gamma-sitosterol and campestanol

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

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

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

Our objective was to measure the systemic absorption of lecithin-emulsified Delta(5)-phytosterols and phytostanols during test meals by use of dual stable isotopic tracers. Ten healthy subjects underwent two single-meal absorption tests in random order 2 wk apart, one with intravenous dideuterated Delta(5)-phytosterols and oral pentadeuterated Delta(5)-phytosterols and the other with the corresponding labeled stanols. The oral-to-intravenous tracer ratio in plasma, a reflection of absorption, was measured by a sensitive negative ion mass spectroscopic technique and became constant after 2 days. Absorption from 600 mg of Delta(5)-soy sterols given with a standard test breakfast was 0.512 +/- 0.038% for sitosterol and 1.89 +/- 0.27% for campesterol. The absorption from 600 mg of soy stanols was 0.0441 +/- 0.004% for sitostanol and 0.155 +/- 0.017% for campestanol. Reduction of the double bond at position 5 decreased absorption by 90%. Plasma t(1/2) for stanols was significantly shorter than that for Delta(5)-sterols. We conclude that the efficiency of phytosterol absorption is lower than what was reported previously and is critically dependent on the structure of both sterol nucleus and side chain.

Topics: Adult; Cholesterol; Cross-Over Studies; Deuterium; Female; Glycine max; Half-Life; Humans; Intestinal Absorption; Kinetics; Male; Middle Aged; Phytosterols; Sitosterols

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

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

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

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

Functional foods with supplementation of plant sterols are already used by millions of people. However, at the same time it is current scientific thinking that elevation of plant sterols in the circulation causes coronary heart disease. Therefore, this study aimed to define the risk for coronary heart disease associated with moderately high plant sterol plasma levels in a cohort of elderly. In this study, we evaluated the association between plant sterols and coronary heart disease in a cohort of 1242 subjects older than 65 years, participating at the Longitudinal Aging Study Amsterdam (LASA). Concentrations of sitosterol, campesterol, brassicasterol and stigmasterol were assessed using highly sensitive and specific gas chromatography-mass spectrometry-selected ion-monitoring. Plant sterol concentrations (and their ratios to cholesterol) were slightly, however, significantly lower in patients with coronary heart disease. Moreover, high plasma concentrations of a marker plant sterol, sitosterol, were associated with a markedly reduced risk for coronary heart disease (OR 0.78, CI 0.62-0.98, p<0.05). In contrast neither plant stanols (sitostanol or campestanol) nor the cholesterol synthesis markers (lathosterol, lanosterol and desmosterol) nor their ratios to cholesterol were significantly different in the study groups. These data suggest that plant sterols could have neutral or even protective effects on development of coronary heart disease, which have to be confirmed in interventional trials.

Topics: Aged; Aged, 80 and over; Cholesterol; Coronary Disease; Cross-Sectional Studies; Female; Humans; Logistic Models; Male; Peripheral Vascular Diseases; Phytosterols; Risk Factors; Sitosterols

To analyze the phytosterol content in plant food commonly consumed in China, and to estimate the intake of phytosterols in Chinese people.. More than 160 types of plant food in 7 kinds were chosen as samples. The contents of beta-sitosterol, campesterol, stigmasterol, beta-sitostanol, campestanol were analyzed by GC methods and the total phytosterols were calculated. The intake of phytosteols in Chinese people was estimated using the data of "Survey on the Status of Nutrition and Health of the Chinese People" in 2002.. The contents of phytosterols in edible oils, nuts, and soybeans were higher than those in other plant food. In cereals, phytosterol contents of wheat flour were much higher than those of rice, the refinements of cereals may decrease the phytosterol contents. The phytosterol contents in vegetables and fruits were lower. The total intake of phytosterols in Chinese people was estimated to be 322.41mg/day, in which 40% may be of edible oil origin and 40% may be of cereal origin.. The results indicated that in the current dietary pattern, increase the intake of wheat, soybean, vegetable and fruit would enhance the phytosterol intake in Chinese.

Topics: China; Fabaceae; Food Analysis; Humans; Oryza; Phytosterols; Sitosterols; Triticum; Vegetables

Dietary sitostanol has a hypocholesterolemic effect because it decreases the absorption of cholesterol. However, its effects on the sitostanol concentrations in the blood and tissues are relatively unknown, especially in patients with sitosterolemia and xanthomatosis. These patients hyperabsorb all sterols and fail to excrete ingested sitosterol and other plant sterols as normal people do. The goal of the present study was to examine the absorbability of dietary sitostanol in humans and animals and its potential long-term effect. Two patients with sitosterolemia were fed the margarine Benecol (McNeill Nutritionals, Ft. Washington, PA), which is enriched in sitostanol and campestanol, for 7-18 wk. Their plasma cholesterol levels decreased from 180 to 167 mg/dL and 153 to 113 mg/dL, respectively. Campesterol and sitosterol also decreased. However, their plasma sitostanol levels increased from 1.6 to 10.1 mg/dL and from 2.8 to 7.9 mg/dL, respectively. Plasma campestanol also increased. After Benecol withdrawal, the decline in plasma of both sitostanol and campestanol was very sluggish. In an animal study, two groups of rats were fed high-cholesterol diets with and without sitostanol for 4 wk. As expected, plasma and liver cholesterol levels decreased 18 and 53%, respectively. The sitostanol in plasma increased fourfold, and sitostanol increased threefold in skeletal muscle and twofold in heart muscle. Campestanol also increased significantly in both plasma and tissues. Our data indicate that dietary sitostanol and campestanol are absorbed by patients with sitosterolemia and xanthomatosis and also by rats. The absorbed plant stanols were deposited in rat tissues. Once absorbed by sitosterolemic patients, the prolonged retention of sitostanol and campestanol in plasma might increase their atherogenic potential.

Topics: Adolescent; Animals; Cholesterol; Diet; Female; Humans; Male; Metabolism, Inborn Errors; Middle Aged; Phytosterols; Rats; Rats, Wistar; Sitosterols; Tissue Distribution; Xanthomatosis

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

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