phytosterols and Metabolic-Syndrome

Evidence suggests that bioactive compounds present in fruits and vegetables, including carotenoids, polyphenols, and phytosterols, may have beneficial effects against the development of obesity and other diseases. The fruits of the Brazilian Cerrado are rich in biologically active compounds but are underexplored by the population being used only locally dietary consumption. The objective of this review is to direct attention to the bioactive compounds already elucidated for the fruits of "Cerrado" cashew (

Topics: Antioxidants; Brazil; Carotenoids; Fruit; Glucose; Humans; Metabolic Syndrome; Phytosterols; Polyphenols

Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs.. Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Topics: Animals; Antioxidants; Carcinoma, Hepatocellular; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Phytosterols; Triterpenes

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

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

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 metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids, diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. Peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins, liver X receptor alpha, retinoid X receptor alpha, farnesoid X receptor alpha, hepatic nuclear factor 4alpha and nuclear factor kappaB contribute to these nuclear actions of bioactive lipids with complex interactions. Recent studies have demonstrated the striking ability of bioactive lipids to regulate the production of physiologically active adipocytokines through PPARgamma activation. In particular, the function of bioactive lipids as dietary adiponectin inducers (dietary insulin sensitizers) deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation.

Topics: Animals; Diet; Female; Humans; Lipids; Male; Metabolic Syndrome; Mice; NF-kappa B; Phytosterols; Receptors, Cytoplasmic and Nuclear; Sterol Regulatory Element Binding Proteins

1. Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is characterized by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL apoA-I particles. 2. Nutritional interventions may favourably alter lipoprotein transport in the metabolic syndrome. We review our collaborative studies, using stable isotopes and compartmental modelling, of the kinetic effects of fish oils, plant sterols (phytosterols) and weight reduction on the dyslipoproteinaemia in this disorder. 3. Fish oil supplementation diminished hepatic secretion of VLDL-apoB and enhanced conversion of VLDL to low-density lipoprotein (LDL)-apoB, without altering catabolism. 4. Plant sterols (phytosterols) did not have a significant effect on plasma concentrations of lipids and lipoprotein or the kinetics of apoB and apoA-I. 5. Modest weight reduction optimally decreased plasma triglyceride and LDL-cholesterol via reduction in hepatic apoB secretion and reciprocal upregulation of LDL catabolism. 6. The scope and potential of future studies using stable isotope tracers is discussed.

Topics: Biological Transport; Diet, Fat-Restricted; Fish Oils; Humans; Lipoproteins; Metabolic Syndrome; Models, Biological; Nutritional Physiological Phenomena; Obesity; Phytosterols; Radionuclide Imaging; Weight Loss

National guidelines indicate patients with elevated low- density lipoprotein cholesterol should consume less than 7% of calories from saturated fat and less than 200 mg of cholesterol. Trans fatty acids should also be limited. Incorporation of functional foods, such as stanol-containing margarine, soy products, and soluble fiber-rich cereals and vegetables can provide further benefit. In addition to weight loss and physical activity, individuals with hypertriglyceridemia benefit from a diet moderate in fat and carbohydrate rather than a low-fat diet. Including monounsaturated or omega-3 fatty acids lowers serum triglycerides. Many of the dietary strategies to optimize serum lipids also contribute to glycemic control in patients with diabetes mellitus.

Topics: Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Dietary Fiber; Energy Intake; Fatty Acids; Fatty Acids, Omega-3; Female; Humans; Hyperlipidemias; Male; Metabolic Syndrome; Obesity; Phytosterols; Soybean Proteins; Triglycerides

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory.

Topics: Adult; Blood Pressure; Cultured Milk Products; Double-Blind Method; Esters; Female; Hemodynamics; Humans; Lipids; Male; Metabolic Syndrome; Middle Aged; Oligopeptides; Phytosterols; Placebos; Posture; Vascular Resistance

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

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

A randomised, cross-over, controlled-feeding study was conducted to evaluate the cholesterol-lowering effects of diets containing pistachios as a strategy for increasing total fat (TF) levels v. a control (step I) lower-fat diet. Ex vivo techniques were used to evaluate the effects of pistachio consumption on lipoprotein subclasses and functionality in individuals (n 28) with elevated LDL levels ( ≥ 2·86 mmol/l). The following test diets (SFA approximately 8 % and cholesterol < 300 mg/d) were used: a control diet (25 % TF); a diet comprising one serving of pistachios per d (1PD; 30 % TF); a diet comprising two servings of pistachios per d (2PD; 34 % TF). A significant decrease in small and dense LDL (sdLDL) levels was observed following the 2PD dietary treatment v. the 1PD dietary treatment (P= 0·03) and following the 2PD dietary treatment v. the control treatment (P= 0·001). Furthermore, reductions in sdLDL levels were correlated with reductions in TAG levels (r 0·424, P= 0·025) following the 2PD dietary treatment v. the control treatment. In addition, inclusion of pistachios increased the levels of functional α-1 (P= 0·073) and α-2 (P= 0·056) HDL particles. However, ATP-binding cassette transporter A1-mediated serum cholesterol efflux capacity (P= 0·016) and global serum cholesterol efflux capacity (P= 0·076) were only improved following the 2PD dietary treatment v. the 1PD dietary treatment when baseline C-reactive protein status was low ( < 103μg/l). Moreover, a significant decrease in the TAG:HDL ratio was observed following the 2PD dietary treatment v. the control treatment (P= 0·036). There was a significant increase in β-sitosterol levels (P< 0·0001) with the inclusion of pistachios, confirming adherence to the study protocol. In conclusion, the inclusion of pistachios in a moderate-fat diet favourably affects the cardiometabolic profile in individuals with an increased risk of CVD.

Topics: Anticholesteremic Agents; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cross-Over Studies; Dietary Fats; Female; Humans; Insulin Resistance; Lipoproteins; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Nuts; Phytosterols; Phytotherapy; Pistacia; Sitosterols; Triglycerides

Several studies have observed decreased levels of lipophilic antioxidants after supplementation with phytosterols and stanols. The aim of this study was to examine the effect of phytosterol supplementation on plasma total antioxidant capacity in patients with metabolic syndrome. In a parallel arm, randomized placebo-controlled design, 108 patients with metabolic syndrome were assigned to consume yogurt beverage which provided 4 g of phytosterols per day or yogurt beverage without phytosterols. The duration of the study was 2 months and the patients in both groups followed their habitual westernized type diet. Blood samples were drawn at baseline and after 2 months, and the total antioxidant capacity of plasma was measured using the ferric reducing antioxidant power of plasma and oxygen radical absorbance capacity assays. After 2 months of intervention, plasma total antioxidant capacity did not differ between and within the intervention and the control groups. Phytosterol supplementation does not affect plasma antioxidant status.

Topics: Adult; Antioxidants; Beverages; Dietary Supplements; Female; Ferric Compounds; Humans; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Reactive Oxygen Species; Yogurt

Several studies have observed a hypocholesterolemic effect of plant sterols in hypercholesterolemic patients on a balanced diet. The aim of this study was to examine the effect of phytosterol supplementation on risk factors of coronary artery disease in metabolic syndrome patients on a Westernized type diet.. In a randomized placebo-controlled design 108 patients with metabolic syndrome were assigned to consume either 2 plant sterol-enriched yogurt mini drink which provided 4 g phytosterols per day, or a yogurt beverage without phytosterols (control). The duration of the study was 2 months and the patients in both groups followed their habitual westernized type diet and recording it on food diaries. Blood samples were drawn at baseline and after 2 months of intervention. After 2 months supplementation with phytosterols, a significant reduction in total cholesterol, LDL-cholesterol, small and dense LDL (sdLDL) levels, as well as, apoB and triglycerides concentrations were observed in the intervention group (P < 0.05) compared to the control group. In addition, phytosterol supplementation lowered serum total cholesterol by 15.9%, LDL-cholesterol by 20.3% and triglyceride levels by 19.1% (P = 0.02, P < 0.001 and P < 0.001, respectively), although the patients kept their habitual westernized type diet. No differences were observed in HDL cholesterol, apoA1, glucose, C-reactive protein, fibrinogen levels and blood pressure.. Phytosterol supplementation improves risk factors of coronary artery disease even if the diet is a westernized type.

Topics: Adult; Aged; Anticholesteremic Agents; Apolipoprotein A-I; Arterial Pressure; Blood Pressure; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diet; Diet Records; Dietary Supplements; Energy Intake; Female; Fibrinogen; Humans; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Risk Factors; Single-Blind Method; Triglycerides; Yogurt

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

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

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

Our purpose was to examine the effects of daily servings of butter, no-trans-fat margarine and plant sterol margarine, within recommended amounts, on plasma lipids, apolipoproteins (Apos), biomarkers of inflammation and endothelial dysfunction, and on the transfer of lipids to HDL particles in free-living subjects with the metabolic syndrome.. This was a randomized, single-blind study where 53 metabolic syndrome subjects (62% women, mean age 54 years) received isocaloric servings of butter, no-trans-fat margarine or plant sterol margarine in addition to their usual diets for 5 weeks. The main outcome measures were plasma lipids, Apo, inflammatory and endothelial dysfunction markers (CRP, IL-6, CD40L or E-selectin), small dense LDL cholesterol concentrations and in vitro radioactive lipid transfer from cholesterol-rich emulsions to HDL. Difference among groups was evaluated by analysis of variance.. There was a significant reduction in Apo-B (-10.4 %, P=0.043) and in the Apo-B/Apo-A-1 ratio (-11.1%, P=0.034) with plant sterol margarine. No changes in plasma lipids were noticed with butter and no-trans-fat margarine. Transfer rates of lipids to HDL were reduced in the no-trans-fat margarine group: triglycerides -42.0%, (P<0.001 vs butter and sterol margarine) and free cholesterol -16.2% (P=0.006 vs sterol margarine). No significant effects were noted on the concentrations of inflammatory and endothelial dysfunction markers among the groups.. In free-living subjects with the metabolic syndrome consumption of plant sterol and no-trans-fat margarines within recommended amounts reduced, respectively, Apo-B concentrations and the ability of HDL to accept lipids.

Topics: Adult; Apolipoproteins; Biomarkers; Butter; Cardiovascular Diseases; Dietary Fats; E-Selectin; Endothelium, Vascular; Fat Substitutes; Female; Humans; Inflammation Mediators; Lipids; Lipoproteins, HDL; Male; Margarine; Metabolic Syndrome; Middle Aged; Phytosterols; Risk Factors; Single-Blind Method

Dietary plant sterols supplementation has been demonstrated in some studies to lower plasma total and LDL cholesterol in hypercholesterolemic subjects. The cholesterol lowering action of plant sterols remains to be investigated in subjects with the metabolic syndrome. In a randomized, crossover study of 2 x 4 week therapeutic periods with oral supplementation of plant sterols (2 g/day) or placebo, and two weeks placebo wash-out between therapeutic periods, we investigated the effects of dietary plant sterols on lipoprotein metabolism in nine men with the metabolic syndrome. Lipoprotein kinetics were measured using [D3]-leucine, gas chromatography-mass spectrometry and compartmental modeling. In men with the metabolic syndrome, dietary plant sterols did not have a significant effect on plasma concentrations of total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, apolipoprotein (apo) B, apoA-I or apoA-II. There were no significant changes to VLDL-, IDL-, LDL-apoB or apoA-I fractional catabolic rates and production rates between therapeutic phases. Relative to placebo, plasma campesterol, a marker of cholesterol absorption was significantly increased (2.53 +/- 0.35 vs. 4.64 +/- 0.59 mug/ml, p < 0.05), but there was no change in plasma lathosterol, a marker of endogenous cholesterol synthesis. In conclusion, supplementation with plant sterols did not appreciably influence plasma lipid or lipoprotein metabolism in men with the metabolic syndrome. Future studies with larger sample size, stratification to low and high cholesterol absorbers and cholesterol balance studies are warranted.

Topics: Aged; Apolipoproteins; Biological Availability; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Dietary Supplements; Gas Chromatography-Mass Spectrometry; Humans; Intestinal Absorption; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Triglycerides

The dysmetabolic syndrome of insulin resistance and visceral obesity is characterized by elevated plasma concentration of triacylglycerol-rich lipoprotein (TRL) remnants that may be related to increased cardiovascular risk. Perturbed hepato-intestinal cholesterol metabolism may play a contributory role in this abnormality. We therefore investigated the association between plasma markers of cholesterol absorption and synthesis with TRL remnant metabolism in 35 men with the metabolic syndrome (MS). Plasma campesterol:cholesterol and lathosterol:cholesterol ratios were measured as estimates of cholesterol absorption and synthesis respectively. Remnant metabolism was assessed by measuring remnant-like particle-cholesterol (RLP-C), apolipoprotein (apo)B-48 and the fractional catabolic rate (FCR) of a labelled remnant-like emulsion. Compared with controls, subjects with the MS had significantly lower plasma campesterol:cholesterol ratio, but higher lathosterol:cholesterol ratio ( P <0.05). Plasma RLP-C and apoB-48 concentrations were also higher ( P <0.01) and the remnant-like emulsion FCR was lower ( P <0.05). The plasma campesterol:cholesterol ratio was inversely correlated ( P <0.05) with plasma triacylglycerols ( r =-0.346), RLP-C ( r =-0.443), apoB-48 ( r =-0.427) and plasma lathosterol:cholesterol ratio ( r =-0.366); the campesterol:cholesterol ratio was also positively correlated with the remnant-like emulsion FCR ( r =0.398, P <0.05). In multiple regression analysis, the significant correlations between plasma campesterol:cholesterol ratio and plasma triacylglycerols, RLP-C, apoB-48 and FCR of the remnant-like emulsion were independent of age, dietary energy and plasma lathosterol. Our findings suggest that in subjects with the MS alterations in cholesterol absorption and synthesis may be closely linked with the kinetic defects in TRL metabolism.

Topics: Apolipoprotein B-48; Apolipoproteins B; Biomarkers; Breath Tests; Case-Control Studies; Cholesterol; Humans; Linear Models; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Triglycerides

We aimed to study the effect of atorvastatin, a statin, on cholesterol synthesis and absorption and VLDL-apoB metabolism in obese men with the metabolic syndrome.. A total of 25 dyslipidaemic obese men were randomized to atorvastatin (n=13) (40 mg/day) or matching placebo (n=12) for 6 weeks. Hepatic secretion and fractional catabolic rate (FCR) of VLDL-apoB was measured using an intravenous bolus of d(3)-leucine before and after treatment. ApoB isotopic enrichment was measured using GCMS and multicompartmental modelling. Plasma lathosterol: cholesterol and campesterol:cholesterol ratios were determined to assess cholesterol synthesis and cholesterol absorption, respectively.. Compared with placebo, atorvastatin significantly decreased (P<0.05) total cholesterol, triglyceride, LDL-cholesterol and VLDL-apoB. Plasma lathosterol:cholesterol ratio decreased from 26.4+/-2.4 to 8.8+/-0.8, while the campesterol:cholesterol ratio increased from 26.5+/-4.4 to 38.6+/-5.8 (P<0.01). Atorvastatin also increased VLDL-apoB FCR from 3.82+/-0.33 to 6.30+/-0.75 pools/day (P<0.01), but did not significantly alter VLDL-apoB secretion (12.8+/-1.7 to 13.8+/-2.0 mg/kg/day).. In obesity, atorvastatin inhibits cholesterogenesis but increases intestinal cholesterol absorption. The increased cholesterol absorption may counteract the inhibitory effect on hepatic VLDL-apoB secretion, but it does not apparently influence enhanced catabolism of VLDL-apoB.

Topics: Anticholesteremic Agents; Apolipoprotein B-100; Apolipoproteins B; Atorvastatin; Cholesterol; Cholesterol, VLDL; Double-Blind Method; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Pyrroles

Topics: Humans; Metabolic Syndrome; Phytosterols; Withania; Withanolides

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

Thirty-five women with metabolic syndrome and high plasma low-density lipoprotein (LDL) cholesterol (≥100 mg/dl) participated in a dietary intervention consisting of a Mediterranean-style low-glycemic-load diet for 12 weeks. Participants were randomly allocated to consume diet only (n=15) or diet plus a medical food containing soy protein and plant sterols (n=20). Plasma concentrations of carotenoids, lipoprotein subfractions and oxidized LDL (OxLDL) were measured. Independent of treatment, women had a significant increase in plasma lutein (P<.0001) and β-carotene (P<.0001), while plasma lycopene was reduced (P<.05) after 12 weeks. Low-density lipoprotein cholesterol was reduced from 138±35 to 114±33 mg/dl (P<.0001). In addition, decreases were observed in the atherogenic subfractions: large very low-density lipoprotein (P<.05), small LDL (P<.00001) and medium high-density lipoprotein (P<.05). Oxidized LDL was significantly reduced by 12% in both groups (P<.01). Changes in OxLDL were inversely correlated with plasma lutein (r=-.478, P<.0001). The data indicate that women complied with the dietary regimen by increasing fruits and vegetable intake. Decreased consumption of high-glycemic foods frequently co-consumed with lycopene-rich tomato sauce such as pasta and pizza may be responsible for the lowering of this carotenoid in plasma after 12 weeks. These results also suggest that plasma lutein concentrations may protect against oxidative stress by reducing the concentrations of OxLDL.

Topics: Adult; beta Carotene; Blood Glucose; Carotenoids; Diet, Mediterranean; Energy Intake; Female; Fruit; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Lutein; Lycopene; Metabolic Syndrome; Middle Aged; Patient Compliance; Phytosterols; Soybean Proteins; Vegetables

The objective was to assess the impact of a Mediterranean-style, low-glycemic-load diet (control group, n = 41) and the same diet plus a medical food (MF) containing phytosterols, soy protein, and extracts from hops and Acacia (MF group, n = 42) on lipoprotein atherogenicity in women with metabolic syndrome. Plasma lipids, apolipoproteins (apos), lipoprotein subfractions and particle size, low-density lipoprotein (LDL) oxidation, and lipoprotein (a) were measured at baseline, week 8, and week 12 of the intervention. Three-day dietary records were collected at the same time points to assess compliance. Compared with baseline, women decreased energy intake from carbohydrate (P < .001) and fat (P < .001), whereas they increased energy intake from protein (P < .001). A significant increase in energy from monounsaturated fatty acids was also observed as well as increases in eicosapentaenoic acid and docosahexaenoic acid, whereas trans-fatty acid intake was reduced (P < .00001). The atherogenic lipoproteins, large very low-density lipoprotein (P < .0001) and small LDL (P < .0001), were reduced, whereas the ratio of large high-density lipoprotein to smaller high-density lipoprotein particles was increased (P < .0001). Apolipoprotein B was reduced for all women (P < .0001), with a greater reduction in the MF group (P < .025). Oxidized LDL (P < .05) and lipoprotein (a) (P < .001) were reduced in both groups at the end of the intervention. Consumption of a Mediterranean-style diet reduces the risk for cardiovascular disease by decreasing atherogenic lipoproteins, oxidized LDL, and apo B. Inclusion of an MF may have an additional effect in reducing apo B.

Topics: Acacia; Adult; Aged; Apolipoproteins; Cardiovascular Diseases; Diet, Mediterranean; Energy Intake; Female; Food, Formulated; Glycemic Index; Humans; Humulus; LDL-Receptor Related Proteins; Lipoprotein(a); Lipoproteins; Metabolic Syndrome; Middle Aged; Oxidation-Reduction; Particle Size; Phytosterols; Plant Extracts; Proanthocyanidins; Risk Factors; Soybean Proteins; Young Adult

Increased plasma phytosterols, which reflect enhanced cholesterol absorption, have been related to an increased risk of cardiovascular disease (CVD). However, high CVD risk conditions, such as obesity, diabetes and the metabolic syndrome (MetS) have been associated with reduced cholesterol absorption. We investigated associations between plasma noncholesterol sterols and MetS components.. With a cross-sectional design, we related MetS components to plasma noncholesterol sterol-to-cholesterol ratios measured by gas chromatography in 674 dyslipidemic patients and 361 healthy subjects participating in a prospective cohort study. Plasma phytosterol-to-cholesterol ratios were inversely associated with all components of the MetS. In the dyslipidemic group, multivariable analyses showed that a 1-SD increase in sitosterol-to-cholesterol ratio was associated with a reduced risk for any MetS feature, ranging from 0.57 (95% CI, 0.45 to 0.71) for visceral adiposity to 0.82 (95% CI, 0.69 to 0.98) for high blood pressure. The risk of having MetS was nearly halved, with ORs of 0.49 (95% CI, 0.38 to 0.64) or 0.56 (95% CI, 0.44-0.70), depending on the definition. Results were opposed for plasma lathosterol, a marker of cholesterol synthesis. Most findings were reproduced in the healthy cohort. ApoE genotype was unrelated to plasma noncholesterol sterols.. In both dyslipidemic and healthy populations, MetS is associated with increased plasma lathosterol, a cholesterol synthesis marker, and decreased plasma sitosterol, a marker of cholesterol absorption. Elevated plasma phytosterols related to a lower frequency of cardiometabolic risk factors, suggesting that they are associated with a reduced CVD risk.

Topics: Adult; Apolipoproteins E; Biomarkers; Cardiovascular Diseases; Cholesterol; Cross-Sectional Studies; Female; Genotype; Homeostasis; Humans; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Phenotype; Phytosterols; Prospective Studies; Risk Factors; Sitosterols

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 +/- 7 vs. 136 +/- 3 10(2) mumol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = -0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.

Topics: Absorption; Aged; Biomarkers; Cholestanol; Cholesterol; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Phytosterols; Squalene

Phytosterols have been proposed to be atherogenic. This research investigates whether plasma concentrations of phytosterols correlate with the manifestation of coronary heart disease.. The CORA study compares clinical, biochemical, and lifestyle factors in consecutive pre- and postmenopausal women with incident coronary heart disease to those in age-matched population-based controls. Controls (n=231) had significantly higher plasma concentrations of the major phytosterol species than cases (n=186) (4.649mg/l vs. 4.092mg/l; p<0.001). Cases had a higher dietary intake of phytosterols, but the ratio of lathosterol over sitosterol did not significantly differ. Phytosterols correlated with cholesterol concentrations of LDL and HDL, the phytosterol-carrying lipoproteins. The age-adjusted odds ratio for the association of total phytosterols and risk of coronary heart disease was 0.69 per 5mg/dl (95% CI 0.46-0.99). After adjustment for LDL- and HDL-cholesterol the odds ratio approached 1 (0.89; 95% CI 0.61-1.30), which was reached after additional adjustment for major risk factors, particularly those reflecting the metabolic syndrome (1.05; 95% CI 0.64-1.97).. Healthy controls had higher unadjusted concentrations of plasma phytosterols, but the adjusted odds ratio for coronary heart disease did not point to an impact of plasma phytosterols on coronary heart disease.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholesterol; Coronary Artery Disease; Female; Humans; Metabolic Syndrome; Middle Aged; Odds Ratio; Phytosterols; Risk Factors; Sitosterols

We investigated the associations between indices of cholesterol metabolism and features of the metabolic syndrome (MS) in the presence and absence of type-2 diabetes (T2DM).. Men with the MS (N=140) and 10 age- and sex-matched controls were recruited. Plasma lathosterol and campesterol were measured by gas chromatography-mass spectrometry, and their ratios to total cholesterol were used to estimate cholesterol metabolism.. Compared with healthy controls, MS subjects had significantly higher lathosterol:cholesterol and lower campesterol:cholesterol ratios (p<0.05). In the MS subjects without T2DM (N=82), campesterol:cholesterol ratio was positively associated with age and negatively associated with plasma triglyceride and insulin concentrations, while in MS subjects with T2DM (N=58), the ratio was positively associated with age and adiponectin concentration, and negatively associated with BMI and insulin. Age and fasting insulin were independent predictors of campesterol:cholesterol ratio in MS subjects with T2DM. There was a significant negative association between plasma lathosterol:cholesterol with campesterol:cholesterol ratio (r=-0.436, p=0.014) in MS subjects without T2DM but not in MS subjects with T2DM.. Cholesterol absorption efficiency was lower and cholesterol synthesis higher in MS subjects with or without T2DM compared with healthy individuals. Moreover, the reciprocal relationship between cholesterol synthesis and cholesterol absorption is lost in the presence of diabetes.

Topics: Adiponectin; Apolipoprotein A-I; Apolipoproteins; Biomarkers; Blood Glucose; Blood Pressure; Cholesterol; Diabetes Mellitus, Type 2; Female; Gas Chromatography-Mass Spectrometry; Homeostasis; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity; Phytosterols; Reference Values; Triglycerides

Components of the metabolic syndrome such as hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol and obesity have been shown to be associated with increased cholesterol synthesis and reduced cholesterol absorption. In the present study, we measured the lathosterol/cholesterol ratio as an index of cholesterol synthesis and the ratios of cholestanol, campesterol and sitosterol to cholesterol as indices of cholesterol absorption, as well as components of the metabolic syndrome, in 324 men and 168 women from the PROCAM study, an epidemiological study in which raised sitosterol was previously associated with increased coronary risk. Our aim was to determine if the indices of cholesterol synthesis and absorption show a graded relationship with severity of metabolic syndrome.. No differences were seen between men and women with regard to the relationship of either the lathosterol/cholesterol or the sitosterol/cholesterol ratios and severity of metabolic syndrome. On multiple regression analysis in men and women together, body mass index showed a positive relationship with the lathosterol/cholesterol ratio (r=0.257, P<0.001) and a negative relationship with the sitosterol/cholesterol ratio (r=-0.221, P<0.001). HDL-cholesterol showed a negative relationship with the lathosterol/cholesterol ratio (r=-0.166, P=0.001). Triglycerides showed a negative relationship with the sitosterol/cholesterol ratio (r=0.141, P=0.005). Overall, these relationships were graded across quintiles of HDL cholesterol, body mass index and triglyceride and across an index of metabolic syndrome severity (number of components present). Only the cholestanol/cholesterol ratio showed a graded relationship with estimated overall coronary risk.. The metabolic syndrome is associated with increased cholesterol synthesis and reduced cholesterol absorption in a relationship that is graded across severity of the individual components of the syndrome and across an index of the severity of the metabolic syndrome as a whole.

Topics: Adult; Aged; Biomarkers; Body Mass Index; Cholesterol; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Phytosterols; Prospective Studies; Regression Analysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Sex Factors

The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality.. We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling.. Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption.. Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.

Topics: Adult; Apolipoprotein B-100; Apolipoproteins B; Biomarkers; Cholesterol; Homeostasis; Humans; Kinetics; Lipoproteins; Lipoproteins, IDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Metabolic Syndrome; Middle Aged; Phytosterols

Topics: Aged; Alcoholic Beverages; Cholesterol, Dietary; Dietary Fats; Dietary Fiber; Energy Intake; Exercise; Fatty Acids, Omega-3; Female; Humans; Hyperlipidemias; Lipoproteins, HDL; Lipoproteins, LDL; Male; Margarine; Metabolic Syndrome; Middle Aged; Phytosterols; Smoking; Triglycerides