cytellin and Hypercholesterolemia

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

This review covers the current knowledge about plant stanol esters as a dietary treatment option for heterozygous familial hypercholesterolemia (he-FH) children. The current estimation of the prevalence of he-FH is about one out of 200⁻250 persons. In this autosomal dominant disease, the concentration of plasma low-density lipoprotein cholesterol (LDL-C) is strongly elevated since birth. Quantitative coronary angiography among he-FH patients has revealed that stenosing atherosclerotic plaques start to develop in he-FH males in their twenties and in he-FH females in their thirties, and that the magnitude of the plaque burden predicts future coronary events. The cumulative exposure of coronary arteries to the lifelong LDL-C elevation can be estimated by calculating the LDL-C burden (LDL-C level × years), and it can also be used to demonstrate the usefulness of dietary stanol ester treatment. Thus, when compared with untreated he-FH patients, the LDL-C burden of using statin from the age of 10 is 15% less, and if he-FH patients starts to use dietary stanol from six years onwards and a combination of statin and dietary stanol from 10 years onwards, the LDL-C burden is 21% less compared to non-treated he-FH patients. We consider dietary stanol treatment of he-FH children as a part of the LDL-C-lowering treatment package as safe and cost-effective, and particularly applicable for the family-centered care of the entire he-FH families.

Topics: Child; Cholesterol, LDL; Female; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Male; Sitosterols

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

The ability of plant polyisoprenoids (polyprenols and polyprenyl phosphates) to diminish the levels of serum cholesterol affecting its biosynthetic pathway are highlighted here. Possible mechanism of such process is discussed. It is also noted that polyisoprenoids can prevent toxic injuries of the liver and restore disturbed hepatic functions. The possibility of polyprenyl phosphates to reveal at the same time anti-inflammatory action suppressing lipoxygenase activity and lowering the levels of proinflammatory cytokines will be illustrated. Attention will be focused on the potential usefulness of plant polyisoprenoids in the course of prevention and treatment of hypercholesterolemia. High efficiency for combined use of polyprenyl phosphate and β-sitosterol, which leads to substantial enhancement of the ability to overcome hypercholesterolemia versus the individual constituents will be demonstrated.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Cholesterol; Humans; Hypercholesterolemia; Lipoxygenase; Phytotherapy; Plants; Sitosterols; Terpenes

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 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

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

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

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

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

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

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

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

The unraveling of genetic defects associated with disorders in lipid metabolism has contributed to the understanding of lipoprotein metabolism and the pathophysiological consequences of a particular mutation. The translation, however, of a single genetic defect into the individual's risk of cardiovascular disease and subsequent treatment strategies is an extremely complex issue that involves the identification of multiple additional determinants, including genetic, metabolic and environmental factors. The discovery of these factors, including genetic determinants of drug efficacy, provides insight into the interaction between regulatory systems traditionally thought to be unrelated and may, in the future, lead to a more complete diagnostic and therapeutic appreciation of the individual patient.

Topics: Animals; Humans; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Hypertriglyceridemia; Hypolipidemic Agents; Lipoproteins; Sitosterols

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

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

Hypercholesterolaemia is a major risk factor for coronary heart disease (CHD). Therefore, the reduction of low-density lipoprotein (LDL) cholesterol is one of the primary targets of the current recommendations to decrease CHD risk in the population. Whereas, the mechanisms involved in de novo cholesterol synthesis and its uptake by cells via the LDL receptor are well known, we still need better understanding about the mechanisms involved in intestinal cholesterol absorption and excretion. The recent discovery of ABCG5 and ABCG8 transporters will significantly improve our understanding of cholesterol trafficking and it will lead to better and new therapeutic strategies to maintain cholesterol homeostasis.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypercholesterolemia; Intestinal Absorption; Polymorphism, Genetic; Risk Factors; Sitosterols; Sterols

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

Topics: Cholesterol, LDL; Humans; Hypercholesterolemia; Hypolipidemic Agents; Margarine; Sitosterols

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

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

Since the unfavorable impact of hypercholesterolemia on the cardiovascular system has been proven, effective, inexpensive and easy to use cholesterol-lowering treatment options have been looked for. In the 1990s as the effect of a few decades of research, stanols have been introduced as new cholesterol-lowering agents. Stanols are derivates of plant sterols, which act through inhibition of intestinal cholesterol absorption. Their incorporation into normal diet fats has led to a significant reduction of both total and LDL cholesterol in investigated subjects, also in those on cholesterol-lowering diet or taking cholesterol-lowering drugs. When the dose considered optimal, i.e. 2-3 g/d, was used, the average reduction was 10% for total and 14% for LDL cholesterol. So far no adverse effects of stanols and no influence on the taste of food have been observed. The possible role of stanols in primary and secondary prevention of cardiovascular diseases still remains to be verified. It seems, however, that stanols have a potential to become a significant element in the treatment of hypercholesterolemia and in preventing its consequences.

Topics: Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Middle Aged; Postmenopause; Sitosterols

After discussing the indications for treatment of familial hypercholesterolemia and the importance of a differential diagnosis, the authors describe drug therapy for the disorder with special attention to combined drug regimens. The surgical treatment of hypercholesterolemia and the treatment of homozygous and other forms of hypercholesterolemia are also detailed.

Topics: Cholestyramine Resin; Colestipol; Drug Therapy, Combination; Heterozygote; Homozygote; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Lipoproteins, LDL; Neomycin; Niacin; Nicotinic Acids; Probucol; Sitosterols; Thyroxine

Topics: Cholestyramine Resin; Dextrothyroxine; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Neomycin; Nicotinic Acids; Oxandrolone; Probucol; Sitosterols; Triglycerides

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

Topics: Diet; Diet Therapy; Dietary Fats; Humans; Hypercholesterolemia; Sitosterols; Sterols

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

The high blood cholesterol level could be prevented by plant stanol ester (Staest) consumption. In addition, the genetic polymorphism of cholesterol transporters might be related with lipid profile and subsequently response to Staest intake.. To investigate the effect of single nucleotide polymorphism in ATP-binding cassette hetero-dimeric G5/G8 (ABCG5/G8) and Niemann-Pick C1 Like1 protein (NPC1L1) gene on LDL-C response subsequent to plant Staest intake in Thai Subjects.. The blood samples were collected from 113 subjects for genotyping. The single nucleotide polymorphisms (SNPs) of ABCG5/G8 positions; rs6720173 (Q604E), rs4148211 (C54Y), rs4148217 (T400K), rs3806471 (5’UTR-145), and NPC1L1; positon; rs2072183 (L272L) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.. After Staest intake, the subjects with QE genotype (Q604E of ABCG5) showed a 4-fold significant decrease in LDL-C level (14.17±10.67%) compared to subjects with QQ genotype (3.50±10.65%) (p = 0.003). Moreover, the pronounced effect of Q604E polymorphism was observed in subjects after intake of Staest with meal. However, no significant difference in these markers was observed in subjects carrying other mutations.. Thus, it could be suggested that non-synonymous gene polymorphism resulted substitution of uncharged glutamine (Q) with negatively charged glutamic acid (E) at position 604, thereby possibly alter the function of transporter proteins. Besides, the genetic variation in these genes might be related with serum lipid profiles. Moreover, Q604E mutation of ABCG5 in each individual with meal effect could lead to particular response towards LDL-C level after Staest intervention.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; Cholesterol, LDL; Genotype; Humans; Hypercholesterolemia; Lipoproteins; Membrane Proteins; Membrane Transport Proteins; Polymorphism, Single Nucleotide; Sitosterols; Thailand

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

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in β-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cholesterol, LDL; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Sitosterols; Treatment Outcome

Plant stanol consumption may improve long-term cholesterol control. The aim of the present study was to evaluate the effectiveness of 2g/day of plant stanols in reducing low-density lipoprotein cholesterol levels in patients with hypercholesterolemia.. This randomized, double-blind, and placebo-controlled study included 182 adults diagnosed with hypercholesterolemia. A yogurt drink containing 2g of plant stanols was administered to 91 participants in the intervention group; 91 participants in the control group received unsupplemented yogurt. The primary end point was the change in the lipid profile at 12 months.. Low-density lipoprotein cholesterol levels at 12 months were significantly more reduced in the stanol intervention group than in the control group: 13.7 (95% confidence interval, 3.2-24.1) mg/dL (P=.011). A reduction of more than 10% in low-density lipoprotein cholesterol was achieved by a significantly higher proportion of participants in the intervention group (relative risk=1.7; 95% confidence interval, 1.1-2.7). In this group, the mean (standard deviation) level of low-density lipoprotein cholesterol decreased by 11.0% (23.9%).. Our results confirm that administration of plant stanols at a dosage of 2 g/day for 12 months significantly reduces (by slightly more than 10%) the concentrations of low-density lipoprotein cholesterol in individuals with hypercholesterolemia. Trial registration (www.ClinicalTrials.gov): Current Controlled Trials NCT01406106.

Topics: Adult; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Lipids; Male; Margarine; Middle Aged; Sitosterols; Time Factors; Treatment Outcome; Yogurt

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

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

Combination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent.. Adult patients (n = 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks.. Significantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of <100 mg/dl and <70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced ∼10-14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced β-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A2 mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable.. Co-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe.

Topics: Absorption; Adult; Atherosclerosis; Azetidines; Biomarkers; Cholesterol, LDL; Coronary Disease; Drug Administration Schedule; Ezetimibe; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Lipoproteins; Male; Pyrimidines; Risk; Rosuvastatin Calcium; Simvastatin; Sitosterols; Sulfonamides; 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

Cardiovascular diseases have become the leading cause of death from chronic diseases in the world. Main risk factors include hypercholesterolemia, which is caused in most cases by a high saturated fat diet. Plant stanol esters partly block cholesterol absorption in the digestive tract and thereby reduce total cholesterol and low-density lipoprotein (LDL) cholesterol serum levels. Based on epidemiological data, a 10 percent reduction of LDL cholesterol leads to a 20 percent decrease in the coronary heart disease risk throughout life. The aim of this study was to evaluate the efficacy of yogurt drink with added plant stanol esters (Benecol® yogurt drink) in higher doses than the typically used (2g/d stanols), in lowering blood lipids in moderately hypercholesterolemic subjects.. A randomized double-blind crossover, placebo-controlled study in moderately hypercholesterolemic subjects (n = 40) aged between 20 and 50 years old.. Yogurt drink with added plant stanols (4 g) as esters (Benecol®, Colanta) consumption compared to regular yogurt drink caused a statistically significant decrease in total cholesterol and low density lipoprotein cholesterol by 7.2% and 10.3%. During the two periods and compared to controls, high-density lipoprotein cholesterol and triglycerides were not significantly different.. Yogurt drink with an active ingredient in Benecol®, plant stanol esters, reduced total cholesterol and LDL cholesterol in moderately hypercholesterolemic subjects.. NCT01461798.

Topics: Administration, Oral; Adult; Anticholesteremic Agents; Beverages; Cholesterol, LDL; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols; Treatment Outcome; Yogurt

We evaluated the cholesterol lowering efficacy of low-fat spoonable yoghurt with 1.9 g/d plant stanols as esters on plasma lipid profiles of Turkish subjects with mild to moderate hypercholesterolemia.. Using a randomised, double-blind, placebo-controlled study design, intervention (n = 35) and control (n = 35) groups consumed either 115 g low-fat yoghurt with 1.9 g/d plant stanols as esters or placebo yoghurt, respectively, for 4 weeks. Seventy subjects with untreated mild to moderate hypercholesterolemia (aged 23-65 years) were recruited. Changes in the lipid profile, including lipoproteins, apolipoproteins, and triglycerides, and anthropometric measurements were monitored at screening, baseline, and at the end of the second, third, and fourth weeks of intervention. The general linear model repeated measures procedure was used to test differences in the repeated continuous variables between study groups.. Serum total cholesterol (4.6%), LDL cholesterol (6.3%), and non-HDL cholesterol (6.2%) concentrations were reduced significantly from baseline in the plant stanol group compared to the control group (p = 0.007, p = 0.005 and p = 0.005, respectively). A variation in the response of serum total and LDL cholesterol between the subjects in plant stanol group was obtained. No clinically significant change in anthropometrical measurements was observed during the intervention.. The spoonable low-fat yoghurt with 1.9 g/d plant stanols as esters lowered total, LDL, and non-HDL cholesterol levels in Turkish subjects with mild to moderate hypercholesterolemia. Nevertheless variation in baseline cholesterol levels, genetic predisposition of the subjects and compliance may contribute to a large individual variability.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol, HDL; Dietary Supplements; Double-Blind Method; Female; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Male; Middle Aged; Sitosterols; Treatment Outcome; Turkey; Yogurt; Young Adult

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

Statins inhibit cholesterol synthesis but can upregulate cholesterol absorption, with higher doses producing larger effects. Ezetimibe inhibits cholesterol absorption but also upregulates synthesis. We tested whether ezetimibe added to on-going statin therapy would be most effective in lowering LDL-cholesterol (LDL-C) in subjects on high-potency statins and whether these effects would be related to alterations in cholesterol absorption (β-sitosterol) and synthesis (lathosterol) markers.. Hypercholesterolemic subjects (n = 874) on statins received ezetimibe 10 mg/day. Plasma lipids, lathosterol, and β-sitosterol were measured at baseline and on treatment. Subjects were divided into low- (n = 133), medium- (n = 582), and high- (n = 159) statin potency groups defined by predicted LDL-C-lowering effects of each ongoing statin type and dose (reductions of ~20-30%, ~31-45%, or ~46-55%, respectively).. The high-potency group had significantly lower baseline lathosterol (1.93 vs. 2.58 vs. 3.17 μmol/l; p < 0.001) and higher baseline β-sitosterol values (6.21 vs. 4.58 vs. 4.51 μmol/l, p < 0.001) than medium-/low-potency groups. Ezetimibe treatment in the high-potency group produced significantly greater reductions from baseline in LDL-C than medium-/low-potency groups (-29.1% vs. -25.0% vs. -22.7%; p < 0.001) when evaluating unadjusted data. These effects and group differences were significantly (p < 0.05) related to greater β-sitosterol reductions and smaller lathosterol increases. However, LDL-C reduction differences between groups were no longer significant after controlling for placebo effects, due mainly to modest LDL-C lowering by placebo in the high-potency group.. Patients on high-potency statins have the lowest levels of cholesterol synthesis markers and the highest levels of cholesterol absorption markers at baseline, and the greatest reduction in absorption markers and the smallest increases in synthesis markers with ezetimibe addition. Therefore, such patients may be good candidates for ezetimibe therapy if additional LDL-C lowering is needed.

Topics: Aged; Anticholesteremic Agents; Apolipoproteins; Azetidines; Biomarkers; C-Reactive Protein; Cholesterol; Cholesterol, LDL; Double-Blind Method; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Multivariate Analysis; Sitosterols; Time Factors; Treatment Outcome; United States

Mediterranean diet is associated with a reduced risk for cardiovascular disease (CVD). Use of plant stanols decreases low density lipoprotein cholesterol (LDL-C) concentrations. We compared the effects of the Mediterranean diet and plant stanol esters on vascular risk factors and estimated CVD (eCVD) risk.. In this prospective, randomized, placebo-controlled study, 150 mildly hypercholesterolaemic subjects were randomized to Mediterranean diet, a spread containing plant stanol esters (2 g/day) or a placebo spread. Vascular risk factors were assessed every month for 4 months and the eCVD risk was calculated using the PROspective- Cardiovascular-Munster (PROCAM), Framingham, and Reynolds risk engines. Placebo had no significant effect on risk factors or eCVD risk. Mediterranean diet gradually induced a significant reduction in total cholesterol (TC), LDL-C, triglycerides, high sensitivity C-reactive protein (hsCRP), blood pressure and eCVD risk (24-32%). The plant stanol ester spread reduced (by 1 month) TC (-14%), LDL-C (-16%), hsCRP (-17%), and estimated CVD risk (26-30%). eCVD risk reduction was sustained at 4th months when the gradual Mediterranean diet eCVD risk reduction became comparable to that of the stanol group.. Plant stanol esters yielded an early, by 1st treatment month, reduction of eCVD risk that resulted from a TC, LDL-C, and hsCRP decrease. eCVD risk reduction on the Mediterranean diet resulted from a change in several CVD risk factors and equaled that of plant stanol at 4 months. The consumption of plant stanol esters by moderately hypercholesterolaemic patients may be a useful option to reduce CVD risk in those who do not adopt a Mediterranean diet.

Topics: Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Condiments; Diet, Mediterranean; Humans; Hypercholesterolemia; Inflammation Mediators; Male; Middle Aged; Risk Factors; Severity of Illness Index; Sitosterols; Time Factors; 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

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

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

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

To investigate the effects of soy milk fortified with plant stanol ester on changes in LDL-cholesterol, fat-soluble vitamins and sex hormones in Thai volunteers.. In a double-blind, placebo-controlled study, 120 mildly hypercholesterolemic Thais were randomly assigned to stanol and control groups that were comparable in lipid profile and body mass index. Subjects consumed regular or 2g stanol-containing soymilk once a day and postprandially for six weeks. The serum lipid profile was measured at weeks 0, 2 and 6; serum fat-soluble vitamins and sex hormones were measured at weeks 0 and 6.. The mean reduction in total cholesterol was 8.2 % in the stanol group (p < 0.0001) and 0.6% in the control group. LDL-cholesterol declined in both groups at week two, but the reduction was maintained to week six only in the stanol group. The mean reduction in LDL-cholesterol was 13.5% in the stanol group (p < 0.0001) at week 6, compared to a 4.6% decrease in the control group. Adjusted serum beta-cryptoxantene and beta-carotene levels decreased at week six for the stanol group. Serum sex hormone levels in both groups remained unchanged.. Consumption of stanol-ester-containing soymilk for six weeks significantly reduced LDL-cholesterol in mildly hypercholesterolemic Thais. No adverse effect on sex hormones was observed However, stanol-ester consumers are at risk of fat-soluble-vitamin deficiencies if the vitamin intake from foods is inadequate.

Topics: Adult; Antioxidants; Cholesterol, LDL; Female; Food, Fortified; Humans; Hypercholesterolemia; Male; Middle Aged; Postprandial Period; Sitosterols; Soy Milk; Thailand

Intake of 2-3 g/d of plant stanols as esters lowers LDL cholesterol level, but there is no information about the efficacy and safety of a respective very high daily intake. We studied the effects of 8.8 g/d of plant stanols as esters on serum lipids and safety variables in subjects with mild to moderate hypercholesterolemia.. In a randomized, double-blind, placebo-controlled study the intervention (n=25) and control (n=24) groups consumed spread and drink enriched or not with plant stanol esters for 10 weeks.. Plant stanols reduced serum total and LDL cholesterol concentrations by 12.8 and 17.3% from baseline and by 12.0 and 17.1% from controls (P<0.01 for all). Liver enzymes, markers of hemolysis, and blood cells were unchanged. Serum vitamins A, D, and gamma-tocopherol concentrations, and the ratios of alpha-tocopherol to cholesterol were unchanged. Serum beta-carotene concentrations decreased significantly from baseline and were different from controls even when adjusted for cholesterol. Serum alpha-carotene concentration and alpha-carotene/cholesterol ratio were not different from controls.. High intake of plant stanols reduced LDL cholesterol values without any other side effects than reduction of serum beta-carotene concentration. However, the end product, serum vitamin A levels, were unchanged. The results suggest that plant stanol ester intake can be increased to induce a greater cholesterol lowering effect.

Topics: Adolescent; Adult; Aged; alpha-Tocopherol; beta Carotene; Biomarkers; Carotenoids; Cholesterol; Diet; Double-Blind Method; Female; Finland; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipids; Male; Middle Aged; Sitosterols; Vitamin A; Vitamin D; Vitamins; 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

The object of our study was to compare the effect of high-dose vs low-dose atorvastatin vs nonstatin-based treatment (cholestyramine plus sitosterol) on cell composition of carotid plaque.. We recruited 60 hypercholesterolemic patients (total cholesterol, 5.83-7.64 mmol/L) eligible for carotid endarterectomy. Three months before surgery, patients were randomized into 3 groups (n=20) receiving atorvastatin 10 mg/day (AT-10) or atorvastatin 80 mg/day (AT-80) or cholestyramine 8 g/day plus sitosterol 2.5 g/day. Analysis of cell composition was performed on endarterectomy specimens.. The 3 treatments resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), although the decrease in total cholesterol and LDL-C was of smaller magnitude in the cholestyramine plus sitosterol group. The 3 regimens did not influence the levels of inflammatory markers (including high-sensitivity C-reactive protein). Macrophage content was significantly lower in the AT-10 group plaques compared to the cholestyramine plus sitosterol group. It was further reduced in the AT-80 group plaques. These differences were no longer significant after adjustment for changes in LDL-C. No difference in lymphocyte number was observed among treatments, whereas the content of smooth muscle cells was higher in the AT- 80 group. An inverse association was observed between LDL-C changes in the 3 groups and macrophage content in the plaques.. Short-term treatment with high-dose statin is superior to a nonstatin lipid-lowering regimen in reducing the macrophage cell content within atherosclerotic lesions, but this effect was determined by the degree of LDL-C-lowering.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Cholestyramine Resin; Endarterectomy, Carotid; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Lymphocyte Count; Macrophages; Male; Pyrroles; Sitosterols

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

We have earlier demonstrated that muesli enriched with oat beta-glucan effectively lowered serum LDL cholesterol. Addition of plant stanols further lowered LDL cholesterol. Besides these hypocholesterolemic effects, beta-glucan and plant stanol esters (PSE) may also affect inflammatory processes. Forty-two mildly hypercholesterolemic subjects randomly consumed for 4 wk (crossover design) control muesli (4.8 g control fiber), beta-glucan muesli (4.8 g oat beta-glucan), or combination muesli (4.8 g oat beta-glucan plus 1.4 g stanol as PSE). Changes in cytokine production (IL-6, IL-8, and TNF-alpha) of LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood were evaluated, as well as changes in plasma high-sensitivity (hs)-CRP. Additionally, changes in expression profiles of 84 genes involved in atherosclerosis metabolism were assessed in isolated PBMC. IL-6, IL-8, and TNF-alpha production by PBMC and whole blood after LPS stimulation did not differ between the treatments. Also high-sensitivity C-reactive protein (hs-CRP) levels were similar. beta-Glucan consumption did not change gene expression, while only 3 genes (ADFP, CDH5, CSF2) out of the 84 genes from the atherosclerotic risk panel were differentially expressed (p < 0.05) after consumption of PSE. Consumption of beta-glucan with or without PSE did not influence inflammatory parameters in mildly hypercholesterolemic subjects.

Topics: Adult; Atherosclerosis; Avena; beta-Glucans; C-Reactive Protein; Cross-Over Studies; Dietary Fiber; Double-Blind Method; Female; Gene Expression; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Inflammation; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Sitosterols; Tumor Necrosis Factor-alpha

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

This study examined whether stanols can exert their cholesterol lowering effect in renal transplant recipients who develop hypercholesterolaemia. The rise in cholesterol is related to the use of cyclosporine. The study was a randomised parallel-group intervention study. The Intervention group (I) was given three months supply of stanol containing food products. Fasting serum lipids were measured monthly. Parameters that might influence serum cholesterol were measured on all subjects at the start of the study period and at three months. These included body weight, blood pressure and drug therapy, dietary intake, exercise, smoking and alcohol intake. 84 patients completed the study. Cholesterol was reduced in both groups. The difference between control (C) and I group reached significance at p = 0.0196. Reduction in cholesterol in subjects also using statins was greater in the I group. Functional foods appear to be effective in reducing cholesterol in this group of patients. Data collection with respect to other factors that influence CV risk suggests that an overall assessment of diet and lifestyle as well as cholesterol lowering should be undertaken.

Topics: Combined Modality Therapy; Cyclosporins; Dietary Supplements; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Sitosterols

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

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

To assess the long-term efficacy and safety profile of ezetimibe 10 mg/day in patients with homozygous sitosterolemia.. This was an extension of a multi-centre, randomised, double-blind, placebo-controlled base study in which patients with homozygous sitosterolemia and plasma sitosterol concentrations > 5 mg/dl were randomised 4 : 1 to ezetimibe 10 mg/day (n = 30) or placebo (n = 7) for 8 weeks. Patients who successfully completed the base study with > 80% compliance to study medication were eligible to enter two, successive, 1-year extension studies in which ezetimibe 10 mg/day was administered in an open-label manner. Patients remained on their current treatment regimen (e.g. bile salt-binding resins, statins and low-sterol diet) during the base and extension studies. Patients had to be off ezetimibe therapy for > or = 4 weeks prior to entering the first extension. Efficacy and safety/tolerability parameters were evaluated every 12 and 26 weeks in the first and second years respectively. The primary efficacy end-point was mean percentage change in plasma sitosterol from baseline to study end for the cohort of patients (n = 21) who successfully completed the second extension study.. Treatment with ezetimibe 10 mg/day led to significant mean percentage reductions from baseline in plasma concentrations of sitosterol (-43.9%; p < 0.001), campesterol (-50.8%; p < 0.001), low-density lipoprotein (LDL) sterols (-13.1%; p < 0.050), total sterols (-10.3%; p < 0.050) and apolipoprotein (apo) B (-10.1%; p < 0.050). No significant changes from baseline were observed for lathosterol, high-density lipoprotein sterol, triglycerides or apo A-1. Maximal reductions in sitosterol and campesterol occurred within the first 52 weeks of treatment and were sustained for the duration of the study. For LDL sterol, total sterols and apo B, maximal reductions were achieved early (by weeks 4 or 16) and waned slightly through the remainder of the study. Overall ezetimibe 10 mg was well tolerated.. In patients with homozygous sitoserolemia, long-term treatment with ezetimibe 10 mg/day for 2 years was effective in reducing plasma plant sterol concentrations with an overall favourable safety and tolerability profile.

Topics: Achilles Tendon; Adolescent; Adult; Aged; Anticholesteremic Agents; Azetidines; Child; Double-Blind Method; Ezetimibe; Female; Homozygote; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols; Treatment Outcome; Young Adult

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

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

Oil-based matrices enriched with plant stanol esters lower serum LDL cholesterol. The effects of low-fat milk products have been less thoroughly examined.. To evaluate the effect of three less explored low-fat milk products enriched with plant stanol esters on serum lipid concentrations in subjects with mild or moderate hypercholesterolemia.. A meta-analysis of four unpublished sub-studies (yoghurt, yoghurt single-shot drink: Studies I and II, or milk). All the substudies were randomized, placebo-controlled, double-blind and had a parallel-group design. They were carried out in order to evaluate the effect of low-fat milk products enriched with plant stanol esters on serum lipid concentration. Each stanol-ester-enriched milk product provided 2 g of stanols per day, and in each study the intervention period was 5 weeks. A total of 199 hypercholesterolemic subjects completed the studies.. The pooled treatment difference in total cholesterol was -3.8% (95% CI -6.0 to -1.7, p < 0.001) when stanol was compared to placebo. In LDL cholesterol, the pooled treatment difference was -4.9% (95% CI -7.8 to -1.8, p = 0.002). There were no significant differences between the groups in pooled HDL cholesterol or triacylglycerol concentrations. The results tended to be more pronounced when we were certain that the yoghurt single-shot drink was ingested with lunch, and when the baseline LDL-cholesterol concentration was > or = 3.5 mmol/l.. These results imply that low-fat milk products enriched with plant stanol esters lower both total cholesterol and LDL cholesterol statistically significantly in subjects with mild or moderate hypercholesterolemia. The changes tended to relate to the baseline LDL-cholesterol concentration.

Topics: Adult; Aged; Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dairy Products; Diet, Fat-Restricted; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Milk; Sitosterols; Treatment Outcome; Yogurt

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

We investigated the effects of stanol (STAEST) and sterol esters (STEEST) on endothelial function in hypercholesterolemic subjects. In addition, associations of variables of cholesterol metabolism with endothelial function were investigated. In a double-blind randomized cross-over study (n=39) with age-matched parallel control group (n=37) the subjects consumed STAEST or STEEST spread (total plant sterols and stanols 1.93-1.98g/day) for 10 weeks each. Controls consumed the spread without sterols or stanols for 20 weeks. At baseline, brachial artery diameter was positively correlated with serum triglycerides (r=0.375, p=0.001) and glucose (r=0.420, p<0.001) and with cholesterol synthesis marker ratios to cholesterol (e.g. desmosterol r=0.540, p<0.001) and negatively with HDL cholesterol (r=-0.309, p=0.008) and absorption marker ratios (e.g. campesterol r=-0.332, p=0.004). During the intervention, LDL cholesterol was reduced by 6-9% from baseline with STAEST and STEEST spreads (p<0.05), and by 9-12%, respectively, from controls (p<0.05). Flow-mediated dilatation did not change during the investigation. Brachial artery diameter was unchanged in controls and during STAEST periods, but it was reduced during STEEST by 2.2% (p=0.012) from STAEST. In conclusion, variables of cholesterol metabolism are associated with brachial artery diameter at baseline. STEEST diminishes brachial artery diameter, but its clinical relevance remains unclear.

Topics: Adult; Aged; Anticholesteremic Agents; Blood Chemical Analysis; Blood Pressure; Brachial Artery; Cholesterol, HDL; Cross-Over Studies; Dietary Fats; Double-Blind Method; Endothelium, Vascular; Female; Finland; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols; Ultrasonography

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

To investigate the cholesterol-lowering effects of a low-fat cheese enriched with plant stanol esters in mildly hypercholesterolaemic subjects, as part of their normal diet.. A randomized double-blind parallel-group study.. Valio Ltd, Helsinki.. Sixty-seven mildly hypercholesterolaemic volunteers (24 men, 43 women) participated in the study, which all of them completed.. The subjects were randomly assigned to the plant stanol ester group or the control group. During the 5-week intervention, the subjects in the stanol group consumed a cheese enriched with 2 g of plant stanols per day, and the subjects in the control group, a control cheese with no plant stanols.. In the stanol ester group, as compared to the control group, both serum total and low-density lipoprotein (LDL) cholesterol decreased significantly, that is, by 5.8% (-0.32 mmol/l, 95% CI -0.50 to -0.15 mmol/l, P < 0.001) and 10.3% (-0.36 mmol/l, 95% CI -0.53 to -0.18 mmol/l, P < 0.001), respectively. There were no significant changes in high-density lipoprotein cholesterol (HDL), triglycerides or apolipoprotein B concentrations between the groups.. Cheese enriched with 2 g of plant stanol in the form of fatty acid esters decreases serum total and LDL cholesterol significantly.

Topics: Adult; Aged; Anticholesteremic Agents; Apolipoproteins B; Cheese; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Food, Fortified; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Middle Aged; Sitosterols; Triglycerides

Plant sterols, incorporated into spreads and other food sources, have been shown to lower serum cholesterol concentrations. The effect of phytostanol supplementation in softgel form has not been assessed. Our objective was to examine the effects of sitostanol as sitostanol ester in softgel form on serum lipid concentrations in hypercholesterolemic individuals. Thirty hypercholesterolemic adults were supplemented with 1.6 g of free phytostanol equivalents as phytostanol ester (2.7 g stanol esters) or placebo per day for 28 d in a randomized, double-blind, parallel study design. Phytostanol supplementation resulted in a significant decrease in total cholesterol (TC) (-8%) and LDL-cholesterol (-9%). There were no alterations in concentrations of HDL-cholesterol or TG. Nor were the ratios of LDL/HDL or TC/HDL altered significantly. Thus, use of phytostanol ester softgel supplements improved serum total and LDL-cholesterol concentrations in hypercholesterolemic individuals.

Topics: Adult; Aged; Anticholesteremic Agents; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols

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

The feasibility of using solid dosage forms containing stanol lecithin to lower human LDL-cholesterol was investigated. The particle size distribution of a coarse aqueous dispersion of a stanol lecithin mixture was determined at various weight ratios of the components. At a stanol-to-lecithin weight ratio of 1.00-1.50, dispersions could be spray dried and the solid reconstituted with water to produce a particle size distribution that was similar to that of the aqueous dispersion from which it was derived. Two solid dosage forms containing this spray-dried stanol lecithin preparation had different disintegration times--tablets less than 10 min and capsules greater than 45 min. Each delivery system was then tested for LDL-cholesterol reduction activity in a placebo-controlled, double-blind clinical trial containing a total of 52 subjects. After a six-week treatment period, the group that received rapidly disintegrating stanol lecithin tablets (1.26 g stanols daily) experienced a decrease in both LDL-cholesterol and the ratio of LDL-cholesterol to HDL-cholesterol by 10.4% (P = 0.01) and 11.5% (P = 0.03), respectively, relative to placebo. On the other hand, with slowly disintegrating capsules (1.01 g daily) there was no statistically significant difference in any lipid parameter between the active group and placebo group. Taken together, these studies demonstrate that for maximum LDL-cholesterol reduction activity the stanol lecithin formulation must be delivered in a rapidly dispersible form to reach the site of cholesterol absorption.

Topics: Administration, Oral; Adult; Chemistry, Pharmaceutical; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Particle Size; Placebos; Sitosterols; Solubility; Tablets

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

High doses of soy protein are able to decrease plasma cholesterolemia significantly, but they unbalance daily protein intake and strongly modify nutritional habits in patients.. To evaluate the antihypercholesterolemic efficacy of a low dose soy protein product with added beta-sitosterol (rapport = 4:1) in 36 moderately hypercholesterolemic subjects.. The study was divided into 3 separate periods of 40 days each: a stabilization diet period, followed by a treatment period during which all subjects took 10 g of the test product once daily and, finally, a wash out period. The following parameters were monitored: weight, dietary habits, plasma lipid levels, glycemia, uric acid, fibrinogenemia and antibodies against oxidized LDL (ox-LDL Ab).. From the end of the stabilization diet period to the end of the supplementation with the soy protein product with added beta-sitosterol we observed a 19.64 +/- 20.32 mg/dL, 8.47 +/- 54.61 mg/dL, 1.69 +/- 10.92 mg/dL, and 7.06 +/- 16.66 mg/dL mean +/- SD decrease respectively in LDL-C (p < 0.001), TG (p = 0.358), VLDLs (p = 0.358) and apoB (p = 0.016) levels, associated with a 1.31 +/- 8.08 mg/dL and 1.03 +/- 19.09 mg/dL mean increase respectively in HDLC (p = 0.251) and apoAI (p = 0.749) plasma concentrations. The dietary supplementation did not influence Lp(a) (p = 0.984) and ox-LDL Ab (p = 0.953) plasma levels. A statistically significant correlation was observed for LDL-C plasma levels, between the end of the stabilization diet period and the end of the period of supplementation with soy proteins with added beta-sitosterols (p < 0.001).. Although further long-term clinical studies are necessary before claims can be made regarding the therapeutic effects of the tested formulation, the preliminary findings regarding its efficacy and safety as an antihypercholesterolemic agent are encouraging.

Topics: Anticholesteremic Agents; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Feeding Behavior; Female; Humans; Hypercholesterolemia; Lipid Peroxidation; Male; Middle Aged; Sitosterols; Soybean Proteins; Treatment Outcome; Triglycerides

The ester of plant stanols significantly reduces plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in Western people. Effects of plant stanol ester-containing spread on plasma levels of TC, LDL-C, and apolipoprotein B (apoB) were studied in a randomized, placebo-controlled trial in Japanese subjects whose diet is low in fat and cholesterol. The effects of plant stanol ester on plasma levels of arteriosclerosis-promoting factors, namely remnants of triacylglycerol (TG)-rich lipoproteins, cholesteryl ester transfer protein (CETP), and oxidized LDL (Ox-LDL), were also studied. The assessment of safety was also made.. One hundred and five healthy volunteers were assigned randomly to one of three groups: placebo spread (n = 35), 2 g/d of plant stanol (3.4 g of stanol ester; n = 34), and 3 g/d of plant stanol (5.1 g of stanol ester; n = 36). Plasma levels of lipids were measured at start of the study, at 2 and 4 wk (end of trial), and at 8 wk (+4 wk). Plasma apoproteins, cholesterol in remnant-like particles which are equivalent to remnants of TG-rich lipoproteins (RLP-C), CETP mass, and Ox-LDL were measured at the beginning and the end of the trial. Plasma levels of plant steroids and fat-soluble vitamins were also measured for the assessment of safety.. Background and dietary composition did not differ among groups. Plasma levels of TC, LDL-C, apoB, apoE, CETP mass, and Ox-LDL were reduced significantly by 6.5%, 9.6%, 8.3%, 4.5%, 6.1%, and 20%, respectively, in the 2 g/d plant stanol group. Plasma levels of TC, LDL-C, apoB, CETP mass, and Ox-LDL were decreased significantly by 5.5%, 7.3%, 5.6%, 3.3%, and 19%, respectively, in the 3 g/d plant stanol group. Plasma levels of plant stanols, plant sterols, retinol, beta-carotene, and alpha-tocopherol did not change in any group, but levels of campestanol increased and alpha-tocopherol decreased slightly in the sitostanol groups.. Plasma levels of TC and LDL-C were significantly reduced by the plant stanol ester-containing spread. The smaller reduction than in Western studies and the lack of dose dependency in this study might be due to the different basal diets. We concluded that plant stanol ester-containing spread is efficacious in reducing plasma LDL-C, apoB, CETP, and Ox-LDL and that 2 g/d plant stanol is adequate for Japanese people. No significant side effects were observed in any group.

Topics: Apolipoproteins B; Carrier Proteins; Cholesterol Ester Transfer Proteins; Cholesterol, LDL; Diet; Dose-Response Relationship, Drug; Female; Glycoproteins; Humans; Hypercholesterolemia; Japan; Lipoproteins, LDL; Male; Middle Aged; Placebos; Sitosterols

The objective of this work was to show that fat-free, lecithin-formulated soy stanols lower cholesterol absorption and serum LDL cholesterol.. Reduction in cholesterol absorption was measured in paired single-meal tests with or without formulated soy stanols (acute test), and changes in serum lipids were investigated in a 10-week, randomized, double-blind parallel trial in which formulated stanols or lecithin vehicle were given three times daily for the last 4 weeks (chronic test).. Forty-five normal or mildly hypercholesterolemic subjects were recruited for both studies. The 21 subjects (16 female, 5 male; mean age 32.5 years) in the absorption studies had the following mean lipid values: LDL cholesterol, 2.79 mmol/L and total cholesterol, 4.73 mmol/L. For the lipid reduction, 24 subjects (16 female, 8 male; mean age 50.6 years) were enrolled with mean LDL cholesterol and total cholesterol of 3.72 mmol/L and 5.66 mmol/L, respectively.. Reduction in cholesterol absorption was measured using a lemonade beverage or egg whites that contained 625 mg stanols. Throughout the chronic study, subjects followed the American Heart Association Step I diet. During the 4-week treatment phase, subjects consumed daily a lemonade-flavored beverage containing either placebo or formulated soy stanols (1.9 g).. Inhibition of cholesterol absorption was determined from the difference in plasma deuterated cholesterol enrichment after a test meal containing stanol-lecithin and one with lecithin vehicle only. In the chronic study, the primary endpoints were changes in LDL and total cholesterol.. Paired or unpaired t tests were used to determine statistical significance.. Stanol-lecithin reduced cholesterol absorption by 32.1% (P=.0045, n=10) and by 38.2% (P=.0022, n=11) when delivered in a lemonade-flavored beverage and in egg whites, respectively. Reduction in cholesterol absorption was strongly related to the initial level of absorbed cholesterol tracer in serum (r(s)=-0.739). Stanol-lecithin given in a beverage reduced total serum cholesterol by 10.1% (P=.0019, n=24) and LDL cholesterol by 14.3% (P=.0016, n=24).. Powdered soy stanol-lecithin lowers cholesterol absorption and LDL cholesterol when consumed in fat-free foods.

Topics: Adult; Anticholesteremic Agents; Cholesterol, Dietary; Cholesterol, LDL; Deuterium; Diet, Fat-Restricted; Double-Blind Method; Female; Glycine max; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Phosphatidylcholines; Sitosterols

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

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

Our aim was to test the hypocholesterolemic effect of a low-dose formulation of soy proteins supplemented with isolated b-sitosterol in a ratio of 4:1 in 20 moderately hypercholesterolemic subjects. The study has been divided in three different periods of forty days each: a stabilization diet period, then a treatment period during which all subjects assumed 10 g one time a day of the tested product and, finally, a wash out period. From the end of the stabilization diet period to the end of the soy protein added in b-sitosterol supplementation we observed a 0.45 +/- 0.30 mmol/L, 0.09 +/- 0.31 mmol/L and 0.17 +/- 0.22 mmol/L mean +/- SE decrease in respectively LDL-C, TG and apoB levels, associated with a 0.12 +/- 0.25 and 0.03 +/- 0.51 mg/dL mean increase respectively in HDL-C and apoA plasma concentrations. According to this recommends, low doses of soy protein added in b-sitosterol seems to be a practical and safe alternative for patients seeking modest reductions in LDL-C (< 15%).

Topics: Apolipoproteins A; Body Weight; Cholesterol, LDL; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Linear Models; Male; Middle Aged; Sitosterols; Soybean Proteins

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

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

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

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 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

This study compares the effect of plant stanol ester spread with a placebo spread on cholesterol in patients taking statin therapy, but who still had elevated low-density lipoprotein (LDL) cholesterol. This was a randomized, double-blind, placebo-controlled clinical trial, with 67 women and 100 men with LDL cholesterol >/=130 mg/dl and triglycerides

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Atorvastatin; Biomarkers; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Drug Therapy, Combination; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Male; Margarine; Middle Aged; Pravastatin; Pyrroles; Simvastatin; Sitosterols; Treatment Outcome; Triglycerides

We studied the rebound of lipoproteins in 20 hypercholesterolemic men [mean total cholesterol (TC) levels 9.6+/-1.8 mmol/l] after LDL-apheresis (LA) to determine the rate of recovery and the change in cholesterol synthesis, and to find a uniform estimation for time-averaged levels. After 10-20 months on biweekly LA using dextran sulfate cellulose columns and concomitant simvastatin administration, time-averaged levels (+/-SD) measured by integration of the area under the curve were as follows: TC 4.4+/-1.0 mmol/l, LDL cholesterol (LDL-C) 2.5+/-1.0 mmol/l, apolipoprotein B (apo B) 1. 3+/-0.3 g/l, triglycerides (TG) 1.7+/-0.7 mmol/l, HDL-C 1.1+/-0.2 mmol/l, and lipoprotein(a) [Lp(a)] 53.7+/-49.4 mg/dl. Mean acute reductions in TC, LDL-C, apo B, Lp(a), and TG were 61, 77, 75, 76, and 62%, respectively. HDL-C levels were not influenced. Median recovery half times for TC, LDL-C, apo B, and Lp(a) were 3.0, 4.0, 2. 3, and 3.5 days, respectively. The rebound of Lp(a) was identical to LDL-C, in 12 and 13 days post-treatment, respectively, whereas apo B and TC returned to pre-treatment levels in 7.5 and 10 days, respectively, due to the fast rebound of VLDL particles. Notwithstanding these differences, time-averaged levels (C(AVG)) could be estimated uniformly for the four latter parameters with the formula: C(AVG)=C(MIN)+0.73(C(MAX)-C(MIN)), where C(MAX) and C(MIN) are the immediate pre- and post-treatment levels. During long-term treatment the whole-body cholesterol synthesis was increased as measured by the ratio lathosterol to cholesterol of 3.24+/-1.49 mmol/mmol, whereas no further transient increase in the recovery period after LA was found. In conclusion, long-term LA and simvastatin therapy induced acute and chronic changes in lipids and lipoproteins showing the feasibility of biweekly treatment. It was shown that time-averaged levels, as a measure for the effective plasma levels, can be accurately estimated from pre- and post-treatment levels only.

Topics: Adult; Aged; Anticholesteremic Agents; Apolipoproteins B; Blood Component Removal; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipoprotein(a); Lipoproteins, LDL; Male; Middle Aged; Simvastatin; Sitosterols; Triglycerides

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

Full-fat sitostanol ester-containing margarine reduces serum total and LDL cholesterol, but the effect of plant stanol ester-containing margarine as part of a low-fat, low-cholesterol diet has not been studied.. We investigated the cholesterol-lowering effects of 2 novel, low-fat stanol ester-containing margarines as part of a low-fat diet recommended for hypercholesterolemic subjects.. In a parallel, double-blind study, 55 hypercholesterolemic subjects were randomly assigned after a 4-wk high-fat diet (baseline) to 3 low-fat margarine groups: wood stanol ester-containing margarine (WSEM), vegetable oil stanol ester-containing margarine (VOSEM), and control margarine (no stanol esters). The groups consumed the margarines for 8 wk as part of a diet resembling that of the National Cholesterol Education Program's Step II diet. The daily mean total stanol intake was 2.31 and 2.16 g in the WSEM and VOSEM groups, respectively.. During the experimental period, the reduction in serum total cholesterol was 10.6% (P < 0.001) and 8.1% (P < 0.05) greater and in LDL cholesterol was 13.7% (P < 0.01) and 8.6% (P = 0.072) greater in the WSEM and VOSEM groups, respectively, than in the control group. Serum campesterol concentrations decreased 34.5% and 41.3% (P < 0.001) in the WSEM and VOSEM groups, respectively. Serum HDL cholesterol, sitostanol, campestanol, beta-carotene, and fat-soluble vitamin concentrations did not change significantly from baseline.. We conclude that the low-fat, plant stanol ester-containing margarines are effective cholesterol-lowering products in hypercholesterolemic subjects when used as part of a low-fat, low-cholesterol diet. They offer an additional, clinically significant reduction in serum cholesterol concentrations to that obtained with a low-fat diet alone.

Topics: Adult; Anticholesteremic Agents; Antioxidants; beta Carotene; Cholesterol, HDL; Diet, Fat-Restricted; Double-Blind Method; Esters; Female; Finland; Humans; Hypercholesterolemia; Male; Margarine; Plant Oils; Sitosterols; Wood

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

We have shown earlier that sitostanol ester margarine lowers serum cholesterol by inhibiting cholesterol absorption so that, theoretically, there could be interference with the absorption of fat-soluble vitamins. Accordingly, we investigated whether sitostanol ester margarine affects the serum levels of vitamin D, retinol, alpha-tocopherol and alpha- and beta-carotenes during 1-year treatment in 102 subjects and 49 controls with moderate hypercholesterolemia. The vitamins were assayed at baseline on home diet, on margarine alone, after 1 year's consumption of sitostanol ester margarine and after an additional 2 months on home diet. In the sitostanol group, serum plant sterols, indicators of cholesterol absorption efficiency, were reduced up to -38% in relation to controls from home diet (P < 0.01) indicating that cholesterol absorption was markedly reduced. Vitamin D and retinol concentrations and the ratio of alpha-tocopherol to cholesterol were unchanged by sitostanol ester. Serum beta-carotenes and alpha-carotene concentration but not proportion were reduced in the sitostanol group from baseline and in relation to controls (P < 0.01). Retinol and vitamin D were unassociated with serum cholesterol, plant sterols or other vitamins, whereas alpha-tocopherol and carotenes were significantly associated with serum plant sterols suggesting that the higher cholesterol absorption efficiency, the higher the alpha-tocopherol and carotene levels in serum. We conclude that sitostanol ester did not affect vitamin D and retinol concentrations and alpha-tocopherol/cholesterol proportion, but reduced serum beta-carotene levels. Alpha-tocopherol and carotenes, but not vitamin D and retinol, were related to serum cholesterol and cholesterol absorption.

Topics: Adult; Anticholesteremic Agents; beta Carotene; Carotenoids; Cholesterol; Chromatography, High Pressure Liquid; Dietary Fats; Double-Blind Method; Humans; Hypercholesterolemia; Intestinal Absorption; Margarine; Middle Aged; Sitosterols; Vitamin A; Vitamin D; Vitamin E

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 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

Effectiveness of a simultaneous inhibition of cholesterol absorption and synthesis, caused by sitostanol ester margarine and pravastatin, was studied to control mild hypercholesterolemia in men with non-insulin-dependent diabetes mellitus (NIDDM) (n = 8). Margarine, 24 g daily, was a basal dietary treatment. Four 7-week intervention periods included margarine, sitostanol (3 g/day) ester margarine, pravastatin (40 mg/day), and sitostanol ester margarine plus pravastatin in a random order. Pravastatin lowered serum total (-32%) and LDL cholesterol (-38%) and apolipoprotein B (-39%) because of enhanced removal (+20%) and decreased production (-26%) of LDL apolipoprotein B, and reduced synthesis (-9%) and turnover (-8%) of cholesterol, which resulted in reduced biliary cholesterol seretion (-18%). Even though serum triglycerides were lowered by 28%, VLDL, IDL, and light and dense LDL became triglyceride-enriched. Despite increasing cholesterol synthesis, sitostanol lowered LDL cholesterol (-14%) by inhibiting cholesterol absorption (-68%) and LDL apolipoprotein B production rate (-20%). Combination of pravastatin and sitostanol ester lowered serum total, VLDL, IDL, and LDL cholesterol and LDL apolipoprotein B by the highest rate, 35%, 50%, 35%, 44%, and 45% from the control margarine period, respectively, because of reduced apolipoprotein B transport rate (but unchanged removal), in both the total and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics were unchanged. In spite of decreased absorption, cholesterol synthesis was not compensatorily increased. In conclusion, simultaneous inhibition of cholesterol absorption and synthesis lowers LDL cholesterol and apolipoprotein B by 44-45% solely through inhibition of LDL apolipoprotein B production rate in hypercholesterolemic NIDDM patients. A combination of statin to sitostanol ester margarine-resistant patients offers a safe and effective measure to normalize abnormally high cholesterol values, probably with a lowered statin dose.

Topics: Absorption; Anticholesteremic Agents; Blood Specimen Collection; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Patient Selection; Pravastatin; Sitosterols; Triglycerides

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

Plant sterols have been shown to reduce dietary cholesterol absorption and hence, total and low-density-lipoprotein (LDL)-cholesterol concentrations in humans. In this study the cholesterol-lowering effects of dietary supplementation with the hydrogenated plant sterol sitostanol (3 g/d) were tested in 33 men with moderate hypercholesterolemia who were consuming an outpatient diet in which dietary cholesterol was restricted to < 200 mg/d. Sitostanol therapy did not significantly lower LDL cholesterol compared with the diet alone. Similarly, sitostanol therapy in conjunction with a cholesterol-lowering regimen of diet and 8 g cholestyramine did not significantly lower LDL-cholesterol concentrations. Hence, although previous reports have suggested that low-dose sitostanol therapy is an effective means of reducing LDL-cholesterol concentrations, its effectiveness may be attenuated when the diet is low in cholesterol.

Topics: Adult; Aged; Cholesterol, Dietary; Cholestyramine Resin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols

Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 +/- 2, 12 +/- 6, 9 +/- 3 and 6 +/- 2%, mean +/- SEM, and HDL cholesterol was increased by 11 +/- 4% (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 +/- 2 to 9 +/- 2% (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Apolipoproteins A; Blood Glucose; Body Mass Index; Brassica; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Energy Intake; Fatty Acids, Monounsaturated; Glycated Hemoglobin; Humans; Hypercholesterolemia; Lipoproteins; Male; Margarine; Middle Aged; Phospholipids; Plant Oils; Rapeseed Oil; Sialic Acids; Sitosterols; Triglycerides; Vitamin E

Effects of small amounts of sitosterol, sitostanol and sitostanol esters (< 1 g/day of free sterols) dissolved in rapeseed oil (RSO) were studied on serum lipids and cholesterol metabolism in patients with primary hypercholesterolemia and different apolipoprotein E phenotypes on an RSO diet. One of the four groups was an RSO-fed control. Serum total and LDL cholesterol reductions were small in different plant sterol-fed groups, tended to be highest in the sitostanol ester group (-7%), but were significantly reduced by about 5% in the combined plant sterol groups. The reductions were -8% in the subjects with epsilon 4 allele and insignificant in those with apo E3/3 phenotype. Cholesterol precursor sterols in serum, markers of cholesterol synthesis, were increased only in the subjects with epsilon 4 allele. Cholesterol absorption was reduced by 7%, being 31% in the subjects with epsilon 4 allele, and fecal elimination of cholesterol was increased, a finding also indicating increased cholesterol synthesis. The changes in cholesterol absorption were related to those in fecal plant sterols (change in dietary intake) and serum total and LDL cholesterol (P = 0.04, 0.01 and 0.05, respectively). Thus, small amounts of dietary plant sterols (< 1 g/day), especially sitostanol esters dissolved in dietary fats, decrease serum total and LDL cholesterol by a proportional decrease in cholesterol absorption which, in turn, is associated with a compensatory increase in cholesterol synthesis. The effects are most consistent in subjects with epsilon 4 allele, but for effective hypocholesterolemic treatment dietary amount of sitostanol ester should exceed 1 g/day.

Topics: Absorption; Adult; Apolipoproteins E; Brassica; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phenotype; Plant Oils; Rapeseed Oil; Sitosterols; Triglycerides

1. Serum cholesterol reduction and changes in cholesterol metabolism were studied during rapeseed oil feeding without and with increasing amounts of sitostanol trans-esterified with rapeseed oil fatty acids and dissolved in rapeseed oil mayonnaise. Fifteen mildly hypercholesterolaemic subjects replaced 50 g of their usual dietary fat by 50 g of rapeseed oil fat mayonnaise for 6 weeks followed by randomization so that eight subjects continued on rapeseed oil mayonnaise alone (control group) for 15 weeks and seven on rapeseed oil mayonnaise with a small dose of sitostanol ester (800 mg/day of sitostanol) for 9 weeks followed by 6 weeks with higher dose of sitostanol ester (2000 mg/day of sitostanol). 2. During the rapeseed oil period the reduction in serum low-density lipoprotein cholesterol was 14% from the home diet. The control-adjusted reduction by the low sitostanol ester dose was 7.4% (not significant) and by the higher dose it was 15.7%. 3. The low dose of sitostanol ester had no consistent effect on cholesterol precursors or cholestanol in serum, reduced serum levels of campesterol and sitosterol by 28.2% and 23.6%, respectively, and reduced cholesterol absorption efficiency significantly from 28.7% to 23.4%. In accordance, faecal excretion of neutral and particularly endogenous neutral sterols increased (16.7% and 19.7%, respectively), but faecal cholesterol elimination and cholesterol synthesis were only insignificantly increased. 4. During the high dose of sitostanol ester the high-density lipoprotein-to low-density lipoprotein-cholesterol ratio increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Brassica; Cholesterol; Cholesterol, LDL; Dietary Fats, Unsaturated; Esterification; Feces; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Sitosterols

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

Effects of neomycin were studied on serum cholesterol and fecal steroids in hypercholesterolemic patients during a short treatment period (4 wk) and a long treatment period (16 mo), using small (1.5 g/d) and large (up to 6 g/d) doses alone and in combination with cholestyramine. In the short-term low-dose study the decrease in serum cholesterol by 21% was associated with a proportionate increase in fecal cholesterol elimination as neutral sterols through impaired cholesterol absorption. Serum cholesterol remained low and fecal steroid excretion remained elevated in the long-term neomycin study. Increasing the dosage from 1.5 to 6 g/d at the end of the 16-mo period brought about a further slight decrease in serum cholesterol and a small further increase in fecal neutral and acidic steroids. The increases in fecal bile acids and fat but not in neutral sterols were positively correlated with the increases in the neomycin dosage. Thus, large neomycin doses can also cause bile acid malabsorption. In another series of patients, a decrease (25%) in serum cholesterol by cholestyramine was associated with a proportional increase in the fecal elimination of cholesterol (2.5-fold) as bile acids. The inclusion of neomycin in cholestyramine therapy further increased fecal steroid output (solely as neutral sterols) by only about one-fifth of that due to cholestyramine, but further decreased serum cholesterol almost to the same extent (-17%) as cholestyramine alone. The overall decrease was 38%, no side effects occurred, and the patients found combination therapy convenient. Neomycin decreased serum cholesterol in different studies by 10+/-2, 17+/-4, and 12+/-4% per 100 mg/d of the increment in fecal steroids, the respective decrease for cholestyramine being only 2.2+/-0.5%. Thus, neomycin effectively reduced serum cholesterol by a relatively small increase in cholesterol elimination (via cholesterol malabsorption) compared with cholestyramine-induced bile acid malabsorption.

Topics: Adult; Bile Acids and Salts; Cholesterol; Cholestyramine Resin; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Feces; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Male; Middle Aged; Neomycin; Sitosterols

In a trial with 59 outpatients with hypercholesterolemia the effect of two different doses of 5.28 and 10,56 g Beta-Sitosterol was compared to placebo. Each treatment phase lasted six weeks. Serum cholesterol decreased on the average under Beta-Sitosterol by 10--13% (p less than 0.05) in correlation with LDL. The triglycerides were not affected; there was a slight increase in the HDL/LDL quotient. The optimal daily dose of Beta-Sitosterol was about 6 gm; the double dose was no more effective.

Topics: Aged; Dose-Response Relationship, Drug; Female; Humans; Hypercholesterolemia; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Sitosterols; Triglycerides

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

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

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

Topics: Cholesterol; Cholesterol, LDL; Desmosterol; Humans; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemia Type II; Lipids; Sitosterols; Squalene; Stigmasterol

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

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

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

The research was performed to delineate how β-sitosterol laurate (β-SLE) consumption influenced serum and hepatic lipids. The results showed that 220 mg/5 mL oil/kg body weight of β-SLE robustly reduced serum total triglyceride and cholesterol levels and the epididymal adipocyte size, and efficiently protected hepatic polyunsaturated fatty acids against lipid peroxidation through superoxide dismutase and glutathione transferase activity enhancement and malondialdehyde level reduction. Based on the changes of fecal cholesterol contents, fecal and hepatic bile acid (BAs) levels, and related protein expression, it was concluded that the mechanisms for lowering serum cholesterol by β-SLE involved (i) the enhanced excretion of fecal cholesterol via down-regulation of intestinal Niemann-Pick C1-like 1 protein; (ii) the increased conversion from cholesterol to primary BAs via up-regulation of cholesterol-7α-hydroxylase and sterol 27-hydroxylase, which was induced by the reduced BAs reabsorption through up-regulating ileal apical sodium-dependent bile acid transporter and ileal bile acid-binding protein.

Topics: Animals; Anticholesteremic Agents; Bile Acids and Salts; Carrier Proteins; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cricetinae; Fatty Acids, Unsaturated; Feces; Humans; Hypercholesterolemia; Ileum; Intestinal Absorption; Liver; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mesocricetus; Sitosterols; Triglycerides

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

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

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

People often hold unduly positive expectations about the outcomes of medicines and other healthcare products. Here the following explanation is tested: people who have a positive outcome tend to tell more people about their disease/treatment than people with poor or average outcomes. Akin to the file drawer problem in science, this systematically and positively distorts the information available to others.. If people with good treatment outcomes are more inclined to tell others, then they should also be more inclined to write online medical product reviews. Therefore, average treatment outcomes in these reviews should be more positive than those found in randomised controlled trials (RCTs). Data on duration of treatment and outcome (i.e., weight/cholesterol change) were extracted from user-generated health product reviews on Amazon.com and compared to RCT data for the same treatments using ANOVA. The sample included 1675 reviews of cholesterol reduction (Benecol, CholestOff) and weight loss (Orlistat) treatments and the primary outcome was cholesterol change (Bencol and CholestOff) or weight change (Orlistat).. People with good treatment outcomes are more inclined to share information about their treatment, which distorts the information available to others. People who rely on word of mouth reputation, electronic or real life, are likely to develop unduly positive expectations.

Topics: Bias; Data Accuracy; Humans; Hypercholesterolemia; Lactones; Orlistat; Outcome Assessment, Health Care; Research Design; Sitosterols; Therapeutics

The contribution of extra virgin olive oil (EVOO) macro- and micro-constituents in heart oxidative and inflammatory status in a hypercholesterolemic rat model was evaluated. Fatty acid profile as well as α-tocopherol, sterol, and squalene content was identified directly in rat hearts to distinguish the effect of individual components or to enlighten the potential synergisms.. Oils and oil-products with discernible lipid and polar phenolic content were used. Wistar rats were fed a high-cholesterol diet solely, or supplemented with one of the following oils, i.e., EVOO, sunflower oil (SO), and high-oleic sunflower oil (HOSO) or oil-products, i.e., phenolics-deprived EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], and HOSO enriched with the EVOO phenolics [HOSO(+)]. Dietary treatment lasted 9 weeks; at the end of the intervention blood and heart samples were collected.. High-cholesterol-diet-induced dyslipidemia was shown by increase in serum total cholesterol, low-density lipoprotein cholesterol, and triacylglycerols. Dyslipidemia resulted in increased malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels, while glutathione and interleukin 6 levels remained unaffected in all intervention groups. Augmentation observed in MDA and TNF-α was attenuated in EVOO, SO(+), and HOSO(+) groups. Heart squalene and cholesterol content remained unaffected among all groups studied. Heart α-tocopherol was determined by oil α-tocopherol content. Variations were observed for heart β-sitosterol, while heterogeneity was reported with respect to heart fatty acid profile in all intervention groups.. Overall, we suggest that the EVOO-polar phenolic compounds decreased MDA and TNF-α in hearts of cholesterol-fed rats.

Topics: alpha-Tocopherol; Animals; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet; Diet, High-Fat; Dyslipidemias; Fatty Acids; Glutathione; Hypercholesterolemia; Inflammation; Interleukin-6; Male; Malondialdehyde; Olive Oil; Oxidative Stress; Phenols; Plant Oils; Rats; Rats, Wistar; Sitosterols; Sunflower Oil; Triglycerides; Tumor Necrosis Factor-alpha

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

The type 1 cholecystokinin receptor (CCK1R) mediates the actions of CCK to support nutritional homeostasis, including post-cibal satiety. However, elevated levels of membrane cholesterol, such as have been observed in metabolic syndrome, interfere with CCK stimulus-activity coupling at the CCK1R, thereby disrupting this important servomechanism. We hypothesize that reversal of the negative impact of cholesterol on this receptor could be useful in the management of obesity.. We have studied the effects of β-sitosterol, a phytosterol structurally related to cholesterol, on CCK receptor function. This included CCK binding and biological activity at wild type CCK1R and CCK2R, as well as at CCK1R in a high cholesterol environment, and at a CCK1R mutant, Y140A, which mimics the behavior of wild type receptor in high cholesterol.. β-sitosterol (100 μM and 10 μM) significantly improved the defective signaling of the CCK1R present in high cholesterol (p < 0.05), without affecting CCK binding affinity. This effect was absent at the CCK1R present in a normal cholesterol environment, as well as at the structurally-related CCK2R. Furthermore, the cholesterol-insensitive Y140A mutant of CCK1R was resistant to the effects of β-sitosterol.. These data suggest that β-sitosterol affects CCK1R function in high cholesterol by competing with cholesterol at a receptor cholesterol-binding site and may shift its conformation toward normal. This phytosterol extends our understanding of the structure-activity relationships for developing a drug that can target the external surface of CCK1R. Since the concentrations of β-sitosterol shown to be effective in this study are similar to serum levels of this compound achievable during oral administration, it may be worthwhile to study possible beneficial effects of β-sitosterol in metabolic syndrome.

Topics: Animals; CHO Cells; Cricetulus; Gene Expression Regulation; Hypercholesterolemia; Hypolipidemic Agents; Receptor, Cholecystokinin A; Signal Transduction; Sitosterols

The present study (i) compared plasma cholesterol-raising activity of free cholesterol (FC) with that of cholesteryl palmitate (CP) and (ii) examined plasma cholesterol-reducing activity of β-sitosterol in FC-induced and CP-induced hypercholesterolemia. Male hamsters were divided into five groups and fed one of the five diets containing no cholesterol (NC), 2.6mmol cholesterol (C), 2.6mmol cholesterol plus 2.6mmol β-sitosterol (C+S), 2.6mmol cholesteryl palmitate (CP), and 2.6mmol CP plus 2.6mmol β-sitosterol (CP+S), respectively, for 8weeks. Hamsters fed diet C had plasma TC of 317.5mg/dl whereas hamsters fed diet CP has plasma TC of 281.3mg/dl. β-Sitosterol reduced plasma TC by 17.4% and 11.6%, respectively, in FC-induced and CP-induced hypercholesterolemia (not significant). It was concluded that plasma cholesterol-raising activity of dietary cholesterol was a function of its chemical forms in diet, and β-sitosterol could similarly suppress the hypercholesterolemia induced by both dietary FC and CP.

Topics: Animals; Cholesterol Esters; Cholesterol, Dietary; Cholesterol, HDL; Cricetinae; Feces; Hypercholesterolemia; Liver; Male; Mesocricetus; Sitosterols; Triglycerides

Cholesterol analogs can be used to treat hypercholesterolemia. The present study was to test the effects of cholesteryl 3β-ethoxy (CE) and cholesteryl 3β-methoxy (CM) on plasma total cholesterol (TC) compared with that of β-sitosterol (SI) in hamsters fed a high cholesterol diet. CM and CE are the methoxy and ethoxy analogs of cholesterol while SI is an analog of cholesterol having an additional ethyl group on the side chain. Results showed that SI at a dose of 0.1% could effectively reduce plasma TC by 18%. The analysis of sterols in the plasma and liver did not detect the presence of SI, proving that it was poorly absorbed in the intestine. In contrast, both CE and CM had no effect on plasma TC. However, CE and CM were found to accumulate in both plasma and liver, indicating that they could be well absorbed in the intestine. It was therefore concluded that analogs having different side chains possessed plasma TC-lowering activity, while analogs or derivatives on the hydroxyl group had no hypocholesterolemic activity.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, Dietary; Cricetinae; Diet, High-Fat; Feces; Hypercholesterolemia; Liver; Male; Organ Size; Sitosterols; Sterols

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

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

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

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

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

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

It is unclear whether plant stanols lower serum LDL-cholesterol concentrations and cholesterol-standardized fat-soluble antioxidant concentrations dose-dependently when consumption exceeds the recommended daily intakes of 2.0-3.0 g.. The objective was to study the relation between plant stanols provided as plant stanol esters on changes in serum concentrations of LDL cholesterol and fat-soluble antioxidants.. Healthy subjects (n = 93) with slightly elevated serum total cholesterol concentrations (5.0-8.0 mmol/L) received, after a 3-wk run-in period, control products (n = 22) or products (margarine and soy-based yogurt) providing 3 g (n = 24), 6 g (n = 22), or 9 g (n = 25) plant stanols provided as fatty acid esters for 4 wk.. Serum LDL cholesterol decreased dose-dependently. Compared with control, decreases in the 3-g group were 0.32 mmol/L (7.4%; P = 0.005 after adjustment for multiple comparisons). An intake of 6 g plant stanols caused an additional decrease of 0.18 mmol/L (4.5%; P = 0.100 compared with the 3-g group). In the 9-g group, a further decrease of 0.22 mmol/L (5.4%) was observed (P = 0.048 compared with the 6-g group). Serum LDL-cholesterol concentrations were lowered by 17.4% in the 9-g group compared with the control group. No effects on cholesterol-standardized beta-carotene concentrations were observed. Even the change of -0.01 mumol/mmol cholesterol (or -9.2%; P = 0.341) in the 3-g group compared with the control group was not statistically significant because of the large variation in response. Serum HDL-cholesterol and triacylglycerol concentrations, cholesterol-standardized alpha-tocopherol and lutein concentrations, and plasma markers reflecting liver and renal function were not affected.. Daily consumption of plant stanols up to 9 g reduces serum LDL-cholesterol concentrations linearly up to 17.4%. For cholesterol-standardized fat-soluble antioxidant concentrations, such a relation could not be ascertained.

Topics: Adult; Aged; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Male; Margarine; Middle Aged; Reference Values; Sitosterols; Triglycerides; Yogurt

Whole-genome sequencing is a potentially powerful tool for the diagnosis of genetic diseases. Here, we used sequencing-by-ligation to sequence the genome of an 11-month-old breast-fed girl with xanthomas and very high plasma cholesterol levels (1023 mg/dl). Her parents had normal plasma cholesterol levels and reported no family history of hypercholesterolemia, suggesting either an autosomal recessive disorder or a de novo mutation. Known genetic causes of severe hypercholesterolemia were ruled out by sequencing the responsible genes (LDLRAP, LDLR, PCSK9, APOE and APOB), and sitosterolemia was ruled out by documenting a normal plasma sitosterol:cholesterol ratio. Sequencing revealed 3 797 207 deviations from the reference sequence, of which 9726 were nonsynonymous single-nucleotide substitutions. A total of 9027 of the nonsynonymous substitutions were present in dbSNP or in 21 additional individuals from whom complete exonic sequences were available. The 699 novel nonsynonymous substitutions were distributed among 604 genes, 23 of which were single-copy genes that each contained 2 nonsynonymous substitutions consistent with an autosomal recessive model. One gene, ABCG5, had two nonsense mutations (Q16X and R446X). This finding indicated that the infant has sitosterolemia. Thus, whole-genome sequencing led to the diagnosis of a known disease with an atypical presentation. Diagnosis was confirmed by the finding of severe sitosterolemia in a blood sample obtained after the infant had been weaned. These findings demonstrate that whole-genome (or exome) sequencing can be a valuable aid to diagnose genetic diseases, even in individual patients.

Topics: Base Sequence; Cholesterol; Female; Genome; Humans; Hypercholesterolemia; Infant; Pedigree; Sequence Analysis, DNA; Sitosterols

Topics: Allylamine; Azetidines; Colesevelam Hydrochloride; Diet, Mediterranean; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Muscular Diseases; Niacin; Pain; Sitosterols

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

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

A newly developed high-performance liquid chromatography/mass spectrometry (HPLC/MS) method has been successfully used to analyze plasma concentrations of various phytosterols (cholestanol and beta-sitosterol) and cholesterol metabolites (desmosterol and lathosterol). This was based on an unusual solvent combination of water/methanol vs. methanol/acetone/n-hexane applied on a Purospher Star RP-18e (125 x 2 mm, 3 microm) column, which proved excellent for the separation, identification and quantification of plasma sterols. Simple solid-phase extraction preparation of plasma samples was performed, followed by the developed fast and robust HPLC separation. Results on four groups of people were compared, those with low, normal and high plasma cholesterol levels and those with high cholesterol levels on statin therapy, and the results were evaluated using linear discriminant analysis (LDA). Variable selection for LDA was achieved using backward removal selection. Highly discriminatory variables were the ratios of desmosterol to sitosterol and of lathosterol to total plasma cholesterol. The latter ratio was also excellent for distinguishing subjects on statin therapy. The success rate of classification was 100%. The present pilot study shows the potential of HPLC/MS analysis and chemometrics for studying cholesterol-related disorders and warrants future full-scale medical study.

Topics: Cholestanol; Cholesterol; Chromatography, High Pressure Liquid; Desmosterol; Discriminant Analysis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Mass Spectrometry; Pilot Projects; Sitosterols; Sterols

The ratio of serum plant sterols to cholesterol is positively correlated with the fractional cholesterol absorption, whereas serum precursors of cholesterol synthesis are positively correlated with cholesterol synthesis. Recently, two ABC (ATP-binding cassette) transporters, ABCG5 and ABCG8, have been described as playing an important role in the absorption and excretion of sterols. In the present study, we tested the hypothesis that genetic variation in ABCG5/ABCG8 influences the levels of serum plant sterol (sitosterol) and cholesterol precursor (lathosterol) in Japanese primary hypercholesterolaemic patients (n = 100). We identified a novel mutation [859T/C (C287R)] and a novel polymorphism [1285A/G (M429V)] at the ABCG5/ABCG8 loci, as well as four polymorphisms reported previously [1810C/G (Q604E), 161G/A (C54Y), 1199C/A (T400K) and 1895C/T (A632V)]. In carriers of the novel M429V variant, the serum level of sitosterol and the sitosterol/cholesterol ratio were significantly higher than those in non-carriers (3.64 compared with 2.56 microg/ml, and 1.45 microg/mg compared with 1.00 microg/mg respectively; P < 0.01 for both), and serum lathosterol tended to be lower (1.95 microg/ml compared with 3.03 microg/ml; P = 0.08), whereas no significant difference was observed in other lipid profiles. These four polymorphisms (1810C/G, 161G/A, 1199C/A and 1285A/G) generated six haplotypes, and the C/G/C/G haplotype was significantly associated with a higher sitosterol level and sitosterol/cholesterol ratio compared with the other five haplotypes (P < 0.05 for both). We conclude that, in 8% of patients with hypercholesterolaemia, the novel ABCG8 M429V variant was associated with higher cholesterol absorption efficiency. Future studies should investigate whether these findings have implications for the optimal cholesterol-lowering drug treatment in hypercholesterolaemic patients.

Topics: Adult; Aged; Aged, 80 and over; ATP-Binding Cassette Transporters; Biomarkers; Cholesterol; Female; Genetic Markers; Heterozygote; Humans; Hypercholesterolemia; Intestinal Absorption; Japan; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Sitosterols

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

The aims of this study were to investigate the consistency of use of plant stanol ester margarine and to characterise consistent and inconsistent users.. A cohort of plant stanol ester margarine users was established based on 14 national surveys conducted by the National Public Health Institute in Finland between 1996 and 1999. A follow-up study questionnaire was developed and sent to 1294 users in 2000.. Subjects who reported using plant stanol ester margarine in both the original survey and the follow-up study were classified as consistent users, and the rest as inconsistent users.. The study population consisted of 1094 subjects aged 18-87 years, 590 men and 504 women.. There were 357 (33%) consistent and 737 (67%) inconsistent users of plant stanol ester margarine in the study population. Consistent users were more likely to be men and to have a higher household income than inconsistent users. Both consistent and inconsistent users were predominantly middle-aged persons with a healthy lifestyle and diet as well as a history of cardiovascular disease. Healthfulness was the main factor affecting bread spread choice among 94% of the consistent users and 59% of the inconsistent users.. The use of plant stanol ester margarine is more often inconsistent than consistent. There is nevertheless a relatively large subgroup of long-term users of plant stanol ester margarine. It is important to examine the health effects especially among these regular users.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Cardiovascular Diseases; Cohort Studies; Diet Surveys; Female; Finland; Humans; Hypercholesterolemia; Income; Life Style; Male; Margarine; Middle Aged; Sex Factors; Sitosterols

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

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

We measured serum cholesterol concentrations and synthesis markers (e.g. serum lathosterol to cholesterol ratio), and absorption markers (e.g. serum campesterol to cholesterol ratio) of cholesterol in 319 good responders (GR; dose 20 mg up to 1 year) and in 115 poor responders (PR; dose increased at 6 weeks to 40 mg) among Finnish participants in the Scandinavian Simvastatin Survival Study at baseline, 6 weeks and 1 year of the simvastatin treatment. The baseline cholesterol level and the ratios of the absorption markers were higher and those of the synthesis markers lower in PR than GR. The ratios of the precursor sterols were negatively related to the baseline cholesterol in GR only (P=0.003). The cholesterol levels, and the ratios of the precursor sterols were decreased and those of the absorption marker sterols increased less consistently in PR than GR by 20 mg, the group differences being only slightly lessened by the dose addition to 40 mg. One-year differences were still frequently significant. The baseline cholesterol concentrations were negatively related to the reduction of the precursor sterol ratios in GR, the change of cholesterol being positively related to those of the synthesis markers and negatively to those of the absorption markers only in PR. Thus, patients needing large statin dose for cholesterol normalization have high absorption and low synthesis of cholesterol, yet baseline synthesis is inversely related to cholesterol level only in GR. The synthesis rate is less markedly reduced by the large than by the small statin dose in the PR, and the reduction is related, in contrast to that in the GR, to lowering of cholesterol.

Topics: Cholestanol; Cholesterol; Desmosterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Simvastatin; Sitosterols

Recent large-scale trials have consistently documented the fact that a 25-35% reduction in low-density lipoprotein cholesterol (LDL-C) can delay the progression of atherosclerosis. This raises the question as to how much it is possible to reduce serum cholesterol using feasible therapies. The aim of this study was to investigate the cholesterol-lowering efficacy of a triple therapy combining bile acid malabsorption with the inhibition of cholesterol synthesis and absorption.. Eleven consecutive hypercholesterolemic coronary patients from Lipid Clinics on a low-fat, low-cholesterol baseline diet added simvastatin (20 mg/day) for three months, and then dietary plant stanol ester margarine (2.25 g of stanols/day) for eight weeks; finally, cholestyramine 8 g/day was added for another eight weeks. This was a before-after trial, in which the results of each period were compared with baseline and those of the previous period. Serum lipids were quantitated using commercial kits, and serum sterols by means of gas-liquid chromatography. Simvastatin lowered LDL-C by 39% (p < 0.001), and additional stanol ester margarine by a further 13% (p < 0.05). The triple treatment led to 67% reduction from baseline (p < 0.001), with all LDL-C values being < 2.6 mmol/L, and increased high-density lipoprotein cholesterol (HDL-C) by 15% (p < 0.01). It also increased the serum lathosterol/cholesterol ratio (p < 0.01), thus indicating an upregulation of cholesterol synthesis, and increased the serum sitosterol ratio (p < 0.01) despite the simultaneous consumption of plant stanols.. The massive reduction in LDL and increase in HDL-C obtained using our triple therapy suggests that the combination of stanol ester with only moderate doses of statin and resin makes it possible to control LDL-C levels effectively in hypercholesterolemic subjects.

Topics: Aged; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Cholestyramine Resin; Coronary Artery Disease; Diet, Fat-Restricted; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Intestinal Absorption; Male; Simvastatin; Sitosterols; Treatment Outcome

Topics: Avena; Cholesterol, Dietary; Dietary Fats; Exercise; Humans; Hypercholesterolemia; Sitosterols

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

Topics: Cholesterol, LDL; Heart Diseases; Humans; Hypercholesterolemia; Intestinal Absorption; Margarine; Sitosterols

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

This paper describes a novel method of producing a microcrystalline oral suspension containing beta-sitosterol in oil for the treatment of hypercholesterolaemia. beta-Sitosterol pseudopolymorphs with different water contents were crystallized from acetone and acetone-water solutions. Structural analyses of the crystals were performed by Karl-Fisher titration, thermogravimetric analyses, X-ray diffraction and near infrared spectroscopy. The suspensions studied were composed of different concentrations of beta-sitosterol, oil and water. Suspensions were prepared by crystallization of hot concentrated solution of beta-sitosterol in oil by cooling with simultaneous agitation and water addition. The structural analyses of the suspensions were performed by X-ray diffraction, near infrared spectroscopy and optical microscopy. The viscosity of the suspensions was analysed as a function of shear stress. beta-Sitosterol was observed to exist in three different forms: anhydrous, hemihydrated and monohydrated crystals. By changing both the beta-sitosterol and the water concentration of the suspension, the crystal size and shape could be controlled. Addition of water resulted in the formation of monohydrated needle-shaped crystals instead of platy-like anhydrous crystals. Needle-shaped particles formed structured suspensions with shear thinning behaviour. By increasing the volume fraction of solid particles in suspension by increasing the water and/or sterol concentration, the viscosity increased. A high sterol concentration resulted in high supersaturation and thus formation of small crystals.

Topics: Administration, Oral; Chemistry, Pharmaceutical; Crystallization; Hypercholesterolemia; Hypolipidemic Agents; Oils; Rheology; Sitosterols; Spectroscopy, Near-Infrared; Suspensions; Technology, Pharmaceutical; Thermogravimetry; X-Ray Diffraction

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

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Cholesterol, Dietary; Humans; Hypercholesterolemia; Lipoproteins; Mutation; Sitosterols

Topics: Humans; Hypercholesterolemia; Hypolipidemic Agents; Margarine; Sitosterols

Topics: Alcohol Drinking; Cholesterol; Dietary Fiber; Female; Garlic; Humans; Hypercholesterolemia; Male; Nuts; Plants, Medicinal; Sitosterols; Soybean Proteins

Topics: Anticholesteremic Agents; Cholesterol, LDL; Coronary Disease; Humans; Hypercholesterolemia; Male; Pravastatin; Sitosterols

We investigated the effect of cholesterol feeding on plasma cholesterol concentrations, hepatic activities and mRNA levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase and hepatic LDL receptor function and mRNA levels in 23 New Zealand White (NZW) and 17 Watanabe heritable hyperlipidemic (WHHL) rabbits. Plasma cholesterol concentrations were 9.9 times greater in WHHL than NZW rabbits and rose significantly in both groups when cholesterol was fed. Baseline liver cholesterol levels were 50% higher but rose only 26% in WHHL as compared with 3.6-fold increase with the cholesterol diet in NZW rabbits. In both rabbit groups, hepatic total HMG-CoA reductase activity was similar and declined > 60% without changing enzyme mRNA levels after cholesterol was fed. In NZW rabbits, cholesterol feeding inhibited LDL receptor function but not mRNA levels. As expected, receptor-mediated LDL binding was reduced in WHHL rabbits. Hepatic cholesterol 7 alpha-hydroxylase activity and mRNA levels were 2.8 and 10.4 times greater in NZW than WHHL rabbits. Unexpectedly, cholesterol 7 alpha-hydroxylase activity was reduced 53% and mRNA levels were reduced 79% in NZW rabbits with 2% cholesterol feeding. These results demonstrate that WHHL as compared with NZW rabbits have markedly elevated plasma and higher liver cholesterol concentrations, less hepatic LDL receptor function, and very low hepatic cholesterol 7 alpha-hydroxylase activity and mRNA levels. Feeding cholesterol to NZW rabbits increased plasma and hepatic concentrations greatly, inhibited LDL receptor-mediated binding, and unexpectedly suppressed cholesterol 7 alpha-hydroxylase activity and mRNA to minimum levels similar to WHHL rabbits. Dietary cholesterol accumulates in the plasma of NZW rabbits, and WHHL rabbits are hypercholesterolemic because reduced LDL receptor function is combined with decreased catabolism of cholesterol to bile acids.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Bile Acids and Salts; Blotting, Northern; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Dose-Response Relationship, Drug; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Lipoproteins, LDL; Liver; Protein Binding; Rabbits; Receptors, LDL; RNA, Messenger; Sitosterols

The degree of serum cholesterol lowering by up to almost maximal inhibition of cholesterol absorption was tested during neomycin and neomycin + sitostanol treatment in six hypercholesterolemic men. Neomycin decreased cholesterol absorption efficiency by 49% and the combination by 79%, and serum cholesterol level by 27% and 36%, respectively. The correlation between the absorption percentage and low density lipoprotein (LDL) cholesterol was significant (r = 0.510), and the regression equation (y = 0.04x + 2.59) suggested that the mean LDL cholesterol content would be about 2.5 mmol/l at zero cholesterol absorption. In conclusion, in hypercholesterolemic subjects, the lowering of LDL cholesterol appears to be limited to a low normal range only by almost totally inhibiting cholesterol absorption.

Topics: Absorption; Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Humans; Hypercholesterolemia; Male; Middle Aged; Neomycin; Sitosterols

Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n = 13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH (n = 14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20%, and increased the pravastatin-lowered precursor:cholesterol ratios by 20% (irrespective of ileal bypass). It also reduced by 20% the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45%, 53% and 17%, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticholesteremic Agents; Cholesterol; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Absorption; Male; Middle Aged; Neomycin; Pravastatin; Sitosterols

The continuous isotope feeding method of Crouse and Grundy (1978. J. Lipid Res. 19: 967-971) for measurement of dietary cholesterol absorption has been modified by using markers labeled with stable isotopes ([2,2,4,4,6-2H5]cholesterol or [25,26,26,26,27,27,27-2H4]cholesterol or [26,26,26,27,27,27-2H6] cholesterol and [5,6,22,23-2H4]sitostanol) quantified by gas-liquid chromatography-selected ion monitoring. Tracing of the isotope distribution of the authentic markers and after their intestinal passage, including the microbiological products (coprostanol and coprostanone) revealed stability of the labels. The new method was evaluated in six monkeys on two occasions by comparison with the original method using radioactively labeled cholesterol and sitosterol. The results obtained by the two different methods were in excellent agreement, and absorption ranged from 49% to 73% (mean 60%) for the stable isotope method and from 51% to 69% (mean 62%) for the radioactive method. The coefficient of variation of cholesterol absorption in animals ranged from 3.9% to 15.1% (mean 7.1%) for stable isotopes and 1.9% to 13.6% (mean 5.7%) for radioactive isotopes. In twelve subjects cholesterol absorption was measured by the new method from total fecal samples frozen immediately and compared to results obtained from small fecal aliquots (approximately 1 g) sent by ordinary mail to the laboratory. A significant correlation of cholesterol absorption between the two different sample handlings was obtained (r = 0.981, P < 0.001). In addition, measurement of cholesterol absorption twice in seven volunteers 2 weeks apart revealed identical results. Thus, the new method is extremely safe and reproducible without radioactive exposure to the subjects and labortory staff and can be used on women of child-bearing age.

Topics: Animals; Cholesterol; Cryopreservation; Deuterium; Feces; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Intestinal Absorption; Macaca fascicularis; Male; Sitosterols

The aim of the present study was to investigate the effect of the hydroxymethylglutaryl (HMG)-CoA reductase inhibitor lovastatin on some aspects of cholesterol metabolism in cholesterol-fed rabbits. The plasma cholesterol concentration was markedly lower in lovastatin-treated rabbits (6 mg/rabbit/day) compared to controls after 36 days of cholesterol-feeding (x +/- S.E.) (19 +/- 4 mmol/l, n = 9 versus 153 +/- 17 mmol/l, n = 7) (P < 0.00001). Intestinal absorption of cholesterol in such rabbits was reduced by 15% in lovastatin-treated rabbits (n = 21) compared to controls (n = 18) (P < 0.025). The results suggest that the hypocholesterolaemic effect of lovastatin in cholesterol-fed rabbits is associated with a decreased intestinal absorption of cholesterol.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Hypercholesterolemia; Intestinal Absorption; Lovastatin; Male; Rabbits; Sitosterols

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

In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary saturated versus polyunsaturated fatty acids, the efficiency of intestinal cholesterol absorption was measured. The feeding of a cholesterol-free purified diet containing saturated fatty acids in the form of coconut fat, when compared with a diet containing corn oil as polyunsaturated fatty acids, did not influence the efficiency of cholesterol absorption in the two rabbit strains. Irrespective of the dietary fat source, the hyperresponsive rabbits absorbed cholesterol more efficiently. It is concluded that the hypercholesterolemic effect of dietary coconut fat versus corn oil is not exerted by influencing cholesterol absorption.

Topics: Animals; Body Weight; Cholesterol; Cholesterol, Dietary; Coconut Oil; Cocos; Corn Oil; Dietary Fats; Feeding Behavior; Hypercholesterolemia; Intestinal Absorption; Liver; Male; Plant Oils; Rabbits; Sitosterols; Species Specificity

In this report, an 11-year-old boy with diffuse tendinous and tuberous xanthomatosis and a plasma sterol concentration of 555 mg/dL, consisting primarily of cholesterol, is described. Three months after changing from an unrestricted diet to a cholesterol-lowering diet, his plasma sterol concentration decreased to 221 mg/dL. Because of the degree and rapidity of his response to diet, sitosterolemia was suspected. According to results of capillary gas-liquid chromatography of his plasma sterols, there was a sitosterol concentration of 31.3 mg/dL (normal less than 1.0 mg/dL), establishing the diagnosis of sitosterolemia. Addition of cholestyramine therapy (8 g/d) to a low sterol diet further lowered his plasma sterol concentration to 173 mg/dL and led to complete regression of all tuberous xanthomata. Tendinous xanthomata regressed at a slower rate. These findings show that the diagnosis of sitosterolemia should be suspected in severely hypercholesterolemic children (total cholesterol greater than 400 mg/dL) whose plasma cholesterol level is highly responsive to dietary manipulation. The rapid and sustained lowering of plasma cholesterol and regression of xanthomata after treatment with diet and cholestyramine suggest that sitosterolemia is a treatable cause of premature atherosclerosis.

Topics: Arteriosclerosis; Child; Cholestyramine Resin; Combined Modality Therapy; Humans; Hypercholesterolemia; Lipid Metabolism, Inborn Errors; Male; Sitosterols; Xanthomatosis

A group of 28 patients with primary hyperlipoproteinaemia [19X lipoprotein (LP) type IIA, 8X type IIB and 1X a normolipidaemic patient with concurrent hyperapoB lipoproteinaemia] were given for a period of three weeks a dietetic preparation containing phytosterols - 12 g/day. This led to a significant drop of total cholesterol and LDL-cholesterol in plasma. The cholesterol concentration in HDL and both its fractions increased, the differences however were not significant. The triglyceride levels did not change. There was a significant drop of the apolipoprotein B (apo-B) concentration in LDL, the apo-A-I in plasma did not change. There was a significant drop of atherogenic indexes TC/HDL-C, LDL-C/HDL-C and apo-B/-A-I. During investigation of the LCAT activity the authors observed a significant rise of the fractional esterification rate associated with a highly significant drop of the free cholesterol concentration in plasma as a result of treatment. Discrimination analysis of parameters of the lipoprotein metabolism and the patients' body weight before treatment helps to assess a function by means of which it is possible in 92.3% of the subjects to predict the success of treatment before the administration of beta-sitosterol.

Topics: Female; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Sitosterols

Platelets from rats with diet-induced or genetically determined hypercholesterolemia are hypersensitive to thrombin through a pathway that is independent of the effects of released ADP or formation of thromboxane A2. We examined production of inositol phosphates by platelets from these hypercholesterolemic rats to determine whether the enhanced responsiveness to thrombin is associated with increased production of inositol trisphosphate (IP3). The opportunity to study rats with hypercholesterolemia determined genetically or induced by diet makes it possible to determine whether any differences in inositol phosphate production are caused by hypercholesterolemia alone rather than to any other effect of the diet used to induce hypercholesterolemia. Platelets were prelabeled with [3H]inositol so that increases in inositol phosphates (IP, IP2, and IP3) upon stimulation with thrombin could be assessed by measuring the amount of label in these compounds. Platelets were preincubated with CP/CPK, to inhibit effects of released ADP, and aspirin, to inhibit formation of thromboxane A2/endoperoxides. In platelets from rats with either form of hypercholesterolemia, the percentage increase in labeling of IP3 was significantly greater 30 seconds after stimulation with low concentrations of thrombin than in platelets from control rats. Increased IP3 formation in platelets from hypercholesterolemic rats indicates that there is increased activity of a pathway(s) leading to IP3 formation and that this may be a mechanism responsible for the thrombin-induced hypersensitivity of these platelets.

Topics: Animals; Aspirin; Blood Platelets; Cholesterol, Dietary; Creatine Kinase; Hypercholesterolemia; Inositol; Inositol Phosphates; Kinetics; Male; Phosphocreatine; Platelet Aggregation; Rats; Rats, Inbred Strains; Sitosterols; Thrombin

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

Platelets from rats made hypercholesterolaemic with a diet enriched with milk fat and cholesterol and containing taurocholate to promote hypercholesterolaemia aggregated more extensively to a low concentration of thrombin than platelets from rats given a milk fat-enriched diet containing sitosterol. Total and specific binding of thrombin to platelets from hypercholesterolaemic rats was significantly greater than in controls when expressed per mg platelet protein, per mumol platelet cholesterol, or per unit relative surface area. Total and specific binding of thrombin per platelet were not different between the groups. However, platelets from hypercholesterolaemic rats had less protein and cholesterol, were smaller and had less surface area than control platelets; platelet cholesterol content expressed per mg platelet protein was not different. Thus, the increase in thrombin-binding to the smaller platelets from hypercholesterolaemic rats during the first 10 s after its addition may be responsible, at least in part, for the hypersensitivity of these platelets to thrombin.

Topics: Animals; Blood Platelets; Cholesterol; Cholesterol, Dietary; Dietary Fats; Hypercholesterolemia; Male; Milk; Protein Binding; Rats; Rats, Inbred Strains; Sitosterols; Taurocholic Acid; Thrombin

Topics: Animals; Cholesterol, Dietary; Humans; Hypercholesterolemia; Sitosterols

Sitostanol (24-ethyl-5 alpha-cholestan-3 beta-ol), a hydrogenated derivative of sitosterol, was administered in a low dose (1.5 g/day) for 4 weeks to 6 patients with hypercholesterolemia. Total cholesterol was reduced significantly after 3 and 4 weeks by 10 and 15%, respectively. The reduction of total cholesterol was entirely due to a fall in LDL cholesterol. Total triglycerides and HDL cholesterol were not altered. Two weeks after cessation of sitostanol administration serum cholesterol returned to pretreatment levels. No significant amounts of sitostanol could be detected in plasma during therapy. These results suggest that low-dose sitostanol might be a useful hypolipidemic agent for the treatment of mild hypercholesterolemia.

Topics: Adult; Cholesterol; Cholesterol, LDL; Dose-Response Relationship, Drug; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols

Topics: Amino Acids, Branched-Chain; Brain Diseases; Choline; Diet; Dyskinesia, Drug-Induced; Hepatic Encephalopathy; Humans; Huntington Disease; Hypercholesterolemia; Lactulose; Memory Disorders; Phosphatidylcholines; Sitosterols; Synaptic Transmission

Cholesterol absorption was measured in chronically hypercholesterolemic dogs by four methods: the fecal recovery method of Borgström (1969, J. Lipid Res. 10: 331-337), the dual isotope method of Zilversmit and Hughes (1974, J. Lipid Res. 15: 465-473), the recovery of cholesterol in thoracic duct lymph collected continuously for 16 hr after a meal, and the recovery of isotopic cholesterol from the liver and plasma 24 hr after the animals consumed an isotope-containing meal. The four methods showed excellent agreement and indicated that dogs fed a cholesterol-rich synthetic diet absorb 5.2 +/- 0.5 g (mean +/- SD) of cholesterol per day and that cholesterol absorption is reasonably constant from week to week in these animals. Separate estimates of cholesterol excretion indicated that these dogs excreted 4.7 +/- 0.5 g of cholesterol per day, and thus were at or near the steady-state with regard to cholesterol input-output. These data, taken together with a previous report (1981, J. Lipid Res. 22: 598-609), indicate that the canine liver can clear up to 300 mg of chylomicron cholesterol/hr, and support the concept that chylomicron remnants do not contribute significantly to the hypercholesterolemia in these animals.

Topics: Animals; Bile; Cholesterol; Cholesterol, Dietary; Chylomicrons; Dogs; Feces; Female; Hypercholesterolemia; Intestinal Absorption; Liver; Lymph; Male; Micelles; Sitosterols; Solubility

The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2-fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Circadian Rhythm; Diabetes Mellitus, Experimental; Eating; Feces; Hypercholesterolemia; Intestinal Absorption; Male; Rats; Rats, Inbred Strains; Reference Standards; Sitosterols; Tissue Distribution

Alterations in lipid content of microvilli membranes, affecting their physical structure, as well as in lipoproteins of rat small intestinal mucosa and of blood plasma were studied in experimental hypercholesterolemia after treatment with crystalline and liposomal preparations of beta-sitosterol. The liposomal preparation of beta-sitosterol exhibited distinctly higher hypocholesterolemic activity as compared with the crystalline sterol. Possible role of structural and functional alterations in enterocyte membranes and in intestinal lipoproteins during absorption of cholesterol as well as inhibition of the processes by means of beta-sitosterol are discussed.

Topics: Animals; Hypercholesterolemia; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Lipid Metabolism; Lipids; Liposomes; Membranes; Microvilli; Phospholipids; Rats; Sitosterols

Topics: Adult; Child; Costs and Cost Analysis; Diet; Food Analysis; Humans; Hypercholesterolemia; Infant; Male; Prostatic Hyperplasia; Sitosterols

Topics: Cholesterol; Cholesterol, Dietary; Dietary Carbohydrates; Dietary Fiber; Energy Metabolism; Glucose; Glycine max; Humans; Hypercholesterolemia; Plant Proteins; Sitosterols; Starch

Every permanent substantiated primary hypercholesterolemia which does not respond adequately to diet must be treated with drugs. For monotherapy first of all fenofibrate, bezafibrate and nicotinic acid derivatives are suitable for the treatment of adult patients. For supportive therapy colestyramine and colestipol come into consideration as well as beta-sitosterol. D-thyroxine and etiroxate should be reserved for refractory cases. Drug therapy is only given for secondary hypercholesterolemias in justifiable exceptions.

Topics: Adult; Bezafibrate; Cholestyramine Resin; Clofibric Acid; Colestipol; Dextrothyroxine; Fenofibrate; Humans; Hypercholesterolemia; Neomycin; Nicotinic Acids; Sitosterols

Topics: Adult; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols

Topics: Cholestyramine Resin; Clofibrate; Colestipol; Dextrothyroxine; Humans; Hypercholesterolemia; Nicotinic Acids; Probucol; Sitosterols

A report on the effects of primary bile acid ingestion alone or in combination with plant sterols on serum cholesterol levels, biliary lipid secretion, and bile acid metabolism. Biliary bile acid and cholesterol secretion were measured in four patients with type IIa hypercholesterolemia before and after randomized treatment periods. During these periods either a bile acid mixture (cholic-chenodeoxycholic 2:1, a proportion similar to that endogenously synthesized in health), at a level of 20 mg/kg, or the same mixture plus sitosterols, 200 mg/kg, was fed. Serum cholesterol and the cholesterol saturation of fasting-state bile was also measured. Pretreatment biliary lipid secretion was within normal limits. Bile acid kinetic measurements were also recorded before treatment and showed that cholic acid synthesis was disproportionately decreased relative to that of chenodeoxycholic acid, a finding previously reported by others. Administration of the bile acid mixture increased biliary bile acid secretion in 3 of 4 patients, but did not influence biliary cholesterol secretion. The combination of sitosterol-bile acid, however, caused a relative decrease in cholesterol secretion in bile, and fasting-state bile became unsaturated in all patients. No change in fecal neutral sterol excretion occurred during the beta-sitosterol-bile acid regimen, suggesting that simultaneous bile acid feeding blocks the compensatory increase in cholesterol synthesis known to be induced by beta-sitosterol feeding in hypercholesterolemic patients. Serum cholesterol levels also fell modestly during the sitosterol-bile acid regimen, the decrease averaging 15%. We conclude that the abnormally low rate of bile acid synthesis in patients with type IIa hyperlipoproteinemia does not influence biliary lipid secretion; that increasing the input of the two primary bile acids into the enterohepatic circulation does not increase biliary cholesterol secretion or lower serum cholesterol levels in such patients; and that the usual increase in cholesterol synthesis induced by beta-sitosterol feeding does not occur if bile acids are administered simultaneously.

Topics: Adult; Bile; Bile Acids and Salts; Cholesterol; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Kinetics; Male; Middle Aged; Sitosterols; Sterols

We studied the effect of polyunsaturated dietary fat upon the 24-hour loss of cholesterol and other sterols from the skin surface of 4 human subjects. They were fed cholesterol-free diets which provided 40% of the total caloric intake from saturated fat (cocoa butter) and then a highly polyunsaturated fat (corn oil). In both dietary fat periods, the daily loss of cholesterol through the skin was similar, 91 and 87 mg in the saturated and polyunsaturated fat periods, respectively. 87 and 89% of the total cholesterol were in the esterified form in the saturated and polyunsaturated dietary fat periods. The sterol composition of the skin surface lipid was not altered. The study suggests that the plasma cholesterol-lowering effect of dietary polyunsaturated fat was not mediated by a change in the loss of cholesterol through human skin.

Topics: Adult; Cholesterol; Cholesterol Esters; Dietary Fats; Energy Intake; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Sitosterols; Skin; Sterols; Stigmasterol

Topics: Adult; Aged; Digitalis Glycosides; Drug Evaluation; Evaluation Studies as Topic; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Sitosterols; Triglycerides

The effects of acute caloric restriction on cholesterol balance and kinetics of plasma cholesterol specific activity were investigated in five hyperlipemic subjects with varying degrees of obesity. Caloric restriction decreased plasma triglycerides by 41 +/- 12%, plasma cholesterol by 11 +/- 9%, and the ratio of esterified to free cholesterol by 12 +/- 7+. Immediately on institution of caloric restriction there appeared to be an influx of tissue cholesterol into plasma and a reduction in endogenous synthesis of cholesterol. The cholesterol balance decreased from 1,469 +/- 441 to 1,212 +/- 349 mg/day and the rate of decay of plasma cholesterol specific activity decreased 62 +/- 3%. The effect of caloric restriction on hepatic synthesis of bile acids was also very prompt. The total fecal bile acids were reduced immediately by 36 +/- 7%. Because the effect on fecal excretion of deoxycholic acid was greater than that on fecal lithocholic acid, it was suggested that hepatic synthesis of cholic acid was reduced more than the synthesis of chenodeoxycholic acid. Caloric restriction did not cause any change in the percentage of absorption of dietary cholesterol (40 +/- 2% versus 42 +/- 3%). These observations are in accord with our model relating cholesterol metabolism with the metabolism of plasma lipoproteins in man.

Topics: Adult; Bile Acids and Salts; Cholesterol; Cholesterol Esters; Cholesterol, Dietary; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Feces; Humans; Hypercholesterolemia; Hyperlipidemias; Kinetics; Male; Middle Aged; Obesity; Sitosterols; Steroids; Triglycerides

To 9 patients with hyperlipoproteinemia type II and treated with different hypolipidemic drugs without success, sitosterol was given for a period of 4 to 16 months. The effective dose was 10.56 to 21.12g beta-sitosterol corresponding to 12 to 24g granulate. One patient developed a serious diarrhoe and dropped out. 4 patients showed an impressive decrease of serum cholesterol levels.

Topics: Adult; Aged; Cholesterol; Dose-Response Relationship, Drug; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Middle Aged; Sitosterols; 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: Adult; Female; Humans; Hypercholesterolemia; Sitosterols; Xanthomatosis

Topics: Absorption; Animals; Anticholesteremic Agents; Body Weight; Carbon Radioisotopes; Chickens; Cholesterol; Cholesterol, Dietary; Diet; Dietary Fats; Evaluation Studies as Topic; Fatty Acids; Hypercholesterolemia; Liver; Male; Oils; Sitosterols; Species Specificity; Structure-Activity Relationship; Triglycerides; Tritium; Zea mays

Topics: Adult; Bile Acids and Salts; Body Weight; Chenodeoxycholic Acid; Cholesterol; Cholic Acids; Chromatography, Gas; Chromatography, Thin Layer; Chromium; Diet; Electrophoresis; Feces; Female; Humans; Hypercholesterolemia; Lipoproteins, LDL; Male; Middle Aged; Sitosterols; Time Factors; Triglycerides

Topics: Adult; Arteriosclerosis; Cholesterol; Cholestyramine Resin; Clofibrate; Coronary Disease; Electrophoresis, Polyacrylamide Gel; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Lipid Mobilization; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Phospholipids; Sitosterols; Triglycerides

Topics: Biochemical Phenomena; Biochemistry; Carbon Isotopes; Cholesterol; Hypercholesterolemia; Lipid Metabolism; Rats; Research; Sitosterols; Sterols

Topics: Arteriosclerosis; Cholesterol; Humans; Hypercholesterolemia; Sitosterols; Sterols

Topics: alpha-Linolenic Acid; Animals; Aorta; Arachidonic Acid; Arteriosclerosis; Cholesterol; Dogs; Estradiol; Hypercholesterolemia; Lipid Metabolism; Lipids; Sitosterols; Sterols

Topics: Animals; Arteriosclerosis; Diet; Humans; Hypercholesterolemia; Rats; Sitosterols; Steroids; Thiouracil

Topics: Cholesterol; Diet; Humans; Hypercholesterolemia; Sitosterols; Steroids

Topics: Animals; Arteries; Arteriosclerosis; Cholesterol; Diet; Fats; Humans; Hypercholesterolemia; Rats; Sitosterols; Steroids; Thiouracil

Topics: Arachidonic Acid; Cholesterol; Humans; Hypercholesterolemia; Niacin; Nicotinic Acids; Safflower Oil; Sitosterols; Sterols

Topics: Arachidonic Acid; Arteriosclerosis; Atherosclerosis; Cholesterol; Humans; Hypercholesterolemia; Safflower Oil; Sitosterols; Steroids

Topics: Amides; Anesthetics, Local; Humans; Hypercholesterolemia; Sitosterols; Steroids

Topics: Cholesterol; Humans; Hypercholesterolemia; Sitosterols; Steroids

Topics: Blood; Cholesterol; Humans; Hypercholesterolemia; Lipids; Lipoproteins; Male; Sitosterols; Steroids