phytosterols and Body-Weight

Hass avocados, the most common commercial avocado cultivars in the world, contain a variety of essential nutrients and important phytochemicals. Although the official avocado serving is one-fifth of a fruit (30 g), according to NHANES analysis the average consumption is one-half an avocado (68 g), which provides a nutrient and phytochemical dense food consisting of the following: dietary fiber (4.6 g), total sugar (0.2 g), potassium (345 mg), sodium (5.5 mg), magnesium (19.5 mg), vitamin A (43 μg), vitamin C (6.0 mg), vitamin E (1.3 mg), vitamin K1 (14 μg), folate (60 mg), vitamin B-6 (0.2 mg), niacin (1.3 mg), pantothenic acid (1.0 mg), riboflavin (0.1 mg), choline (10 mg), lutein/zeaxanthin (185 μg), phytosterols (57 mg), and high-monounsaturated fatty acids (6.7 g) and 114 kcals or 1.7 kcal/g. The avocado oil consists of 71% monounsaturated fatty acids (MUFA), 13% polyunsaturated fatty acids (PUFA), and 16% saturated fatty acids (SFA), which helps to promote healthy blood lipid profiles and enhance the bioavailability of fat soluble vitamins and phytochemicals from the avocado or other fruits and vegetables, naturally low in fat, which are consumed with avocados. There are eight preliminary clinical studies showing that avocado consumption helps support cardiovascular health. Exploratory studies suggest that avocados may support weight management and healthy aging.

Topics: Body Weight; Carbohydrates; Cardiovascular Diseases; Carotenoids; Dietary Fiber; DNA Damage; Eye Diseases; Fatty Acids; Food, Organic; Humans; Neoplasms; Nutrition Surveys; Osteoarthritis; Persea; Phenols; Phytosterols; Randomized Controlled Trials as Topic; Skin Diseases; Trace Elements; Vitamins

The pistachio is a nutrient-dense nut with a heart-healthy fatty-acid profile as well as protein, dietary fiber, potassium, magnesium, vitamin K, γ-tocopherol, and a number of phytochemicals. The pistachio's unique green and purple kernel color is a result of its lutein and anthocyanin content. Among nuts, pistachios contain the highest levels of potassium, γ-tocopherol, vitamin K, phytosterols, and xanthophyll carotenoids. Five published randomized cardiovascular trials have shown that pistachios promote heart-healthy blood lipid profiles. Exploratory clinical studies suggest that pistachios help maintain healthy antioxidant and anti-inflammatory activity, glycemic control, and endothelial function. When consumed in moderation, pistachios may help control body weight because of their satiety and satiation effects and their reduced net metabolizable energy content. One study with subjects in a weight-loss program demonstrated lower body mass index and triglyceride levels in individuals who consumed pistachios compared with those who consumed an isocaloric pretzel snack. Emerging research suggests that the addition of pistachios to high-glycemic meals may lower the overall postprandial glycemic response. This review examines the nutrients and phytochemicals in pistachios as well as the potential health effects of these nuts.

Topics: Antioxidants; Blood Glucose; Body Weight; Cardiovascular Diseases; Humans; Nutritive Value; Phytosterols; Pistacia

Cholesterol absorption and synthesis are inter-regulated, so if one changes then the other changes in the opposite direction. The regulation and detailed mechanism of cholesterol absorption have been intensely investigated. Inhibition of cholesterol absorption has become an additional factor for cholesterol lowering. Agents inhibiting cholesterol absorption, mainly plant stanols and sterols or ezetimibe, usually lower low-density lipoprotein cholesterol in monotherapy by less than 20%, indicating that these inhibitors can normalize cholesterol levels only in patients with a modest baseline hypercholesterolemia. Body weight, especially obesity with and without diabetes, and dietary plant sterols alter cholesterol absorption differently. This article briefly reviews some special questions of cholesterol absorption under these conditions.

Topics: Absorption; Body Mass Index; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Male; Phytosterols; Prognosis; Sensitivity and Specificity; Treatment Outcome

Hyperglycemia is a major public health problem worldwide and there is increasing demand for prevention of postprandial hyperglycemia in diabetic, prediabetic, and healthy humans.. We investigated whether rice bran and triterpene alcohol and sterol preparation (TASP) lowered hyperglycemia in mice and humans. Brown rice and white rice supplemented with TASP lowered the postprandial hyperglycemia in humans. TASP and its components (cycloartenol [CA], 24-methylene cycloartanol, β-sitosterol, and campesterol) decreased postprandial hyperglycemia in C57BL/6J mice. Glucose transport into everted rat intestinal sacs and human HuTu80 cells transfected with sodium-glucose cotransporter-1 (SGLT1) was significantly reduced by the addition of CA. Intracellular localization analysis suggested that SGLT1 translocation to the apical plasma membrane was inhibited when the cells were treated with CA.. We demonstrated for the first time that TASP from rice bran lowered postprandial hyperglycemia in mice and humans. The smaller increase in blood glucose following TASP consumption may be due to the CA-induced decrease in glucose absorption from the intestine, which may be related to decreased membrane translocation of SGLT1.

Topics: Adult; Animals; Blood Glucose; Body Mass Index; Body Weight; Cell Line, Tumor; Cholesterol; Dietary Fiber; Humans; Hyperglycemia; Insulin; Male; Mice; Mice, Inbred C57BL; Oryza; Phytosterols; Rats; Rats, Wistar; Single-Blind Method; Sitosterols; Sodium-Glucose Transporter 1; Sterols; Triterpenes

Very-low-birth-weight (VLBW) infants are dependent on parenteral nutrition after birth. A parenteral lipid emulsion with a multicomponent composition may improve growth and neurodevelopment and may prevent liver injury, which is often observed in association with long-term parenteral nutrition with pure soybean oil. Our aim was to evaluate the safety and efficacy of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triacylglycerol, 25% olive oil, and 15% fish oil compared with a conventional pure soybean oil emulsion in VLBW infants.. We conducted a double-blind randomized controlled trial in VLBW infants randomized to parenteral nutrition with the multicomponent (study group) or pure soybean oil emulsion (control group) from birth at a dose of 2 to 3 g · kg(-1) · day(-1) until the infants were receiving full enteral nutrition. We assessed efficacy by growth rates and measuring plasma fatty acid profiles (representative subset). Safety was evaluated by assessing hematologic and biochemical parameters, potentially harmful phytosterol concentrations (same subset), and clinical neonatal outcome parameters.. Ninety-six infants were included (subsets n = 21). The multicomponent emulsion was associated with higher weight and head circumference z scores during admission. Plasma eicosapentaenoic acid and docosahexaenoic acid concentrations were higher in the study group. The hematological, biochemical, and neonatal outcomes were not different between groups, whereas the plasma concentrations of phytosterols were higher in the control group.. The multicomponent lipid emulsion was well tolerated and associated with improved growth and higher plasma fatty acid profiles in VLBW infants in comparison with the pure soybean oil emulsion.

Topics: Body Weight; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fat Emulsions, Intravenous; Female; Fish Oils; Head; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Male; Olive Oil; Organ Size; Parenteral Nutrition; Phytosterols; Plant Oils; Soybean Oil; Triglycerides

Long-term dietary weight loss results in complex metabolic changes. However, its effect on cholesterol metabolism in obese subjects is still unclear.. We assessed the effects of 2 y of weight loss achieved with various diet regimens on phytosterols (markers of intestinal cholesterol absorption), lanosterol (marker of de novo cholesterol synthesis), and changes in apolipoprotein concentrations.. We conducted the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT-a study of low-fat, Mediterranean, and low-carbohydrate diets). We assessed circulating phytosterol and lanosterol concentrations and their ratios to cholesterol and apolipoproteins A-I and B-100 in 90 DIRECT participants at 0, 6, and 24 mo.. We observed a significant upregulation of the markers of cholesterol absorption (campesterol: +16.8%, P < 0.001) and a downregulation of the markers of cholesterol synthesis (lanosterol: -16.5%, P = 0.008) during the active weight-loss phase (first 6 mo, weight loss of 5%, 6%, and 10% in the 3 diet groups, respectively), followed by a rebound (campesterol: -6.2%, P = 0.045; lanosterol: +43.7%, P < 0.001) during the next 18 mo (weight gain of 1%, 1%, and 2% in the 3 diet groups, respectively). HDL cholesterol continuously increased during the study (17.0%, P < 0.001), whereas LDL cholesterol remained constant. At the end of the 24-mo follow-up period, campesterol (P < 0.001) and lanosterol (P = 0.016) amounts were significantly higher than baseline values. The concentration of apolipoprotein B-100 correlated with cholesterol metabolism (ρ = 0.299 and P = 0.020 for lanosterol; ρ = -0.105 and NS for campesterol), and the homeostasis model assessment of insulin resistance correlated with lanosterol (ρ = 0.09, P = 0.001).. Long-term weight loss is related to a characteristic response suggestive of altered cholesterol and apolipoprotein metabolism. Various diets have a similar effect on these effects. DIRECT is registered at clinicaltrials.gov as NCT00160108.

Topics: Adult; Apolipoprotein A-I; Apolipoprotein B-100; Body Weight; Cholesterol; Diet, Reducing; Humans; Lanosterol; Male; Middle Aged; Obesity; Phytosterols; Statistics, Nonparametric; Weight Loss

Coronary heart disease (CHD) is the leading cause of death in the United States. Elevated levels of plasma total cholesterol (TC), and particularly plasma low density lipoprotein-cholesterol (LDLC), are primary contributing factors to CHD. Dietary plant sterols (phytosterols) have been shown to significantly reduce plasma TC and LDLC in humans, primarily through inhibition of intestinal cholesterol absorption, and are potentially effective agents for reduction of CHD risk. Although a variety of phytosterol-containing foods are currently available, phytosterol-enriched eggs, which represent a potential value-added product, are conspicuously absent from the marketplace. Therefore, the objectives of this study were 1) to enrich shell eggs with phytosterols; and 2) to determine if feeding phytosterols to hens elicits egg compositional changes, particularly that of yolk cholesterol content. Sixteen 32-wk-old White Leghorn hens were fed a corn-soy-based layer diet without (n = 8) or with (n = 8) 1 g of supplemental soy sterols/100 g of diet for 28 d.. Hen performance was determined on an individual basis, and 1 egg/hen per week was collected, processed, and analyzed for yolk cholesterol, CP, crude fat (CF), and phytosterol content. There was no effect (P > 0.05) of supplemental dietary phytosterols on 28-d weight gain, feed consumption, feed efficiency, plasma TC, hen-day egg production, egg weights, egg component weights, and yolk cholesterol, CP, and CF contents. Small amounts of campesterol were present in most of the eggs (average of 0.29 and 1.02 mg/yolk for control vs. soy sterol-fed hens, respectively; P < or = 0.05), whereas only 3 of the 80 analyzed eggs contained trace amounts of beta-sitosterol and none contained any detectable stigmasterol. It was concluded that phytosterols are either poorly absorbed from the chicken intestine or, if they are absorbed, they are efficiently secreted back into the intestinal lumen, most likely via as yet uncharacterized adenosine triphosphate-binding cassette transporters.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Chickens; Diet; Dietary Supplements; Eggs; Female; Oviposition; Phytosterols

To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio).. For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study.. Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and -2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=-0.34, n=50, P=0.017; diastolic: r=-0.29, n=50, P=0.041).. A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

Topics: Blood Pressure; Body Weight; Cholesterol; Cholesterol, Dietary; Diet Records; Dietary Fiber; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Obesity; Phytosterols; Prunus; Soybean Proteins; Weight Loss

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

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

Previous studies with plant sterols (PS) and cocoa flavanols (CF) provide support for their dietary use in maintaining cardiovascular health. This double-blind, placebo-controlled, cross-over study evaluated the efficacy of daily consumption of a cocoa flavanol-containing dark chocolate bar with added PS on serum lipids, blood pressure, and other circulating cardiovascular health markers in a population with elevated serum cholesterol. We recruited 49 adults (32 women, 17 men) with serum total cholesterol concentrations of 5.20-7.28 mmol/L and blood pressure of < or = 159/99 mm Hg. Following a 2-wk lead-in utilizing the AHA style diet, participants were randomized into 2 groups and instructed to consume 2 cocoa flavanol-containing dark chocolate bars per day with (1.1 g sterol esters per bar) or without PS. Each 419-kJ bar was nutrient-matched and contained approximately 180 mg CF. Participants consumed 1 bar 2 times per day for 4 wk then switched to the other bar for an additional 4 wk. Serum lipids and other cardiovascular markers were measured at baseline and after 4 and 8 wk. Blood pressure was measured every 2 wk. Regular consumption of the PS-containing chocolate bar resulted in reductions of 2.0 and 5.3% in serum total and LDL cholesterol (P < 0.05), respectively. Consumption of CF also reduced systolic blood pressure at 8 wk (-5.8 mm Hg; P < 0.05). Results indicate that regular consumption of chocolate bars containing PS and CF as part of a low-fat diet may support cardiovascular health by lowering cholesterol and improving blood pressure.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Cacao; Cardiovascular Diseases; Cross-Over Studies; Female; Flavonols; Humans; Lipids; Male; Middle Aged; Phytosterols

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

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

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

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

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

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

Consumption of plant sterols or stanols increases their respective serum concentrations, whereas plant sterols might reduce serum concentrations of plant stanols and vice versa. This suggests that changes in serum plant sterol and stanol concentrations depend on the ratio of plant sterols to stanols in the diet. To examine this in more detail, healthy men (n = 15) and women (n = 29) consumed in random order for 3 wk 1.5 g/d of plant sterols plus 0.5 g of plant stanols (high sterol margarine), 1 g of each (low sterol margarine) or control margarine. Sterols and stanols were provided as fatty acid esters. Compared with the control period, serum cholesterol-standardized campesterol and sitosterol concentrations increased by 33 (P < 0.001) and 19% (P < 0.002), respectively, during the high sterol period, but by only 20 (P < 0.001) and 11% (P = 0.001), respectively, during the low sterol period. During the high sterol period, these values for campestanol and sitostanol were 18 (P = 0.063) and 1% (P = 0.630), and during the low sterol period 25 (P = 0.105) and 7% (P = 0.163), respectively. Effects on LDL cholesterol were similar. We therefore conclude that changes in serum plant sterol and stanol concentrations are not greatly affected by the simultaneous consumption of plant sterols and plant stanols, but are proportional to intakes. Furthermore, both mixtures were equally effective in lowering serum LDL cholesterol concentrations.

Topics: Adolescent; Adult; Body Weight; Cholesterol, LDL; Cross-Over Studies; Diet; Female; Humans; Lipids; Lipoproteins; Male; Margarine; Middle Aged; Osmolar Concentration; Phytosterols; Reference Values; Sterols

Oil-based products enriched with plant stanol esters can lower low-density lipoprotein (LDL) cholesterol concentrations by 10-14%. Effectiveness of low-fat products, however, has never been evaluated, although such products fit into a healthy diet. We therefore examined the effects of plant stanol esters emulsified into low-fat yoghurt (0.7% fat) on fasting concentrations of plasma lipids and lipid-soluble antioxidants, which may also change by plant stanol consumption. Sixty non-hypercholesterolemic subjects first consumed daily three cups (3 x 150 ml) of placebo yoghurt for 3 weeks. For the next 4 weeks, 30 subjects continued with the placebo yoghurt, while the other 30 subjects received three cups of experimental yoghurt. Each cup provided 1 g of plant stanols (0.71 g sitostanol plus 0.29 g campestanol) as its fatty acid ester. LDL cholesterol (mean+/-S.D.) increased by 0.06+/-0.21 mmol/l in the placebo group, but decreased by -0.34+/-0.30 mmol/l in the experimental group. The difference in changes between the two groups of 0.40 mmol or 13.7% was highly significant (P<0.001; 95% confidence interval for the difference, (-)0.26 -(-)0.53 mmol/l). Effects were already maximal after 1 week. HDL cholesterol and triacylglycerol concentrations did not change. Total tocopherol levels increased by 1.43 micromol/mmol LDL cholesterol (14.0%, P=0.015). beta-carotene levels, however, decreased by -0.02 micromol/mmol LDL cholesterol (-14.4%, P=0.038). Decreases in absolute beta-carotene concentrations were found in all apoB-containing lipoproteins. LDL-cholesterol standardised phytofluene levels decreased by 21.4+/-25.7% (P<0.001), while other plasma carotenoid (lutein/zeaxanthin, beta-cryptoxanthin, lycopene and alpha-carotene) levels did not change significantly. We conclude that low-fat yoghurt enriched with plant stanol esters lowers within 1 week LDL cholesterol to the same extent as oil-based products. LDL-cholesterol standardised concentrations of tocopherol increased. The observed decrease in beta-carotene levels, as found in many other studies, appears not to be limited to the LDL fraction.

Topics: Adolescent; Adult; Aged; Antioxidants; Body Weight; Cholesterol; Diet, Fat-Restricted; Double-Blind Method; Female; Humans; Intestinal Mucosa; Lipids; Lipoproteins; Male; Middle Aged; Netherlands; Phytosterols; Plants; Sitosterols; Solubility; Stigmasterol; Yogurt

Treatment with carbamazepine (CBZ) affects cholesterol concentrations, but little is known about the precise nature and underlying mechanisms of changes in lipoprotein metabolism. We investigated prospectively the effects of CBZ on lipid metabolism in normolipemic adults. In 21 healthy males, lipoprotein and noncholesterol sterol concentrations were measured before and during treatment with CBZ for 70 +/- 18 days. Thirteen subjects underwent kinetic studies of apolipoprotein-B (ApoB) metabolism with the use of endogenous stable isotope labeling. Lipoprotein kinetic parameters were calculated by multicompartmental modeling. Significant increases in total cholesterol, in ApoB-containing lipoproteins [very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low-density lipoprotein (LDL)], and in triglycerides, but not in high-density lipoprotein (HDL), were observed. Lipoprotein particle composition remained unchanged. Mean fractional catabolic and production rates of ApoB-containing lipoproteins were not significantly different, although mean production rates of VLDL and IDL were substantially increased (+46 +/- 139% and +30 +/- 97%, respectively), whereas mean production of LDL remained unchanged (+2.1 +/- 45.6%). Cholestanol in serum increased significantly but not the concentrations of plant sterols (campesterol, sitosterol) and the cholesterol precursors (lathosterol, mevalonic acid). There was a significant correlation between the decrease in free thyroxine and the increase in IDL cholesterol. Treatment with CBZ increases mainly ApoB-containing lipoproteins. CBZ seems not to influence endogenous cholesterol synthesis or intestinal absorption directly. The increase is neither related to increased ApoB production nor to decreased catabolism but is rather due to changes in the conversion cascade of IDL particles, most likely as an indirect effect through a decrease in thyroid hormones.

Topics: Adult; Anticonvulsants; Arteriosclerosis; Body Composition; Body Weight; Carbamazepine; Cholestanol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diet; Humans; Hydrocortisone; Intestinal Absorption; Lipoproteins; Male; Mevalonic Acid; Phytosterols; Sitosterols

The safety and tolerability of three levels of plant sterol-esters administered in reduced-fat spread and salad dressing vs. control products were evaluated in this randomized, double-blind, four-arm parallel study.. Eighty-four free-living men and women consumed reduced-fat spread and salad dressing providing 0.0 g/day (n = 21), 3.0 g/day (n = 21), 6.0 g/day (n = 19) or 9.0 g/day (n = 23) of phytosterols as esters for an eight-week treatment period.. Side effects did not differ among the groups during the study, and there were no study product-related serious adverse events. There were no changes in clinical laboratory values in response to phytosterol intake. Blood concentrations of all fat-soluble vitamins remained within normal reference ranges, and there were no differences in serum vitamin responses among the four groups. Alpha- and trans-beta-carotene levels were reduced in the 9.0 g/day group vs. control (p < 0.05), but all carotenoid values remained within normal ranges throughout the study. All groups receiving phytosterols had significant increases in serum campesterol vs. control (p < 0.001), but beta-sitosterol responses did not differ from control. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol responses did not differ significantly among the groups. The total:HDL cholesterol response in the 9.0 g/day group was significantly different from the control group response (-9.6% vs. 2.6%, p < 0.05). A median increase of 7.8% in serum triglycerides was observed in the control group, which differed significantly from the response in the 3.0 g/day arm (-13.3%, p < 0.05).. The results of this study indicate that phytosterol esters are well tolerated and show no evidence of adverse effects at a daily intake of up to 9.0 g of phytosterols for eight weeks.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Body Weight; Carotenoids; Creatine Kinase; Diet; Diet Records; Dietary Fats; Double-Blind Method; Esterification; Female; Food; Humans; Lipids; Male; Middle Aged; Phytosterols; Vitamins

A pine wood based stanol ester mixture-composed of sitostanol (92%) and campestanol (8%) effectively lowers cholesterol absorption and consequently LDL-cholesterol concentrations. It has been postulated that the less absorbable plant sterols reduce cholesterol absorption more effectively. As sitostanol is absorbed less than campestanol, we decided to examine if a vegetable oil based stanol ester mixture with 68% sitostanol and 32% campestanol is less effective than the wood based stanol ester mixture. For this, 112 non-hypercholesterolemic men and women consumed for 4 weeks a rapeseed oil (LEAR) based margarine and shortening. For the next 8 weeks, 42 subjects continued with these products, while the other subjects received products with a vegetable oil (n=36) or a pine wood based stanol ester mixture (n=34). Consumption of 3.8 g vegetable oil based stanols (2.6 g sitostanol plus 1.2 g campestanol) lowered LDL cholesterol 14.6+/-8.0% (-0.37 mmol/l; vs. the control group; P<0.001; 95% CI for the difference, -0.22 to -0. 51 mmol/l). Four grams pine wood based stanols (3.7 g sitostanol plus 0.3 g campestanol) showed a comparable decrease of 12.8+/-11.2% (-0.34 mmol/l; P<0.001; 95% CI-0.18 to-0.51 mmol/l). Decreases in LDL cholesterol were not different between the two experimental groups (P=0.793), while apoE genotype did not have a major impact on this hypocholesterolemic response. Serum HDL cholesterol and triacylglycerol concentrations were not changed. The decreases in apo B in both experimental groups differed significantly (P<0.001) from changes in the control group. Coagulation and fibrinolytic parameters were not affected. We therefore conclude that vegetable oil and wood based stanol ester mixtures, with a different sitostanol/campestanol ratio, have similar LDL cholesterol lowering effects in a non-hypercholesterolemic population.

Topics: Adult; Anticholesteremic Agents; Apolipoproteins E; Blood Coagulation; Body Weight; Cholesterol; Drug Combinations; Fatty Acids, Monounsaturated; Female; Fibrinolysis; Hemostasis; Humans; Lipids; Male; Middle Aged; Phytosterols; Plant Oils; Polymorphism, Genetic; Rapeseed Oil; Reference Values; Sitosterols

Coronary patients with low baseline ratios of serum cholestanol and plant sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events during simvastatin treatment in the Scandinavian Simvastatin Survival Study. Thus, in the present study, serum cholesterol, its precursor sterols (reflecting cholesterol synthesis), plant sterols (campesterol and sitosterol), and cholestanol were measured before and during a 5-year period of placebo treatment (n=433) and simvastatin treatment (n=434) in patients from a subgroup of the Scandinavian Simvastatin Survival Study to determine whether changes in cholesterol synthesis and serum levels were related to cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ratios of plant sterols to cholesterol were increased in relation to increasing baseline ratios of cholestanol quartiles. The latter predicted 5-year ratios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twice higher in the lowest versus the highest quartile. The ratios of plant sterols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline cholestanol quartiles. Simvastatin reduced serum cholesterol more (P=0.003) in the lowest versus the highest cholestanol quartile during the 5-year treatment period. The results show for the first time that baseline cholesterol metabolism, measured by serum noncholesterol sterols, predicts the effectiveness of simvastatin in reducing cholesterol synthesis and serum levels of cholesterol. The drug suppresses the synthesis of cholesterol markedly more effectively in subjects with high than with low baseline synthesis but reduces respective serum cholesterol levels less markedly than synthesis. Subjects with high cholesterol absorption and low synthesis may need a combination therapy to lower more effectively their serum cholesterol levels and prevent an increase in the levels of plant sterols.

Topics: Anticholesteremic Agents; Body Weight; Cholestanol; Cholesterol; Coronary Disease; Desmosterol; Humans; Phytosterols; Placebos; Simvastatin; Sitosterols; Sterols

The objective of the study was to evaluate the effects of plant stanol esters and bran fiber on lipids, stool weight and stool frequency in preschool children.. The present study was a 13 week open cross-over study designed to evaluate the effects of plant stanol ester in healthy two to five year old preschool children. After a one week lead-in, eligible children were randomly assigned to begin with either Diet Phase A (plant stanol ester) or Phase B (wheat bran fiber). Each diet phase was four weeks long, followed by a two-week wash-out, and then cross-over to the alternate diet. During Diet Phase A children consumed three eight-gram servings of a spread, each containing one gram of plant stanols, for total daily dose of three grams. During Diet Phase B, children added five grams of dietary fiber to their diet for the first two weeks and then ten grams for the second two weeks.. Overall, for the whole study group, plant-stanol-ester spread use yielded a decrease in total cholesterol of 19.9 mg/dL (12.4% reduction from baseline) and a 14.6 mg/dL decrease in LDL cholesterol (15.5% reduction from baseline). There were no significant changes in HDL-cholesterol or triglyceride levels. A predominately insoluble dietary fiber supplement derived from wheat bran, as expected, yielded a small but non-significant decrease in total cholesterol of 6.1 mg/dL, a four percent reduction from baseline.. Results demonstrated that preschool age children could adhere to a program requiring consumption of three daily servings of spread containing plant stanol ester and that this level of consumption resulted in a significant decrease in total cholesterol and LDL cholesterol after a four week period. In addition, consumption of plant stanol ester was not associated with any short-term adverse health effects.

Topics: Body Weight; Child, Preschool; Cholesterol, LDL; Cross-Over Studies; Diet; Dietary Fiber; Esters; Feces; Female; Humans; Lipids; Male; Phytosterols; Triticum

Topics: Aged; Arteriosclerosis; Autopsy; Body Weight; Cholecystectomy; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Diet; Diet Therapy; Dietary Fats; Fats, Unsaturated; Fatty Acids, Unsaturated; Humans; Male; Middle Aged; Obesity; Phytosterols; Time Factors

Canola oil (Can) and several vegetable oils shorten the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). Although similar lifespan shortening has been reported for partially hydrogenated Can, the efficacy of fully hydrogenated oils on the lifespan remains unknown. The present study aimed to investigate the lifespan of SHRSP fed diets containing 10 % (w/w) of fully hydrogenated Can (FHCO) or other oils.. Survival test: Upon weaning, male SHRSP were fed a basal diet for rodents mixed with one of the test oils -i.e., FHCO, Can, lard (Lrd), and palm oil (Plm) throughout the experiment. The animals could freely access the diet and drinking water (water containing 1 % NaCl), and their body weight, food intake, and lifespan were recorded. Biochemical analysis test: Male SHRSP were fed a test diet with either FHCO, Can, or soybean oil (Soy) under the same condition, except to emphasize effects of fat, that no NaCl loading was applied. Soy was used as a fat source in the basal diet and was set the control group. Blood pressures was checked every 2 weeks, and serum fat levels and histological analyses of the brain and kidney were examined after 7 or 12 weeks of feeding.. During the survival study period, the food consumption of FHCO-fed rats significantly increased (15-20 % w/w) compared with that of rats fed any other oil. However, the body weight gain in the FHCO group was significantly less (10-12 %) than that in the control group at 9-11 weeks old. The FHCO (> 180 days) intervention had the greatest effect on lifespan, followed by the Lrd (115 ± 6 days), Plm (101 ± 2 days), and Can (94 ± 3 days) diets. FHCO remarkably decreased the serum cholesterol level compared with Can and the systolic blood pressure from 12 to 16 weeks of age. In addition, while some rats in the Can group exhibited brain hemorrhaging and renal dysfunction at 16 weeks old, no symptoms were observed in the FHCO group.. This current study suggests that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

Topics: Animals; Blood Pressure; Body Weight; Brain; Cholesterol; Dietary Fats; Eating; Fatty Acids; Hydrogenation; Hypertension; Kidney; Longevity; Male; Palm Oil; Phytosterols; Rapeseed Oil; Rats; Rats, Inbred SHR; Soybean Oil; Stroke; Survival Analysis

This article presents the results of comprehensive studies to analyze the effect of a mixture of phytoecdysteroids extracted from the juice of Serratula coronata L. on the productivity and vitality of ducklings when grown for meat, and the optimal doses of its inclusion in the diet of the bird are revealed. The methodological basis of this study was the earlier works of domestic and foreign scientists on the topic under study. In the studies, a mixture of ecdysteroids extracted from the juice of the Serratula coronata L. was used according to the method developed by a team of scientists of the Ufa Federal Research Center of the Russian Academy of Sciences (Patent RU 2151598). The object of the study was the young ducks of the cross breed "Agidel 34" of the Beijing breed. It was established that the use of phytoecdysteroids in the diets of ducklings at a dose of 1.0 mg/l of drinking water allowed to increase the safety of the livestock by 4.0%, live weight by 4.5% (p <  0.01), average daily live weight gain by 3.0-3.5%, gutted carcass weight - 7.1%. At the same time, feed costs per unit of production decreased by 2.0%, and the profitability of duck meat production increased by 5.2%.

Topics: Animal Feed; Animals; Body Weight; Diet; Dietary Supplements; Ducks; Ecdysteroids; Meat; Phytosterols; Plant Extracts; Poultry; Poultry Products

Recently, embryo muscle development, which is crucial for postnatal skeletal muscle growth, has been investigated widely. Nutrients in ovo were suggested to be critical in embryo muscle development since the chick growth mostly relies on nutrients in eggs at the early developmental stage. Phytosterol esters (PE), which are derived from the reactions between phytosterols and fatty acids, were demonstrated to have important effects on lipid and cholesterol metabolism regulation. In order to reveal the effect of maternal lipid metabolism on the deposition of nutrients in eggs and the development of embryonic muscles, broiler hens were fed with a diet supplemented with 5% PE or control diet. Lipid deposition in eggs and growth of the hatched chicks were studied. We found that PE increased bile acid (BA) deposition in the eggs and serum of hens (p=0.02 and p<0.01, respectively), altered insulin and glucose level differentially in female and male offspring, and promoted body weight (p=0.02 for male and female on day 49), muscle fiber density (p=0.02 for female on day 49), and myogenin and myogenic determination factor (myoD) expression (p=0.03 and p=0.02 on day 49) by the activation of BA receptors in female, but not in male, offspring. Our study determined for the first time that PE promoted muscle development of chicks hatching from eggs laid by the hens, through regulating bile acid (BA) deposition and this may be attributed to the activation of BA receptors.

Topics: Animals; Bile Acids and Salts; Body Weight; Chickens; Dietary Supplements; Female; Glucose; Insulin; Lipid Metabolism; Male; Muscle Development; Ovum; Phytosterols; Sex Factors

Evidence indicates that wood pulp-derived sterols (WS) have beneficial effects on cardiovascular diseases. The present study aimed to (i) investigate the serum cholesterol-lowering activity of dietary WS and (ii) investigate the effects of dietary WS on the balance of gut microbiota in hamsters fed with a high-fat diet. Thirty-six hamsters were divided into four groups fed on a normal chow diet (NCD), a high-fat diet (HFD), or HFD plus 0.1% or 0.5% wood pulp-derived sterols (WSL, WSH), respectively, for 6 weeks. Levels of serum total cholesterol, triglyceride, HDL-C, non-HDL-C, and non-HDL-C/HDL-C ratio in hamsters fed the NCD were originally 120.4 mg dL-1, 235.8 mg dL-1, 71.7 mg dL-1, 48.7 mg dL-1 and 0.68 mg dL-1, which were elevated by being fed the HFD to 187.7 mg dL-1, 389.5 mg dL-1, 92.3 mg dL-1, 95.3 mg dL-1 and 1.03 mg dL-1, and alleviated completely by being fed the WSH. The excretion of total fecal neutral sterols was dose-dependently increased with the amounts of dietary WS. Furthermore, dietary supplementation with WS modulated the relative abundance of gut microbiota compared with the HFD group. Spearman's correlation analysis revealed that Bacteroides, Allobaculum, Coprobacillus, Lactobacillus, Akkermansia, Coprococcus, and Oscillospira were correlated negatively with most of the serum metabolic parameters and cholesterol metabolic parameters, whereas Desulfovibrio was positively correlated with most of the lipid metabolism-associated parameters. Taken together, dietary supplementation with WS was found to have cholesterol-lowering activity, in part mediated by modulating the gut microbiota in a positive way and regulating the cholesterol absorption and metabolism-related genes.

Topics: Animals; Body Weight; Cholesterol; Cricetinae; Diet, High-Fat; Eating; Gastrointestinal Microbiome; Gene Expression Regulation; Heart; Kidney; Liver; Male; Mesocricetus; Organ Size; Phytosterols; Wood

The effect of oryzanol (well known hypolipidemic component in rice bran oil) and its chemical constituents- ferulic acid (FA) and phytosterols on hypolipidemia were investigated.. Docking (in silico) studies showed that FA had a better binding ability with lipase while sterols bound well with HMG-CoA reductase. Further in vivo studies of feeding high fat (30%) to rats increased body weights, serum TC, TG, non-HDL-C and reduced HDL-C were observed, compared to normal diet fed group (ND). ORZ treated groups alleviated the lipid profile. Furthermore, increased organ weights, higher intestinal lipase activity, and liver lipid peroxidation was observed in the high-fat group (HF). These effects were ameliorated in oryzanol concentrate fed groups (ORZ). Higher fecal fat was found in ORZ groups, analysis of fecal matter by mass spectroscopy revealed the presence of FA. In vitro, a bile acid binding study supported the strong affinity of sterol towards bile acids. In conclusion, oryzanol in the intestine is cleaved into FA and sterol by intestinal lipase enzymes both lipase and HMG-CoA reductase activities were inhibited, respectively. These hydrolysates eliminated the bile acids, thus lowering lipid profiles.

Topics: Animals; Bile Acids and Salts; Body Weight; Coumaric Acids; Drinking; Eating; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Lipase; Male; Oryza; Phenylpropionates; Phytosterols; Protein Binding; Rats, Wistar

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

Nymphaea stellata (Willd.) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, scientific evidence supporting its mechanism of action is lacking. Here, we showed that an N. stellata flower chloroform extract (NSFCExt) has significant plasma glucose lowering ability. Furthermore, an active compound was identified and purified by column chromatography, and the structure of this compound, nymphayol, was determined by X-ray crystallographic analysis. Nymphayol was tested for its effects on insulin secretion by RIN-5F cells cultured in low or high glucose medium; we found that nymphayol treatment improved glucose-stimulated insulin secretion in vitro. Additionally, insulin sensitization and glucose uptake were increased in L6 myotubes. Nymphayol was administered to type 2 diabetic male Wistar rats at several doses (5, 10 or 20 mg/kg/day) for 45 days. After nymphayol administration, the plasma glucose concentration was significantly (p⩽0.05) lower (60.33%) than in control diabetic rats, and the plasma insulin level increased in a dose-dependent manner. In addition, the cellular insulin response was analyzed in type 2 diabetic rats; oral administration of nymphayol increased IRS1 phosphorylation and GLUT4 protein expression in liver and muscle. Nymphayol significantly (p⩽0.05) restored the levels of HbA1c, hepatic glycogen and hepatic glucose-metabolizing enzyme (hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, glycogen synthase and glycogen phosphorylase) activity in diabetic rats. The administration of glibenclamide, a reference drug (600 μg/kg), also produced a significant (p⩽0.05) reduction in blood glucose in STZ-nicotinamide induced diabetic rats. The results suggest that nymphayol may be a useful therapy for diabetes because it stimulates insulin secretion and promotes glucose absorption.

Topics: Animals; Biological Transport; Blood Glucose; Body Weight; Cell Line; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drinking; Gene Expression Regulation; Glucose; Glucose Transporter Type 4; Glycated Hemoglobin; Glycogen; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Liver; Male; Muscle Fibers, Skeletal; Phytosterols; Rats; Rats, Wistar; Reactive Oxygen Species

Increased serum concentrations of plant sterols, including stigmasterol, during parenteral nutrition (PN) have been linked with serum biochemical signs of intestinal failure-associated liver disease (IFALD), whereas clinical data on their correlation to histologic liver injury have been limited.. We studied interrelations between serum noncholesterol sterols and histologic liver injury in pediatric-onset intestinal failure (IF).. Serum plant sterols (stigmasterol, avenasterol, sitosterol, and campesterol), cholestanol, and cholesterol precursors (cholestenol, lathosterol, and desmosterol) were measured in 50 IF patients at a median age 7.3 y and in 86 matched controls. Forty patients underwent liver biopsies. Sixteen patients had been receiving PN for 45 mo, and 34 patients had received PN for 9.1 mo but had not received PN for 5.4 y.. Serum plant sterols were higher in patients who were currently receiving PN than in controls and were related to conjugated bilirubin (r = 0.799-0.541, P < 0.05). During PN, the ratio of serum stigmasterol to cholesterol was 3.3-fold higher in patients with portal inflammation, and the ratio of avenasterol to cholesterol was 3.9-fold higher in patients with cholestasis (P < 0.05 for both). Ratios of stigmasterol and avenasterol to cholesterol were correlated with portal inflammation (r = 0.549-0.510, P < 0.05), cholestasis (r = 0.501-0.491, P = 0.048-0.053), and serum bile acids (r = 0.591-0.608, P < 0.05). The median (IQR) ratio of serum cholestanol to cholesterol was higher during (269 100× μg/mg cholesterol; 203-402 100× μg/mg cholesterol) than after (175 100× μg/mg cholesterol; 156-206 100× μg/mg cholesterol; P < 0.001) weaning off PN and was correlated with cholestasis (r = 0.428), portal inflammation (r = 0.511), and fibrosis (r = 0.323, P < 0.05 for all). After weaning off PN, ratios of cholestenol and lathosterol to cholesterol were >2-fold higher in patients with persistent liver steatosis than in those without steatosis or controls (P < 0.01 for all), whereas lathosterol was correlated with the steatosis grade (r = 0.320, P < 0.050).. Increased serum stigmasterol and avenasterol concentrations parallel the portal inflammation and cholestasis during PN, thereby reinforcing their contribution to IFALD. A bile acid malabsorption-driven increase in cholesterol synthesis underpins persistent liver steatosis after weaning off PN. Serum cholestanol reflects liver injury in IF patients.

Topics: Adolescent; Bile Acids and Salts; Body Mass Index; Body Weight; Child; Child, Preschool; Cholestanol; Cholesterol; Cross-Sectional Studies; Female; Humans; Intestinal Diseases; Intestines; Liver Diseases; Male; Parenteral Nutrition; Phytosterols; Prospective Studies; Stigmasterol

There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development.. Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10). Plasma and arterial wall cholesterol and PS concentrations, lesion area, macrophage infiltration, and mRNA expression from LOX-1, CD36, ABCA1 and ABCG1 in peritoneal macrophages were measured. After 16 weeks, the plasma cholesterol concentration in PS mice was lower than that in the controls (p = 0.02) and in the arterial wall (p = 0.03). Plasma PS concentrations were higher in PS-fed animals than in controls (p < 0.0001); however, the arterial wall PS concentration did not differ between groups. The atherosclerotic lesion area in the PS group (n = 5) was smaller than that in controls (p = 0.0062) and the macrophage area (p = 0.0007). PS correlates negatively with arterial lipid content and macrophage (r = -0.76; p < 0.05). PS supplementation induced lower ABCG1 mRNA expression (p < 0.05).. Despite inducing an increase in PS plasma concentration, PS supplementation is not associated with its accumulation in the arterial wall and prevents atherosclerotic lesion development.

Topics: Absorption; Animals; Aorta; Arteries; Atherosclerosis; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Body Weight; CD36 Antigens; Cholesterol; Feeding Behavior; Lipids; Lipoproteins; Macrophages; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols; Receptors, LDL; Scavenger Receptors, Class E

Dietary phytosterol supplements are readily available to consumers since they effectively reduce plasma low-density lipoprotein cholesterol. Several studies on cell cultures and xenograft mouse models suggest that dietary phytosterols may also exert protective effects against common cancers. We examined the effects of a dietary phytosterol supplement on tumor onset and progression using the well-characterized mouse mammary tumor virus polyoma virus middle T antigen transgenic mouse model of inherited breast cancer. Both the development of mammary hyperplastic lesions (at age 4 weeks) and total tumor burden (at age 13 weeks) were reduced after dietary phytosterol supplementation in female mice fed a high-fat, high-cholesterol diet. A blind, detailed histopathologic examination of the mammary glands (at age 8 weeks) also revealed the presence of less-advanced lesions in phytosterol-fed mice. This protective effect was not observed when the mice were fed a low-fat, low-cholesterol diet. Phytosterol supplementation was effective in preventing lipoprotein oxidation in mice fed the high-fat diet, a property that may explain - at least in part - their anticancer effects since lipoprotein oxidation/inflammation has been shown to be critical for tumor growth. In summary, our study provides preclinical proof of the concept that dietary phytosterols could prevent the tumor growth associated with fat-rich diet consumption.

Topics: Animals; Antigens, Viral, Tumor; Antineoplastic Agents, Phytogenic; Body Weight; Cholesterol; Diet, High-Fat; Dietary Supplements; Female; Lipoproteins; Lipoproteins, HDL; Mammary Neoplasms, Experimental; Mice; Mice, Transgenic; NF-kappa B; Oxidation-Reduction; Phytosterols

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

To investigate the adrenal effect of a phytosterol (PS) additive, 80 male Japanese quail were divided into four sub-groups and fed 0, 40, 400, and 4,000 ppm of PS, respectively, for 21 days. Subsequently, 50% of the birds from each dosage group were subjected to a 6-day adrenal function test, whereby they were injected with long-lasting adrenocorticotropin (ACTH). The remaining quail in each PS dosage group were raised under normal conditions. The groups receiving 400 and 4000 ppm PS exhibited decreased serum levels of LDL-cholesterol with and without ACTH stimulation (P < 0.01). No amount of dose of PS changed serum corticosterone (CORT) under normal conditions (P > 0.05). Enhancement of CORT was observed on the 2nd and the 6th days of the ACTH challenge in birds receiving 400 ppm (P < 0.05). Average ACTH-induced CORT levels in the 400 ppm group were higher than in the 0 ppm group (P < 0.01). Our results demonstrated that PS can boost ACTH-induced CORT levels in male Japanese quail.

Topics: Adrenal Cortex Function Tests; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Anticholesteremic Agents; Body Weight; Cholesterol, LDL; Corticosterone; Coturnix; Dietary Supplements; Male; Organ Size; Phytosterols; Thymus Gland

Disodium ascorbyl phytostanol phosphate (FM-VP4) is a synthetic compound derived from sitostanol and campestanol that has proved to be efficient as a cholesterol-lowering therapy in mice and human subjects. However, the mechanism of action of FM-VP4 remains unknown. The present study tests the ability of FM-VP4 to alter intestinal and liver cholesterol homeostasis in mice. Female C57BL/6J mice were fed either a control chow or a 2 % FM-VP4-enriched diet for 4 weeks. FM-VP4 reduced the in vivo net intestinal cholesterol absorption and plasma and liver cholesterol concentrations by 2.2-, 1.5- and 1.6-fold, respectively, compared with control mice. Furthermore, FM-VP4 also showed an impact on bile acid homeostasis. In FM-VP4 mice, liver and intestinal bile acid content was increased by 1.3- and 2.3-fold, respectively, whereas faecal bile acid output was 3.3-fold lower. FM-VP4 also increased the intestinal absorption of orally administered [3H]taurocholic acid to small intestine in vivo. Inhibition of intestinal cholesterol absorption by FM-VP4 was not mediated via transcriptional increases in intestine liver X receptor (LXR)-alpha, adenosine triphosphate-binding cassette transporter (ABC)-A1, ABCG5/G8 nor to decreases in intestinal Niemann-Pick C1-like 1 (NPC1L1) expression. In contrast, FM-VP4 up-regulated liver LXRalpha, ABCA1, ABCG5, scavenger receptor class BI (SR-BI) and hydroxymethylglutaryl coenzyme A reductase (HMGCoA-R) gene expression, whereas it down-regulated several farnesoid X receptor (FXR)-target genes such as cytochrome P450 family 7 subfamily A polypeptide 1 (CYP7A1) and Na+/taurocholate co-transporter polypeptide (NTCP). In conclusion, FM-VP4 reduced intestinal cholesterol absorption, plasma and liver cholesterol and affected bile acid homeostasis by inducing bile acid intestinal reabsorption and changed the liver expression of genes that play an essential role in cholesterol homeostasis. This is the first phytosterol or stanol that affects bile acid metabolism and lowers plasma cholesterol levels in normocholesterolaemic mice.

Topics: Animals; Bile Acids and Salts; Body Weight; Cholesterol; Energy Intake; Humans; Intestinal Absorption; Intestine, Small; Liver; Liver Circulation; Male; Mice; Mice, Inbred C57BL; Phytosterols; Reverse Transcriptase Polymerase Chain Reaction; RNA

The differences in cholesterol metabolism after the 2 most common forms of obesity surgery, Roux-en-Y gastric bypass (RYGB) and gastric banding (GB), have not been well characterized. In this study, effects of RYGB and GB on cholesterol absorption and synthesis were investigated. To this aim, 1-year follow-up of cholesterol metabolism in 2 nonrandomized cohorts undergoing either RYGB (n = 29; age, 45.2 +/- 7.7 years; body mass index [BMI], 46.0 +/- 6.1 kg/m(2)) or GB (n = 26; age, 45.9 +/- 8.6 years; BMI, 50.1 +/- 7.7 kg/m(2)) was performed in a university hospital center specializing in the treatment of morbid obesity. Serum markers of cholesterol synthesis (cholestenol, desmosterol, and lathosterol) and cholesterol absorption (campesterol, sitosterol, avenasterol, and cholestanol) were measured preoperatively and at follow-up and expressed as ratios to cholesterol. As expected based on observed weight loss (25% after RYGB and 17% after GB, P < .001 between groups), both operations decreased serum levels of cholesterol synthesis markers by 12% to 28% (all Ps < .001). A decrease in cholesterol absorption markers was only observed after RYGB (-26% for sitosterol) and not after GB (+16%, P = 2 x 10(-6) for difference between the groups). The difference in sitosterol ratio between the groups remained significant after adjustment for age, BMI, fasting insulin levels, and nutritional status (P = 2 x 10(-4)), indicating a specific effect related to RYGB. We conclude that decrease in cholesterol absorption is a novel beneficial effect of RYGB. Together with an improved control of blood glucose, this may contribute to a better cardiovascular risk profile after RYGB.

Topics: Adult; Anastomosis, Roux-en-Y; Bariatric Surgery; Blood Glucose; Body Height; Body Mass Index; Body Weight; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Female; Gastric Bypass; Humans; Intestinal Absorption; Liver; Male; Middle Aged; Obesity; Phytosterols; Sterols

Using pure phytoecdysteroids isolated from Ajuga iva (L.) Schreber (Lamiales: Lamiaceae) and Silene nutans L. (Caryophyllales: Caryophyllaceae), plants known for their high ecdysteroid content, a study was carried out on the effects of ingestion of four different phytoecdysteroids (20-hydroxyecdysone, polypodine B, ponasterone A and makisterone A) on the growth and development of the Indian meal moth, Plodia interpunctella Hübner (Lepidoptera: Pyralidae) larvae when added at a concentration of 200 ppm in their diet. The experiments clearly showed the susceptibility of P. interpunctella to phytoecdysteroid ingestion. The toxicity of phytoecdysteroids manifested itself by a decrease in larval weight, induction of cannibalism and an increase of mortality, together with disruption of development. The severity of the phytoecdysteroid effect on P. interpunctella depended on the structure of the molecule. The results demonstrate that the minimal structural differences existing between these four phytoecdysteroids significantly affected their toxicity toward P. interpunctella. Makisterone A was the most toxic of the four compounds towards P. interpunctella larvae. In conclusion, phytoecdysteroids ingestion evokes disruptive growth effects on P. interpunctella. This work supports a role for phytoecdysteroids in plant defence against phytophagous insects.

Topics: Ajuga; Animals; Body Weight; Cannibalism; Ecdysone; Food Deprivation; Larva; Molecular Structure; Moths; Pest Control, Biological; Phytosterols; Pupa; Silene

Metabolic syndrome is associated with subsequent development of cardiovascular diseases and type 2 diabetes. It is characterized by reduced response to insulin, central obesity, and dyslipidemia. Intake of plant sterols (PS) has been shown to confer a healthier lipid profile and ameliorate cardiovascular disease risk factors in experimental animals and humans. In this study we used an animal model of type 2 diabetes to assess the effects of a preparation of PS esterified to high oleic sunflower oil fatty acids mixed with dietary diacylglycerol (PS-HOSO) on diabetic related metabolic parameters. Psammomys obesus (P. obesus) were fed high energy (HE) diet supplemented by either PS-HOSO or control oil. Following 4.5 weeks of intervention, animals were divided into fasting and non-fasting modes prior to outcome measurements. Glucose and insulin levels as well as blood lipid profile, body weight, and fat accumulation were evaluated in fasting and non-fasting modes.. P. obesus fed with a HE diet displayed a characteristic heterogeneity in their blood glucose and insulin levels with a subset group displaying type 2 diabetes symptoms. PS-HOSO treatment significantly reduced total cholesterol (24%, P < 0.001) and non-HDL cholesterol (34%, P < 0.01) compared to the control diet. Among fasting animals, body weight at end point and epididymal fat-to-liver weight ratio were significantly (P < 0.05 each) reduced (7% and 16%, respectively) compared to controls. Interestingly, fasting blood glucose levels were similar between groups, whereas plasma insulin level at end point was 44% lower in the PS-HOSO group compared to control group (P < 0.0001). PS-HOSO supplementation to diabetes-prone gerbils counteracts the increase in body weight and epididymal fat accumulation, and also results in a drop in circulating insulin levels. These effects are pointing out that PS-HOSO may serve as a functional ingredient for metabolic syndrome or diabetic sufferers, which not only influences body weight, but also prevents or reverses insulin resistance and hyperlipidemia.

Topics: Animals; Blood Glucose; Body Weight; Diglycerides; Gerbillinae; Insulin; Liver; Male; Oleic Acid; Organ Size; Phytosterols

This study examined the dietary effects of enzymatically modified sesame oil with caprylic acid (structured lipids, SL) and phytosteryl esters (PE) on blood lipid profiles and cardiovascular parameters of spontaneously hypertensive rats (SHR) fed high-fat and high-cholesterol (HFHC) diets. The dietary groups were: normal diet (control), sesame oil (SO), SL, SO fortified with PE (SOP), and SL fortified with PE (SLP). After 9 weeks of feeding, the body weights, liver weights, and liver weight/body weight ratios in all HFHC-fed groups were higher than controls. Plasma total and LDL cholesterol levels in all HFHC-fed groups were similar to one another but higher than those in controls. Plasma HDL cholesterol levels in rats fed SOP and SLP were higher than those in controls or rats fed SO and SL. Plasma HDL/total cholesterol ratios in rats fed SOP and SLP were similar to those in controls and were higher than those in rats fed SO and SL. There was no difference in plasma lipid profiles between rats fed SO and SL. Arterial blood pressures (BP) in conscious HFHC-fed rats were similar to those in controls whereas heart rates (HR) in all HFHC-fed groups were similar to one another but were higher than that in controls. These findings demonstrate that (1) the dietary effects of SL on plasma lipid profiles and resting BP and HR are similar to those of SO, (2) PE had positive effects on plasma lipid profiles, and (3) 9-week intake of SL and PE did not have pronounced effects on resting BP but induced tachycardia in SHR.

Topics: Animals; Blood Pressure; Body Weight; Cardiovascular System; Diet; Dietary Fats; Disease Models, Animal; Heart Rate; Hypertension; Male; Organ Size; Phytosterols; Rats; Rats, Inbred SHR; Sesame Oil; Tachycardia

Purpose of this study was to examine the dose dependant effects of sesame seed powder as a dietary supplement on hypercholesteraemic and oxidative stress conditions in male albino rats. Sesame seed (Sesamum indicum) powder was administered at 5% and 10% dose levels along with either normal or hypercholesteraemic diet for duration of four weeks. Administration of sesame seed powder to hypercholesteraemic rats resulted in a significant decline in plasma, hepatic total lipid and cholesterol levels and, plasma LDL-cholesterol levels with an increase in plasma HDL-cholesterol levels. Further, these animals also showed increased fecal excretion of cholesterol, neutral sterol and bile acid along with increases in hepatic HMG-CoA reductase activity and bile acid content. Additionally sesame seed feeding improved the hepatic antioxidant status (catalase and SOD enzyme activities) with a reduction in lipid peroxidation. No significant changes in lipid and antioxidant profiles occurred in the normocholesteraemic rats administered with sesame seed powder. These beneficial effects of sesame seed on hypercholesteraemic rats appeared to be due to its fiber, sterol, polyphenol and flavonoid content, enhancing the fecal cholesterol excretion and bile acid production and as well as increasing the antioxidant enzyme activities.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Ascorbic Acid; Bile Acids and Salts; Body Weight; Cholesterol; Diet; Eating; Feces; Hydroxymethylglutaryl CoA Reductases; Indicators and Reagents; Lipid Metabolism; Lipid Peroxidation; Lipids; Liver; Male; Organ Size; Phenylhydrazines; Phytosterols; Rats; Seeds; Sesamum; Sterols

Current evidence suggests that neo formation of the anabolic steroid boldenone (androsta-1,4-diene-17-ol-3-one) occurs in calves' faecal material, making it difficult to distinguish between illegally administered boldenone and its potential endogenous presence. This strengthens the urgent need to elucidate the pathway leading to boldenone formation. In our laboratory, the invertebrate Neomysis integer (Crustacea, Mysidacea) was used since 2004 as an alternative model for the partial replacement of vertebrate animals in metabolisation studies with illegal growth promotors and veterinary drugs, e.g. boldenone. The present study evaluates the metabolic capacity of other invertebrates, the brine shrimp Artemia franciscana and maggots of the greenbottle fly Lucilia sericata. The first results indicate that maggots of L. sericata are able to convert phytosterols and -stanols, nowadays in substantial amounts added to animal feed, into androsta-1,4-diene-3,17-dione (ADD), the precursor of boldenone, at a yield of 0.10-0.14% (p<0.001, significance compared to endogenous excretion of maggots) but not to boldenone itself. Furthermore, beta-testosterone, an endogenous hormone, was transformed into androst-4-ene-3,17-dione (AED), ADD and beta-boldenone at a significant (p<0.001, significance compared to endogenous excretion of maggots) yield of circa 13%, 0.80% and 2.2%, respectively. In future studies these results are of value to further evaluate the use of maggots of L. sericata as an invertebrate model in metabolisation studies.

Topics: Anabolic Agents; Androstadienes; Animals; Artemia; Body Weight; Chemistry Techniques, Analytical; Chromatography, Liquid; Diptera; Larva; Mass Spectrometry; Models, Chemical; Phytosterols; Quality Control; Steroids; Testosterone

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

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

Disodium ascorbyl phytostanol phosphate (FM-VP4) is a cholesterol absorption inhibitor, a new class in cholesterol-lowering drug. Previous research on the lipid-lowering and anti-atherosclerotic effects of this drug has reported that administration of FM-VP4 results in a decrease in body mass. This study examined the FM-VP4 dose-dependent mass loss in mice and investigated some potential mechanisms by which decreased mass accumulation may have occurred. The effect of FM-VP4 administration on pre-obese mice was also tested.. We conducted a dose-dependent study on mouse growth, food and water intake, organ mass, femur length, resting metabolic rate (RMR), maximal oxygen consumption under various conditions (VO(2swim) and VO(2heliox)), and fecal fat and plasma assessment for cholesterol and non-esterified fatty acids (NEFA) in mice fed a low fat (LF) or high fat (HF) diet, with or without FM-VP4. The ratio of lean to fat body mass of each animal was also assessed using magnetic resonance spectroscopy. To establish the effect of FM-VP4 on pre-existing obesity, mice were fed a high fat diet for 57 days, followed by administration of a diet containing 2% (w/w) FM-VP4 for 93 days.. Animals exhibit a dose-dependent decline in body mass without a concomitant decrease in food intake, water intake, spleen, heart, or kidney mass, femur length or lean body mass. A dose-dependent trend toward a reduction in fat mass was observed in both high fat and low fat diet groups, becoming significant at a 1 and 2% FM-VP4 dosage (w/w). No FM-VP4 induced change in food or water intake, or resting metabolic rate was observed; however, an increase in VO(2swim) was observed in the 2% FM-VP4 group over HF control. These findings were also observed in the pre-obese group treated with 2% FM-VP4.. We found a dose dependent reduction in mass accumulation in mice treated with FM-VP4. This loss of mass is not due to an increase in resting metabolic rate or decreased food or water intake. The only tissues exhibiting a decrease in mass with FM-VP4 treatment are liver and body fat. Fecal fat content increased significantly with FM-VP4 treatment in a dose-dependent manner, suggesting that the treatment reduces mass accumulation through decreased absorption or increased excretion of lipids.

Topics: Adipose Tissue; Animals; Anticholesteremic Agents; Body Composition; Body Weight; Dose-Response Relationship, Drug; Feces; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Phytosterols

The aim of this study was to investigate the effects of different phytosterols and their analogs on colonic mucosal cell proliferation in hamsters.. Hamsters (n=70) were randomly assigned to seven groups after a 2-week acclimation and fed the experimental diet for 5 weeks. Diets included (i) the semipurified diet with no cholesterol (Con), (ii) the Con diet plus 0.25% cholesterol (Ch-con), or the Ch-con diet with (iii) 1% phytosterols (Ste), (iv) 1% phytostanols (Sta), (v) 1.76% sterol esters (esterified to fish oil, SteF), (vi) 0.71% stanol esters (esterified to ascorbic acid [disodium ascorbyl phytostanol phosphate, FM-VP4], 0.7% StaA) and (vii) 1.43% stanol esters (1.4% StaA), respectively. After 5 weeks on experimental diet, hamsters were sacrificed, and colons were collected. Colonic mucosal cell proliferation was measured by immunohistochemistry using monoclonal antibodies against antigen Ki-67.. Colonic mucosal cell proliferation was 21.4% (P<.01) lower in the 0.7%, but not 1.4%, StaA relative to the Ch-con group. In addition, a lower (-13.9%) cell proliferation was observed in the SteF group in comparison to the Ch-con group; however, this difference achieved only a borderline level of statistical significance (P=.069). No differences were observed between Con and Ch-con, as well as among Ste, Sta, 1.4% StaA and Ch-con treatments.. Plant stanols esterified to ascorbic acid may possess anticarcinogenic properties in the colon by suppressing colonic mucosa cell proliferation; however, this effect was not observed with free plant sterols or stanols.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Body Weight; Cell Division; Cholesterol, Dietary; Colon; Cricetinae; Eating; Esterification; Intestinal Mucosa; Male; Mesocricetus; Phytosterols

We have previously shown strong pro-atherogenic effects of probucol in apolipoprotein E-knockout (apo E-KO) mice. The aims of the present study were to investigate whether (a) dietary phytosterols reduce probucol-induced atherogenesis and (b) beneficial interactions exist between these agents. Male apo E-KO mice fed with an atherogenic diet supplemented with phytosterols or probucol or their combination for 14 weeks. Single therapy with either phytosterols or probucol resulted in a 25% reduction in plasma total cholesterol (TC) concentrations as compared to the control group. The effects of the combination therapy were more profound (60% reduction). While phytosterols reduced atherogenesis by 60%, probucol caused an increase of 150% in atherogenesis. Addition of phytosterols to probucol substantially reduced pro-atherogenic effects of probucol. This was associated with improved high density lipoprotein (HDL) concentrations. The ratio of TC to HDL cholesterol was markedly reduced in the combination therapy group as compared to the probucol-treated group. A strong positive association between the ratio of TC to HDL cholesterol and the extent of atherosclerotic lesions was observed. The coronary arteries of the probucol-treated group showed various stages of atherogenesis from infiltration of monocytes into intima to complete occlusion of the vessel by atheromatous lesions. Such pathological findings were not observed in the combination therapy group. Approximately 40% of the mice in the probucol-treated group and 10% of the animals in the combination therapy group developed skin lesions. Further studies warrant the investigation of the underlying mechanisms of the observed beneficial interactions between dietary phytosterols and probucol.

Topics: Animals; Anticholesteremic Agents; Apolipoproteins E; Atherosclerosis; Body Weight; Cholesterol; Cholesterol, HDL; Diet; Drug Antagonism; Male; Mice; Mice, Knockout; Phytosterols; Probucol

To identify the causative substances for the shortening of survival time by rapeseed (Canola) oil in stroke-prone spontaneously hypertensive rats (SHRSP), SHRSP were fed on a standard chow supplemented with 10 w/w% soybean oil (control), rapeseed oil, one of the fractions of rapeseed oil obtained by super critical gas extraction (SCE) under a pressure of 180-bar or 350-bar, at 40 degrees C, or the residue from the extraction (with 0.5% NaCl in drinking water). In another series of experiment, SHRSP were fed for 8 weeks on the above-mentioned diets without salt loading and autopsied. Fatty acid compositions in these diets were similar, except in the soybean oil diet, and phytosterol contents were: (diet containing) 180-bar fraction>residue>rapeseed oil>350-bar fraction>soybean oil. Survival times in the rapeseed oil, 350-bar fraction and residue groups were shorter than, whereas that in the 180-bar fraction was similar to in the soybean oil group. In the 8-week feeding experiment, chronic nephropathy was found frequently in the groups other than the soybean oil group. The heart weights were higher in the rapeseed oil and residue groups. Cerebral necrosis was found in the residue group. Taken together, the followings are concluded, (1) Neither the fatty acid composition, nor the amount of phytosterols in the diets appeared to be decisive in the shortening of life. (2) SCE appeared to produce a safe (180-bar) fraction, though it failed to separate clearly the causative substances into specific fractions. (3) The factors that facilitate the genetic disease of SHRSP appear to exist in rapeseed oil. However, they might not be identical to those responsible for the life-shortening, since there were no findings common across the rapeseed oil, 350-bar and residue groups, which showed similar life-shortening.

Topics: Algorithms; Animals; Body Weight; Diet; Drinking; Eating; Fatty Acids; Fatty Acids, Monounsaturated; Kidney Function Tests; Male; Organ Size; Phytosterols; Plant Extracts; Plant Oils; Rapeseed Oil; Rats; Rats, Inbred SHR; Soybean Oil; Survival Analysis; Time Factors

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

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

Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol, significantly reduced visceral fat weight and the concentration of triacylglycerol in serum and liver of rats. Dietary campestenone dramatically increased the activities and the mRNA expressions of mitochondrial and peroxisomal enzymes involved in beta-oxidation in the liver. Campestenone activated human peroxisome proliferator-activated receptor (PPAR) alpha as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. In contrast, dietary campestenone reduced the activities and the mRNA expressions of enzymes involved in fatty acid synthesis, except for the malic enzyme. Dietary campestenone decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was significantly higher in the feeding of campestenone in rats. Dietary campestenone reduced hepatic cholesterol concentration and increased fecal excretion of neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol was reduced by the coadministration of campestenone in rats cannulated in the thoracic duct. These observations suggest a possibility that campestenone has an ability to prevent coronary heart disease by improving obesity and abnormality of lipid metabolism.

Topics: Animals; Body Weight; Cholesterol; Energy Metabolism; Fatty Acids; Feces; Intra-Abdominal Fat; Liver; Male; Oxidation-Reduction; Oxidoreductases; Phytosterols; PPAR alpha; Rats; Rats, Inbred Strains; RNA, Messenger; Steroids; Sterol Regulatory Element Binding Protein 1

This study was undertaken to investigate the effects of pumpkin seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T-P) prostate growth in rats.. Forty adult Wistar rats were divided into five groups, including: one control group, rats treated with vehicle only, one group treated with T-P, and two groups of T-P-treated rats, one receiving orally pumpkin seed oil alone and one group receiving orally pumpkin seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to-body weight ratio was determined after sacrifice. The total protein concentration was measured by using a protein assay. Some ventral prostatic tissues were histologically examined after hematoxylin-eosin staining.. Histological sections of the ventral prostate showed that the architecture of the prostate glands became hyperplastic in the T-P rats, but not in the control or vehicle-treated animals. As compared with the control or vehicle group, T-P rats had a significantly higher prostatic weight-to-body weight ratio for the ventral prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001, respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or pumpkin seed oil combined with Phytosterol-F had a significantly lower weight ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and significantly lower protein levels within both lobes (p=0.03 and p=0.003, respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had some additive effect on the total protein synthesis within the ventral prostate (p=0.02).. Pumpkin seed oil alone or combined with Phytosterol-F can block the T-P-induced increases in prostatic weight-to-body weight ratio and protein synthesis.

Topics: Animals; Body Weight; Cucurbita; Disease Models, Animal; Drug Therapy, Combination; Male; Phytosterols; Phytotherapy; Plant Oils; Plant Preparations; Prazosin; Prostate; Prostatic Hyperplasia; Rats; Rats, Wistar; Seeds; Testosterone; Treatment Outcome

This paper presents the results of a study whose aim was to test the effects of several doses of pectin and phytosterols on the body weight gain and the FA content in female guinea pigs. The treatments resulted from supplementing with pectin and plant sterol a guinea pig diet (rich in saturated FA), following a 3 x 3 factorial design, with three levels of pectin (0, 3.67 and 6.93%) and three levels of phytosterols (0, 1.37, and 2.45%). Seventy-two female Dunkin Hartley guinea pigs were randomly assigned to the treatment groups (8 animals/group), the duration of the treatment being 4 wk. Pectin dietary intake led to a significant increase in body weight (P < 0.001), food consumption (P = 0.025), and feed efficiency (P < 0.001), but no influence of phytosterols on weight gain or food consumption was detected. We found a significant negative effect of the addition of phytosterols on lauric, myristic, and palmitic acid contents in feces, and a positive effect on their concentration in plasma and liver, but no significant effect on stearic acid content. Apparent FA absorption was assessed by calculating the ratio of FA in feces and diets that the absorption of the different FA could be compared, and the negative effect of phytosterol supplementation on these ratios, especially for lauric and myristic acids, was established.

Topics: Animals; Body Weight; Chromatography, Gas; Dietary Fats; Eating; Fatty Acids; Feces; Female; Guinea Pigs; Liver; Pectins; Phytosterols

The aim of the current study was to examine the effects of very long chain fatty acids (VLCFA) alone at 2 dietary levels, or in combination of VLCFA at the lower level with lecithin (LT) or phytosterols (PS), on lipid profiles and cholesterol biosynthesis in hamsters. Seventy-five male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 weeks before being randomly assigned into 5 groups of 15 animals each fed semisynthetic diets for 4 weeks. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a polyunsaturated to saturated fatty acids ratio of 0.4. Groups 2 to 5 were fed the control diet and given 25 mg/kg BW per day of VLCFA (Licowax) (VLCFA25), 50 mg/kg BW per day of VLCFA (VLCFA50), 25 mg/kg BW per day of VLCFA+1000 mg/kg BW per day of LT (VLCFA25/LT), and 25 mg/kg BW per day of VLCFA+1000 mg/kg BW per day of PS (Cholestatin, VLCFA25/PS), respectively. Results showed that HDL-cholesterol (HDL-C) levels were not changed by VLCFA25, although increased by VLCFA50 (P<.05) relative to control. Total cholesterol (T-C) and non-HDL-C levels were not affected by VLCFA25 and VLCFA50 as compared with control. VLCFA25/LT had higher (P<.02) T-C and HDL-C levels than any other treatments and increased (P<.05) liver weight relative to control. In contrast, VLCFA25/PS reduced T-C (P=.0004) and non-HDL-C (P=.007) without effect on HDL-C levels compared with control. Triglyceride levels were not affected by any treatment. Cholesterol biosynthesis rate was higher (P<.05) in animals fed VLCFA25 and VLCFA50 than those fed control or VLCFA25/LT or VLCFA25/PS. Results suggest that PSs can decrease total and non-HDL-C cholesterol, whereas VLCFA may increase HDL-C in hamsters.

Topics: Animals; Body Weight; Cholesterol; Cholesterol, HDL; Cricetinae; Eating; Fatty Alcohols; Kinetics; Lipids; Liver; Male; Mesocricetus; Organ Size; Phytosterols

Patients with mixed dyslipidemias (increased LDL cholesterol and triglyceride as well as low HDL cholesterol levels) benefit from a combination of lipid-modifying drugs such as statins, niacin, fibrates and ezetemibe. However, safety, tolerability and cost are a concern in drug combination therapy. Dietary phytosterols reduce LDL cholesterol, and niacin or fenofibrate primarily reduces triglyceride and increases HDL-cholesterol levels. Thus, we hypothesized that a combination of phytosterols with niacin or fenofibrate will synergistically impact lipoprotein profile and atherogenesis in apo E-KO mice. Phytosterols alone significantly reduced plasma total cholesterol levels (14.1 vs. 16.9 mmol/L, P < .05) and the extent of atherosclerosis (0.42 vs. 0.15 mm(2), P < .05). The addition of fenofibrate to phytosterols increased plasma total cholesterol levels by >50% (14.1 vs. 21.6 mmol/L, P < .05) and decreased HDL-cholesterol concentrations by 50% (0.8 vs. 0.4 mmol/L). These changes were accompanied by slight reductions in the extent of atherosclerosis (0.42 vs. 0.34 mm(2), P > 0.05) as compared to controls, suggesting other potential anti-atherogenic effects of fenofibrate. Unlike fenofibrate, niacin caused an increase of 150% (P < .05) in HDL-cholesterol concentrations and a decrease of 22% (P < .05) in total cholesterol levels which were associated with significant reductions (65%, P < .05) in atherosclerotic lesion size as compared to controls. Neither the addition of niacin nor of fenofibrate reduced plasma triglyceride levels. In conclusion, the addition of niacin to phytosterols synergistically increases HDL-cholesterol levels, while a combination of phytosterols and fenofibrate results in no synergistic effects in apo E-KO mice. Further studies in other animal models are needed to establish synergetic effects between these lipid-modifying dietary and pharmacological agents.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Body Weight; Cholesterol; Cholesterol, HDL; Diet; Fenofibrate; Hypolipidemic Agents; Lipid Metabolism; Male; Mice; Mice, Knockout; Niacin; Phytosterols; Triglycerides

The aim of this study was to assess the efficacy of a novel water-soluble phytostanol analog, disodium ascorbyl phytostanyl phosphates (DAPP), on plasma lipid levels and red blood cell fragility in hamsters fed atherogenic diets. For 5 wk, 50 male Golden Syrian hamsters were fed a semipurified diet without added cholesterol (noncholesterol, group 1), or a semipurified diet with 0.25% cholesterol (cholesterol-control, group 2). Groups 3-5 were fed the cholesterol-control diet with an addition of 1% phytostanols (diet 3), 0.71% DAPP (DAPP 0.7%, diet 4), or 1.43% DAPP (DAPP 1.4%, diet 5). Diets 4 and 5 provided 0.5 and 1% phytostanols, respectively. Supplementation of 0.71 and 1.43% DAPP decreased plasma total cholesterol concentrations by 34 (P < 0.001) and 46% (P< 0.001), respectively, in comparison with the cholesterol-control group, whereas free stanols reduced (P = 0.007) plasma cholesterol concentrations by 14%. Similarly, non-HDL-cholesterol concentrations were reduced by 39 (P < 0.001) and 54% (P < 0.001) in hamsters supplemented with DAPP 0.7% and DAPP 1.4%, respectively, relative to the cholesterol-control group. The hypocholesterolemic effect of DAPP 1.4% was threefold stronger than that of free stanols. In hamsters supplemented with DAPP 1.4%, plasma TG concentrations were 45% lower (P= 0.018) than in cholesterol-control-fed hamsters, whereas no such beneficial effect was observed in the free stanol group. Erythrocyte fragility was unaffected by DAPP or free phytostanols. Results of the current study demonstrate that DAPP lowers cholesterol more efficiently than free stanols, without an adverse effect on erythrocyte fragility in hamsters.

Topics: Animals; Body Weight; Cholesterol; Cricetinae; Male; Osmotic Fragility; Phytosterols; Sitosterols; Solubility; Water

In an attempt to combine the hypocholesterolemic properties of plant sterols with the hypotriglyceridemic action of fish oil FA, plant sterols have recently been esterified to fish oil n-3 PUFA. The objective of this study was to determine the effects of plant sterols esterified to n-3 PUFA on plasma lipid levels and erythrocyte fragility. For 5 wk, male Golden Syrian hamsters were fed diets varying in cholesterol and plant sterol content: (i) Non-cholesterol (semipurified diet with no added cholesterol or plant sterols) (ii), Cholesterol (0.25% cholesterol) (iii), Sterols (0.25% cholesterol plus 1% nonesterified plant sterols), or (iv) Fish oil esters of plant sterols (0.25% cholesterol plus 1.76% EPA and DHA sterol esters, providing 1% plant sterols). The addition of fish oil esters of plant sterols to the cholesterol diet decreased (P = 0.001) plasma total cholesterol levels by 20%, but nonesterified plant sterols did not have such a beneficial impact. In addition, non-HDL cholesterol concentrations were 29% lower in hamsters fed fish oil esters of plant sterols than in hamsters fed nonesterified plant sterols (P < 0.0001). Despite higher (P < 0.0001) plant sterol levels in whole erythrocytes of hamsters fed nonesterified plant sterols and fish oil esters of plant sterols compared with hamsters fed no plant sterols, no difference was observed in erythrocyte fragility. The present results show that EPA and DHA esters of plant sterols have a hypocholesterolemic effect in hamsters, and that these new esters of plant sterols exert no detrimental effect on erythrocyte fragility.

Topics: Animals; Body Weight; Cricetinae; Erythrocytes; Esters; Fatty Acids; Feeding Behavior; Fish Oils; Lipids; Male; Mesocricetus; Models, Animal; Phytosterols; Weight Gain

The purpose of this study was to determine if Disodium Ascorbyl Phytostanol Phosphates (FM-VP4) alters animal body weight and plasma lipid levels in a dietary-induced obese mouse model.. Twenty-four C57BL6 mice (28 days old) were housed individually and fed a standard mouse diet for 2 weeks upon arrival. After 2 weeks the animals were weighed and divided in 4 groups of similar average weight, and the groups received a low fat (10% kcal from fat) and high fat (45% kcal from fat) diet with or without FM-VP4 (2% w/w) for 12 continuous weeks. Food, water and caloric intake and body weight were recorded on a daily basis throughout the duration of the study. Following the 12th week of the study all animals were humanely sacrificed and blood and abdominal fat pads were harvested for further analysis. Plasma cholesterol, triglyceride, AST/ALT and creatinine levels were measured using enzymatic kits.. There is a significant difference in weight gain between the low-fat diet and the low-fat diet + 2% w/w FM-VP4 treatment groups (P<0.05), as well as between the high-fat diet and the high-fat diet + 2% w/w FM-VP4 treatment groups (P<0.05). However, the reduction of weight gain of the high-fat diet + 2% FM-VP4 treatment group compared to the high-fat group was 51%, while the reduction in weight gain between the low-fat diet + 2% w/w FM-VP4 treatment group and the low-fat diet group was 17% over the duration of the study. No significant differences in food and water intakes, serum creatinine and AST/ALT levels were observed between the four groups. No significant differences in caloric intake between the low-fat diet and the low-fat diet + 2% w/w FM-VP4. However, a significant difference in caloric intake between high-fat diet and the high-fat diet + 2% w/w FM-VP4 treatment groups was observed. In addition, significant reductions in plasma cholesterol levels and abdominal fat pad weight between diet alone and diet + FM-VP4 treatment groups were observed.. These findings suggest that FM-VP4 may have potential weight-loss and cholesterol lowering activity in both High Fat and Low Fat Diets treated groups.

Topics: Abdominal Fat; Animals; Anti-Obesity Agents; Body Weight; Cholesterol; Diet, Fat-Restricted; Dietary Fats; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Obesity; Phytosterols

Vegetable oil spreads containing phytosterol-esters are marketed as a cholesterol-lowering functional food in more than 20 countries worldwide. An extensive package of safety data has shown phytosterol-esters to be safe for human use. However, even though phytosterols are very stable molecules, oxidation may occur at low levels under extreme heating conditions, resulting in phytosterol oxides. As there is some suggestion of adverse biological effects in the literature for the related cholesterol oxidation products, safety data have been generated for phytosterol oxides. A phytosterol oxide concentrate (POC) was generated by prolonged heating of phytosterol-esters in the presence of oxygen. The genotoxicity and subchronic toxicity of this mixture was assessed in a series of in vitro genotoxicity assays (bacterial mutation, chromosome aberration and micronucleus) and a subchronic feeding study in the rat. Results showed that a phytosterol oxide concentrate containing approximately 30% phytosterol oxides did not possess genotoxic potential and no obvious evidence of toxicity when administered in the diet of the rat for 90 consecutive days. In the latter study, a NOEL was established at an estimated dietary level of phytosterol oxides of 128 mg/kg/day for males and 144 mg/kg/day for females. In conclusion, these materials have been shown to raise no obvious concerns for human safety.

Topics: Administration, Oral; Animals; Body Weight; Chromosome Aberrations; Consumer Product Safety; Dose-Response Relationship, Drug; Eating; Esters; Female; Male; Micronucleus Tests; Mutagenicity Tests; No-Observed-Adverse-Effect Level; Oxidation-Reduction; Oxides; Phytosterols; Random Allocation; Rats; Rats, Wistar; Risk Assessment; Salmonella typhimurium; Toxicity Tests

The purpose of this investigation was to determine the effects of Phytostanol Phosphoryl Ascorbate (FM-VP4) on insulin resistance, hyperglycemia, plasma lipid levels, body weight, and gastrointestinal absorption of exogenous cholesterol in Zucker (fa/fa) fatty and lean rats. A group of 12 age-matched male obese (n = 6) and lean (n = 6) Zucker rats were administered 250 mg/kg twice a day (as 2% FM-VP4 in drinking water) for 30 consecutive days. Fasted blood samples prior to and following treatment were taken from all rats for glucose, lipid, insulin, and leptin determination. An oral glucose tolerance test was also carried out at the end of the treatment protocol. In addition, male obese (n = 7) and lean (n = 8) Zucker rats were coadministered a single oral gavage of [(3)H]cholesterol plus cold cholesterol with or without FM-VP4 (20 mg/kg) dissolved in Intralipid and the plasma concentration of the radiolabel was determined 10 h following the dose. FM-VP4 30-day treatment did not alter body weight, morning glucose, insulin, lipids, and leptin concentrations. There was no alteration in glucose tolerance in the nondiabetic, normoglycemic lean group; however, there was a highly significant improvement in glucose tolerance in the fatty group following FM-VP4 treatment. In addition, the insulin response to oral glucose showed no significant change in nondiabetic lean rats, whereas there was a change in the insulin secretory profile in the fatty group following FM-VP4 treatment. Furthermore, following a single oral gavage of FM-VP4 resulted in a significant decrease in the percentage of radiolabeled cholesterol absorbed. These findings suggest that FM-VP4 treatment to fatty Zucker rats could result in increased glucose responsiveness of the insulin secreting pancreatic beta cells. Furthermore, our findings suggest that FM-VP4 may only be effective presystemically. Systemic administration of FM-VP4 is warranted to determine the therapeutic potential of this effect.

Topics: Animals; Blood Glucose; Body Weight; Cholesterol; Cholesterol, Dietary; Glucose Tolerance Test; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Intestinal Absorption; Leptin; Lipids; Male; Obesity; Phytosterols; Rats; Rats, Zucker

Phytosterols or plant sterols (PS) enter the ecosystem via pulp mill effluents. They are also consumed by the general population of developed countries in natural remedies and margarines to lower elevated serum cholesterol levels. This study screened the endocrine and enzymatic parameters of the field vole (Microtus agrestis) for the effects of subchronic PS exposure at three doses (0, 5, or 50 mg of PS kg(-1) day(-1)). PS at 5 or 50 mg kg(-1) day(-1) decreased the relative liver weight of the voles. The kidney glycogen phosphorylase activity decreased at 5 or 50 mg kg(-1) day(-1), but the liver glycogen phosphorylase activity increased at 5 mg kg(-1) day(-1). The plasma estradiol and testosterone concentrations of males were higher due to PS supplement at 5 mg kg(-1) day(-1). This can be due to increased sex steroid synthesis from PS precursors. Biotransformation enzyme activities were not affected. PS caused multiple, previously unreported effects that were more pronounced at a low dose. As 5 mg PS kg(-1) day(-1) is the recommended dose for various health products, a thorough risk assessment of the effects and interactions of PS is warranted.

Topics: Animals; Arvicolinae; Body Weight; Carbohydrate Metabolism; Eating; Female; Gonadal Steroid Hormones; Humans; Kidney; Lipid Metabolism; Liver; Male; Organ Size; Phytosterols; Radioimmunoassay; Random Allocation

The current study was carried out to examine the effects of policosanols and phytosterols, alone and in combination, on lipid profiles, cholesterol biosynthesis, and tissue histopathological changes in hamsters. Fifty male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 wk before being randomly assigned into 5 groups of 10 animals each fed semisynthetic diets for 4 wk. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a PUFA to saturated FA ratio of 0.4. Groups 2 to 5 were fed the control diet and given Octa-6 [a policosanol mixture from sugar cane wax, 25 mg/kg body weight (BW)], Ricewax (a policosanol mixture from rice wax with 50% being converted to the corresponding acids, 50 mg/kg BW), phytosterols (Cholestatin; 1,000 mg/kg BW), and Ricewax (50 mg/kg BW) plus phytosterols (1,000 mg/kg BW), respectively. The results showed that there was no difference between Octa-6 and Ricewax treatments in any of the lipid parameters measured, and both had similar levels of triglyceride (TG), total cholesterol (T-C), and HDL cholesterol (HDL-C) as the control. Octa-6 but not Ricewax increased (P = 0.03) non-HDL-C as compared with the control. Phytosterols reduced T-C (P < 0.0003) and HDL-C (P < 0.004) without a significant effect on TG and non-HDL-C as compared to the control. Ricewax plus phytosterols had effects similar to those with phytosterols alone. Free cholesterol synthetic rates were not different among the treatments. Policosanols or phytosterols did not show any toxic effects in liver, heart, brain, or kidney. Results suggest that, although phytosterols reduce T-C and HDL-C levels, policosanols have no significant favorable effect in changing lipid levels in hamsters.

Topics: Animals; Anticholesteremic Agents; Body Weight; Cholesterol; Cricetinae; Diet; Drug Synergism; Fatty Alcohols; Lipids; Liver; Male; Mesocricetus; Phytosterols; Triglycerides

Phytosterols (PS) are the analogues of animal cholesterol in various plants. beta-Sitosterol is a PS used in margarines and natural remedies to lower elevated serum cholesterol levels. PS enter the ecosystem via pulp mill effluents. The study investigated the endocrine and metabolic effects of PS on the female raccoon dog (Nyctereutes procyonoides), a canid omnivore. Eight female animals were exposed perorally to 8 mg PS/kg/d for 4 wk with 8 animals in the control group. In the PS-treated females, there was a transitory decrease in the plasma estradiol concentrations with an increase in the plasma follicle-stimulating hormone levels. The plasma triiodothyronine concentrations were higher in the PS group. Serum lipid concentrations decreased in PS-treated and control animals. This probably represents a seasonal adaptation. Most of the cholesterol in raccoon dog serum was high-density lipoprotein cholesterol, unlike that in humans but similar to some other carnivores. Liver and kidney ethoxyresorufin O-deethylase activities were lower in the PS treated females. Data indicate that raccoon dogs may not be a sentinel species for PS effects.

Topics: Animals; Biotransformation; Body Weight; Carnivora; Cholesterol, HDL; Endocrine Glands; Female; Hormones; Kidney; Lipids; Lipoproteins, HDL; Liver; Metabolism; Mixed Function Oxygenases; Organ Size; Phytosterols; Testosterone; Triglycerides

Phytosterols or plant sterols (PS) are consumed as natural remedies and margarines by the general population in developed countries to lower elevated serum cholesterol levels. They are also present in high concentrations in pulp mill effluents. The aim of the study was to screen the endocrine and metabolic parameters of the European polecat (Mustela putorius) for the effects of PS. The results showed an increase in the plasma estradiol and TH levels with no effects on the hypophyseal regulatory hormones. The plasma ghrelin levels decreased. PS also affected intermediary metabolism. The liver glycogen content increased as did the kidney glucose-6-phosphatase activity. The liver lipase esterase activity, on the other hand, decreased due to PS. In serum lipids the total cholesterol did not change, but the low-density lipoprotein levels increased and the high-density lipoprotein-cholesterol ratio decreased. PS had widespread previously unreported effects on the physiology of the polecat. The multiple effects indicate the need of a thorough risk assessment of the effects and interactions of PS.

Topics: Animals; Body Weight; Carnivora; Dose-Response Relationship, Drug; Endocrine Glands; Estradiol Congeners; Estrogens, Non-Steroidal; Female; Glycogen; Hormones; Hypolipidemic Agents; Inactivation, Metabolic; Isoflavones; Kidney; Lipids; Liver; Male; Metabolism; Organ Size; Phytoestrogens; Phytosterols; Plant Preparations; Sitosterols

Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes.. Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios.. The study population was divided into normal-weight (body mass index, 24.1 +/- 0.4 kg/m2; mean +/- SEM; n = 20) and obese (31.0 +/- 0.5 kg/m2; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 +/- 78 vs. 1077 +/- 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 +/- 1 vs. 40 +/- 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non-obese groups. Serum sex hormone-binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R2 = 24%) and body mass index (R2 = 15%) were the only variables explaining the variability of cholesterol synthesis.. Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.

Topics: Absorption; Bile Acids and Salts; Blood Glucose; Body Mass Index; Body Weight; Cholestanol; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Feces; Female; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Phytosterols; Regression Analysis; Sex Hormone-Binding Globulin; Sterols

Juvenile female rainbow trout was exposed for 4.5 months (June to October) to two dilutions of untreated and activated sludge treated whole mill effluent from a pulp mill producing bleached ECF pulp. Two controls were used, on fed ad libitum and a second receiving 0.5% feed of the body weight. All effluent exposed groups were fed ad libitum. Mean weight of the fish was measured monthly. At the end of the experiment a number of physiological and biochemical parameters were analyzed in order to establish the physiological status of the exposed fish in comparison with unexposed fish that obtained ad libitum or restricted amount of feed. The fish exposed to treated effluent grew significantly more than ad libitum control fish until August, whereupon growth retarded in fish exposed to the lower effluent dilution (400 v/v). The growth of fish exposed to untreated effluent did not deviate significantly from the control fed ad libitum. The results from the hematological analysis clearly showed that fish fed restricted amount of feed deviated significantly in most parameters compared with the control fed ad libitum. Fish exposed to treated effluent showed a response pattern similar to that of the control fed restricted amount of feed, whereas the fish exposed to untreated effluent showed a response pattern that did not deviate from that of the ad libitum control. The metabolic parameters suggested that fish exposed to treated effluent had a higher metabolic demand than ad libitum control and that the energy allocation at the end of the experiment was directed to processes other than growth. The responses on hematology were mainly a consequence of the increased energy demand and were not primary effects. The implications of using feed related parameters at field studies are discussed.

Topics: Animal Feed; Animals; Bile; Body Weight; Chemical Industry; Cytochrome P-450 CYP1A1; Female; Food Deprivation; Gonadal Steroid Hormones; Hematologic Tests; Hepatocytes; In Vitro Techniques; Industrial Waste; Microsomes, Liver; Oncorhynchus mykiss; Paper; Phytosterols; Sewage; Thyroid Hormones; Vitellogenins; Water Pollutants, Chemical; Water Purification

This study was designed to determine the effects of a novel hydrophilic phytostanol analog, FM-VP4, on total plasma cholesterol, total plasma triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations after acute oral administration to gerbils. Gerbils were administered a standard gerbil diet for 4 continuous weeks, and daily water and food intake was monitored and replaced. The diet contained either no FM-VP4 (control) or FM-VP4 at the following concentrations: 0.25, 0.50, 1.0, or 2.0% w/w; six gerbils were fed each diet formulation. After 4 weeks of receiving a single diet formulation, blood was obtained from each gerbil by cardiac puncture and the animals were sacrificed humanely. Plasma obtained from this blood was analyzed for total cholesterol, total triglyceride, and HDL cholesterol levels by standard enzymatic and precipitation techniques. LDL cholesterol levels were calculated using the Friedewald equation. Administration of dietary FM-VP4 resulted in significant decreases in total plasma cholesterol and LDL cholesterol concentrations compared with controls. Dietary FM-VP4 at concentrations of 1% and 2% (w/w) decreased total plasma cholesterol by 3.4 mmol/L compared with controls. This decrease was entirely due to the loss of cholesterol from the LDL pool because LDL cholesterol was decreased by 3.3 and 3.2 mmol/L after 1% and 2% (w/w) FM-VP4, respectively. There were no significant changes in plasma triglyceride or HDL cholesterol concentrations after the administration of FM-VP4. Animals administered 1% or 2% (w/w) FM-VP4 also had significantly lower body weight after 4 weeks of treatment compared with the other groups. However, no unusual behavior was observed in these animals. No major differences in daily water or food intake were observed throughout the study. These findings indicate that FM-VP4 decreases total and LDL cholesterol concentrations.

Topics: Animals; Anticholesteremic Agents; Body Weight; Cholesterol; Cholesterol, LDL; Drinking; Eating; Gerbillinae; Lipids; Male; Phytosterols

The dietary effect of phytosterols (PS) versus cholesterol on the growth and metastasis of the PC-3 human prostate cancer cells in SCID mice was studied. Also, their direct effect on the growth and migration of these cells in vitro was analysed. In the in vivo experiment, SCID mice were fed a diet containing 2% of either PS mixture or cholesterol plus 0.2% cholic acid and implanted with 2 x 10(6) tumour cells per mouse. Tumour growth was monitored for 8 weeks post inoculation. Animals fed the PS diet had tumours 40-43% smaller than those fed the cholesterol diet. Furthermore, the number of mice with lymph node and lung metastasis was almost one-half that of the cholesterol-fed group. In the in vitro studies, both beta-sitosterol and campesterol inhibited the growth of PC-3 cells by 70% and 14%, respectively, while cholesterol supplementation increased the growth by 18% when compared with controls. PS inhibited the invasion of PC-3 cells into Matrigel-coated membranes by 78% while cholesterol increased it by 43% as compared with the cells in the control media. Migration of tumour cells through 8 microm pore membranes was reduced by 60-93% when the PC-3 cells were in PS media, as compared with a 67% increase after cholesterol supplementation. PS supplementation reduced the binding of PC-3 cells to laminin by 15-38% and fibronectin by 23% while cholesterol increased binding to type IV collagen by 36%. It was concluded that PS indirectly (in vivo as a dietary supplement) and directly (in tissue culture media) inhibited the growth and metastasis of PC-3 cells. beta-Sitosterol was more effective than campesterol in offering this protection in most of the parameters studied.

Topics: Animals; Body Weight; Cell Adhesion; Cholesterol; Humans; Male; Mice; Mice, SCID; Models, Animal; Neoplasm Metastasis; Phytosterols; Prostatic Neoplasms; Sitosterols; Tumor Cells, Cultured

RICOM-1013-J (Ricinus communis var minor) administered orally once to each of 12 women volunteers at a dose of 2.5-2.7 g per 8 months, protected against pregnancy over a period of 7-8 months of study. A study of the effect of a contraceptive dose (20 mg/kg) on metabolic parameters in rat (food and water in-take, urine and faecal output and body weight) over a period of 4 months showed a slight decrease in all the parameters in the first 1-8 weeks. This effect was reversible attaining pretreatment levels from week 16. The LD(50) in an acute toxicity test in mice was 63.1 +/- 16.0 g/kg s.c. Determination of blood urea, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)) and bicarbonate (HCO$_¿3¿ ¿-¿$)as a measure of renal function and alkaline phosphatase (ALP), transaminases (GPT and GOT) and transpeptidases (GGT) as a measure of liver function showed that liver function profiles in pretreated rats were not significantly different from control (p < 0.05) on day 21 to day 150. However, serum levels of ALP and GGT at day 120 to day 150 were moderately but significantly elevated (p > 0.05) compared with the control. There were no significant changes in renal function profiles in pretreated rats (p < 0.05) compared with the control. The results of the liver and renal function profiles in women volunteers showed that there were no significant (p < 0.05) changes in renal functions on day 206 following RICOM-1013-J administration. However, serum levels of ALP and GGT showed a slight rise in about 70% of volunteers, whereas bilirubin and transaminases levels were normal. The present results indicate a very high efficacy and margin of safety of RICOM-1013-J in women volunteers. The increase in ALP and GGT in both animal and women volunteers suggest mild intrahepatic cholestatic changes which may be attributed to an oestrogenic effect of RICOM-1013-J.

Topics: Adult; Animals; Body Weight; Contraceptive Agents, Female; Diuresis; Drinking Behavior; Feces; Feeding Behavior; Female; Humans; Kidney Function Tests; Liver Function Tests; Male; Mice; Mice, Inbred BALB C; Phytosterols; Pregnancy; Rats; Rats, Wistar

We evaluated the effects of a phytosterol mixture (FCP-3PI) on the regression of atherosclerotic lesions in male apo E-deficient mice. Atherosclerosis was induced in fifteen mice by a "Western-type" diet containing 9% (w/w) fat and 0.15% (w/w) cholesterol over a period of 18 weeks (Induction phase). Then, two mice were used to evaluate the development of atherosclerosis, and the rest was divided into the control (n=6) and treated (n=7) groups. The control group was fed mouse chow (4.5% w/w fat) and the treated group fed the same chow supplemented with 2% (w/w) FCP-3PI for an additional 25 weeks (Regression phase). The mice developed severe hypercholesterolemia and advanced atherosclerotic lesions over the induction phase. During the first 6 weeks of regression phase, plasma cholesterol concentrations decreased at a similar rate (35%) in both groups of control and phytosterol-treated mice. Although evidence of lesion regression was not observed in either group of mice, the treated group had slightly smaller lesion size than the controls. During the induction phase, each mouse developed atherosclerotic lesions averaging 0.025 mm2 per week. However, during the regression phase, this was decreased to approximately one fifth and one third in the treated and control groups, respectively. Thus, compared to the end of the induction phase, the control group had a 40% increase in the lesion size, while this increase was only 28% in the treated animals. In conclusion, our previous findings along with a small decrease in the atherosclerotic lesion size observed in the treated group in the present study suggest that FCP-3PI treatment may slow the development of atherosclerotic lesions in apo E-deficient mice; however, a longer regression period may yield a greater benefit.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Body Weight; Cholesterol; Disease Models, Animal; Male; Mice; Phytosterols; Xanthomatosis

Plant stanol esters are intended for use as an ingredient in food to reduce the absorption of cholesterol from the gastrointestinal tract. Consumption of plant stanol esters has a demonstrated diet-derived public health benefit, as shown by numerous clinical studies. Plant stanol esters are ring-saturated analogs of common dietary sterols that are transesterified with fatty acids from vegetable oils such as canola oil. The reproductive and developmental toxicity of plant stanol esters was investigated in male and female Wistar rats during F0 and F1 generations using dietary concentrations of 1.75, 4.38, and 8.76% stanol esters (equivalent to 1, 2.5, and 5% total stanols). No adverse treatment-related effects were noted on reproductive performance of male or female rats in any dose group. Increased food consumption was observed in high-dose F0 generation males throughout the entire premating period and in F1 males at specific time periods during the premating period. This increase in food consumption was also observed in F0 generation females (mid- and high-dose groups) and F1 generation females (low-, mid-, and high-dose groups) at specific time periods throughout the 10-week premating period. At different intervals throughout the gestation and lactation periods, increased food consumption was observed in F0 generation females of the mid- and high-dose groups, while increased food consumption was noted in F1 generation females of the mid- and high-dose groups during gestation, but not during lactation. Such increases in food consumption are expected as a result of the animals' attempt to compensate for the reduced caloric value of the test diet compared to controls. No adverse developmental effects were noted in F1 or F2 pups of the low- and mid-dose groups based on evaluation of the following parameters: litter size, pup mortality, pups weights, and sex ratio. However, a treatment-related effect on body weight and body weight change was observed in both F1 and F2 male and female pups of the high-dose group, particularly during the latter stages of lactation (postnatal days 14 and 21) in F1 pups, and during the majority of the lactation period (postnatal days 4-21). Lower body weight in the high-dose pups is attributed to a reduction in the caloric value of the test diet compared to control. The pups, unlike adult animals, are particularly sensitive to reductions in caloric value of feed since they are in a rapid growth phase of their development. It is l

Topics: Animals; Body Weight; Dihydrotestosterone; Female; Male; Phytosterols; Rats; Rats, Wistar; Reproduction

Phytosterol esters (PE) are intended for use as a novel food ingredient, primarily in margarines and spreads as a functional component with plasma cholesterol lowering activity. Phytosterols and their esters are present naturally in vegetable oils and on average people consume 200 mg/day, but their consumption at this level is not sufficient to lower plasma cholesterol levels. Therefore, through the incorporation of PE into margarines/spreads, the intake can be increased by approximately 10-fold by consuming the PE-containing margarine/spread at normal intake levels. As part of an extensive programme of safety evaluation studies a subchronic rat toxicity study has been conducted in which groups of Alpk:AP(f)SD (Wistar derived) rats (20 males and 20 females/group) were fed diets containing PE at levels of 0, 0.16, 1.6, 3.2 and 8.1% (w/w) in the diet for 90 days. Throughout the study, clinical observations, body weights, and food and water consumption were measured. At the end of the study the rats were subjected to a full post-mortem examination, cardiac blood samples were taken for clinical pathology, selected organs were weighed, and a full tissue list was taken for subsequent histological examination. There were no treatment-related changes that were considered to be of toxicological significance. Therefore, a nominal PE concentration of 8.1% was considered to be the no-observed-adverse- effect level (NOAEL) following daily oral administration to rats for 90 days. This was equivalent to a dose of 6.6 g/kg body weight/day PE or 4.1 g/kg/day phytosterol.

Topics: Administration, Oral; Animals; Body Weight; Diet; Drinking; Drug Administration Schedule; Eating; Esters; Female; Food Additives; Male; Phytosterols; Rats; Rats, Wistar; Risk Assessment; Toxicity Tests

Phytosterol esters (PE) are intended for use as a novel food ingredient with plasma cholesterol lowering activity which works by inhibiting the absorption of cholesterol from the gut. Although PE are naturally present in the normal diet, the levels are insufficiently large to ensure lowering of plasma cholesterol levels. Therefore PE may be added to spreads to achieve the desired cholesterol lowering activity. As part of an extensive programme of safety evaluation studies a two-generation reproduction study has been conducted in Wistar rats, in which the possible effect of PE on male and female reproductive performance and on the growth and development of the offspring was studied. Rats were fed diets containing PE at levels of 0, 1.6, 3.2 and 8.1% (w/w) PE over two successive generations, and a wide range of reproductive and developmental parameters, including sexual maturation parameters and oestrous cycle length, were determined. Macroscopic and microscopic examinations were conducted including a histological examination of selected organs from F1- and F2-weanlings and from F0- and F1-parental animals. Daily clinical observations did not reveal any unusual findings. In both generations, no effects of PE were observed on pup mortality (calculated on litter basis), precoital time, mating index, male and female fertility index, female fecundity index, gestation index, duration of gestation, number of females with stillborn pups, post-implantation loss and pup development. Furthermore, PE had no effect on sexual maturation parameters (preputial separation and vaginal opening) and oestrous cycle length. In addition, there were no dose-related effects on selected organs following histological examination. In conclusion, dietary administration of up to 8.1% PE (equivalent to a dose of 2.5 to 9.1 g PE/kg body weight/day, dependent on the period of the study) during two generations had no effect on reproduction of parental F0- and F1-generation Wistar rats, nor on the development of the F1- and F2-pups, nor on the sexual maturation of the F1-weanlings. Therefore, a nominal dietary PE concentration of 8.1% (equivalent to a dose of 2.5-9.1 g PE/kg body weight/day or 1.54-5.62 g phytosterol/kg body weight/day dependent on the period of the study) was considered to be the no-observed-adverse-effect level following daily oral administration of PE for two successive generations.

Topics: Animals; Body Weight; Diet; Eating; Esters; Estrus; Female; Fertility; Male; Phytosterols; Pregnancy; Rats; Rats, Wistar; Reproduction; Sexual Maturation

To examine how variable sitostanol (SI) levels in phytosterol-supplemented diets influence plasma and hepatic lipid concentrations, fifty hamsters were divided into five groups and fed semipurified diets containing 0.25% (w/w) cholesterol for 45 days ad libitum. Four groups were fed this diet with 1% (w/w) phytosterol mixtures which contained 0.01% (w/w) SI derived from soybean, 0.2% (w/w) SI derived from tall oil, 0.2% (w/w) synthetic SI mixture (SIM) and 1% (w/w) pure SI, respectively. A control group did not receive phytosterols. Dietary SI supplementation at 1% (w/w) decreased total and non-apolipoprotein-A cholesterol levels in plasma by 34% (P=0.001) and 55% (P=0.04), respectively, whereas mean plasma total cholesterol level in the 0.2% (w/w) SI group was 23% (P=0.001) lower than that of the control group. Conversely, plasma lipid profile in hamsters fed 1 or 0.2% (w/w) SI did not differ from the 0.01% (w/w) SI group. Liver weights were 15 and 20% (P=0.012) higher in the control group compared with those fed 0.01% and 1% (w/w) SI, respectively, while the hepatic cholesterol content in the control group was greater (P<0.0001) than that of all other groups. Plasma campesterol levels were higher (P=0.04) in the 0.01% and 0.2% (w/w) SI fed groups than in the control, 0.2% (w/w) SIM and 1% (w/w) SI groups. Hepatic sitosterol content was elevated (P=0.002) in the SIM fed group compared to other groups. We conclude that dietary SI effect is proportional to its concentration in phytosterol mixtures and in the diet. Dietary SI lowered plasma cholesterol levels at concentrations higher than 0.2% (w/w) in hamsters. (c) 1998 Elsevier Science B.V.

Topics: Animals; Anticholesteremic Agents; Body Weight; Cholesterol; Cholesterol, HDL; Cricetinae; Diet; Eating; Lipids; Liver; Organ Size; Phytosterols; Plant Oils; Sitosterols

The present study investigated the role of phytosterols in colonic cell proliferation and examined the possible role of protein kinase C (PKC) in this process. A total of 18 male Sprague-Dawley rats weighing 240-270 g were fed, for a period of 22 days, one of three experimental diets: a control diet, a diet supplemented with 0.2% cholic acid, or a diet supplemented with 0.2% cholic acid + 2% dietary phytosterols. Two hours before decapitation, animals were injected with 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg body wt ip). Cell proliferation in the proximal colon was measured using a monoclonal antibody to BrdU. PKC activity in the proximal colonic mucosa was assayed using a myelin basic protein as a substrate. Cell proliferation was significantly increased by 276% with 0.2% cholic acid feeding compared with controls. The presence of 2% phytosterols in the diet abolished the cholic acid-induced hyperplasia. Cholic acid induced a 31% expansion of the proliferative zone. Only the cytosolic PKC was significantly lower in the phytosterol-fed group. Neither the total PKC nor the particulate PKC demonstrated an effect of phytosterols on enzyme activity. In conclusion, we found that dietary supplementation with 2% phytosterol has a significant protective effect on enhanced cell proliferation and that this effect is not mediated through the PKC system.

Topics: Animals; Body Weight; Bromodeoxyuridine; Cell Division; Cholic Acid; Cholic Acids; Colon; Diet; Eating; Intestinal Mucosa; Male; Phytosterols; Protein Kinase C; Rats; Rats, Sprague-Dawley

The effects on Wistar rat body weight were examined after a single subcutaneous (s.c.) or oral (p.o.) administration of dipalmitoylphosphatidylcholine (DPPC) liposomes composed of soybean-derived sterols (SS) and their glucosides (SG) with or without entrapping recombinant human erythropoietin (Epo) for 1 week. Body weight increased significantly after both types of administration compared with the control groups irrespective of the existence of Epo. The neutral lipid concentration in plasma increased with the increase in body weight whereas the total contents of cholesterol and high density lipoprotein cholesterol in the plasma did not change significantly. The SS and SG suspensions following p.o. administration, however, did not alter the body weight. These findings suggest that liposomal SS and SG may be absorbed through the intestinal membrane and induce a change in the uptake of lipid, in contrast to the suspension state. SS in liposomes significantly increased body weight more than SG after p.o. administration.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Administration, Oral; Animals; Body Weight; Drug Carriers; Erythropoietin; Glucosides; Glycine max; Injections, Subcutaneous; Lipids; Liposomes; Male; Phytosterols; Rats; Rats, Wistar

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

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

Isoprothiolane at a dose of 250 mg/kg or phytosterol 50 mg/kg was orally administered to rats once a day for 2 weeks. Basal [U-14C]glucose conversion rate to total lipids in isolated adipocytes of the rats was significantly decreased by treatment with isoprothiolane (54%) or phytosterol (82%). Adipocytes from the rats with isoprothiolane released less glycerol than those from control rats only at an epinephrine concentration of 10 microM. The serum level of total cholesterol was depressed by phytosterol ingestion. The level of non-esterified fatty acids (NEFA) was increased by isoprothiolane. Desaturation in fatty acid composition of phospholipid or cholesterol ester was observed in serum, liver and adipose tissue of the rats treated with either drug. These results suggest that either drug may have common effects by preventing lipid deposition into adipocytes and accelerating fatty acid desaturation in tissue lipids.

Topics: Adipose Tissue; Animals; Body Weight; Cells, Cultured; Cholesterol; Cholesterol Esters; Epinephrine; Fatty Acids; Fatty Acids, Nonesterified; Fungicides, Industrial; Insulin; Lipid Metabolism; Lipids; Lipolysis; Liver; Male; Phospholipids; Phytosterols; Rats; Rats, Inbred Strains; Thiophenes; Triglycerides

In this study, the relation of plasma levels of lathosterol (an indicator of whole body cholesterol synthesis) and plant sterols (indicator of cholesterol absorption) with age, sex, weight, height, plasma lipids, and lipoproteins, and with apolipoprotein (apo) E phenotype, was investigated in a group of 160 nuclear families consisting of twins living with their parents. Lathosterol was higher in fathers than in mothers, but not different between boys and girls. In each of these four groups, there was a strong correlation with plasma and low-density lipoprotein (LDL)-cholesterol and -triglyceride, as well as with body weight, but not with height or high-density lipoprotein (HDL)-cholesterol. In adults, lathosterol was inversely correlated with plant sterols. Lathosterol was higher in children with E4/3 phenotype than in those with E3/3 or E3/2; in adults, lathosterol did not differ among the various E phenotypes. The plasma levels of the two plant sterols, campesterol and beta-sitosterol, were highly correlated with each other, and also with plasma or LDL-cholesterol, in each of the four groups. Plant sterols were higher in adults or children with E4/3 phenotype as compared with those with other phenotypes. In multivariate analysis (performed separately for two groups of adults and children) plasma cholesterol, plasma plant sterols, plasma triglycerides, and weight were found to make significant contributions to the variation of lathosterol in all groups, and E phenotype and sex only in one group, while age did not contribute in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age Factors; Anthropometry; Apolipoproteins E; Body Height; Body Weight; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Lipids; Male; Middle Aged; Netherlands; Phenotype; Phytosterols; Prognosis; Regression Analysis; Sex Characteristics; Triglycerides; Twins, Dizygotic; Twins, Monozygotic

To study the effects of dietary phytosterols on plasma cholesterol, Wistar rats were fed diets containing a cholesterol overload (24 mg/day), to which phytosterols were added or not (24 or 96 mg/day). The cholesterol overload led to a marked increase in cholesterol, mainly linked to very-low-density and low-density lipoproteins. Phytosterols reduced those effects, the highest dose being most efficient. No undesirable effect was observed either on body or on liver weights. This shows that low doses of phytosterols are sufficient to significantly decrease a plasma cholesterol enhancement induced by a dietary cholesterol overload.

Topics: Animals; Body Weight; Cholesterol, Dietary; Lipids; Lipoproteins; Liver; Male; Phytosterols; Rats; Rats, Inbred Strains; Triglycerides

Hypolipidemic effects of gamma-oryzanol (OZ) and cycloartenol ferulic acid ester (CAF) on the hyperlipidemia induced by ingestion of a high cholesterol diet (HCD) in male Sprague-Dawley rats were investigated. The test drugs were given orally and intravenously, daily for 12 days with the HCD feeding. The oral administration with OZ and CAF at 100 mg/kg daily for 6 or 12 days did not apparently prevent the hyperlipidemia induced by HCD-feeding. The intravenous administrations with OZ and CAF at 10 mg/kg for 6 days significantly inhibited the increases in serum total cholesterol (TC), phospholipid (PL) and free cholesterol by HCD. OZ and CAF did not inhibit the decreases of TC in high density lipoprotein (HDL-TC) and HDL-PL by HCD. The increases of atherogenic index [( TC-HDL-TC]/[HDL-TC] and [PL-HDL-PL]/[HDL-PL]) with the HCD feeding were reduced by the intravenous administrations of OZ and CAF. Triglyceride, nonesterified fatty acid, lactate dehydrogenase and transaminase (GOT and GPT) markedly decreased below the control level by the intravenous administrations of OZ and CAF for 12 days. These results suggest that the intravenous administrations of OZ and CAF may have accelerated the excretion of lipids in the blood.

Topics: Animals; Blood Proteins; Body Weight; Cholesterol, Dietary; Cinnamates; Coumaric Acids; Enzymes; Hyperlipidemias; Hypolipidemic Agents; Male; Organ Size; Phenylpropionates; Phytosterols; Rats; Rats, Inbred Strains

In male Wistar rats fed diets containing different plant steroids, including sitosterols, diosgenin, digitonin and saponin from gypsophila, biliary cholesterol secretion significantly increased 50% to 300%, whereas biliary bile salt and phospholipid showed minor changes. Both cholesterol and phospholipid outputs were coupled to biliary bile salt output in a curvi-linear relationship which could be fitted by rectangular hyperbolae, in the animals fed with different plant steroids. The theoretical maximal biliary cholesterol output significantly increased by 200% in sitosterol-fed rats and 500% in diosgenin-fed animals. No changes were found in the kinetic characteristics of biliary phospholipid outputs. Adding 2% cholesterol to the diosgenin diet abolished the increment of biliary cholesterol output induced by the plant steroid. The intraperitoneal injection of 45 mumol/kg body wt per day (3 days) diosgenin, a C27-sapogenin, and 65 mumol/kg body wt. per day (3 days) tomatidin, a C27-alkaloid, incorporated in phosphatidylcholine-taurocholate liposomes significantly increased biliary cholesterol output by 70%. These experiments indicated that the plant steroid-induced biliary cholesterol output was independent of the inputs of cholesterol from the diet and from hepatic cholesterogenesis modified by the plant steroid. It was apparent that the profound changes of biliary cholesterol secretion were the consequence of direct effects of the steroids on the intrahepatocytic regulatory mechanisms of biliary cholesterol secretion. This novel effect appears to be a universal characteristic of plant steroids, since it can be elicited by sitosterols, C27-sapogenins, C27-alkaloids, and saponins of the cholanic and beta-amirinic group.

Topics: Animals; Bile; Bile Acids and Salts; Body Weight; Cholesterol; Cholesterol, Dietary; Diosgenin; Kinetics; Male; Phospholipids; Phytosterols; Rats; Rats, Inbred Strains; Steroids

Effects of spinasterol and sitosterol on plasma and liver cholesterol levels and biliary and fecal sterol and bile acid excretions were examined with male mice. Both phytosterols were added to the diet at a 1% concentration and fed to mice for 15 days. Spinasterol increased the fecal cholesterol excretion and decreased the plasma and liver cholesterol levels, the bile acid pool size and the fecal bile acid excretion, especially those derived from chenodeoxycholic acid. Fecal coprostanol excretion remained unchanged. These changes were similar to those produced by sitosterol. These data led to the conclusions 1) that spinasterol, as well as sitosterol, inhibits cholesterol absorption, resulting in decreases of the plasma and liver cholesterol levels and 2) that when cholesterol absorption is inhibited, the synthesis of bile acids, especially that of chenodeoxycholic acid, decreases, suggesting that the dietary cholesterol is preferentially metabolized to chenodeoxycholic acid in mice.

Topics: Animals; Bile; Bile Acids and Salts; Body Weight; Cholesterol; Feces; Liver; Male; Mice; Phospholipids; Phytosterols; Sitosterols; Sterols; Stigmasterol

Topics: Animals; Body Weight; Hyperlipidemias; Hypolipidemic Agents; Lipid Metabolism; Liver; Male; Nicotinic Acids; Organ Size; Pantetheine; Phytosterols; Rats; Rats, Inbred Strains; Sulfhydryl Compounds; Vitamin E

A mutant safflower oil, rich in oleic acid, was used for a critical test of the hypothesis that polyunsaturated fats act as co-carcinogens. Weanling female rats were each given 5 mg of 7,12-dimethylbenz(alpha)anthracene. They were then pair-fed diets containing 20%, by weight, of conventional high-linoleic safflower oil; a mutant high-oleic safflower oil; or coconut oil. Half of each group received supplementary DL-alpha-tocopherol. Tumors were identified by two observers, by palpation. Data on incidence of tumors and on numbers of tumors per affected rat led to similar conclusions. At 16 weeks, there were significant differences when supplementary tocopherol was included in the diet: the group fed high-oleic safflower oil had more tumors than the group fed coconut oil. This difference was not seen in the absence of supplementary tocopherol. When the data for tocopherol-supplemented and unsupplemented subgroups were combined, the high-oleic safflower oil group had significantly more tumors than did the coconut oil group. The high-linoleic safflower oil group was not significantly different from either of the other groups. In all groups, histologic examination of the largest tumor in each rat revealed more benign tumors, mostly duct papillomas, than carcinomas.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Body Weight; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Cocarcinogenesis; Cocos; Dietary Fats; Drug Synergism; Female; Linoleic Acids; Mammary Neoplasms, Experimental; Oils; Oleic Acids; Phytosterols; Rats; Safflower Oil; Vitamin E