phytosterols and Dyslipidemias

Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient's confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations.

Topics: Berberine; Dietary Supplements; Dyslipidemias; Humans; Lipids; Phytosterols

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

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

The aim of this review is to summarize the available clinical efficacy and safety data related to the most studied and used lipid-lowering nutraceuticals.. A growing number of meta-analyses of randomized clinical trials supports the effectiveness and tolerability of some lipid-lowering nutraceuticals such as red yeast rice, plant sterols and stanols, soluble fibers, berberine, artichoke extracts, bergamot polyphenol fraction, garlic, green tea, and spiruline. No significant safety concern has been raised for the use of such products. Association of more lipid-lowering nutraceuticals and of some nutraceuticals with lipid-lowering drugs has been tested as well. Current evidence suggests that some clinically tested lipid-lowering nutraceuticals could be safely used to improve plasma lipid levels in subjects affected by mild-to-moderate dyslipidaemia with low cardiovascular risk.

Topics: Dietary Supplements; Dyslipidemias; Humans; Hypolipidemic Agents; Lipids; Phytosterols

The LDL-cholesterol (LDL-C) lowering effect of plant sterols/stanols (PSS) is summarized in several meta-analyses showing a dose-response relationship with intakes of 1.5 to 3 g/day lowering LDL-C by 7.5% to 12%. This review summarizes evidence for the impact of various factors potentially influencing the LDL-C-lowering efficacy of PSS. PSS are efficacious in all food formats and in food supplements. Some factors related to food format, e.g., solid vs. liquid foods, seem to impact efficacy, while there is no difference between free PSS and esters. Compared to multiple daily intakes, once-a-day intake of PSS, especially in the morning with light breakfast, leads to a sub-optimal LDL-C lowering. However, intake frequency seems influenced by intake occasion, i.e., with or without a meal, and time of day. Meal intake is a critical factor for an optimal LDL-C lowering efficacy of PSS. While age has no impact, gender is suggested to influence the LDL-C lowering effect of PSS with greater reductions reported for men than women; but overall evidence is inconclusive and larger studies show no gender by treatment interaction. In conclusion, PSS are efficacious in all foods and food supplements; for optimal efficacy they should be consumed with a (main) meal and twice daily.

Topics: Adult; Biomarkers; Child; Child, Preschool; Cholesterol, LDL; Diet, Healthy; Dietary Supplements; Down-Regulation; Dyslipidemias; Female; Humans; Male; Meals; Middle Aged; Phytosterols; Protective Factors; Recommended Dietary Allowances; Risk Factors; Treatment Outcome; Young Adult

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

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

Cardiovascular diseases are the primary cause of death and the leading cause of disability in industrialized countries. Dyslipidemia is a major independent and reversible risk factor for these diseases: it is estimated that a reduction of 1 mmol/l (38 mg/dl) of LDL cholesterol is associated with a risk of developing a cardiovascular complication reduced by 25%, a reduction potentially achieved by life-style improvement associated to adequate dietary supplementation with bioactive substances.. The aim of this review is to focus on the major phytochemical nutraceuticals combinations supported by clinical trials that have demonstrated positive effects in the treatment of dyslipidemia.. There are many nutraceuticals with significant lipid-lowering properties: most of them are used in association with a low dosage, because that permits to reduce the risk of side effects and theoretically to improve efficacy. In fact, natural products with different synergetic lipid-lowering could be combined: they can reduce the absorption of lipids from the bowel and/or increase their excretion (soluble fibers, plant sterols, probiotics), enhance the hepatic uptake of cholesterol (berberine, soybean proteins), inhibit Hydroxy-Methil-Gglutaryl Coenzyme A reductase enzyme and consequently the hepatic synthesis of cholesterol (monacolins, policosanols, allicin, soybean proteins, bergamot); furthermore some products are able to reduce the oxidation of the LDL and increase the thermogenesis and lipid metabolism (chlorogenic acid).. Rational combinations of nutraceuticals with different lipid-lowering activities, whether associated with an appropriate lifestyle, should provide an alternative to drug treatment in patients in primary cardiovascular disease prevention with mildly added cardiovascular risk and in some statin-intolerant patients.

Topics: Berberine; Biological Products; Cholesterol; Clinical Trials as Topic; Dietary Supplements; Drug Therapy, Combination; Dyslipidemias; Fatty Alcohols; Humans; Lipids; Phytosterols; Phytotherapy; Plant Proteins; Silymarin

Non-cholesterol sterols have been used as markers of cholesterol intestinal absorption and hepatic synthesis, leading to a better understanding of cholesterol homeostasis in humans. This review discusses the main noncholesterol sterols that are clinically useful, different methods to quantify the factors associated with blood concentration, and the potential role of non-cholesterol sterols in the diagnosis and treatment of different types of dyslipidemia. The main indication is the use of non-cholesterol sterols for the diagnosis of rare diseases associated with defects in cholesterol synthesis or anomalies in the absorption and/or elimination of phytosterols. However, other potential uses, including the diagnosis of certain hypercholesterolemias and the individualization of lipid-lowering therapies, are promising as they could help treat a wider population.

Topics: Bile Acids and Salts; Cholesterol; Dyslipidemias; Ezetimibe; Humans; Membrane Proteins; Membrane Transport Proteins; Oxysterols; Phytosterols; Pravastatin; Sterols

Dyslipidemias have been shown to bear a close association with an increased risk of cardiovascular diseases, atherosclerosis in particular. As efforts are being made to find alternative therapies and ways to prevent disease, there is a corresponding rise in public interest in food and/or active food components that contribute to an improved lipid profile and, thus, to better health. Besides supplying the basic nutrients necessary for well-being, some foods add further physiologic benefits. In fact, specific foods and bioactive components could be beneficial in controlling dyslipidemias. From a review of the literature on foods and bioactive compounds, their recommended quantities, and expected effects, we found that the following nutrients and food components could positively impact the lipid profile: monounsaturated and polyunsaturated fatty acids, soluble fiber, vegetable proteins, phytosterols, and polyphenols. Therefore, incorporating these components into the regular diets of individuals is justified, because they contribute additional positive effects. This suggests that they also be recommended in clinical practice.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Dietary Fiber; Dyslipidemias; Energy Intake; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Food; Health Promotion; Humans; Lipids; Phytosterols; Plant Proteins, Dietary; Polyphenols

This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk.. Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation.. Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.

Topics: Animals; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Dyslipidemias; Humans; Inflammation; Lipids; Phytosterols; Sitosterols; Triglycerides

More than 200 clinical trial reports and several meta-analyses have demonstrated that phytosterols (PSs), natural components of plants, induce clinically relevant reductions in blood low-density lipoprotein cholesterol levels. Here we review data regarding the biochemical effects and potential cardiovascular benefit of PSs as part of the dietary management of dyslipidemia. In addition to discussing the efficacy, effectiveness, and safety of PSs as hypocholesterolemic agents, this review provides an overview of PSs as an adjunctive therapy to cholesterol-lowering pharmaceuticals. Given this lack of evidence regarding the benefits of PSs for reducing cardiovascular end points, this review also discusses the present knowledge that exists about the ability for therapeutic dosages of PSs to confer protection from cardiovascular-related mortality and morbidity. Finally, this review summarizes the factors that affect PS efficacy and the Canadian regulations that govern the use of PSs as cholesterol-lowering agents in foods and supplements.

Topics: Anticholesteremic Agents; Azetidines; Dietary Supplements; Dyslipidemias; Ezetimibe; Humans; Phytosterols; Treatment Outcome

Plant sterols and stanols are naturally occurring constituents of plants and as such normal components of our daily diet. The consumption of foods enriched in plant sterols and stanols may help to reduce low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analyses have shown that consuming approximately 2.5 g plant sterols or stanols per day lowers serum LDL-C concentrations up to 10%, with little additional benefit achieved at higher intakes. However, recent studies evaluating plant stanol intakes up to 9 g/d have indicated that LDL-C concentrations can be reduced up to 17%, which suggests that more pronounced reductions can be achieved at higher intakes. Studies describing effects of high plant sterol intakes on serum LDL-C concentrations are not consistent. Besides the effects of higher than advocated intakes on serum LDL-C concentrations, several topics will be discussed in this review. First, besides the well-characterized effect of plant sterols and stanols on serum LDL-C concentrations, evidence is now emerging of their effects on triacylglycerol metabolism, which makes them highly attractive for interventions in metabolic syndrome-like populations. Secondly, there is an ongoing debate whether increased plant sterol concentrations are associated with an increased cardiovascular disease risk or not. For this there are at least two possible explanations. First, the potential atherogenicity of increased plant sterol concentrations might be ascribed to the formation of plant sterol oxidation products (so-called oxyphytosterols) or secondly, elevated serum plant sterol concentrations should only be seen as surrogate markers for characterizing subjects with high intestinal cholesterol absorption. Finally, we discuss recent studies, which suggest that plant sterols and stanols can improve endothelial dysfunction in subjects at risk, although evidence is limited and more research is needed.

Topics: Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Humans; Molecular Targeted Therapy; Phytosterols; Risk Factors

Investigating cholesterol metabolism, which derives from balancing cholesterol synthesis and absorption, opens new perspectives in the pathogenesis of dyslipidemias and the metabolic syndrome (MS). Cholesterol metabolism is studied by measuring plasma levels of campesterol, sitosterol and cholestanol, that is, plant sterols which are recognised as surrogate cholesterol-absorption markers and lathosterol or squalene, that is, cholesterol precursors, which are considered surrogate cholesterol-synthesis markers. This article presents current knowledge on cholesterol synthesis and absorption, as evaluated by means of cholesterol precursors and plant sterols, and discusses patterns of cholesterol balance in the main forms of primary hyperlipidaemia and MS. Understanding the mechanism(s) underlying these patterns of cholesterol synthesis and absorption will help to predict the response to hypolipidemic treatment, which can then be tailored to ensure the maximum clinical benefit for patients.

Topics: Biomarkers; Cholestanol; Cholesterol; Dyslipidemias; Humans; Lipid Metabolism; Metabolic Syndrome; Phytosterols; Sitosterols

The efficacy and safety of phytosterols for the management of dyslipidemia are reviewed.. Phytosterols have been evaluated in over 40 clinical trials. The incorporation of 2 g of phytosterols daily into margarine, mayonnaise, orange juice, olive oil, low-fat milk, yogurt, and tablets is associated with significant reductions in low-density-lipoprotein (LDL) cholesterol from baseline over 1-12 months in adults with normal or high cholesterol, in children, and in patients with type 2 diabetes mellitus. Phytosterol dosages of 1.6-3 g daily have been shown to reduce LDL cholesterol by 4.1-15% versus placebo within the first month of therapy. One meta-analysis found mean reductions of 10-11%, but results vary. Several placebo-controlled trials found that the addition of phytosterols to statin therapy was associated with reductions of 7-20% in LDL cholesterol for up to 1.5 years. Overall, phytosterols are useful for reducing LDL cholesterol in patients who cannot reach their treatment goal by diet alone or who are taking maximum tolerated doses of statins. These products offer an alternative to statins in patients who cannot take statins or whose statin dosage is restricted because of potential drug interactions or concomitant diseases. Commonly reported adverse effects are primarily gastrointestinal in nature.. Phytosterol therapy produces an average 10-11% reduction in LDL cholesterol concentration, but it is unknown whether this effect persists beyond two years. Phytosterol products are well tolerated and have few drug interactions, but their long-term safety has not been established. Current evidence is sufficient to recommend phytosterols for lowering LDL cholesterol in adults.

Topics: Adult; Animals; Child; Cholesterol, LDL; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Dyslipidemias; Herb-Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Phytosterols

To review the literature on select alternative therapies for the management of dyslipidemia.. Searches of MEDLINE and PubMed (1965-March 2006) were conducted using the key terms omega-3-fatty acids, policosanol, plant stanols and sterols, flaxseed, red yeast rice, guggulipid, garlic, fiber, almonds, and cholesterol and/or lipids.. Meta-analyses, published in English and involving adults, that incorporated randomized, controlled trials on alternative therapies for dyslipidemia were reviewed. Additionally, trials published subsequent to the meta-analyses were reviewed. Articles deemed relevant were included in this review.. Of the aforementioned alternative therapies, randomized controlled trials were found for omega-3-fatty acids, policosanol, plant stanols and sterols, flaxseed, red yeast rice, guggulipid, garlic, fiber, almonds, and soy. Studies for each of these agents report varying degrees of lipid reduction. Based on published data, effective therapeutic options for lipid-lowering include intake of fiber, intake of plant stanols/sterols, replacement of animal protein with soy protein, and substitution of foods high in saturated fat with those with monounsaturated fatty acids (eg, dry roasted almonds). Adding omega-3-fatty acids is effective for reducing triglycerides in patients with hypertriglyceridemia. Well-designed studies with long-term outcome data are necessary to further define the role for guggul, red yeast rice, policosanol, garlic, and flaxseed in the management of dyslipidemia.. Alternative therapeutic approaches with complementary therapies are becoming increasingly popular among patients. It is important for healthcare providers to be familiar with the safety and efficacy of these agents to facilitate optimal outcomes for patients with dyslipidemia.

Topics: Complementary Therapies; Dyslipidemias; Humans; Meta-Analysis as Topic; Phytosterols; Phytotherapy

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

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

Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain.. We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353).. There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06).. These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

Topics: Aged; Biomarkers; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Phytosterols; Pyrimidines; Sitagliptin Phosphate; Sitosterols; Time Factors; Treatment Outcome

In literature, there are several studies about the effects of nutraceutical combinations at fasting, but data in post-prandial phase are lacking.. We planned a study to evaluate the efficacy and safety of a nutraceutical agent containing fermented red rice, phytosterols and olive polyphenols compared to placebo in a sample of Caucasian patients with low cardiovascular risk, both at fasting and after an oral fat load.. Eighty patients were randomized to receive, as addition to diet and physical activity, a nutraceutical combination containing fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols or placebo (control group), once a day.. We evaluated at baseline, and after 3 months: body mass index, fasting plasma glucose, lipid profile, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial-leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and after an oral fat load.. Nutraceutical combination gave a reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We recorded a reduction of soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and sE-selectin in the group treated with nutraceutical combination, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). Parameters recorded during oral fat load improved compared to the oral fat load performed at baseline with the nutraceutical combination.. The nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols seems to be effective in improving lipid profile and markers of endothelial damage in dyslipidemic patients in primary prevention at low risk for developing cardiovascular disease. The true novelty of this study, however, is the improvement of endothelial damage after an oral fat load compared to placebo.

Topics: Biomarkers; Body Mass Index; Cholesterol, LDL; Curcumin; Dietary Supplements; Dyslipidemias; E-Selectin; Female; Humans; Intercellular Adhesion Molecule-1; Lipids; Male; Middle Aged; Olea; Oryza; Phytosterols; Polyphenols; Triglycerides

Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG).. In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585).. Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ.. In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.

Topics: Adult; Australia; Blood Glucose; Cholesterol, LDL; Diabetes Mellitus, Type 2; Double-Blind Method; Dyslipidemias; Female; Humans; Insulin; Male; Middle Aged; Phytosterols; Risk Assessment; Treatment Outcome; Triglycerides

Fenofibrate and extended-release (ER) niacin similarly raise high-density lipoprotein cholesterol (HDL-C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre-β1-HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER-niacin (0.5 g/day for 3 week, then 1 g/day) in a cross-over study. Both treatments increased HDL-C (16 %) and apolipoprotein (apo) A-I (7 %) but only fenofibrate increased apoA-II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low-density lipoprotein cholesterol and positively correlated with end of treatment apoA-II. ApoA-II in isolated HDL in vitro bound more lutein than apoA-I. Xanthophylls were increased by ER-niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre-β1-HDL was significantly decreased by fenofibrate (-19 %, p < 0.0001), with little change (3.4 %) for ER-niacin. Although fenofibrate and ER-niacin similarly increased plasma HDL-C and apoA-I, effects on plasma xanthophylls, phytosterols and pre-β1-HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA-II in xanthophyll metabolism.

Topics: Apolipoprotein A-II; Cross-Over Studies; Dyslipidemias; Female; Fenofibrate; High-Density Lipoproteins, Pre-beta; Humans; Hypolipidemic Agents; Lutein; Male; Middle Aged; Niacin; Phytosterols; Xanthophylls; Zeaxanthins

This study investigated the efficacy, safety, tolerability, and pharmacokinetics of a novel cholesterol absorption inhibitor, FM-VP4, comprising disodium ascorbyl sitostanol phosphate (DASP) and disodium ascorbyl campestanol phosphate (DACP).. In phase 1, 30 men received a single dose of 100, 200, 400, 800, 1,600, or 2,000 mg FM-VP4 or placebo. In phase 2, 100 men were treated with 100, 200, 400, or 800 mg/day of FM-VP4 or placebo for 4 weeks.. The drug was well tolerated at each single or multiple dose level. After 4 weeks of treatment, low-density lipoprotein cholesterol (LDL-C) levels changed by 2.7% in the placebo group and by 2.9%, -4.2%, and -4.6% in the 100, 200, and 800 mg/day groups, respectively, which was not statistically significant. However, 400 mg/day of FM-VP4 significantly decreased LDL-C by 6.5% (p=0.02). Phase 1 showed that DACP and DASP were absorbed into plasma with a median t(max) of 12 h for both components, and clearance was slow with a mean t(1/2lambda) of 57 h. During 4 weeks of treatment, steady state was reached by approximately 8 days.. This study demonstrated that up to 800 mg/day of FM-VP4 is safe and well tolerated for at least 4 weeks. Furthermore, the higher doses significantly reduced LDL-C by 7% compared with baseline or by 10% compared with placebo, with the maximum effect reached at 400 mg/day.

Topics: Adult; Anticholesteremic Agents; Area Under Curve; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Dyslipidemias; Electrocardiography; Gas Chromatography-Mass Spectrometry; Half-Life; Heart Rate; Humans; Male; Middle Aged; Phytosterols; Placebos

The objective of this study was to show that plant sterols in tablet form provide additional low-density lipoprotein (LDL) cholesterol lowering for patients on statin therapy. Dispersible phytosterol tablets were tested in a double-blind, placebo-controlled, parallel clinical trial. Twenty-six patients who were following the American Heart Association Heart Healthy Diet and on long-term statin therapy were studied for 9 weeks. After 3 weeks of placebo treatment, the subjects were randomized to receive either 1.8 g of soy stanols or placebo for 6 weeks in addition to their usual statin regimen. Stanol tablets reduced LDL cholesterol 9.1% (p = 0.007) or 12.2 mg/dl. Total cholesterol was reduced by 12.9 mg/dl (p = 0.03). A strong inverse correlation (r(s) = -0.82, p = 0.0007) was found between the baseline LDL cholesterol and the percent change in LDL cholesterol observed after stanol treatment. The additional LDL cholesterol lowering with stanol/lecithin tablets provided a potential adjunctive therapy for patients who have not reached their target LDL cholesterol goal during statin therapy.

Topics: Adult; Aged; Cholesterol, LDL; Double-Blind Method; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Male; Middle Aged; Phosphatidylcholines; Phytosterols; Tablets

Topics: Anticholesteremic Agents; Dyslipidemias; Enzyme Inhibitors; Fatty Acids, Omega-3; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Peripheral Arterial Disease; Phytosterols

Cholesterol is derived via de novo synthesis and dietary absorption. Both processes can be monitored by determination of non-cholesterol sterol concentrations (lathosterol for synthesis; sitosterol and campesterol for absorption). The hypocholesterolemia that occurs during acute illness is a result of a multifactorial inability to compensate for the increased needs for this metabolite. The aim of this study was to examine the plasma cholesterol profile and both processes of cholesterol acquisition during acute upper gastrointestinal haemorrhage with emphasis on liver cirrhosis.. Thirty five patients with acute upper gastrointestinal bleeding (cirrhosis n=14, non-cirrhosis n=21) were evaluated over a 6 day period. The control cohort consisted of 100 blood donors. Serum concentrations of total, LDL (low-density lipoprotein) and HDL (high-density lipoprotein) cholesterol were measured enzymatically. Sterol concentrations were analysed using gas chromatography, data were statistically analysed.. In all patients, we found lower plasma levels of total cholesterol (P Conclusion: Our results showed substantial abnormalities in the cholesterol plasma profile including both the processes of cholesterol acquisition in patients with upper acute gastrointestinal bleeding. The patients with or without liver cirrhosis had similar trends in cholesterol plasma levels. Depression of cholesterol synthesis was, however, prolonged in the cirrhotic group and the data also suggest a different phytosterol metabolism.

Topics: Acute Disease; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Phytosterols

Dyslipidemia is a major risk factor for cardiovascular disease, the leading cause of preventable death worldwide. As a result, a full understanding of the factors influencing dyslipidemia is urgently necessary. Bile acids have been recognized as regulators of lipid metabolism, and neutral sterols may influence serum lipid levels. Therefore, this analysis was conducted to better understand the relationship between bile acids, neutral sterols, and dyslipidemia.. We examined cross-sectional associations between selected fecal metabolites and serum lipids or markers of dyslipidemia in 1387 participants of the KORA FF4 study using linear and logistic regression models.. We found positive associations between fecal bile acids and serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-c), total cholesterol, triglycerides and markers of dyslipidemia, though associations were seen most consistently with triglycerides and hypertriglyceridemia. We also found positive associations between fecal cholesterol and serum LDL-c, total cholesterol, triglycerides, hypertriglyceridemia and high serum total cholesterol, though only associations with triglycerides or hypertriglyceridemia remained significant after applying the Bonferroni correction. Unexpectedly, several fecal plant sterols were positively associated with serum lipids and the associated markers of dyslipidemia. However, many of these associations were no longer statistically significant after adjusting for multiple testing.. Our results provide insight into the role that bile acids may play in the development or progression of dyslipidemia. However, further confirmation of these results is warranted. Longitudinal and experimental studies are necessary to clarify the mechanisms behind these associations and to determine causality.

Topics: Adult; Aged; Aged, 80 and over; Bile Acids and Salts; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Disease Progression; Dyslipidemias; Feces; Female; Germany; Health Surveys; Humans; Male; Middle Aged; Phytosterols; Triglycerides

Phytosterol-rich fraction (PRF) obtained from palm fatty acid distillate (PFAD) was investigated for its effect on blood serum lipid profile of dyslipidemia rats. Dyslipidemia was induced by force feeding cholesterol to five groups of rats; one group was a control or normal group. Cholesterol force-fed groups were treated with 0, 10, 20, 30, and 40 mg PRF/kg/day for 4 weeks. All groups of rats were fed standard diet. A normal group was fed standard diet without PRF treatment and cholesterol force feeding. Lipid profile was measured every week (0, 1, 2, 3, and 4). Four-week treatment resulted in significant blood serum lipid profile improvement. PRF improved blood serum lipid profile by decreasing total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol level and increasing high density lipoprotein (HDL) cholesterol level. The doses of PRF significantly affected blood serum lipid profile as well as duration of PRF treatment. PRF inhibited cholesterol absorption, which delayed blood serum total cholesterol rise. Cholesterol absorption inhibition was also indicated by higher fecal cholesterol concentration after PRF feeding. These results indicate the beneficial effect of PRF in the treatment of dyslipidemia.

Topics: Animals; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Dyslipidemias; Lipids; Male; Palm Oil; Phytosterols; Rats; Rats, Wistar; Triglycerides

Pistachios contain beneficial substances such as unsaturated fatty acids, phytosterols, and polyphenols. In the present study, we investigated if pistachio consumption is able to prevent or to revert hyperglycemia, dyslipidemia, hepatic steatosis, and adipose tissue morphological alterations caused by high fat diet (HFD) in the mouse. Moreover, the impact of pistachio intake on the mRNA expression of peroxisome proliferator-activated receptor γ (

Topics: Adipose Tissue; Animals; Cholesterol; Diet; Diet, High-Fat; Dyslipidemias; Fatty Acid Synthases; Fatty Liver; Hypertriglyceridemia; Lipid Metabolism; Liver; Male; Mice, Inbred C57BL; Mice, Obese; Nuts; Obesity; Phytosterols; Pistacia; Plant Extracts; Polyphenols; PPAR gamma; RNA, Messenger; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1

Certain lipid-lowering drugs increase bile lithogenicity. Here we investigated whether long-term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1, alters bile lithogenicity in patients with hepatobiliary diseases.. Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed.. Serum levels of campesterol, total cholesterol, and low-density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients.. Long-term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.

Topics: Anticholesteremic Agents; Bile; Cholesterol; Dyslipidemias; Ezetimibe; Fatty Liver; Female; Gallstones; Humans; Lipid Metabolism; Lipoproteins; Male; Middle Aged; Phytosterols; Ursodeoxycholic Acid

Topics: Dyslipidemias; Humans; Phytosterols; Sterols

Dietary modifications including healthy eating constitute one of the first line strategies for prevention and treatment of atherosclerotic cardiovascular diseases (CVD), including atherosclerosis. In this study, we assessed anti-atherogenic effects of a combination of wild rice and phytosterols in low-density lipoprotein receptor knockout (LDL-r-KO) mice. Male LDL-r-KO mice were divided into four groups and fed with: (1) control diet; (2) the control diet containing 60% (w/w) wild rice; (3) the control diet containing 2% (w/w) phytosterols; or (4) the control diet containing both wild rice and phytosterols for 20weeks. All diets were supplemented with 0.06% (w/w) dietary cholesterol. Blood samples, hearts, and feces were collected and used for biochemical and histological examination. Consumption of 60% (w/w) wild rice in combination with 2% (w/w) phytosterols significantly reduced the size and severity of atherosclerotic lesions in the aortic roots as compared to those in the control group. This effect was associated with significant reductions in plasma total, LDL and VLDL cholesterol concentrations as well as an increase in fecal cholesterol excretion. In conclusion, the dietary combination of wild rice and phytosterols prevents atherogenesis in this animal model. Further investigations are needed to understand mechanisms of action and potential clinical outcome of such dietary intervention.

Topics: Adiposity; Animals; Anticholesteremic Agents; Aorta; Atherosclerosis; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Cholesterol, VLDL; Dietary Supplements; Dyslipidemias; Feces; Functional Food; Male; Mice, Knockout; Myocardium; Phytosterols; Poaceae; Receptors, LDL; Seeds

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

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

Topics: Animals; Anticholesteremic Agents; Cardiovascular Diseases; Dyslipidemias; Humans; Phytosterols; Sitosterols

Various human trials and pre-clinical studies have suggested that dietary plant sterols possess hypotriacylglycerolaemic properties apart from their cholesterol-lowering properties. We hypothesised that phytosterols (PS) might attenuate triacylglycerolaemia by interfering with the deleterious effects of cholesterol overload in the liver. In the present study, twenty hamsters (Mesocricetus auratus) with diet-induced combined hyperlipidaemia were fed a high-fat diet (HFD, n 10) or a HFD supplemented with soyabean PS (n 10) for 40 d. In parallel, a healthy group was fed a standard diet (n 10). PS normalised fasting plasma cholesterol concentrations completely after 20 d and were also able to normalise serum TAG and NEFA concentrations after 40 d. HFD feeding caused microvesicular steatosis and impaired the expression of key genes related to fatty acid oxidation such as PPARA, carnitine palmitoyltransferase-Iα (CPT1A) and phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver. PS treatment completely protected against HFD-induced steatosis and resulted in a normalised hepatic gene expression profile. The protection of the hepatic function by PS was paralleled by increased faecal cholesterol excretion along with a 2-fold increase in the biliary bile acid (BA):cholesterol ratio. The present study supports the conclusion that long-term consumption of PS can reduce serum TAG and NEFA concentrations and can protect against the development of fatty liver via different mechanisms, including the enhancement of BA synthesis. The results of the present study place these compounds as promising hepatoprotective agents against fatty liver and its derived pathologies.

Topics: Animals; Bile Acids and Salts; Carnitine O-Palmitoyltransferase; Cholesterol; Cricetinae; Diet, High-Fat; Dyslipidemias; Fatty Acids, Nonesterified; Fatty Liver; Gene Expression; Glycine max; Lipogenesis; Liver; Male; Mesocricetus; Non-alcoholic Fatty Liver Disease; Phosphoenolpyruvate Carboxykinase (GTP); Phytosterols; PPAR alpha; Triglycerides

Topics: Anticholesteremic Agents; Dyslipidemias; Humans; Phytosterols

The effects of ezetimibe on cholesterol metabolism in HIV-infected patients receiving boosted protease inhibitors have not been thoroughly assessed. The aim of this study was to assess cholesterol homeostasis in patients with PI associated dyslipidemia and its relationship with the response to treatment with the cholesterol-absorption inhibitor ezetimibe.. Fifteen patients with ritonavir-boosted PI-containig therapy and LDL-cholesterol > 3.36 mmol/L (>130 mg/dL) were assessed at baseline and after an 8-week course of ezetimibe 10 mg/d. Serum non-cholesterol sterols were measured at each visit as markers of cholesterol synthesis and absorption. Total-, LDL-, and HDL-cholesterol triglycerides, apolipoproteins A1 and B, high sensitivity C-reactive protein, CD4 cells and HIV-1 RNA were also measured.. Ezetimibe treatment was well tolerated in all patients and resulted in significant reductions in total cholesterol (-11.4%, p = .002), LDL-cholesterol (-20.4%, p = .003), non-HDL-cholesterol (-13.4%, p = .002) and apolipoprotein B (-9.1%, p = .021). Treatment with ezetimibe was associated with decreased cholesterol absorption markers (campesterol-to-cholesterol ratio -43.0%, p = .001; sitosterol-to-cholesterol ratio -41.9%, p = .001) and increased synthesis markers (lathosterol-to-cholesterol ratio 53.2%, p = .005). Baseline absorption or synthesis markers were unrelated to the response to treatment. CD4 cell count and plasma HIV-1 RNA remained unchanged.. The level of cholesterol absorption or synthesis does not appear to be a major determinant of the responsiveness to ezetimibe in patients on ritonavir-boosted PI-containing therapy.. EudraCT: 2006-006156-36.

Topics: Adult; Aged; Anticholesteremic Agents; Azetidines; C-Reactive Protein; Cholesterol; Cholesterol, LDL; Dyslipidemias; Ezetimibe; Female; HIV Infections; Humans; Lipid Metabolism; Male; Middle Aged; Phytosterols; Protease Inhibitors

Rice bran enzymatic extract (RBEE) has advantages compared to the original rice bran or its oils including water solubility, lack of rancidity and increased content in high nutritional proteins and nutraceutical compounds, particularly phytosterols, γ-oryzanol and tocols. Our aim was to determine the beneficial effects of RBEE in the pathogenesis of metabolic syndrome in obese Zucker rats.. Obese Zucker rats and their lean littermates were fed a 1 and 5 % RBEE-supplemented diet (O1, O5, L1 and L5). Simultaneously, obese and lean Zucker rats, fed a standard diet, were used as controls (OC and LC, respectively). Body weight, food and water intake, and systolic blood pressure were weekly evaluated. After treatment, biochemical assays of serum glucose, insulin, triglycerides (TG), total cholesterol (TC), non-esterified fatty acids (NEFA), adiponectin and nitrates (NO((x))) were determined.. RBEE treatment reduced circulating levels of TG and TC, whereas increased HDL-cholesterol without altering NEFA values in obese rats. The extract also induced a significant dose-dependent reduction of hypertension linked to obesity. RBEE of 5 % improved insulin resistance and subsequently reduced HOMA-IR index without altering serum glucose levels. Obese animals treated with RBEE showed partial restoration of adiponectin levels and a significant attenuation of pro-inflammatory values of NO((x)).. These findings evidence the nutraceutical properties of RBEE against the pathogenesis of metabolic syndrome by attenuating dyslipidemia, hypertension and insulin resistance as well as by restoring hypoadiponectinemia associated to obesity.

Topics: Adiponectin; Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diet; Dyslipidemias; Fatty Acids, Nonesterified; Hypertension; Insulin; Insulin Resistance; Metabolic Syndrome; Nitrates; Obesity; Oryza; Phenylpropionates; Phytosterols; Plant Extracts; Rats; Rats, Zucker; Triglycerides; Water

Quantification of plasma noncholesterol sterols allows the study of cholesterol absorption and synthesis. A pattern of low cholesterol absorption and high synthesis has been demonstrated in patients with obesity and insulin resistance. To understand the relationship between cholesterol absorption/synthesis and visceral obesity, we investigated surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) in dyslipidaemic patients with different representation of abdominal fat, estimated by ultrasonographic measurement of visceral fat area (VFA).. In 126 patients with primary hyperlipaemias, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled with mass spectrometry. Visceral and subcutaneous fats were evaluated by ultrasonography. The study population was divided into two groups on the basis of VFA median values, below/equal and above 154 cm(2) . RESULTS Patients with higher VFA had significantly higher lathosterol levels (median 109 vs. 76 × 10(2) μmol/mmol cholesterol P < 0·004), body mass index, waist circumference, blood pressure, triglycerides, insulin, homoeostatic model assessment (HOMA)-IR and lower high-density lipoprotein (HDL)-C. VFA was positively correlated with lathosterol (ρ = 0·35, P < 0·001) and negatively with HDL-C (ρ = -0·43, P < 0·001), campesterol (ρ = -0·23, P = 0.01) and sitosterol (ρ = -0·35, P < 0·001). VFA was an independent predictor of lathosterol values (β = 0·389, P < 0·0001, P of the model < 0·0001);age, systolic blood pressure, BMI, waist circumference, triglycerides, HDL-C and HOMA failed to enter the final equation..   In hyperlipidaemic patients, the amount of visceral fat correlates with cholesterol synthesis; the use of ultrasonographic detection of abdominal adiposity allows a better characterization of cholesterol pathway, potentially useful for a tailored therapeutic approach.

Topics: Adult; Body Fat Distribution; Body Mass Index; Cholesterol; Chromatography, Gas; Dyslipidemias; Female; Humans; Intra-Abdominal Fat; Male; Mass Spectrometry; Middle Aged; Phytosterols; Sitosterols; Statistics as Topic; Ultrasonography; Waist Circumference

We investigated how liver fat content (LFC) influences cholesterol metabolism by quantifying liver fat using proton magnetic resonance spectroscopy and by measuring the serum concentrations of lathosterol, a marker of cholesterol synthesis, and sitosterol and campesterol, two markers of cholesterol absorption. We also evaluated whether this relationship could be modified by statin therapy. The study was conducted in 263 patients with type 2 diabetes, 137 of whom (52.0%) received statin therapy.. One hundred and sixty-five patients (62.7%) had steatosis (LFC>5.5%). We performed specific analyses in patients without statin therapy and in patients treated with statin therapy. In both groups, the lathosterol to cholesterol ratio correlated positively with LFC, and in multivariate analysis, the lathosterol to cholesterol ratio was associated with LFC independently of age, gender and BMI. Sitosterol and campesterol concentrations were not associated with LFC.. Our study suggests that in patients with type 2 diabetes, LFC is associated with an increase in cholesterol synthesis that is independent of obesity or diabetes mellitus. Statin therapy does not modify this relationship.

Topics: Aged; Biomarkers; Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Fatty Liver; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Linear Models; Liver; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Phytosterols; Risk Factors; Sitosterols; Treatment Outcome

In India, Azadirachta indica is typically known as 'neem tree' and its leaves has long been used in the ayurvedic medical tradition as a treatment for diabetes mellitus. In-depth chromatographic investigation on chloroform extract resulted in identification of one new tetranortriterpenoid. Structural elucidation was established on the basis of spectral data as 24,25,26,27-tetranor-apotirucalla-(apoeupha)-1α-senecioyloxy-3α,7α-dihydroxy-14,20,22-trien-21,23-epoxy named by us as meliacinolin (1). The present study investigated the effect hypoglycaemic, hypolipidemic, oxidative stress, insulin resistance, α-glucosidase and α-amylase of 1 from A. indica. Diabetic rats were treated with 1 for 28 d and a set of biochemical parameters were studied including: glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. We also looked into liver function by determining glucose-6-phosphatase, glucokinase and hexokinase activities, and the effect on insulin level. While in vitro inhibition of α-glucosidase and α-amylase enzyme activities were used as indices of effect on glucose absorption. As a result we found that blood glucose level, serum biochemical parameters, hepatic enzymes, thiobarbituric acid reactive substances, and insulin level were restored in streptozotocin (STZ)-diabetic mice to normal levels with 1. Meliacinolin inhibited α-glucosidase and α-amylase activities. We conclude that meliacinolin can efficiently inhibit insulin resistance, improvement of renal function, lipid abnormalities, and oxidative stress, indicating that its therapeutic properties may be due to the interaction of meliacinolin with multiple targets involved in diabetes pathogenesis. α-Glucosidase and α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia prevents the digestion of carbohydrates.

Topics: alpha-Amylases; Animals; Azadirachta; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dyslipidemias; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Insulin; Insulin Resistance; Kidney; Liver; Male; Mice; Niacinamide; Oxidative Stress; Phytosterols; Phytotherapy; Plant Extracts; Streptozocin; Thiobarbituric Acid Reactive Substances

To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL) cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods.. The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL) cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose.. We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (re)absorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory) mechanisms.

Topics: Algorithms; Atorvastatin; Cholesterol, LDL; Computer Simulation; Dose-Response Relationship, Drug; Drug Synergism; Dyslipidemias; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Models, Biological; Phytosterols; Phytotherapy; Pyrroles

Patients with dyslipidemia and advanced renal failure are at markedly increased risk of cardiovascular morbidity and mortality. We evaluated the efficacy and safety of ezetimibe administration to patients with endstage renal failure (ESRF) who are undergoing hemodialysis. Ezetimibe at 10 mg/day was given to 20 patients for 12 weeks. Efficacy was determined by monitoring lipids, and safety was determined by monitoring clinical and laboratory parameters. We also evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis. Compared to baseline values, LDL-cholesterol (LDL-C) was reduced by 24.9% (p<0.005) after 12 weeks of ezetimibe administration. Treatment with ezetimibe did not change HDL-cholesterol, triglyceride and HbA1c values but caused a significant reduction in remnant like particles-cholesterol (RLP-C, p<0.05) and high-sensitive C-reactive protein (hsCRP, p<0.05). Ezetimibe therapy decreased cholesterol absorption markers (campesterol and sitosterol) and increased a marker of cholesterol synthesis (lathosterol). A highly significant correlation was observed between alterations in LDL-C and campesterol levels in response to ezetimibe therapy. No patients reported musculoskeletal symptoms. None of the patients experienced elevations in their creatine kinase or liver transaminase levels. Ezetimibe not only reduced serum LDL-C, but also RLP-C and hsCRP, in ESRF patients. Inhibition of cholesterol absorption by ezetimibe is an important therapeutic option in these patients due to its efficacy and safety.

Topics: Aged; Anticholesteremic Agents; Azetidines; C-Reactive Protein; Cholesterol; Dyslipidemias; Ezetimibe; Female; Glycated Hemoglobin; Humans; Linear Models; Male; Middle Aged; Phytosterols; Renal Dialysis; Renal Insufficiency; Triglycerides