stigmastanol and campesterol

Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Clinical Trials as Topic; Esters; Humans; Hypolipidemic Agents; Myocardial Ischemia; Phytosterols; Sitosterols

Clinical safety of consuming plant stanol ester spreads during pregnancy and lactation, the impact on maternal and infant serum and breast-milk cholesterol and the ratios (micromol/mmol of cholesterol) of synthesis and absorption markers were evaluated. Pregnant women (n 21) were randomised to control and dietary intervention groups, the intervention including advice to follow a balanced diet and to consume spreads enriched with plant stanol esters. Participants were followed during and after pregnancy and their infants up to 1 year of age. A mean 1.1 (sd 0.4) g consumption of plant stanols during pregnancy and 1.4 (sd 0.9) g 1 month post-partum increased sitostanol and the markers for cholesterol synthesis, lathosterol, lathosterol/campesterol and lathosterol/sitosterol, and reduced a marker for cholesterol absorption, campesterol, in maternal serum. In breast milk, desmosterol was lower in the intervention group, while no differences were detected between the groups in infants' serum. Plant stanol ester spread consumption had no impact on the length of gestation, infants' growth or serum beta-carotene concentration at 1 and 6 months of age, but the cholesterol-adjusted serum beta-carotene concentration was lowered at 1 month in the intervention group. Plant stanol ester spread consumption appeared safe in the clinical setting, except for potential lowering of infants' serum beta-carotene concentration, and was reflected in the markers of cholesterol synthesis and absorption in mothers' serum, encouraging further studies in larger settings.

Topics: Analysis of Variance; beta Carotene; Biomarkers; Child Development; Cholesterol; Desmosterol; Female; Humans; Infant; Infant, Newborn; Lactation; Margarine; Milk, Human; Phytosterols; Pregnancy; Safety; Sitosterols; Squalene

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

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

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

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

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

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

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

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

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

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

Dietary plant sterols (phytosterols) have been shown to lower plasma lipid concentrations in animals and humans. However, the effect of phytosterol intake from tall oil on cholesterol and phytosterol metabolism has not been assessed in subjects fed precisely controlled diets.. Our objective was to examine the effects of sitostanol-containing phytosterols on plasma lipid and phytosterol concentrations and de novo cholesterol synthesis rate in the context of a controlled diet.. Thirty-two hypercholesterolemic men were fed either a diet of prepared foods alone or a diet containing 1.7 g phytosterols/d for 30 d in a parallel study design.. No overall effects of diet on total cholesterol concentrations were observed, although concentrations were lower with the phytosterol-enriched than with the control diet on day 30 (P < 0.05). LDL-cholesterol concentrations on day 30 had decreased by 8.9% (P < 0.01) and 24.4% (P < 0.001) with the control and phytosterol-enriched diets, respectively. HDL-cholesterol and triacylglycerol concentrations did not change significantly. Moreover, changes in circulating campesterol and beta-sitosterol concentrations were not significantly different between phytosterol-fed and control subjects. In addition, there were no significant differences in fractional (0.091 +/- 0.028 and 0.091 +/- 0.026 pool/d, respectively) or absolute (0.61 +/- 0.24 and 0.65 +/- 0.23 g/d, respectively) synthesis rates of cholesterol observed between control and phytosterol-fed subjects.. Addition of blended phytosterols to a prudent North American diet improved plasma LDL-cholesterol concentrations by mechanisms that did not result in significant changes in endogenous cholesterol synthesis in hypercholesterolemic men.

Topics: Adult; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chromatography, Gas; Humans; Hyperlipidemias; Male; Middle Aged; Phytosterols; Sitosterols; Triglycerides

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

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

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

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

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

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

Topics: Cholesterol; Chromatography, High Pressure Liquid; Flow Injection Analysis; Ion Mobility Spectrometry; Limit of Detection; Mass Spectrometry; Phytosterols; Sitosterols; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Sewage pollution is a principal factor of decreasing water quality, although it has not been considered a real impact in Amazonia that is still considered a pristine environment around the world. Thus, this study aimed to assess the levels of sewage contamination in sediments from three streams crossing Manaus - a Brazilian city of 2,403,796 inhabitants in the heart of the Amazon rain forest. Cholesterol, cholestanol, brassicasterol, ergosterol, stigmasterol, β-sitosterol, campesterol, stigmastanol, coprostanol, and epicoprostanol levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). The fecal indicator, coprostanol, was found in high concentrations (509-12 830 ng g

Topics: Biomarkers; Brazil; Cholestadienols; Cholestanol; Cholestanols; Cholesterol; Chromatography, Liquid; Drug Contamination; Environmental Monitoring; Feces; Geologic Sediments; Phytosterols; Rivers; Sewage; Sitosterols; Sterols; Tandem Mass Spectrometry; Water Pollutants; Water Pollution; Water Quality

There has been an increasing interest during recent years in the role of the gut microbiome on health and disease. Therefore, metabolites in human feces related to microbial activity are attractive surrogate marker to track changes of microbiota induced by diet or disease. Such markers include 5α/β-stanols as microbiome-derived metabolites of sterols. Currently, reliable, robust, and fast methods to quantify fecal sterols and their related metabolites are missing. We developed a liquid chromatography-high-resolution mass spectrometry (LC-MS/HRMS) method for the quantification of sterols and their 5α/β-stanols in human fecal samples. Fecal sterols were extracted and derivatized to N, N-dimethylglycine esters. The method includes cholesterol, coprostanol, cholestanol and sitosterol, 5α/β-sitostanol, campesterol and 5α/β-campestanol. Application of a biphenyl column permits separation of isomeric 5α- and 5β-stanols. Sterols are detected in parallel reaction monitoring (PRM) mode and stanols in full scan mode. HRMS allows differentiation of isobaric β-stanols and the [M + 2] isotope peak of the coeluting sterol. Performance characteristics meet the criteria recommended by Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Analysis of fecal samples from healthy volunteers revealed high interindividual variability of sterol and stanol fractions. Interestingly, cholesterol and sitosterol showed similar fractions of mainly 5β-stanols. In contrast, campesterol is substantially converted to 5α-campestanol and might be a poorer substrate for bacterial metabolism. Robust and fast quantification of fecal sterols and their related stanols by LC-MS/HRMS offers great potential to find novel microbiome-related biomarker in large-scale studies.

Topics: Cholesterol; Chromatography, Liquid; Feces; Gastrointestinal Microbiome; Humans; Limit of Detection; Phytosterols; Sitosterols; Sterols; Tandem Mass Spectrometry

Sterols are components present in the fat fraction of infant formulas (IFs). Their characterization is therefore of interest, though there are no official reference methods for their analysis in these matrices.. To validate a gas chromatographic method with flame ionization detection for the determination of animal (cholesterol and desmosterol) and plant sterols (brassicasterol, campesterol, stigmasterol, β-sitosterol and sitostanol) found in IFs. All correlation coefficients obtained for the calibration curves of sterols studied were >0.99. Limits of detection (<1 μg/100 mL) and quantification (<4 μg/100 mL) are suitable for sterols determination in IFs. The within-assay precision ranged from 1.6% to 8.8%, while the between-assay precision was <10% for most of sterols. Accuracy was satisfactory and was calculated by recovery assays (ranging 93-108%). The analytical parameters obtained showed the suitability of the proposed method for the determination of sterols in IFs.

Topics: Calibration; Cholestadienols; Cholesterol; Chromatography, Gas; Desmosterol; Flame Ionization; Infant Formula; Limit of Detection; Phytosterols; Reproducibility of Results; Sitosterols; Stigmasterol

The bioaccessibility (BA) of total and individual plant sterols (PS) of four commercial PS-enriched fermented milk beverages (designated as A to D) was evaluated using in vitro gastrointestinal digestion including the formation of mixed micelles. The fat content of the samples ranged from 1.1 to 2.2% (w/w), and PS enrichment was between 1.5 and 2.9% (w/w). β-Sitosterol, contained in all samples, was higher in samples A and B (around 80% of total PS). The campesterol content was C (22%) > A (7%) > B (5%). Sitostanol was the most abundant in sample D (85%). Stigmasterol was only present in sample C (33%). The greatest BA percentage for total PS corresponded to samples A and B (16-17%), followed by sample D (11%) and sample C (9%). The total BA was not related to the protein, lipid or PS content of the beverages, whereas samples with higher carbohydrates and fiber contents showed lower BA. The BA of the individual PS differed according to the sample considered, and was not related to the PS profile of the sample, thus indicating strong dependency upon the matrix (PS ingredient and other components). Although in vivo studies should be carried out to better assess the functionality of PS in functional foods such as enriched fermented milk beverages, our in vitro study is a useful preliminary contribution to evaluation of the efficacy of these products.

Topics: Biological Availability; Cholesterol; Cultured Milk Products; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Digestion; Food, Fortified; Functional Food; Gastrointestinal Tract; Micelles; Models, Biological; Phytosterols; Sitosterols; Stigmasterol

A mixture of phytosterols/-stanols, consisting of 75% β-sitosterol, 12% sitostanol, 10% campesterol, 2% campestanol, and 1% others, was esterified with linoleic acid. The resulting mixture of phytosteryl/-stanyl linoleates was subjected to thermal oxidation at 180 °C for 40 min. A silica solid-phase extraction was applied to separate a fraction containing the nonoxidized linoleates and nonpolar degradation products (heptanoates, octanoates) from polar oxidation products (oxo- and hydroxyalkanoates). In total, 15 sitosteryl, sitostanyl, and campesteryl esters, resulting from oxidation of the acyl chain, could be identified by GC-FID/MS. Synthetic routes were described for authentic reference compounds of phytosteryl/-stanyl 7-hydroxyheptanoates, 8-hydroxyoctanoates, 7-oxoheptanoates, 8-oxooctanoates, and 9-oxononanoates, which were characterized by GC-MS and two-dimensional NMR spectroscopy. The study provides data on the formation and identities of previously unreported classes of acyl chain oxidation products upon thermal treatment of phytosteryl/-stanyl fatty acid esters.

Topics: Cholesterol; Esters; Hot Temperature; Linoleic Acids; Molecular Structure; Oxidation-Reduction; Phytosterols; Sitosterols

Ross Lake lies within the City of Flin Flon (Manitoba, Canada), a mining community originally formed by the Hudson Bay Mining and Smelting Company (now Hudbay Minerals Inc.) in 1927. At the time of this investigation, a continuous effluent stream from Hudbay Minerals (approximately 80 years) and a discontinuous and unknown amount of raw and minimally treated municipal sewage (>20 years, likely ending in 1951) was discharged into the north basin of the lake. Maximum concentrations of fecal sterols, such as coprostanol and terrestrial phytosterols, such as: β-sitosterol, campesterol, stigmastanol were measured in vertical sections of sediment cores, collected from Ross Lake, in the 15-16-cm section, which likely corresponds to the 1930s. Concentrations of coprostanol increased from <1 μg g(-1) in older sediments, to 252.3 μg g(-1) organic carbon at the peak. Observed changes in concentrations of sterols, in combination with radiometric dating and changes to sediment physicochemical characteristics, support the conclusion that sediments of a depth of less than 17.5-cm depth were deposited during the post-industrial era from approximately 1930 onwards. Ratios of coprostanol to cholesterol>1, peaking at 3.6 are consistent with anecdotal information that municipal sewage was discharged into Ross Lake during the early years of urbanization, prior to changes in treatment of sewage and discharge practices that began in 1951. Finally, historical concentrations of terrestrial phytosterols followed trends similar to those of coprostanol and cholesterol and may possibly be the result of an increase in the flux of terrestrial organic matter into Ross Lake as the result of regional deforestation due to logging and fire.

Topics: Cholesterol; Environmental Monitoring; Feces; Geologic Sediments; History, 20th Century; History, 21st Century; Lakes; Manitoba; Phytosterols; Sewage; Sitosterols; Waste Disposal, Fluid; Water Pollutants; Water Purification

This study has determined oil, fatty acid (FA) and phytosterols content during the ripening of the Tunisian Onopordum acanthium L. seeds. In total, nine FAs and six phytosterols were identified. The main FAs were linoleic acid (0.18-8.06 mg/g of seed) followed by oleic acid (0.051-2.45 mg/g of seed), palmitic acid and stearic acid. Pentadecanoic acid was detected, for the first time, in unripe fruits and the two last stages of development were characterised by a relative abundance of erucic acid. Overall, β-sitosterol (34.5-77.79% of total sterols) was the major 4-desmethylsterols during maturation. The first episodes of growth were characterised by the best amounts of stigmasterol and campesterol, while stigmastanol and Δ7 sitosterol had quoted the semi-ripe and fully ripe fruits; however, cholesterol was absent. These findings are useful in understanding a potential new source of important natural compounds (Phytosterols and USFA) found in this fruit and when harvest should be undertaken to optimise desired FA and phytosterols content.

Topics: Cholesterol; Fatty Acids; Fruit; Linoleic Acid; Oleic Acid; Onopordum; Phytosterols; Plant Oils; Seeds; Sitosterols; Stigmasterol; Tunisia

Triterpenoid compounds found in free and ester forms in extracts of entire fruits and leaves and in fruit and leaf cuticular waxes of bilberry (Vaccinium myrtillus L.) collected in Finland and Poland were identified and quantitated by gas chromatography-mass spectrometry coupled to a flame ionization detector (GC-MS/FID). The main bilberry triterpenoid profile consisted of α- and β-amyrin, α- and β-amyrenone, campesterol, cholesterol, citrostadienol (in berries), cycloartanol, erythrodiol, lupeol, 24-methylenecycloartanol, sitosterol, sitostanol, stigmasterol, stigmasta-3,5-dien-7-one, uvaol, oleanolic and ursolic aldehydes, and oleanolic, ursolic, 2α-hydroxyoleanolic, and 2α-hydroxyursolic acids. Friedelin and D:A-friedooleanan-3β-ol were found only in Finnish plants, whereas D:C-friedours-7-en-3β-ol and taraxasterol were found only in Polish plants. To our knowledge, this is the first thorough description of triterpenoid compounds in this species. The presented results revealed that the triterpenoid profile of bilberry varied considerably between different organs of the plant, regardless of the plant origin, as well as between plant samples obtained from the two geographical locations.

Topics: Anthocyanins; Cholesterol; Finland; Fruit; Gas Chromatography-Mass Spectrometry; Molecular Structure; Oleanolic Acid; Phytosterols; Plant Extracts; Plant Leaves; Poland; Sitosterols; Triterpenes; Vaccinium myrtillus

Much interest has focused on the cholesterol-lowering effects of phytosterols (plant sterols) but limited data suggests they may also possess anti-carcinogenic activity. Conjugated linoleic acids (CLA), sourced from meat and dairy products of ruminant animals, has also received considerable attention as a potential anti-cancer agent. Therefore, the aims of this project were to (i) examine the effects of phytosterols and CLA on the viability and growth of human intestinal Caco-2 cells and (ii) determine their potential genoprotective (comet assay), COX-2 modulatory (ELISA) and apoptotic (Hoechst staining) activities. Caco-2 cells were supplemented with the phytosterols campesterol, beta-sitosterol, or beta-sitostanol, or a CLA mixture, or individual CLA isomers (c10t12-CLA, t9t11-CLA) for 48 h. The three phytosterols, at the highest levels tested, were found to reduce both the viability and growth of Caco-2 cells while CLA exhibited isomer-specific effects. None of the phytosterols protected against DNA damage. At a concentration of 25 microM, both c10t12-CLA and t9t11-CLA enhanced (P<0.05) oxidant-induced, but not mutagen-induced, DNA damage. Neither the phytosterols nor CLA induced apoptosis or modulated COX-2 production. In conclusion, campesterol, beta-sitosterol, beta-sitostanol, c10t12-CLA, and t9t11-CLA were not toxic to Caco-2 cells, at the lower levels tested, and did not exhibit potential anti-carcinogenic activity.

Topics: Caco-2 Cells; Cell Membrane; Cell Survival; Cholesterol; Comet Assay; Cyclooxygenase 2; DNA Damage; Enzyme-Linked Immunosorbent Assay; Humans; Hydrogen Peroxide; L-Lactate Dehydrogenase; Linoleic Acid; Methylnitronitrosoguanidine; Mutagens; Phytosterols; Protective Agents; Sitosterols

To analyze the phytosterol content in food plant materials and Chinese traditional herbal medicines commonly used in China.. 18 kinds of food plant materials and 32 kinds of Chinese traditional herbal medicines, which were commonly used in functional food, were chosen as samples. The contents of beta-sitosterol, campesterol, stigmasterol, beta-sitostanol were analyzed by GC methods and the percent of each ingredient were calculated.. The contents of phytosterols in 18 kinds of food plant materials were from 14.8 mg/100 g to 208.3 mg/100 g, while the content of phytosterols in 32 Chinese traditional herbal medicines were from 9.4 mg/100 g to 280.3 mg/100 g. In most samples, beta-sitosterol is the largest part of total phytosterol.. Phytosterols were existed in 50 kinds of food plant materials and Chinese traditional herbal medicines commonly used in functional food, maybe phytosterol is an important functional ingredient in some plant materials.

Topics: Cholesterol; Chromatography, Gas; Drugs, Chinese Herbal; Phytosterols; Plants, Medicinal; Sitosterols; Stigmasterol; Vegetables

Rapeseed oil (RSO) is a novel source of plant sterols, containing the unique brassicasterol in concentrations higher than allowed for plant sterol blends in food products in the European Union. Effects of RSO sterols and stanols on aortic atherosclerosis were studied in cholesterol-fed heterozygous Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n 18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma campestanol (P < 0.001) and sitostanol (P < 0.001) and aortic campestanol (P < 0.05) compared with controls. Feeding RSO sterol esters increased concentrations of plasma campesterol (P < 0.001), sitosterol (P < 0.001) and brassicasterol (P < 0.001) and aortic campesterol (P < 0.01). Significantly lower plasma cholesterol (P < 0.001) was recorded in the treated groups after 3 weeks and throughout the study. LDL-cholesterol was reduced 50 % in the high-dose RSO sterol ester (P < 0.01) and high-dose RSO stanol ester (P < 0.001) groups compared with controls. Atherosclerotic lesions were found in three rabbits in each of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P < 0.001) in response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration of brassicasterol were well tolerated. They were hypocholesterolaemic and inhibited experimental atherosclerosis in cholesterol-fed Hh-WHHL rabbits. A significant uptake of plant sterols into the blood and incorporation of campesterol and campestanol into aortic tissue was recorded.

Topics: Animals; Aorta; Atherosclerosis; Cholestadienols; Cholesterol; Cholesterol, Dietary; Fatty Acids, Monounsaturated; Female; Heterozygote; Hyperlipidemias; Lipids; Male; Phytosterols; Plant Oils; Rabbits; Rapeseed Oil; Sitosterols

We elucidated the molecular mechanism(s) underlying sterol trafficking by investigating alterations in gene expression in response to increased retention of dietary phytosterols and phytostanols in stroke-prone spontaneously hypertensive (SHRSP) and normotensive Wistar Kyoto (WKY) inbred rats.. SHRSP and WKY inbred rats were fed a control diet or a diet supplemented with phytosterols or phytostanols (2 g/kg diet).. Intake of phytosterols and phytostanols increased their incorporation in plasma, red blood cells, liver, aorta and kidney, but decreased cholesterol levels in liver and aorta in both rat strains. Phytosterol intake up-regulated mRNA expression of intestinal Npc1l1 and Abcg8, and hepatic Abcg5, Abca1, Cyp27a1 and Hmgcr. Phytostanol intake up-regulated Npc1l1 and Srebp2, but down-regulated Abcg5 mRNA expression in small intestine. Phytostanols also up-regulated Abca1 expression in SHRSP rats, but down-regulated Abca1 expression in WKY inbred rats. Compared to phytosterols, dietary phytostanols reduced phytosterol levels in plasma, red blood cells, and kidney, as well as altered mRNA levels of hepatic Abca1,Cyp27a1, and Hmgcr and intestinal Abcg5/8, Hmgcr and Srebp2.. Altered expression of multiple sterol-regulatory genes may contribute to the incorporation and cholesterol-lowering actions of phytosterols and phytostanols. Phytosterols and phytostanols may act through different mechanism(s) on cholesterol and phytosterol/phytostanol trafficking.

Topics: Animals; Anticholesteremic Agents; Cholestadienols; Cholesterol; Gene Expression Regulation; Hypolipidemic Agents; Jejunum; Liver; Male; Organ Specificity; Phytosterols; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Sitosterols; Sterols

To investigate the dietary phytosterol intake of elderly women in three different cities of China, and to compare the main dietary sources, so that to discuss the relationship of dietary phytosterol intake and serum lipids.. Based on the dietary pattern, women more than 50 years old from Beijing, Hefei and Urumchi were chosen as testers, 80 - 100 people for each city respectively. The dietary survey was done by continues 24 hours review of two days, the plant food were collected and the phytosterol content (include beta-sitosterol, campesterol, stigmasterol, sitostanol) were analyzed by GC methods, the total phytosterols content were calculated. The dietary phytosterol intake were calculated and serum lipids were also analyzed in all the testers.. Testers from Beijing, Hefei and Urumchi were 100, 101 and 84 respectively. The average dietary phytosterol intake of people in Beijing and Hefei were 340.3 mg/d and 313.5 mg/d, the main sources were plant oil and cereals, while the average dietary phytosterol intake of people in Urumchi were 550.4 mg/d, higher than the other two cities (t values were 9.369, 10.420, respectively, both P values < 0.01), the main source in Urumchi was cereal (provide 53.1% of the total phytosterol intake). The laboratory results showed, testers in Urumchi had significantly lower serum TC content ((4.04 +/- 0.78) mmol/L) than that in Beijing ((4.89 +/- 0.91) mmol/L) and Hefei ((4.71 +/- 0.83) mmol/L) (t value were 6.766 and 5.401 respectively, both P values < 0.01); serum TG content in Urumchi((1.01 +/- 0.48) mmol/L) was also lower than that in Beijing ((1.31 +/- 0.53) mmol/L) and Hefei ((1.66 +/- 0.75) mmol/L) (t values were 3.343 and 7.293 respectively, both P values < 0.01); the serum glucose is also lower in testers in Urumchi ((5.02 +/- 2.18) mmol/L) compared with testers in Beijing ((5.69 +/- 1.53) mmol/L, t = 2.561, P < 0.05) and Hefei ((5.78 +/- 1.53) mmol/L, t = 2.934, P < 0.01).. Different dietary pattern result in significantly different dietary phytosterol intake in elder women in three cities, higher, phytosterol intake seemed to contribute to lower serum lipids.

Topics: Aged; Aged, 80 and over; China; Cholesterol; Cholesterol, Dietary; Female; Humans; Lipids; Middle Aged; Phytosterols; Sitosterols; Urban Population

We investigated the difference between the molecular structures of plant sterols and stanols that affect the solubilization of cholesterol in bile salt micelles (in vitro study). First, the aqueous solubility of beta-sitosterol, beta-sitostanol, and campesterol was determined by considering the specific radioactivity by using a fairly small quantity of each radiolabeled compound. The order of their aqueous solubilities was as follows: cholesterol > campesterol > beta-sitostanol > beta-sitosterol. The maximum solubility of cholesterol and the above mentioned sterol/stanol in sodium taurodeoxycholate and sodium taurocholate solutions (single solubilizate system) was measured. Moreover, the preferential solubilization of cholesterol in bile salt solutions was systematically studied by using different types of plant sterols/stanols. The solubilization results showed that the cholesterol-lowering effect was similar for sterols and stanol. Thermodynamic analysis was applied to these experimental results. The Gibbs energy change (Delta G degrees ) for the solubilization of plant sterols/stanols showed a negative value larger than that for cholesterol.

Topics: Cholesterol; Micelles; Phytosterols; Sitosterols; Solubility; Taurocholic Acid; Taurodeoxycholic Acid; Thermodynamics

The plant sterols campesterol, beta-sitosterol and beta-sitostanol were investigated for potential immunomodulatory effects in Jurkat T cells. Treatments involved supplementing cells with or without concanavalin A (ConA) or phorbol-12-myristate-13-acetate plus ionomycin (PMA+IoM) in the presence or absence of increasing concentrations (10-100 microM) of each plant sterol for 24 h. None of the plant sterols significantly affected mitogen-stimulated IL-4, IL-10 or IFN-gamma production. However, campesterol, beta-sitosterol and beta-sitostanol significantly suppressed mitogen-induced IL-2 production in a dose-dependent manner. Both bisindolylmaleimide-I (BIM-I), a specific protein kinase C (PKC) inhibitor, and the immunosuppressant drug known as Tacrolimus (FK506), an IL-2 inhibitor, prevented mitogen-stimulated IL-2 production in Jurkat cells. Treatment with PMA+IoM alone significantly increased PKC activity and the presence of BIM-I prevented PKC activation by PMA+IoM. Following 24 h treatments, the plant sterols did not affect PMA+IoM-enhanced PKC activity, cellular calcium content or calcineurin activity. Intracellular cyclic 3',5'-adenosine monophosphate (cAMP) levels were significantly reduced by PMA+IoM. The presence of FK506 prevented a PMA+IoM-induced reduction of intracellular cAMP. Likewise the plant sterols behaved in a similar manner as FK506. Our findings suggest that the suppression of IL-2 by the plant sterols was not mediated via PKC inhibition and that their effects occurred possibly via cAMP modulation and/or a calcium/calcineurin-independent pathway.

Topics: Cell Division; Cell Survival; Cholesterol; Concanavalin A; Cytokines; Enzyme Inhibitors; Humans; Immunologic Factors; Immunosuppressive Agents; Indoles; Interleukin-2; Jurkat Cells; Lymphocyte Activation; Maleimides; Phytosterols; Protein Kinase C; Sitosterols; T-Lymphocytes; Tacrolimus; Tetradecanoylphorbol Acetate

Plant sterol and stanol esters were separated on a Luna hexyl-phenyl column using a gradient of acetonitrile (90-100%) in water. The eluted compounds were detected by atmospheric pressure chemical ionization (APCI)-mass spectroscopy (MS) in the positive mode. Sterol and stanol esters produced [M + H - HOOCR](+) ions. Application of the hyphenated technique-LC-MS-allowed differentiation between a number of esters of sitosterol, campesterol, stigmasterol, and (tentatively) avenasterol, as well as sitostanol and campestanol esters. With cholesteryl decanoate used as the internal standard, the method showed good linearity, precision, and reproducibility. The method required minimal sample pretreatment and can be applied to samples with high water content (juices) as well as samples with high oil content (margarine spreads). The method could be useful for the analysis of sterol and stanol esters in fortified food products.

Topics: Anticholesteremic Agents; Beverages; Cholesterol; Chromatography, High Pressure Liquid; Citrus; Esters; Fruit; Margarine; Mass Spectrometry; Phytosterols; Sensitivity and Specificity; Sitosterols; Stigmasterol

Campesterol is present in all the phytosterol-containing dietary hypocholesterolemic agents in current use. Campesterol is absorbed more efficiently than sitosterol, and the question of its possible atherogenicity has been raised. To test this possibility, rabbits were fed either a semipurified, cholesterol-free diet that has been shown to be atherogenic for this species or the same diet augmented with 0.5 g of phytosterol-rich diet preparations (spreads) containing either sitosterol or sitostanol. The diets contained 295 mg phytosterol per 100 g. After 60 d, serum cholesterol levels in the two phytosterol groups were 78 +/- 4 mg/dL (sitosterol) and 76 +/- 4 mg/dL (sitostanol), respectively. The serum cholesterol level of rabbits fed the control diet was 105 +/- 8 mg/dL. Serum campesterol (microg/mL) levels were higher than sitosterol or sitostanol levels in all groups. Aortic phytosterols were present in nanogram quantities compared to cholesterol, which was present in microgram quantities. The ratio of campesterol/sitosterol/sitostanol in the aortas was: control, 1.00:0.43:0.02; sitosterol, 1:00:0.32:0.01; sitostanol, 1:00:0.34:0.11. Aortic campesterol was present at 4% the concentration of aortic cholesterol, sitosterol at 1.4%, and sitostanol at 0.14%. Aortic lesions were not present in any of the animals.

Topics: Animals; Aorta; Cholesterol; Chromatography, Gas; Diet; Esters; Male; Phytosterols; Rabbits; Sitosterols; Weight Gain

Cholesterol and other sterols exit the body primarily by secretion into bile. In patients with sitosterolemia, mutations in either of two ATP-binding cassette (ABC) half-transporters, ABCG5 or ABCG8, lead to reduced secretion of sterols into bile, implicating these transporters in this process. To elucidate the roles of ABCG5 and ABCG8 in the trafficking of sterols, we disrupted Abcg5 and Abcg8 in mice (G5G8(-/-)). The G5G8(-/-) mice had a 2- to 3-fold increase in the fractional absorption of dietary plant sterols, which was associated with an approximately 30-fold increase in plasma sitosterol. Biliary cholesterol concentrations were extremely low in the G5G8(-/-) mice when compared with wild-type animals (mean = 0.4 vs. 5.5 micromol ml) and increased only modestly with cholesterol feeding. Plasma and liver cholesterol levels were reduced by 50% in the chow-fed G5G8(-/-) mice and increased 2.4- and 18-fold, respectively, after cholesterol feeding. These data indicate that ABCG5 and ABCG8 are required for efficient secretion of cholesterol into bile and that disruption of these genes increases dramatically the responsiveness of plasma and hepatic cholesterol levels to changes in dietary cholesterol content.

Topics: Animal Feed; Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Bile; Biological Transport; Chimera; Cholestanol; Cholesterol; Cholesterol, Dietary; Crosses, Genetic; Dietary Fats; Female; Gene Targeting; Intestinal Absorption; Intestinal Mucosa; Lipoproteins; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols; Sitosterols

Plant sterols in vegetable foods might prevent colorectal cancer.. The objective was to study plant sterol intakes in relation to colorectal cancer risk in an epidemiologic study.. The study was performed within the framework of the Netherlands Cohort Study on Diet and Cancer in 120852 subjects who completed a baseline questionnaire in 1986. After 6.3 y of follow-up, 620 colon and 344 rectal cancer cases were detected. A case-cohort approach was used to calculate confounder-adjusted rate ratios (RRs) and their 95% CIs for quintiles of plant sterol intake.. The total mean (+/-SD) intake of campesterol, stigmasterol, beta-sitosterol, campestanol, and beta-sitostanol was 285 +/- 97 mg/d. Major contributors to plant sterol intake were bread (38%), vegetable fats (26%), and fruit and vegetables (21%). For men, there was no clear association between intake of any of the plant sterols and colon cancer risk when age, smoking, alcohol use, family history of colorectal cancer, education level, and cholecystectomy were controlled for. Adjustment for energy did not alter the result. For rectal cancer, adjustment for energy resulted in positive associations between risk and campesterol and stigmasterol intakes. For women, there was no clear association between intake of any of the plant sterols and colorectal cancer risk.. A high dietary intake of plant sterols was not associated with a lower risk of colon and rectal cancers in the Netherlands Cohort Study on Diet and Cancer.

Topics: Aged; Bread; Case-Control Studies; Cholesterol; Cohort Studies; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Fats; Female; Follow-Up Studies; Fruit; Humans; Hypolipidemic Agents; Male; Middle Aged; Netherlands; Phytosterols; Prospective Studies; Rectal Neoplasms; Risk Factors; Sitosterols; Stigmasterol; Surveys and Questionnaires; Vegetables

As part of an extensive safety evaluation programme, a series of studies has been conducted to determine the fate of phytosterols in the rat. Rats were dosed by oral gavage with 14C-labelled samples of cholesterol, beta-sitosterol or beta-sitostanol or (3)H-labelled samples of beta-sitostanol, campesterol, campestanol or stigmasterol dissolved in sunflower seed oil. Urine and faeces were collected for up to 96 hours after dosing. There was no quantification of biliary excreted material in these studies. Animals were sacrificed and either prepared for whole body autoradiography or tissues and carcass remains were assayed for 14C or (3)H. The overall absorption of phytosterols was low as judged by tissue and carcass levels of radioactivity. Elimination from the body was mainly in the faeces and was initially very rapid, but traces of material were still being excreted at 4 days after dosing. While total absorption of the phytosterols could not be fully quantified without biliary excretion data, it was clear that cholesterol was absorbed to the greatest extent (27% of the dose in females at 24 hours). Campesterol (13%) was absorbed more than beta-sitosterol and stigmasterol (both 4%) which were absorbed more than beta-sitostanol and campestanol (1-2%). The absorption of phytosterols was slightly greater in females than males. For each test material, the overall pattern of tissue distribution of radioactivity was similar, with the adrenal glands, ovaries and intestinal epithelia showing the highest levels and the longest retention of radioactivity.

Topics: Animals; Autoradiography; Cholesterol; Female; Intestinal Absorption; Male; Phytosterols; Rats; Sitosterols; Stigmasterol; Tissue Distribution

We measured the percent absorption, turnover, and distribution of campestanol (24-methyl-5alpha-cholestan-3beta-ol) in a sitosterolemic homozygote, her obligate heterozygous mother, and three healthy human control subjects. For reasons relating to sterol hyperabsorption, the homozygote consumed a diet low in plant sterols that contained campestanol at about 2 mg/day. The heterozygote and three control subjects were fed a diet supplemented with a spread that contained campestanol at 540 mg/day and sitostanol (24-ethyl-5alpha-cholestan-3beta-ol) at 1.9 g/day as fatty acid esters. Plasma campestanol concentrations determined by capillary gas-liquid chromatography were 0.72 +/- 0.03 mg/dl in the homozygote, 0.09 +/- 0.04 mg/dl in the heterozygote, and 0.05 +/- 0.03 mg/dl for the control mean. After simultaneous pulse labeling with [3alpha-(3)H]campestanol intravenously and [23-(14)C]campestanol orally, the maximum percent absorption measured by the plasma dual-isotope ratio method as a single time point was 80% in the homozygote, 14.3% in the heterozygote, and 5.5 +/- 4.3% as the mean for three control subjects. Turnover (pool size) values estimated by mathematical analysis of the specific activity versus time [3alpha-(3)H]campestanol decay curves were as follows: 261 mg in the homozygote, 27.3 mg in the heterozygote, and 12.8 +/- 7.6 mg in the three control subjects (homogygote vs. controls, P < 0.001). The calculated production rate (mg/24 h) equivalent to actual absorption in the presence of dietary sterols and stanols was 0.67 mg/day or 31% of intake in the homozygote, 2.1 mg/day or 0.3% of intake in the heterozygote, and 0.7 +/- 0.3 mg/day or 0.1% of intake in the three control subjects. However, the excretion constant from pool A (K(A)) was prolonged markedly in the homozygote, but was 100 times more rapid in the heterozygote and three control subjects.Thus, campestanol, like other noncholesterol sterols, is hyperabsorbed and retained in sitosterolemic homozygotes. However, campestanol absorption was only slightly increased in the sitosterolemic heterozygote and removal was as rapid as in control subjects.

Topics: Adolescent; Adult; Carbon Radioisotopes; Cholesterol; Diet; Female; Half-Life; Heterozygote; Homozygote; Humans; Intestinal Absorption; Kinetics; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Phytosterols; Sitosterols; Tritium

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

Unesterified cholesterol (UC) that is taken up by the liver from lipoproteins is rapidly mixed by exchange with liver UC. Thus, it is not possible to quantitate the transport of UC from different lipoproteins into bile using radiolabeled UC. However, plant sterols do not exchange with UC and are secreted in bile with the same kinetics as UC. To compare the contribution to bile of sterols from different lipoproteins, we perfused isolated rat livers with VLDL, LDL, and HDL that were obtained from patients with hereditary phytosterolemia and were rich in plant sterols. After 30-min recirculating perfusions, hepatic concentrations of plant sterols were not different after different lipoproteins were perfused. However, biliary plant sterol secretion was markedly different: with the perfusion of either VLDL or LDL there was no increase in plant sterols in bile, but with perfusion of HDL, the secretion of plant sterols was increased two- to threefold (P = 0.0005). The increase in biliary plant sterols was detected 5-10 min after HDL was added to perfusates and was similarly large for each of three individual plant sterols that was tracked. Results show that when sterol transport from lipoproteins into bile can be determined, only HDL provides a vehicle for UC elimination in bile that is consistent with its putative function in reverse cholesterol transport.

Topics: Animals; Bile; Biological Transport; Cholesterol; Chromatography, High Pressure Liquid; Humans; Hypolipoproteinemias; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Liver; Male; Perfusion; Phytosterols; Rats; Rats, Sprague-Dawley; Sitosterols

Absorption of dietary cholesterol, campesterol, and sitosterol, cholesterol balance, and fecal excretion of plant sterols were determined in three unrelated patients with phytosterolemia and three healthy volunteers during constant intake of cholesterol and plant sterols using accurate gas-liquid chromatography-mass spectrometry techniques. Each subject received a mixture of [26,26,26,27,27,27-2H6]cholesterol, [6,7,7-2H3]sitostanol, and [6,7,7-2H3]campesterol together with two non-absorbable markers, [5,6,22,23-2H4]sitostanol and chromic oxide. Feces were collected from days 5 to 7 and absorption of different sterols was calculated from the intestinal disappearance of the different sterols relative to [5,6,22,23-2H4]sitostanol and chromic oxide. The results obtained by the two markers were not different and the absorption of cholesterol averaged 53 +/- 4% for the patients (mean +/- SD) and 43 +/- 3% for the volunteers. Campesterol absorption averaged 24 +/- 4% in patients and 16 +/- 3% in healthy volunteers, whereas sitosterol absorption averaged 16 +/- 1% and 5 +/- 1%, respectively. Cholesterol synthesis expressed by body weight varied considerably in the two groups but appeared to be about 5 times lower in patients than in controls. Administration of a high dose of sitostanol (0.5 g t.i.d.) to two patients was followed by a reduction in cholesterol absorption by 24% and 44%, an increase in fecal output of cholesterol and steroids derived from cholesterol and plant steroids, and a marked reduction of serum cholesterol, campesterol, and sitosterol. Under the conditions used, inhibition of cholesterol absorption by sitostanol was not followed by a significant rise in cholesterol synthesis. The time of observation was, however, too short to allow final conclusion on this. The results show that the absolute difference in absorption rate of different sterols between the patients and healthy volunteers was about the same. As a consequence, increasing hydrophobicity causes a relative decrease of absorption rates. Thus, patients with phytosterolemia seem to have a generally increased absorption of sterols rather than a loss of a specific discriminatory mechanism, and oral administration of sitostanol seems to be an interesting new approach for treatment of phytosterolemia.

Topics: Absorption; Adult; Anticholesteremic Agents; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Deuterium; Dietary Fats; Feces; Female; Humans; Intestinal Mucosa; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Phytosterols; Sitosterols; Steroids; Sterols

To investigate the action and mechanism of a dietary phytosterol mixture naturally containing sitostanol, derived from tall-oil, on circulating cholesterol and lipoprotein levels, five groups of rats were fed a control elemental diet (group 1), a control elemental diet with 1% cholesterol alone (group 2) or with sitostanol mixtures or a sitostanol-free mixture supplemented at 0.2% (group 3), 0.5% (group 4) or 1% (group 5) of dietary levels. One per cent supplementation of sitostanol (21%) compared with sitostanol-free mixtures decreased (P < 0.02) total serum cholesterol. Dietary sitostanol (16% or 21%) mixture at 1% dietary levels decreased (P < 0.05) low density lipoprotein (LDL) cholesterol and increased (P < 0.05) high density lipoprotein (HDL) cholesterol levels. The decrease of LDL and increase of HDL cholesterol were correlated (P < 0.01) with the level of sitostanol mixture in the diet. Consumption of the sitostanol-containing mixture (1% dietary levels) caused a compensatory increase in cholesterol synthesis as indicated by elevated (P < 0.05) lathosterol/ cholesterol ratios in plasma and hepatic cholesterol fractional synthesis rate (FSR) (P < 0.02). Both sitostanol and sitostanol-free mixtures at 0.5% or 1% dietary intake levels increased plasma campesterol and beta-sitosterol levels, while plasma sitostanol levels were negligible. The absence of sitostanol in plasma and the increase in cholesterol synthesis induced by dietary sitostanol mixtures in addition to elevation of plasma campesterol and beta-sitosterol by sitostanol or sitostanol-free mixtures suggest that sitostanol mixtures effectively modify circulating lipoprotein cholesterol concentrations at the level of the intestine, rather than internally at the level of cholesterogenesis.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats, Unsaturated; Drug Interactions; Eating; Glycine max; Liver; Male; Phytosterols; Plant Oils; Rats; Rats, Wistar; Sitosterols; Structure-Activity Relationship

This study was undertaken to compare the ability of two plant sterols to reduce serum levels of lipids and to compare their mechanism of action in nine children with severe familial hypercholesterolemia (total and low-density lipoprotein cholesterol concentrations averaged 9.57 mmol/L (370 mg/dl) and 7.87 mmol/L (301 mg/dl)). After a 3-month strict diet, the children were given sitosterol pastils (2 gm three times a day) for 3 months, followed by a 7-month course of sitostanol (0.5 gm three times a day). Serum lipoprotein levels and serum concentrations of campesterol and sitosterol were determined in all nine children, and the fecal excretion of neutral and acidic sterols were determined in seven children at the end of each therapeutic regimen. Sitosterol reduced low-density lipoprotein cholesterol levels by 20% (p < 0.01); sitostanol reduced low-density lipoprotein cholesterol levels by 33% after 3 months and 29% after 7 months (p < 0.01 compared with diet; p < 0.05 compared with sitosterol). Although sitosterol did not alter serum concentrations of campesterol and sitosterol, a significant reduction did occur during sitostanol therapy (-47% and -51%, respectively; p < 0.01). Fecal excretion of neutral sterols increased from 6.7 mg/kg per day during the control period to 9.7 mg/kg per day during sitosterol administration (p < 0.05), and to 12.6 mg/kg per day during sitostanol administration (p < 0.05 compared with diet and sitosterol periods), indicating an increase in the inhibition of intestinal cholesterol absorption. All children completed the study and no obvious side effects occurred. The data indicate that sitostanol, even with a dose four-fold lower than that of sitosterol, was significantly more effective in reducing elevated levels of low-density lipoprotein cholesterol, and the reduction in serum lipid levels was of the same magnitude as that observed with systemic lipid-lowering drugs. These results suggest that sitostanol, a nonabsorbable plant sterol, could be the drug of choice for treating familial hypercholesterolemia in childhood.

Topics: Adolescent; Alanine Transaminase; Alkaline Phosphatase; Apolipoproteins B; Carotenoids; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Feces; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II; Male; Phytosterols; Sitosterols; Sterols

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