering efficacy was observed between plant steryl laurate and plant stanyl laurate, and free plant sterols and stanols dissolved in liquid emulsion could also significantly decrease serum cholesterol levels and markedly increase fecal cholesterol excretion. These results suggested that the esterified plant sterols/stanols had comparable effects to the free plant sterols/stanols in lowering serum TC levels but that they did gain a solubility advantage from the free plant sterols/stanols. Therefore, plant steryl/stanyl laurate could be considered as a potential nutraceutical or functional ingredient to reduce or prevent atherosclerosis and its related complications.

Topics: Administration, Oral; Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Disease Models, Animal; Humans; Hypercholesterolemia; Male; Mice; Phytosterols; Sitosterols

Plant sterols such as sitosterol and campesterol are frequently applied as functional food in the prevention of atherosclerosis. Recently, it became clear that plasma derived plant sterols accumulate in murine brains. We questioned whether plant sterols in the brain are associated with alterations in brain cholesterol homeostasis and subsequently with brain functions. ATP binding cassette (Abc)g5-/- mice, a phytosterolemia model, were compared to Abcg5+/+ mice for serum and brain plant sterol accumulation and behavioral and cognitive performance. Serum and brain plant sterol concentrations were respectively 35-70-fold and 5-12-fold increased in Abcg5-/- mice (P<0.001). Plant sterol accumulation resulted in decreased levels of desmosterol (P<0.01) and 24(S)-hydroxycholesterol (P<0.01) in the hippocampus, the brain region important for learning and memory functions, and increased lanosterol levels (P<0.01) in the cortex. However, Abcg5-/- and Abcg5+/+ displayed no differences in memory functions or in anxiety and mood related behavior. The swimming speed of the Abcg5-/- mice was slightly higher compared to Abcg5+/+ mice (P<0.001). In conclusion, plant sterols in the brains of Abcg5-/- mice did have consequences for brain cholesterol metabolism, but did not lead to an overt phenotype of memory or anxiety related behavior. Thus, our data provide no contra-indication for nutritional intake of plant sterol enriched nutrition.

Topics: Affect; Animals; Anxiety Disorders; Atherosclerosis; ATP-Binding Cassette Transporters; Behavior, Animal; Brain; Cholesterol; Desmosterol; Diet; Hippocampus; Homeostasis; Hydroxycholesterols; Hypercholesterolemia; Intestinal Diseases; Lanosterol; Lipid Metabolism, Inborn Errors; Male; Maze Learning; Memory; Mice; Mice, Mutant Strains; Phytosterols; Sitosterols; Stigmasterol

Phytosterolemia is a rare autosomal recessive lipid storage disease. It is caused by mutations of ABCG5 and ABCG8 genes and characterized by the increased plasma levels of plant sterols. The common clinical manifestations include tendon and tuberous xanthomas and premature coronary heart disease; it has occasionally been associated with hematologic abnormalities.. We report a phytosterolemia patient presenting exclusively with macrothrombocytopenia and stomatocytic hemolysis and discuss its clinical significance.. The patient, aged 31 years, was born of a consanguineous marriage. He had epistaxis from childhood and underwent splenectomy because of thrombocytopenia, anemia and splenomegaly at the age of 9 years. His blood film showed prominent stomatocytes and macroplatelets. High performance liquid chromatography showed a grossly elevated level of phytosterols in the blood. The patient was confirmed to be a homozygote of missense mutation R419H in ABCG5.. We describe a phytosterolemia patient whose clinical manifestations were macrothrombocytopenia, stomatocytic hemolysis and splenomegaly, without the common features of this disorder. Our results suggest that blood cells could be a target for the toxic effect of plasma plant sterols, which should be measured in patients with unexplained stomatocytosis and/or macrothrombocytopenia in order to determine if they have phytosterolemia.

Topics: Adult; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP-Binding Cassette Transporters; Blood Platelets; Cell Size; Consanguinity; Erythrocytes, Abnormal; Hemolysis; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation, Missense; Phytosterols; Splenomegaly; Thrombocytopenia

To study the clinical features and ABCG5/ABCG8 gene mutations of three pedigrees of phytosterolemia presented with macrothrombocytopenia and hemolysis.. Erythrocyte and platelet morphology were examined under light microscope. Plasma sterol levels were measured by high pressure/performance liquid chromatography method. All of ABCG5 and ABCG8 exons and intron-exon boundaries were directly sequenced to identify mutations, the corresponding gene mutation sites of three families members and healthy individuals were detected.. All the patients presented macrothrombocytopenia, hemolysis, splenomegaly and xanthomas. The blood smears showed large platelets, some as large as erythrocytes, and abnormal erythrocyte shapes, such as stomatocytes. Plasma concentrations of phytosterols, especially sitosterol were markedly elevated (30 fold) in the affected patients. Four mutations were identified in these three pedigrees, ABCG5 C20896T (R446X) and A20883G, ABCG8 del43683-43724 and del1938C-1939G/ins1938T. The latter three were novel mutations reported for the first time.. Phytosterolemia associated with macrothrombocytopenia and hemolysis is a new subtype of this disease. Plasma phytosterols and related gene analysis should be performed when ever an unexplained macrothrombocytopenia, especially combined with haemolysis or/and stomatocytosis.

Topics: Adult; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Blood Platelets; DNA Mutational Analysis; Erythrocytes, Abnormal; Female; Hemolysis; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Mutation; Pedigree; Phytosterols; Platelet Count; Thrombocytopenia

Topics: Anticholesteremic Agents; Azetidines; Blood Pressure; Cholesterol, Dietary; Dietary Proteins; Ezetimibe; Female; Humans; Hypercholesterolemia; Hypertension; Lipid Metabolism; Male; Milk Proteins; Phytosterols; Soybean Proteins

Mutations in ABCG5 or ABCG8 transporters are responsible for sitosterolemia, an autosomal recessive disease characterized by the accumulation of plant sterols. The aim of this study was to investigate the effects of ABCG5 and ABCG8 deficiency on TG metabolism in mice. Experiments were carried out in wild-type (G5/G8+/+) mice, mice heterozygous for ABCG5 and ABCG8 deficiency (G5/G8+/-) and ABCG5/G8-deficient (G5/G8-/-) mice fed a chow diet. Plasma TG were 2.6 and 4.3-fold higher in fasted G5/G8+/- and G5/G8-/- mice, respectively, than in G5/G8+/+ mice. Postprandial TG were 5-fold higher in G5/G8-/- mice. TG metabolism studies indicate that: first, the fractional catabolic rate was significantly lower in G5/G8+/- (1.3-fold) and G5/G8-/- mice (1.5-fold) compared to G5/G8+/+ and postheparin plasma lipoprotein lipase activities were significantly lower in G5/G8+/- (1.8-fold) and G5/G8-/- mice (5.4-fold) than in G5/G8+/+. Second, liver TG secretion was 1.3-fold higher in G5/G8+/- and G5/G8-/- than in G5/G8+/+ mice and this was associated with an increase in liver LXR, FAS, ACAC and CD36 gene expression. Third, TG intestinal secretion, determined after an oral fat gavage of glycerol tri[9,10(n)-(3)H] oleate, was 5.8-fold higher in G5/G8-/- than in G5/G8+/+ mice. Also, the HOMA index was 2.6-fold higher in G5/G8-/- than in G5/G8+/+ mice, reflecting a degree of insulin resistance. In conclusion, ABCG5/G8 deficiency in mice fed a chow diet markedly raises TG levels by impairing TG catabolism and by increasing liver and intestinal TG secretion.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Biological Transport; CD36 Antigens; fas Receptor; Fasting; Gene Expression; Heterozygote; Homozygote; Hypercholesterolemia; Hypertriglyceridemia; Intestinal Diseases; Intestinal Mucosa; Intestines; Lipid Metabolism, Inborn Errors; Lipoproteins; Liver; Liver X Receptors; Metabolic Networks and Pathways; Mice; Mice, Knockout; Orphan Nuclear Receptors; Phytosterols; Postprandial Period; Triglycerides

Topics: Anticholesteremic Agents; Dietary Supplements; Drug Interactions; Humans; Hydroxycholesterols; Hypercholesterolemia; Phytosterols

The aim of the paper was to describe a new formula (Antilip®) consisting of very low dosages of polyglucosamine, phytosterols and Monascus purpureus. It was given to subjects affected by high cholesterol levels.. The formula was used in combination with mild physical exercise (8 MET/h/week) and mild diet (reduction of cholesterol intake through foods containing <80 mg/100 g). The product combination was tested in an 8-week registry study, comparing those subjects to 33 subjects with no Antilip® treatment but following the same mild exercise training and diet.. Results showed that Antilip® was effective in significantly reducing the total cholesterol levels from 268+/-23.2 to 201+/-11.4, whereas in the control group the reduction was almost absent (from 273+/-27 to 267+/-28).. Data shows that Antilip® is a safe and effective treatment for hypercholesterolemia.

Topics: Acetylglucosamine; Adult; Aged; Cholesterol; Diet; Exercise; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Monascus; Phytosterols; Plant Extracts; Registries; Treatment Outcome

Phytosterolemia is one of the genetic disorders causing hypercholesterolemia and atherosclerosis together with the accumulation of plant sterol in plasma and tissues. The mutations in ABCG5 and ABCG8 genes, encoding sterolin-1 and -2, respectively, are responsible for phytosterolemia.. We performed genetic analyses on 2 Japanese phytosterolemia patients.. We identified 2 mutations in the ABCG5 gene in these patients. The first patient was homozygous for a novel mutation, which was a 19-base pair tandem repeat insertion in exon 7, leading to a premature termination at codon 288. The second patient was a compound heterozygote; one of the mutations was the same as that found in the first patient, while the other mutation was a C to T substitution in exon 10, resulting in a premature termination at codon 446 (R446X). No other mutation was found in the ABCG5 and ABCG8 genes.. This result was concordant with previous observations that found most Asian phytosterolemia patients possessed mutations in the ABCG5 gene, and the site of the novel mutation was completely different from these previous reports, necessitating the extensive analyses for phytosterolemia.

Topics: Adult; Atherosclerosis; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Exons; Female; Humans; Hypercholesterolemia; Lipoproteins; Middle Aged; Mutation; Phytosterols

Topics: Cardiovascular Diseases; Cholesterol, LDL; Dietary Fats; Dietary Supplements; Female; Food, Fortified; Humans; Hypercholesterolemia; Life Style; Male; Nonprescription Drugs; Phytosterols; Phytotherapy; Practice Guidelines as Topic

Phytosterols reduce cholesterol absorption and low-density lipoprotein cholesterol concentrations, but the quantity and physiological significance of phytosterols in common diets are generally unknown because nutrient databases do not contain comprehensive phytosterol data. The primary aim of this study was to design prototype phytosterol-deficient and high-phytosterol diets for use in controlled feeding studies of the influence of phytosterols on health. A second aim was to quantify the phytosterol content of these prototype diets and three other diets consumed in the United States. This study was conducted from June 2001 to September 2008 and involved designing, preparing, and then analyzing five different diets: an experimental phytosterol-deficient control diet, a relatively high-phytosterol diet based on the Dietary Approaches to Stop Hypertension diet, American Heart Association diet, Atkins lifetime maintenance plan, and a vegan diet. A single day of meals for each diet was homogenized and the resulting composites were analyzed for free, esterified, and glycosylated phytosterols by gas chromatography. Independent samples t tests were used to compare the diets' total phytosterol content. The total phytosterol content of the experimental phytosterol-deficient diet was 64 mg/2,000 kcal, with progressively larger quantities in Atkins, American Heart Association, vegan, and the high-phytosterol Dietary Approaches to Stop Hypertension diet (163, 340, 445, and 500 mg/2,000 kcal, respectively). Glycosylated phytosterols, which are often excluded from phytosterol analyses, comprised 15.9%+/-5.9% of total phytosterols. In summary, phytosterol-deficient and high-phytosterol diets that conform to recommended macronutrient guidelines and are palatable can now be used in controlled feeding studies.

Topics: Cholesterol, Dietary; Chromatography, Gas; Diet, Carbohydrate-Restricted; Diet, Sodium-Restricted; Diet, Vegetarian; Dose-Response Relationship, Drug; Food Analysis; Humans; Hypercholesterolemia; Patient Satisfaction; Phytosterols; Taste

To study patterns of phytosterol intakes in the Irish population from enriched sources.. An interview-assisted questionnaire, which recorded information on sociodemographics, product types, intake amounts and patterns of intake. Independent samples t tests, one-way ANOVA and cross-tabulations were used to establish significant relationships between groups of variables. The top tertile of phytosterol intakes was also calculated.. Point-of-purchase of phytosterol-enriched products in Irish supermarkets.. Four hundred and sixty-eight consumers (186 men and 282 women) of phytosterol-enriched foods.. The mean phytosterol intake from enriched sources for the sample population was 2.45 g/d. Men had greater intakes than women (2.71 g/d v. 2.29 g/d, respectively). A total of 62 % of consumers were unaware of the importance of consuming fruit and vegetables while taking these products. The majority of respondents reported that they had high cholesterol (61 %) and 22 % of consumers also took cholesterol-lowering medication (statins). In total, 23 % had phytosterol intakes >3.0 g/d and the majority of consumers (58 %) had been consuming these products for >1 year. The mean intake for respondents with phytosterol intakes >3.0 g/d was 4.1 g/d and 74 % of this subgroup had been consuming these products for >1 year.. In general, phytosterol intakes are within efficacious levels in the Irish population. However, there appears to be a subgroup that has been consuming these products at intakes greater than current recommendations for >1 year.

Topics: Adult; Analysis of Variance; Diet; Female; Food, Fortified; Humans; Hypercholesterolemia; Ireland; Male; Phytosterols; Surveys and Questionnaires

The role of statins in secondary prevention of cardiovascular disease is well established. However, there is debate about the most effective approach to primary prevention. This study simulated the effects of directed versus global approaches for intervention on coronary heart disease (CHD) event rates.. A primary prevention population was generated by computer simulation derived from data from the National Health Survey for England. The efficacy of reductions in cholesterol, treatment to cardiovascular risk targets and effects of phytosterols or statins were assessed.. A 0.5 mmol/L reduction in population total cholesterol would result in a 10.4% reduction in CHD events, while 1.0 mmol/L, 1.5 mmol/L and 2.0 mmol/L reductions would achieve 21.0%, 30.6% and 41.9% reductions respectively. In statin-based cardiovascular risk targeted strategies, use of simvastatin 40 mg would result in 1.8% reduction by UK National Service Framework targets of 30%/decade CHD risk and 7.2% reduction in events for a 20%/decade target assuming perfect adherence. Similarly, aggressive primary prevention with 40 mg atorvastatin would result in a 2.5% or 10% reduction in events. Universal use of 10 mg simvastatin following an over-the-counter approach would result in a 25% reduction in CHD events. In contrast, whole population consumption of sitostanol/sitosterol products would result in 11.8% reduction.. Targeting and treating high-risk individuals may be beneficial for them and rewarding for medical practitioners. However, this approach has minimal effects on the population burden of atherosclerotic disease. This study suggests that universal therapy with phytosterols and/or wider availability of statins has the potential to dramatically decrease rates of CHD.

Topics: Anticholesteremic Agents; Cholesterol; Computer Simulation; Coronary Disease; Cost-Benefit Analysis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Nonprescription Drugs; Phytosterols; Primary Prevention; Risk Factors

Topics: Anticholesteremic Agents; Drug Therapy, Combination; Humans; Hypercholesterolemia; Nonprescription Drugs; Phytosterols; Vitamins

The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Topics: Cardiovascular Diseases; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Diet, Mediterranean; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Evidence-Based Medicine; Exercise; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Hypercholesterolemia; Life Style; Male; Micronutrients; Nutritional Physiological Phenomena; Osteoporosis, Postmenopausal; Phytosterols; Soybean Proteins; Trans Fatty Acids; Weight Loss

Topics: Cholesterol; Cholesterol, LDL; Dietary Supplements; Humans; Hypercholesterolemia; Phytosterols; Vitamins

Topics: Anticholesteremic Agents; Humans; Hypercholesterolemia; Phytosterols

A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods.. For 12 months, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (23 g/1000 kcal). Fifty-five subjects completed the study.. Over the 1 year, data on completers indicated small but significant reductions in hemoglobin (-1.5+/-0.6 g/l, P=0.013), hematocrit (-0.007+/-0.002 l/l, P<0.001), red cell number (-0.07+/-0.02 10(9)/l, P<0.001) and neutrophils (-0.34+/-0.13 10(9)/l, P=0.014). Mean platelet volume was also increased (0.16+/-0.07 fl, P=0.033). The increase in red cell osmotic fragility (0.05+/-0.03 g/l, P=0.107) did not reach significance.. These small changes in hematological indices after a cholesterol-lowering diet are in the direction, which would be predicted to reduce CHD risk. Further research is needed to clarify whether the changes observed will contribute directly or indirectly to cardiovascular benefits beyond those expected from reductions previously seen in serum lipids and blood pressure.

Topics: Adult; Aged; Aged, 80 and over; Cholesterol; Cholesterol, Dietary; Coronary Disease; Dietary Fiber; Erythrocyte Deformability; Female; Hematocrit; Humans; Hypercholesterolemia; Male; Middle Aged; Neutrophils; Phytosterols; Prunus; Risk Factors; Soybean Proteins

Studies on effectiveness of phytosterol/-stanol-enriched margarines in the community have received low priority. For postlaunch monitoring purposes including risk-benefit analyses, it is needed to investigate both exposure and effectiveness of these margarines.. To study the use and effectiveness of phytosterol/-stanol-enriched margarine.. The study population consisted of 2379 subjects that participated in a community intervention study ('Hartslag Limburg') aged 28-76 years. In 1998 and 2003, blood samples for total and high-density lipoprotein (HDL) cholesterol were obtained. A general questionnaire and food frequency questionnaire (FFQ) were administered. From 1999 onwards, phytosterol/-stanol-enriched margarines were introduced on the Dutch market. On the basis of 2003 data, subjects were classified in users of (a) phytosterol/-stanol-enriched margarine, (b) cholesterol-lowering drugs, (c) the combination (both enriched margarine and drugs) and (d) neither enriched margarines nor cholesterol-lowering drugs.. Mean (+/-s.d.) daily intake of phytosterol-enriched margarine (n=99) and phytostanol-enriched margarine (n=16) was 14+/-9 g. From 1998 to 2003, total serum cholesterol concentration changed significantly different among the four groups: in the combination users -2.04+/-1.50 mmol/l (-29%), in cholesterol-lowering drug users -1.09+/-1.17 mmol/l (-17%), in the enriched margarine users -0.24+/-0.75 mmol/l (-4%) and in non-users +0.10+/-0.72 mmol/l (+2%)(P<0.05).. Recommended doses are not consumed, but phytosterol/-stanol-enriched margarines can modestly reduce serum total cholesterol in the community. These margarines cannot equal the effect of cholesterol-lowering drugs, but may act additively. Further investigation of the health effects that may occur during simultaneous cholesterol lowering drugs and phytosterol-or -stanol-enriched margarines usage is important, as well as community education about the cholesterol lowering foods and drugs.. Netherlands Organization for Health Research and Development (ZonMW) (data collection of Hartslag Limburg and further data- analyses).

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Diet; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Margarine; Middle Aged; Phytosterols; Product Surveillance, Postmarketing; Risk Assessment; Sitosterols; Surveys and Questionnaires; Time Factors

The hypolipidaemic effects of plant sterols are well established. However, mechanisms by which plant sterols lower plasma cholesterol levels, particularly at the molecular level, have not been clearly elucidated. The objective of the present study was to determine whether different plant sterol analogues reduce plasma cholesterol levels by up regulating the sterol transporters ABCG5 and ABCG8 in the liver and/or small intestine. Male Golden Syrian hamsters were divided into eight groups. Groups 1 and 2 were fed a maize starch-casein-sucrose-based diet that did not contain cholesterol (control; Con) or the Con diet with the addition of 0.25 % cholesterol (Ch-Con). Groups 3-8 were fed the Ch-Con diet supplemented with 1 % plant sterols, 1 % plant stanols, 1 % of a plant sterol and stanol mixture (50:50), 1.76 % plant sterol-fish oil esters, or 0.71 or 1.43 % stanol-ascorbic acid esters, respectively. After 5 weeks, the Ch-Con diet up regulated the ABCG5 mRNA expression and tended (P = 0.083) to increase ABCG8 mRNA expression in the liver, but did not affect both genes' expression in the small intestine compared with the Con diet. Hamsters fed 0.7 % stanol esters showed lower plasma cholesterol levels (P < 0.001) and also lower liver ABCG5 mRNA expression (P < 0.05) compared with the Ch-Con diet. Plant stanols, stanol esters, and sterol esters did not affect the ABCG5 or ABCG8 mRNA expressions in the liver and intestine although they reduced plasma cholesterol levels. These results suggest that plant sterols and their derivatives reduce plasma cholesterol levels independently from the mRNA expression of ABCG5 and ABCG8 transporters.

Topics: Animals; ATP-Binding Cassette Transporters; Body Weight; Cholesterol; Cholesterol, HDL; Cricetinae; Diet; Eating; Hypercholesterolemia; Intestine, Small; Liver; Male; Mesocricetus; Phytosterols; Up-Regulation

Atherosclerotic lesions are characterized by an accumulation of inflammatory cells and lipids. Osteopontin (OPN) is a cell-binding phosphoprotein, and it seems to promote the development of atherosclerosis. The purpose of our study was to find out whether plasma levels of OPN are associated with cholesterol metabolites in plasma or tissues.. Forty-three normal or mildly hypercholesterolaemic subjects, aged 31 to 69, were studied. The plasma level of OPN correlated negatively with muscle lathosterol (r = -0.52, P < 0.0001) and with the muscle lathosterol to muscle cholesterol ratio (r = -0.48, P = 0.001). Lathosterol concentrations in muscle (P = 0.003) and in relation to cholesterol (P = 0.005) were also significantly different among the OPN tertiles. OPN correlated negatively and significantly with muscle lathosterol in men (r = -0.58, P = 0.001, n = 29) but not in women (r = -0.21, P = 0.48, n = 14). Correspondingly, it also correlated negatively and significantly with the muscle lathosterol to muscle cholesterol ratio (r = -0.60, P = 0.001) in men but not in women (r = -0.13, P = 0.65). Plasma levels of OPN had a non-significant inverse correlation with plasma lathosterol and the plasma lathosterol to plasma cholesterol ratio. Plasma OPN concentrations were not related to plant sterols, cholesterol and 27-hydroxycholesterol.. Tissue markers of cholesterol synthesis were related to plasma OPN, particularly in men. This suggests that there is interplay between OPN and cholesterol metabolism in human cells.

Topics: Adult; Aged; Analysis of Variance; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Enzyme-Linked Immunosorbent Assay; Female; Finland; Humans; Hydroxycholesterols; Hypercholesterolemia; Male; Middle Aged; Muscle, Skeletal; Osteopontin; Phytosterols; Severity of Illness Index; Sex Factors; Triglycerides

Topics: Cholesterol, HDL; Cholesterol, LDL; Food, Fortified; Humans; Hypercholesterolemia; Phytosterols; Sitosterols

Topics: Absorption; Animals; Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Disease Models, Animal; Humans; Hypercholesterolemia; Intestinal Mucosa; Lipoproteins; Membrane Proteins; Membrane Transport Proteins; Phytosterols; Randomized Controlled Trials as Topic

Cyclosporine-induced hypercholesterolemia is a major concern after solid organ transplantation. Reducing this side effect of cyclosporine by dietary agents may be safe, cost-effective, and attractive to both patients and health professionals.. In this study, the interactions between dietary phytosterols (2% w/w) and cyclosporine (0.02% w/w) in regard to blood cyclosporine concentrations, lipoprotein profile, and histological and morphometrical features of atherosclerotic lesions were studied over 14 weeks in apolipoprotein E-knockout mice.. Cyclosporine alone increased plasma non-HDL cholesterol, and triglyceride concentrations and reduced HDL-cholesterol levels as compared to controls. However, these changes were not associated with further increases in atherogenesis as compared to controls. Unlike cyclosporine, phytosterols reduced non-HDL cholesterol and atherosclerosis, and increased HDL-cholesterol concentrations, as compared to the control group. The addition of dietary phytosterols to cyclosporine reduced the extent of cyclosporine-induced hypercholesterolemia, but not cyclosporine-induced hypertriglyceridemia. The extent of atherosclerosis in the combination therapy group was significantly lower than that in the control group or cyclosporine-treated group. Blood cyclosporine concentrations were comparable between the two groups of cyclosporine-treated and the combination therapy groups at the end of the study.. This study suggests that simultaneous consumption of dietary phytosterols and cyclosporine may attenuate posttransplant hypercholesterolemia associated with the immunosuppressive cyclosporine. Additional studies are required to understand the mechanisms by which dietary phytosterols reduce cyclosporine-induced hypercholesterolemia.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Body Weight; Cyclosporine; Diet; Humans; Hypercholesterolemia; Immunosuppressive Agents; Lipids; Male; Mice; Mice, Knockout; Phytosterols; Transplants

Topics: Adult; Aged; Aged, 80 and over; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Erythrocytes; Fatty Acids; Female; Glycated Hemoglobin; Humans; Hypercholesterolemia; Insulin; Male; Middle Aged; Phytosterols; Phytotherapy; Randomized Controlled Trials as Topic; Treatment Outcome

Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods.. Our aims were to determine the effectiveness of consuming a combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin.. For 12 mo, 66 hyperlipidemic participants were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin.. At 3 mo and 1 y, mean (+/-SE) LDL-cholesterol reductions appeared stable at 14.0 +/- 1.6% (P < 0.001) and 12.8 +/- 2.0% (P < 0.001), respectively (n = 66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n = 21 of 66) had LDL-cholesterol reductions of >20% at 1 y (x +/- SE: -29.7 +/- 1.6%). The LDL-cholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r = -0.42, P < 0.001). Only 2 of the 26 participants with <55% compliance achieved LDL-cholesterol reductions >20% at 1 y.. More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Cholesterol, Dietary; Cholesterol, LDL; Combined Modality Therapy; Dietary Fiber; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Patient Compliance; Phytosterols; Prunus; Soybean Proteins; Treatment Outcome

Topics: Allylamine; Azetidines; Cholesterol, LDL; Cholinergic Antagonists; Colesevelam Hydrochloride; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Niacin; Phytosterols

Hypercholesterolaemia is one of the main factors contributing to the appearance and progression of CVD, which is the main cause of death in the adult population of industrialized societies. By 2020, projections suggest that it will continue to hold first place, by then causing 37 % of all deaths. Therapeutic life-style changes to reduce cardiovascular risk include dietary modifications, such as the inclusion of phytosterols or plant sterols (known since the 1950s to reduce cholesterol levels). These help prevent the absorption of cholesterol and thus condition a reduction in total cholesterol and LDL-cholesterol levels, and ultimately in cardiovascular mortality. The fat-soluble nature of these sterols rendered margarine one of the best vehicles by which to supply them in the diet. Indeed, margarine was the first food to contain cholesterol-reducing phytosterols to be approved by the EU (in agreement with its regulations on new foods and food ingredients, 258/97/CE). Presently, phytosterols can be emulsified with lecithin and thus delivered in non-fat or low-fat foods and beverages. Margarine and dairy products (yoghurt and milk) enriched in phytosterols have proved better at lowering total cholesterol and LDL-cholesterol levels than have enriched cereals and their derivatives, although all can be of help, depending on the characteristics of each subject. The reduction in carotenoid bioavailability caused by sterols is minimized by increasing fruit and vegetable consumption. Individuals who habitually consume phytosterols should also follow traditional advice such as eating less dietary fat and increasing their physical activity. Phytosterols have been shown to be safe and effective in lowering cholesterol levels in many rigorous studies. In few areas of nutrition is there such consensus. Diet professionals should feel comfortable in prescribing phytosterols/stanols for the treatment of hypercholesterolaemia. They are safe whether taken alone or in combination with cholesterol-reducing drugs, such as statins and fibrates. Reinforcement counselling is essential, as therapy is effective only if compliance is good.

Topics: Adult; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Combined Modality Therapy; Diet; Humans; Hypercholesterolemia; Lipid Metabolism; Margarine; Nutrition Policy; Phytosterols; Risk; Safety; Yogurt

Plant sterols are widely distributed in human diet but are poorly absorbed so that their plasma levels are very low. However, when fed in large amounts, they lower plasma cholesterol levels by interfering with cholesterol absorption. We have studied the effect of 4 weeks of feeding a chow diet supplemented with 1% plant sterols [brassicasterol (6.3%), campesterol (28.5%), stigmasterol (15.6%) and sitosterol (49.6%)], with or without SCH 58235 (a derivative of ezetimibe), 30 mg/kg per day, known to suppress intestinal cholesterol absorption, on plasma, tissue, biliary, and fecal sterols in Wistar and wild-type Kyoto (WKY) rats, and their metabolism by intestinal bacteria.. After 2 weeks of feeding control or experimental diet, rats were given [3alpha-(3)H]sitosterol intravenously and [4-(14)C]sitosterol by mouth, and blood was collected after 1, 2, 3, and 5 days after labeling to determine sitosterol absorption. Feces were collected during the last 3 days and freeze dried. At the end of feeding, bile fistulas were created in 3 rats of each strain and bile was collected for 1 hour. All rats were then sacrificed and plasma and liver were collected for sterol measurements and activities of hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and cholesterol 27-hydroxylase.. Wild-type Kyoto rats were hypercholesterolemic compared to Wistar rats and had increased plant sterols in the plasma. Plasma cholesterol tended to be lower in WKY rats after feeding with plant sterol-enriched diet whereas plant sterol levels rose to approximately 31% of plasma sterols in WKY and 14% in Wistar rats. However, brassicasterol and stigmasterol, with a double bond at C-22, constituted less than 3.5% of total plasma plant sterols. After feeding, biliary plant sterols increased 2.25-fold in Wistar and 1.5-fold in WKY rats, suggesting less hepatic clearance in WKY rats. SCH 58235 feeding significantly increased plasma as well as biliary cholesterol levels in both the untreated and plant sterol-fed WKY rats, and the plasma plant sterols showed a tendency to increase but did not reach significant level. Intestinal bacteria in both rat strains metabolized all plant sterols to mainly the 5beta-H-stanols. However, the C-22 double bond was stable to bacterial degradation. Intestinal absorption of sitosterol and cholesterol was increased 1.5- and 1.3-fold, respectively, in the WKY rats as compared to the Wistar rats, and plant sterol feeding lowered absorption of these sterols in both strains. Absorption of both these sterols was also lowered in SCH 58235-treated rats in both strains and was further lowered when SCH 58235 and plant sterols were simultaneously fed. The activity of the rate-limiting enzyme, HMG-CoA reductase, was increased 1.57-fold in Wistar rats and 1.27-fold in WKY rats that were fed plant sterols as compared to untreated rats.. (1) Plant sterol absorption was increased whereas hepatic elimination of all sterols was diminished in WKY rats accounting for elevated cholesterol and plant sterol levels. (2) The 1% plant sterol-enriched diet tended to lower plasma cholesterol levels whereas SCH 58235 feeding significantly increased plasma cholesterol levels in the WKY rats. (3) Intestinal absorption of sterols with C-22 double bond is diminished and the side-chain double bond is resistant to intestinal bacteria.

Topics: Animals; Azetidines; Cholesterol; Diet; Ezetimibe; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Intestinal Absorption; Male; Phytosterols; Rats; Rats, Inbred WKY; Rats, Wistar; Species Specificity

The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery.. We prospectively investigated the effects of the bilio-intestinal bypass (BI-bypass) with a wide cholecysto-jejunal anastomosis and of adjustable gastric banding (AGB) on blood lipid concentrations in obese patients. To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass, daily fecal sterol excretion was measured by gas-liquid chromatography (GLC).. At 1 year after BI-bypass compared to baseline, the hypercholesterolemic (n=18) and the normocholesterolemic (n=19) patients significantly reduced total (-38% and -27%, respectively), LDL (-47% and -24%, respectively) and HDL (-11% and -13%, respectively) cholesterol and total / HDL cholesterol ratio (-25% and -13%, respectively). At 1 year after AGB, the total / HDL cholesterol ratio was significantly decreased (-11%) compared to baseline in hypercholesterolemic (n=12) but not in normocholesterolemic (n=6) patients, while total and LDL cholesterol were not affected in both groups. At 3 years after BI-bypass compared to baseline, the hypercholesterolemic (n=9) and the normocholesterolemic (n=11) patients significantly reduced total (-43% and -28%, respectively) and LDL (-53% and -29%, respectively) cholesterol and total / HDL cholesterol ratio (-38% and -21%, respectively). The BI-bypass induced a significant (P <0.005; n=7) 6-fold increase in mean fecal cholesterol output.. The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output. BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia.

Topics: Adult; Bile Acids and Salts; Biliopancreatic Diversion; Cholestanol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Feces; Female; Follow-Up Studies; Gastric Bypass; Humans; Hypercholesterolemia; Jejunoileal Bypass; Male; Obesity, Morbid; Phytosterols; Prospective Studies; Triglycerides

Topics: Anticholesteremic Agents; Cholesterol; Consumer Product Safety; Food, Fortified; Humans; Hypercholesterolemia; Insurance, Health, Reimbursement; Netherlands; Phytosterols

A blood cholesterol-lowering margarine containing plant sterolesters was the first functional food placed on the European food market pursuant to the regulation (EC) 258/97. In the following years nine further applicants submitted the request to add plant sterol compounds to dairy products, cheeses, bakery products, sausages, plant oils and other products. The European Scientific Committee on Food (SCF) declared a precautionary intake limit of 3 g plant sterols per d by multiple dietary sources. Using the consumption data of the German National Food Consumption Study, carried out from 1985 to 1988 with 23 209 participants, we hypothetically added 0.3-2 g plant sterols to usual daily servings of ten different food products, selected from the novel food applications. We calculated the prospective plant sterol intake regarding each kind of enriched food and by stepwise accumulation of different functional foods in three enrichment scenarios. Within our enrichment context we find a phytosterol intake satiation, if multiple plant sterol-enriched foods are eaten. An enrichment amount of 2 g plant sterols per proposed food serving size results in an intake maximum of 13 g/d.

Topics: Dairy Products; Diet; Food, Fortified; Germany; Humans; Hypercholesterolemia; Maximum Allowable Concentration; Meat Products; Models, Biological; Phytosterols

Plant stanol esters provide a novel approach to lowering plasma low-density lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by a long period of research into the cholesterol-lowering properties of plant sterols and, recently, plant stanols. Both classes of compound competitively inhibit the absorption of cholesterol and thus lower its level in plasma. Initial impressions were that stanols were more effective and safer than sterols, but the negative outcome of a study led to the recognition that the lipid solubility of free stanols was very limited. This was overcome by esterifying them with fatty acids, with the resultant stanol esters being freely soluble in fat spreads. This led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995. The coincident publication of the year-long North Karelia study conclusively demonstrated the long-term LDL-lowering efficacy of plant stanol esters. Variables that might influence the efficacy of stanol esters include dose, frequency of administration, food vehicle in which the stanol ester is incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol by 6% to 15%. This effect is maintained, appears to be similar with once-daily or divided dosage, and is independent of the fat content of the food vehicle. Short-term studies suggest that equivalent amounts of plant sterol and stanol esters are similarly effective in lowering LDL, the main difference being that plasma plant sterol levels increase on plant sterols and decrease on plant stanols. The clinical significance of these changes remains to be determined.

Topics: Adsorption; Cholesterol, LDL; Diet; Drug Administration Schedule; History, 20th Century; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Plant Extracts; Sitosterols

Cholesterol absorption is frequently determined using the plasma dual stable-isotope ratio method (PDSIRM). However, this method involves intravenous injection of stable-isotope-labeled cholesterol with simultaneous oral administration of differently labeled cholesterol, which results in high study costs and involves additional ethical considerations. The objective of the present study was to validate a simpler single-isotope method for determining cholesterol absorption against PDSIRM by using data from two previous studies. Enrichments of carbon-13 (13C and deuterium in red blood cells were analyzed by using differential isotope ratio MS. The area under the curve of 13C-enrichment in the plasma free-cholesterol pool was found to be significantly correlated with cholesterol absorption measured by using PDSIRM for study 1 (r = 0.85, P < 0.0001) and study 2 (r = 0.81, P < 0.0001). Average 13C-enrichment correlated with the area under the curve of 13C-enrichment in the plasma free cholesterol for both study 1 (r = 0.98, P < 0.0001) and study 2 (r = 1.00, P < 0.0001). Study 1 examined the efficacy and mechanisms of unesterified plant sterols and stanols on lipid profiles in hypercholesterolemic men and women, while study 2 investigated the effects of phytosterol vs. phytostanol esters on plasma lipid levels and cholesterol kinetics in hyperlipidemic men. Experimental approaches to determine cholesterol absorption were identical between the two studies. Consequently, in both studies, correlations (r = 0.88, P < 0.0001 for study 1, and r = 0.82, P < 0.0001 for study 2) were found between the average 13C-enrichment of plasma free cholesterol and cholesterol absorption measured by PDSIRM. These results suggest that a single-isotope-labeled cholesterol tracer approach can be used as a reliable noninvasive method to replace PDSIRM for examining changes in cholesterol absorption.

Topics: Absorption; Adult; Area Under Curve; Carbon Radioisotopes; Cholesterol; Deuterium; Erythrocytes; Esters; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Hyperlipidemias; Kinetics; Lipids; Male; Middle Aged; Phytosterols; Reproducibility of Results

Niemann-Pick C1 Like 1 (NPC1L1) is a protein localized in jejunal enterocytes that is critical for intestinal cholesterol absorption. The uptake of intestinal phytosterols and cholesterol into absorptive enterocytes in the intestine is not fully defined on a molecular level, and the role of NPC1L1 in maintaining whole body cholesterol homeostasis is not known. NPC1L1 null mice had substantially reduced intestinal uptake of cholesterol and sitosterol, with dramatically reduced plasma phytosterol levels. The NPC1L1 null mice were completely resistant to diet-induced hypercholesterolemia, with plasma lipoprotein and hepatic cholesterol profiles similar to those of wild type mice treated with the cholesterol absorption inhibitor ezetimibe. Cholesterol/cholate feeding resulted in down-regulation of intestinal NPC1L1 mRNA expression in wild type mice. NPC1L1 deficiency resulted in up-regulation of intestinal hydroxymethylglutaryl-CoA synthase mRNA and an increase in intestinal cholesterol synthesis, down-regulation of ABCA1 mRNA, and no change in ABCG5 and ABCG8 mRNA expression. NPC1L1 is required for intestinal uptake of both cholesterol and phytosterols and plays a major role in cholesterol homeostasis. Thus, NPC1L1 may be a useful drug target for the treatment of hypercholesterolemia and sitosterolemia.

Topics: Animals; Biological Transport; Cholesterol; Cholesterol, Dietary; Homeostasis; Hypercholesterolemia; Intestinal Absorption; Intestinal Mucosa; Lipoproteins; Liver; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sitosterols; Triglycerides

Ezetimibe (Ezetrol), recently launched in Belgium by Merck Sharp& Dohme and Schering Plough, is presented as 10 mg tablets. It belongs to a new class of lipid-lowering agents that selectively inhibit the intestinal absorption of cholesterol and phytosterols. Its mechanism of action results in a synergistic cholesterol-lowering effect together with a statin that inhibits cholesterol synthesis by the liver. Ezetimibe, at a daily dose of 10 mg, is indicated, in combination with a statin, as adjuvant treatment to diet in patients with primary hypercholesterolaemia (homozygote or heterozygote familial form and non-familial polygenic form) not well controlled with a statin alone. In case of statin contra-indication or intolerance, ezetimibe can be used in monotherapy. Its tolerance profile is excellent. Statin-ezetimibe combination allows to significantly reduce total and LDL cholesterol levels and increases the percentage of hypercholesterolaemic patients who will reach the target levels recommended in the international guidelines against atherosclerosis. However, such a combination should still prove its efficacy in reducing cardiovascular morbidity and mortality in large prospective clinical trials.

Topics: Anticholesteremic Agents; Azetidines; Cardiovascular Diseases; Cholesterol; Drug Therapy, Combination; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Phytosterols; Treatment Outcome

Both plant sterols and lecithin are used as dietary supplements for lowering blood cholesterol in Western countries. This study evaluated the possibility of an additive effect of these ingredients on the regulation of lipid concentrations and cholesterol metabolism. Male Sprague-Dawley rats were randomly divided into three groups, and fed one of the following diets for 5 weeks; high cholesterol diet (HCD), phytosterol mixture-supplemented diet (PD, HCD+0.25% phytosterols), or phytosterol mixture and lecithin-supplemented diet (PLD, PD+0.15% lecithin). Feeding the PD for 5 weeks resulted in a 34% and 41% decrease in plasma total- and VLDL+LDL-cholesterol levels, respectively, and a 23% decrease in hepatic cholesterol content compared to those for the HCD rats (p < 0.05). These cholesterol-lowering properties of the phytosterol mixture were also associated with the down-regulation of hepatic acyl CoA:cholesterol acytransferase (ACAT) activity (p < 0.05). Addition of lecithin plus phytosterol mixture to the hypercholesterolemic diet did not significantly affect blood and hepatic lipid concentrations (with the exception of 36% decrease in hepatic triglyceride level, p < 0.05) as well as hepatic ACAT activity compared to feeding the hypercholesterolemic diet supplemented with phytosterol alone. These results indicate that combining lecithin, at a 0.15% level, with a phytosterol mixture-supplemented diet does not exhibit an additive effect in regulating hepatic ACAT activity or lowering blood cholesterol in hypercholesterolemic rats.

Topics: Animals; Cholesterol, Dietary; Dietary Supplements; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Male; Phosphatidylcholines; Phytosterols; Rats; Rats, Sprague-Dawley; Sterol O-Acyltransferase

Topics: Absorption; Cholesterol; Corn Oil; Humans; Hypercholesterolemia; Phytosterols

Topics: Anticholesteremic Agents; Diarrhea; Dietary Supplements; Food Additives; Humans; Hypercholesterolemia; Margarine; Phytosterols; Probiotics; Yogurt

Serum contains noncholesterol sterols, which are reliable markers of cholesterol metabolism, but their presence and importance in different lipoproteins have been insufficiently studied.. Serum and lipoprotein cholesterol precursors squalene, cholestanol, desmosterol and lathosterol (markers of cholesterol synthesis) and cholestanol and plant sterols (markers of cholesterol absorption), and absorption efficacy and absolute synthesis of cholesterol were studied at baseline and during 6-month atorvastatin (80 mg day(-1)) treatment by the sterol balance technique in men with type 2 diabetes.. At baseline, approximately 14% of serum squalene was transported by VLDL, 12% by IDL, 40% by LDL and 30% by HDL. The respective values for the noncholesterol sterols were approximately 8, 4, 61 and 26%. The squalene to cholesterol ratios were highest in VLDL and IDL, those of cholestanol, desmosterol and absorption marker sterols were gradually higher, and that of lathosterol lower from VLDL to HDL. Atorvastatin reduced LDL cholesterol by approximately 50%, decreased the absolute cholesterol synthesis and turnover by approximately 40%, but increased significantly the fractional and mass absorption of cholesterol. In accordance with the fecal data, the ratios of the precursor sterols to cholesterol were reduced (-50%), but those of squalene (+48%) and the absorption sterols increased (e.g. 2.6-fold for sitosterol) similarly in each lipoprotein, but progressively from VLDL to HDL.. Effective lowering of LDL cholesterol by large dose of statin is associated with decreased synthesis and turnover of cholesterol and increased fractional and mass absorption of cholesterol. These changes are detectable by noncholesterol sterols in serum and in different lipoprotein fractions.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Feces; Heptanoic Acids; Humans; Hypercholesterolemia; Intestinal Absorption; Lipids; Lipoproteins; Liver; Male; Middle Aged; Phytosterols; Pyrroles; Squalene

Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P < 0.05) and the MPS diet by 35% (P < 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rapeseed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.

Topics: Administration, Oral; Animals; Chemistry, Pharmaceutical; Cholesterol, Dietary; Fatty Acids, Monounsaturated; Female; Hypercholesterolemia; Hypolipidemic Agents; Intestinal Absorption; Lipid Peroxidation; Obesity; Phytosterols; Plant Oils; Powders; Rapeseed Oil; Rats; Rats, Zucker; Sitosterols

Topics: Dietary Supplements; Humans; Hypercholesterolemia; Phytosterols

The short-term cholesterol-lowering efficacy of plant stanol esters has been open to debate, and the data from different clinical studies with hypercholesterolemic subjects are variable, partly due to lack of systematic studies. Therefore, we investigated the time in days needed to obtain the full cholesterol-lowering effect of stanol esters in hypercholesterolemic subjects.. Eleven mildly to moderately hypercholesterolemic subjects consumed stanol ester margarine (2.0 g/day of stanols) as a part of their habitual diet for 14 days and the changes in serum lipid values were measured three times at 4, 8 and 15 days after the initiation of test margarine consumption (0 day). The returning of serum lipid concentrations to baseline was measured two times after 2 or 3 days and after 7 days of the end of the test margarine consumption.. Serum LDL cholesterol concentrations were reduced from 0 day (4.51 +/- 0.66 mmol/l) by 3.5% (P = ns), 9.9% (p < 0.05) and 10.2% (P < 0.05) at 4, 8 and 15 days, respectively. Serum campesterol/total cholesterol ratio, an indirect marker of intestinal cholesterol absorption, was significantly reduced on day 4 already. After ending the stanol ester use serum cholesterol concentrations began to return rapidly and after 7 days serum LDL cholesterol was 5.3% less than the initial value (P = ns).. The specific effect of plant stanol esters on serum LDL cholesterol can fully be obtained within 1-2 weeks of the use of plant stanol ester-enriched margarine.

Topics: Adult; Aged; Analysis of Variance; Anticholesteremic Agents; Biomarkers; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Female; Humans; Hypercholesterolemia; Lipids; Male; Margarine; Middle Aged; Phytosterols; Phytotherapy; Sitosterols; Time Factors

Low birth weight may be associated with high levels of cholesterol in later life through genetic factors that affect both birth weight and cholesterol metabolism. Alterations in cholesterol synthesis and absorption may play an important role in this association. We examined birth weight and plasma ratios of a precursor of cholesterol, lathosterol (an estimate of cholesterol synthesis), and plant sterols, campesterol and beta-sitosterol (estimates of cholesterol absorption), to cholesterol in 53 dizygotic and 58 monozygotic adolescent twin pairs. After adjustment for current weight, birth weight was not associated with the ratios of lathosterol, campesterol, and beta-sitosterol either in the overall sample [+0.07 micro mol/mmol/kg (95% confidence interval: -0.11 to 0.25), p = 0.5; +0.02 micro mol/mmol/kg (-0.33 to 0.37), p = 0.9; and -0.04 micro mol/mmol/kg (-0.23 to 0.15), p = 0.8, respectively] or in the intrapair analysis in dizygotic twins [+0.27 micro mol/mmol/kg (-0.28 to 0.82), p = 0.3; -0.03 micro mol/mmol/kg (-1.07 to 1.01), p = 1.0; and +0.04 micro mol/mmol/kg (-0.56 to 0.64), p = 0.9, respectively] or in the intrapair analysis in monozygotic twins [+0.54 micro mol/mmol/kg (-0.09 to 1.18), p = 0.09; -0.60 micro mol/mmol/kg (-1.59 to 0.39), p = 0.2; and -0.43 micro mol/mmol/kg (-0.99 to 0.14), p = 0.14, respectively]. Plasma levels of lathosterol, campesterol, and beta-sitosterol, which are indicators of cholesterol synthesis and absorption, thus do not explain the association of low birth weight with high levels of total and LDL cholesterol. As an alternative hypothesis, we suggest that a decrease in cholesterol clearance may play an important role.

Topics: Absorption; Adolescent; Biomarkers; Birth Weight; Cholesterol; Diseases in Twins; Female; Humans; Hypercholesterolemia; Infant, Low Birth Weight; Infant, Newborn; Male; Phytosterols; Risk Factors; Sitosterols; Twins, Dizygotic; Twins, Monozygotic

Plant sterols, soy proteins, and viscous fibers are advised for cholesterol reduction but their combined effect has never been tested. We therefore assessed their combined effect on blood lipids in hyperlipidemic subjects who were already consuming a low-saturated fat, low-cholesterol diet before starting the study. The test (combination) diet was 1 month in duration and was very low in saturated fat and high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), and viscous fibers (9 g/1,000 kcal) obtained from foods available in supermarkets and health food stores. One subject also completed 2 further diet periods: a low-fat control diet and a control diet plus 20 mg/d lovastatin. Fasting blood lipids, blood pressure, and body weight were measured prior to and at weekly intervals during the study. The combination diet was rated as acceptable and very filling. The diet reduced low-density lipoprotein (LDL)-cholesterol by 29.0% +/- 2.7% (P <.001) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol by 26.5% +/- 3.4% (P <.001). Near maximal reductions were seen by week 2. In the subject who took Mevacor and control diets each for 4 weeks, the reduction in LDL:HDL-cholesterol on Mevacor was similar to the combination diet. We conclude that acceptable diets of foods from supermarkets and health food stores that contain recognized cholesterol-lowering dietary components in combination (a dietary portfolio) may be as effective as the starting dose of older first-line drugs in managing hypercholesterolemia.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Cholesterol; Diet; Dietary Fiber; Female; Humans; Hypercholesterolemia; Lipids; Lipoproteins, LDL; Male; Middle Aged; Phytosterols; Plant Proteins, Dietary; Viscosity

Topics: Anticholesteremic Agents; Diet; Humans; Hypercholesterolemia; Phytosterols; Phytotherapy; Sitosterols

Used as a substitute for normal dietary intake of saturated fatty acids, margarines containing plant sterols can cause a modest reduction in serum total cholesterol and low-density lipoprotein cholesterol levels. They have been shown effective in patients with mild hypercholesterolemia, but they are also useful in the general population.

Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Coronary Disease; Costs and Cost Analysis; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Margarine; Phytosterols; Randomized Controlled Trials as Topic; Simvastatin; Sitosterols; Time Factors

The Food and Drug Administration (FDA) is authorizing the use, on food labels and in food labeling, of health claims on the association between plant sterol/stanol esters and reduced risk of coronary heart disease (CHD). FDA is taking this action in response to a petition filed by Lipton (plant sterol esters petitioner) and a petition filed by McNeil Consumer Healthcare (plant stanol esters petitioner). Based on the totality of publicly available evidence, the agency has concluded that plant sterol/stanol esters may reduce the risk of CHD.

Topics: Coronary Disease; Food Labeling; Humans; Hypercholesterolemia; Hypolipidemic Agents; Phytosterols; Risk Factors; United States; United States Food and Drug Administration

Topics: Animals; Blood Proteins; Diet; Fatty Acids; Hypercholesterolemia; Phytosterols; Protein Binding; Rats; Rats, Wistar

Serum noncholesterol sterols, cholesterol precursors and plant sterols, are indicators of cholesterol absorption and synthesis. Serum plant sterol concentrations correlate positively with cholesterol absorption, but have also been found to correlate with dietary unsaturated to saturated fatty acid ratios. We studied the concentration of serum noncholesterol sterols during four different fat-modified diets, (1) high-fat, saturated fat-enriched (control), (2) reduced-fat, sunflower oil-enriched (SO-enriched), (3) rapeseed oil-enriched (RO-enriched), and (4) reduced-fat, saturated fat-enriched (reduced-fat), followed for 6 months in hypercholesterolemic subjects in a parallel design. The proportion of lathosterol (micrograms per 100 mg cholesterol), a precursor of cholesterol synthesis, increased significantly (P < .05) in both SO-enriched (mean +/- SD 147 +/- 57 v 167 +/- 76, 0 v 6 months) and RO-enriched (147 +/- 54 v 157 +/- 52) groups, where the reduction in low-density lipoprotein (LDL) cholesterol was also significant. The proportion of sitosterol, a plant sterol, decreased significantly in the control group (137 +/- 48 v 122 +/- 42), and the proportion of another plant sterol, campesterol, increased in the RO-enriched group (280 +/- 141 v 333 +/- 162), reflecting changes in the use of vegetable oils in these two groups rather than increased cholesterol absorption. In the whole study population, the proportion of linoleic and alpha-linolenic acid (a marker of the use of RO) in cholesterol esters (CEs) correlated (P < .001) with the proportion of sitosterol (r = .43) and campesterol (r = .36) in serum at the end of the study. In conclusion, serum cholesterol precursors were found to be useful indicators of cholesterol metabolism, but changes in serum plant sterols reflected dietary changes rather than cholesterol metabolism during long-term dietary intervention with fat-modified diets.

Topics: Adult; Apolipoproteins E; Cholesterol; Dietary Fats; Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Osmolar Concentration; Phenotype; Phytosterols; Prodrugs; Sterols

Cholesterol and lipoprotein metabolism was studied in mildly hypercholesterolemic nonobese men with NIDDM to find out which metabolic parameters regulate serum cholesterol level in these NIDDM subjects.. Nonobese NIDDM subjects (n = 13) and control subjects (n = 18) with serum cholesterol > or = 6.0 and triglycerides < or = 2.5 mmol/l were studied on a similar monoene-enriched diet. Cholesterol absorption was studied with peroral double isotopes and by measuring serum plant sterols with gas-liquid chromatography; cholesterol synthesis was studied by measuring sterol balance and by measuring serum cholesterol precursor sterols; and LDL kinetics was measured with 131I-labeled autologous apoprotein (apo) B.. Cholesterol absorption was significantly lower in NIDDM subjects than in the control subjects, as detected by low serum plant sterol levels and absorption percentage (23 vs. 29%, P < 0.05). Cholesterol synthesis was significantly higher in NIDDM subjects than in the control subjects, as detected by precursor sterols or balance data (18 vs. 12 mg.kg-1.day-1, P < 0.01), cholesterol turnover (19 vs. 13 mg.kg-1.day-1, P < 0.01), and LDL apo B removal (0.343 vs. 0.267 pools/day, P < 0.01). Serum total and LDL cholesterol levels were inversely correlated with cholesterol synthesis, which was positively related to the catabolism of LDL apo B and negatively related to cholesterol absorption efficiency.. In this small selected group of mildly hypercholesterolemic nonobese NIDDM subjects, the regulation of serum cholesterol levels was achieved by the homeostasis between cholesterol absorption, synthesis, and LDL fractional catabolism. Cholesterol turnover and removal of LDL apo B were high in NIDDM subjects, compared with the control subjects, whereas cholesterol absorption efficiency was abnormally low Because of the relatively small number of selected subjects, the present results are not directly applicable to the overall NIDDM population.

Topics: Absorption; Apolipoproteins B; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Fats; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Reference Values

To study exogenous sterol metabolism during the suppression or stimulation of cholesterol biosynthesis induced by treatments for hyperlipidemia, we determined plasma plant sterol concentrations before and after administration of an HMG-CoA reductase inhibitor, pravastatin, and compared these with changes in these plasma sterol levels by the bile-sequestrating resin, cholestyramine. The effects of the drugs were also studied in a sitosterolemic patient who has had increased plasma levels of plant sterols. Plasma cholesterol levels determined by the HPLC method were decreased significantly after administration of pravastatin. Plasma plant sterol (sitosterol and campesterol) as well as cholestanol concentrations were also significantly reduced. Cholestyramine administration decreased plasma levels of cholesterol, but did not change those of plant sterols in the hypercholesterolemic subjects. Pravastatin had little effect in a sitosterolemic patient on plasma levels of sterols, where cholestyramine decreased the plasma levels of both cholesterol and cholestanol. These results indicate that treatment with the HMG-CoA reductase inhibitor decreases plasma plant sterol concentrations, and suggest that the increased plasma plant sterol levels in sitosterolemia might not be due to the decreased cholesterol biosynthesis in vivo.

Topics: Acyl Coenzyme A; Adult; Anticholesteremic Agents; Cholestyramine Resin; Chromatography, High Pressure Liquid; Enzyme Inhibitors; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Pravastatin

Rapeseed oil fed to 24 hypercholesterolemic patients (50 g/day) reduced serum cholesterol (-8.5%) and cholestanol concentrations but increased those of campesterol and sitosterol. Continuation of rapeseed oil alone or with added sitosterol (625 mg/day) or sitostanol (630 mg/day) had no further effect on serum cholesterol. Rapeseed oil with sitosterol increased further its own proportion to cholesterol in serum but reduced that of campesterol while rapeseed oil with sitostanol reduced the proportions of both sitosterol and campesterol proportionately to the pretreatment values. The changes in the campesterol and sitosterol proportions were negatively and positively related to each other during the sitosterol and sitostanol additions, respectively. Thus, concentrations of unsaturated plant sterols in serum reflect their dietary intakes, saturated plant sterols are virtually not absorbed, plant sterols interfere with absorption of unsaturated structurally different plant sterols and cholestanol, and plant sterol-induced reduction of sterol absorption may be positively related to absorption efficiency of sterols.

Topics: Adult; Body Weight; Brassica; Cholesterol; Dietary Fats; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Plant Oils; Sitosterols

The hypocholesterolaemic mechanism of activated charcoal was studied in seven patients with primary hypercholesterolaemia. The reduction of serum cholesterol was correlated with the serum concentrations of cholesterol precursors and of two plant sterols. Activated charcoal, 8 g t.i.d. for 4 weeks, reduced serum concentration of total cholesterol by 27% (P less than 0.01). The effect was accompanied by a moderate elevation (P less than 0.05) in serum squalene and desmosterol concentrations and by a marked increase (up to 300-700%) in serum lathosterol and delta 8 lathosterol concentrations. The levels of two plant sterols, campesterol and beta-sitosterol, were unchanged or only slightly decreased by the use of activated charcoal. The decrease of serum cholesterol concentration had significant negative correlations with serum lathosterol and delta 8 lathosterol, and significant positive correlations with serum cholestanol and beta-sitosterol. These observations suggest an increased cholesterol synthesis upon treatment with activated charcoal, probably caused by the interference with the enterohepatic circulation of bile acids.

Topics: Anticholesteremic Agents; Charcoal; Cholesterol; Desmosterol; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Sitosterols

Attempts were made to develop an animal model for phytosterolemia. Infusion of Intralipid containing 0.2% sitosterol in rats gave circulating levels of sitosterol of about 2.5 mmol/l, which is similar to or higher than those present in patients with untreated phytosterolemia. In addition, the infusions gave serum levels of cholesterol nearly twice those obtained in rats infused with Intralipid alone or Intralipid containing 0.2% cholesterol. The hepatic HMG-CoA reductase activity was unaffected or slightly increased by the sitosterol infusions (not statistically significant). The cholesterol 7 alpha-hydroxylase activity was slightly depressed (ca. 30%). In the case of 7 alpha-hydroxylation of endogenous cholesterol, the depression reached statistical significance (p less than 0.05). The microsomal content of sitosterol in the sitosterol-infused rats was about 30% of that of microsomal cholesterol. The effect of sitosterol on 7 alpha-hydroxylation of cholesterol was investigated by incubations of acetone powder of rat liver microsomes with mixtures of cholesterol and sitosterol. Sitosterol mixed with cholesterol to a composition similar to that found in the above microsomal fraction had a depressing effect on 7 alpha-hydroxylation of cholesterol. This degree of depression was of the same magnitude as that found in the sitosterol infusion experiments. The possibility is discussed that the hypercholesterolemia obtained in the beta-sitosterol-infused rats is due to the inhibitory effect of sitosterol on the cholesterol 7 alpha-hydroxylase.

Topics: Animals; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Disease Models, Animal; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Male; Microsomes, Liver; Phytosterols; Rats; Rats, Inbred Strains; Sitosterols; Steroid Hydroxylases

Topics: Cholestanol; Cholesterol; Humans; Hypercholesterolemia; Hyperlipoproteinemias; Phytosterols; Skin Diseases; Xanthomatosis

Topics: Child, Preschool; Diagnosis, Differential; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Phytosterols; Xanthomatosis

To test the hypothesis that high-responding rhesus monkeys should have a greater degree of feedback inhibition of hepatic cholesterol biosynthesis than the low-responding monkeys because the former group absorbs a higher percentage of cholesterol than the later group, we determined the relative rates of cholesterol biosynthesis by measuring plasma desmosterol levels while feeding triparanol along with diets high and low in cholesterol and with or without 2% plant sterols. The build-up of plasma desmosterol was more rapid in low-responders than in high-responders on all diets; the difference was significant only on diets low in plant sterols. In both groups, adding plant sterols to either diet increased the initial slope of plasma desmosterol build-up (significant only for high cholesterol diet). The mean percent cholesterol absorption in high-responders was significantly higher than in low-responders on high and low cholesterol diets with low levels of plant sterols. On adding 2% plant sterols to both diets, the percent cholesterol absorption decreased significantly and became essentially the same in both groups. Triparanol feeding decreased plasma cholesterol significantly in both groups on both diets; the decrease in the low-responders was smaller than in high-responders. Addition of plant sterols to either diet also reduced plasma cholesterol in both groups, but the decrease was significant only in the high-responders on high cholesterol diet. The study demonstrates that high-responders have a greater degree of feedback inhibition of cholesterol biosynthesis than low-responders probably because of higher absorption of cholesterol. The results also indicate that both endogenous and exogenous cholesterol are effective mediators of the feedback inhibition mechanism.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Desmosterol; Feedback; Hypercholesterolemia; Intestinal Absorption; Macaca mulatta; Male; Phytosterols; Triparanol

A fourth case is described in which phytosterolaemia, earlier diagnosed as familial hypercholesterolaemia, was associated with normocholesterolaemia, hypersplenism and premature atherosclerotic arterial disease requiring a three-vessel coronary bypass at the age of 29 years. During a follow-up of 5 years 22-26% and 27-30% of serum and bile sterols were plant sterols, respectively. In addition to campesterol and beta-sitosterol, stigmasterol and a fourth major plant sterol, tentatively identified as avenasterol, were found in bile, and in free and esterified forms in all serum lipoproteins. Analysis of faecal steroids and measurement of biliary lipid secretion indicated that in addition to enhanced absorption of plant sterols their decreased biliary secretion contributed to the development of phytosterolaemia. Impaired biliary cholesterol secretion was compensated for by a markedly reduced cholesterol but normal bile acid synthesis and resulted in bile undersaturated with respect to cholesterol, in a reduced intestinal cholesterol pool and in a very low faecal excretion of cholesterol as neutral sterols. Cholestyramine brought about a modest increase in cholesterol elimination as bile acids, increased cholesterol synthesis as evidenced by the sterol balance value and the increased cholesterol precursors squalene and methyl sterols in plasma and bile, and reduced the plasma cholesterol by 21% and plant sterols by 16%, but had no effect on the biliary composition of main sterols.

Topics: Absorption; Adult; Arteriosclerosis; Bile; Bile Acids and Salts; Cholesterol; Cholestyramine Resin; Coronary Disease; Feces; Humans; Hypercholesterolemia; Hyperlipidemias; Lipid Metabolism; Lipoproteins; Male; Phytosterols; Squalene; Xanthomatosis

Topics: Animals; Anticholesteremic Agents; Fatty Acids, Nonesterified; Hypercholesterolemia; Liver; Male; Phytosterols; Rats; Stigmasterol

We have evaluated the efficacy of plant sterol preparations from two different sources and in two different physical forms in lowering the plasma cholesterol of a total of 46 patients with type II hyperlipoproteinemia when given in addition to appropriate diet therapy. In addition, the mechanisms of the hypocholesterolemic effect were investigated in 7 patients by a sterol balance technique. The maximal mean cholesterol lowering in response to any preparation was 12 percent, although it was much greater in some individual patients. Sterol balance data showed that plant sterols inhibit cholesterol absorption with maximal negative cholesterol balance in adults at a dose of 3 g/day of a tall oil sterol suspension. Interestingly, maximal plasma cholesterol reduction in the adult outpatients on this preparation was seen at the same dose level. Since the tall oil sterol suspension is relatively palatable and is poorly absorbed, it has potential value as an adjunct to dietary therapy in patients with mild hypercholesterolemia for whom long-term drug therapy is deemed advisable.

Topics: Cholesterol; Humans; Hypercholesterolemia; Hyperlipidemias; Phytosterols; Triglycerides

Studies were carried out to determine effects of combined chemotherapy in patients with hyperlipidemia. In one study, 14 patients were treated first with colestipol and then with the combination of colestipol and clofibrate. In a second study, six patients were given clofibrate followed by addition of phytosterols. The following measurements were made in most patients: (1) plasma lipid concentrations, (2) fecal excretions of neutral steroids and bile acids, and (3) lipid composition of gallbladder bile. In six patients of the first study, hepatic secretion rates of biliary lipids and pool sizes of bile acids were also estimated. In the first study, colestipol alone caused a marked increase in fecal bile acids that resulted in a sizable decrease in plasma cholesterol concentrations (average 21 percent). In several patients, however, triglycerides were increased somewhat by colestipol. Despite interruption of the enterohepatic circulation of bile acids, the bile acid pool was not reduced, since a compensatory increase took place in bile acid synthesis. Also, except in one patient who developed gallstones following institution of colestipol, saturation of gallbladder bile with cholesterol was not markedly increased by this drug alone. Addition of clofibrate frequently produced a further decrement in plasma cholesterol, and the mild hypertriglyceridemia induced by colestipol was reversed. However, colestipol plus clofibrate usually caused a striking increase in saturation of gallbladder bile. Previous studies have shown that clofibrate causes a flux of cholesterol from tissue pools by simultaneously decreasing cholesterol synthesis and increasing its excretion. To further increase cholesterol excretion, phytosterols, which block cholesterol absorption, were added to clofibrate in the second study. Although phytosterols did not cause a further reduction in plasma cholesterol in these particular patients, they nevertheless greatly enhanced cholesterol excretion.

Topics: Adult; Bile; Bile Acids and Salts; Cholesterol; Clofibrate; Colestipol; Drug Therapy, Combination; Feces; Humans; Hypercholesterolemia; Hyperlipidemias; Lipid Metabolism; Liver; Male; Middle Aged; Phytosterols; Polyamines; Steroids; Triglycerides

Plasma phytosterol (plant sterol) levels were studied in 26 infants on various commercial formulas, in 36 infants on breast or cow's milk formulas, in 101 normal and 22 hypercholesterolemic children on a free diet, and in 32 hypercholesterolemic children on a low-cholesterol diet. Commercial formulas, poor in animal fats and enriched with vegetable oils, and low-cholesterol, phytosterol-rich diets generally elevated total plasma phytosterol levels in infants and hypercholesterolemic children from normal mean levels of 2 mg/100 ml to about 9 mg/100 ml. The implications of long-term three- to five-fold elevations of the plasma phytosterols (campesterol, stigmasterol, beta-sitosterol) in infancy and childhood are unknown. Watchful prospective analysis of plasma phytosterol levels may be useful, particularly in regards to otherwise unanticipated long-term effects of cholesterol-poor, phytosterol rich diets.

Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Cholesterol; Cholesterol, Dietary; Diet; Dietary Fats; Humans; Hypercholesterolemia; Infant; Infant Food; Infant, Newborn; Milk; Milk, Human; Phytosterols; Sitosterols; Stigmasterol

Direct gas liquid chromatography (GLC) of total plasma lipids showed small peaks (0.5-1.5% of total free sterol area) corresponding to free C28 and C29 sterols in ca. 50% of some 3,000 normal subjects and patients with hyperlipemia. Comparable proportions of similar peaks were present in the sterol fraction isolated from the red blood cells of many of these subjects. The maximum levels of these components in the plasma and red blood cells of domestic and laboratory animals were up to 10 times higher than those seen in man. Detailed gas chromatography/mass spectrometry analyses of the plasma lipids from a much more limited number of subjects and animals showed that the GLC peaks corresponding to the free C28 and C29 sterols were largely due to the plant sterols campesterol, stigmasterol, and beta-sitosterol. In all instances, variable amounts (0.05-0.2% of the total free sterol area) of 7-dehydrocholesterol, desmosterol, lanosterol, and cholesterol alpha-oxide were also detected. While the total content and composition of the plasma plant sterols appeared to vary greatly among the subjects, it never exceeded 2% of total sterol in the normal subjects and patients examined. There was no evidence for a significant increase in the plant sterol content of the plasma of patients with hypercholesterolemia or hypertriglyceridemia.

Topics: Animals; Cholesterol; Chromatography, Gas; Desmosterol; Erythrocytes; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Hyperlipidemias; Phytosterols; Sitosterols; Species Specificity

Topics: Animals; Bile; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Chylomicrons; Clofibrate; Feces; Feedback; Humans; Hypercholesterolemia; Intestinal Mucosa; Lipoproteins; Liver; Nicotinic Acids; Phytosterols; Rats; Time Factors; Triglycerides