title: Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant women: effects on serum cholestanol and other non-cholesterol sterols. Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons. Sitosterol prevents obesity-related chronic inflammation. Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort Serum Plant Sterols Associate with Gallstone Disease Independent of Weight Loss and Non-Alcoholic Fatty Liver Disease Circulating markers for biosynthesis of cholesterol and bile acids are not depressed in asymptomatic gallstone subjects. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Elevated serum squalene and cholesterol synthesis markers in pregnant obese women with gestational diabetes mellitus1 Evidence for a short-term stimulatory effect of insulin on cholesterol synthesis in newly insulin-treated diabetic patients. The lipid-lowering effect of ezetimibe in pure vegetarians Published, JLR Papers in Press, September 11, 2006. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity. Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes Lipid-lowering effects of ezetimibe for hypercholesterolemic patients with and without type 2 diabetes mellitus. Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study. Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study Published, JLR Papers in Press, October 30, 2006. Cholesterol absorption decreases after Roux-en-Y gastric bypass but not after gastric banding.
abstract: BACKGROUND Our aim was to investigate whether intestinal binding of bile acids by guar gum , a dietary fibre , relieves cholestasis and pruritus in intrahepatic cholestasis of pregnancy . METHODS Forty-eight pregnant women with cholestasis and pruritus were r and omized double-blind to guar gum and placebo until the time of delivery , and 20 healthy pregnant women were used as control subjects . The pruritus score and serum bile acids , lipids and non-cholesterol sterols were measured at baseline , at least 2 weeks after treatment , just before delivery and up to 4 weeks after delivery . RESULTS The increase in serum bile acids and worsening of pruritus were prevented by guar gum in relation to placebo ( P < 0.05 ) . Serum cholesterol was unchanged , but increased cholesterol precursor sterol values suggested that cholesterol synthesis was increased by guar gum .  Serum cholestanol proportion , an indicator of cholestasis , was related to pruritus but was unaffected by guar gum . CONCLUSION We conclude that in intrahepatic cholestasis of pregnancy and pruritus , guar gum treatment is beneficial in relieving pruritus , even although indicators of cholestasis are only partially reduced To assess the validity of two techniques used to measure human cholesterol synthesis , the rate of uptake of deuterium ( D ) into plasma free cholesterol ( FC ) , and plasma cholesterol precursor ( squalene , lanosterol , desmosterol and lathosterol ) levels were compared in 14 women [ 65–71 yr with low density lipoprotein-cholesterol (LDL-C)≥3.36 mmol·l−1 ] . Subjects consumed each of six diets for 5-wk periods according to a r and omized crossover design . The experimental diets included a baseline diet ( 39 % energy as fat , 164 mg chol·4.2 MJ−1 ) and five reduced-fat diets ( 30 % of energy as fat ) , where two-thirds of the fat was either soybean oil ; squeeze , tub or stick margarines ; or butter . Fractional and absolute synthesis rates ( FSR and ASR ) of FC were determined using the deuterium incorporation ( DI ) method , while cholesterol precursor levels were measured using gas-liquid chromatography . Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present . There was good agreement among levels of the various cholesterol precursors . In addition , FSR in pools/d ( p·d−1 ) and ASR in grams/d ( g·d−1 ) were strongly associated with lathosterol ( r=0.72 and 0.71 , P=0.0001 ) , desmosterol ( r=0.75 and 0.75 , P=0.0001 ) , lanosterol ( r=0.67 and 0.67 ) , and squalene ( r=0.69 and 0.68 ) when levels of the precursors were expressed as μmol·mmol−1C . Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts ( μmol·L−1 ) . The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods . In conclusion , the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis Background This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease ( NAFLD ) with hypercholesterolemia . Methods Serum sample s of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated .  Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC – MS)/MS . These data were then compared with those of 36 sex- and age-matched healthy controls . In addition , changes in these markers produced by treatment with pitavastatin were evaluated . Results Serum non-cholesterol sterols , reflecting intestinal cholesterol absorption , were significantly lower in the NAFLD patients compared to the controls , and the cholesterol synthesis marker , the ratio of lathosterol to cholesterol , was not significantly different between the two groups . Serum proportions of liver X receptor α ( LXRα ) lig and oxysterols ( ratios to cholesterol ) were significantly elevated in the NAFLD patients compared to the controls . The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance ( HOMA-IR ) were significantly correlated . The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment , from 3 months after initiation of the treatment , and the suppression remained significant during the observation period . The markers representing cholesterol absorption were unchanged at 3 months , but had significantly increased at 12 months . Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment . Conclusions : We speculate that serum LXRα lig and oxysterol levels ( relative to cholesterol ) could be surrogate markers of insulin resistance , and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD BACKGROUND Because of hyperglycemia and hyperinsulinemia , diabetic persons have higher cholesterol synthesis and lower cholesterol absorption rates than do nondiabetic persons . Differences in plant sterol efficacy between diabetic and nondiabetic persons have not been examined . OBJECTIVE The objective was to compare the degree of response of plasma lipid concentrations and glycemic control to plant sterol consumption in a controlled diet between hypercholesterolemic type 2 diabetic and nondiabetic subjects . DESIGN Fifteen nondiabetic subjects and 14 diabetic subjects participated in a double-blinded , r and omized , crossover , placebo-controlled feeding trial . The diet included 1.8 g/d of either plant sterols or cornstarch placebo over 21 d , separated by a 28-d washout period . RESULTS Plant sterol consumption significantly reduced ( P < 0.05 ) LDL-cholesterol concentrations from baseline in both nondiabetic and diabetic subjects by 15.1 % and 26.8 % , respectively . The diabetic subjects had significantly ( P < 0.05 ) lower absolute concentrations of total cholesterol after treatment than did the nondiabetic subjects ; however , there was no significant difference in the percentage change from the beginning to the end of the trial . There was also a significant decrease ( P < 0.05 ) in absolute non-HDL-cholesterol concentrations after treatment in both groups . CONCLUSIONS The results showed that plant sterols are efficacious in lowering LDL cholesterol and non-HDL cholesterol in both diabetic and nondiabetic persons .  Plant sterol consumption may exist as a dietary management strategy for hypercholesterolemia in persons with type 2 diabetes The physiological roles of phytosterols in chronic inflammation , which are believed to be involved in the underlying mechanisms for metabolic diseases , have yet to be eluci date d. Therefore , in the present study , we aim ed to eluci date the physiological roles of phytosterols in both clinical studies and animal experiments . We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects ( n=46 ) and non-diabetic subjects ( n=178 ) . Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels . When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet , we observed that the increase in body weight , the fatty liver changes , and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake . We also observed that the plasma IL-6 and TNF-α levels , the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6 , TNF-α , and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice . These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease . Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol  have been measured in 25 patients ( either normocholesterolemic or hypercholesterolemic ) with primary biliary cirrhosis and in control subjects . To evaluate cholesterol synthesis , serum levels of lathosterol were measured , and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols . In normocholesterolemic patients with primary biliary cirrhosis , lathosterol was significantly lower than in normocholesterolemic controls ( P < 0.05 ) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls . Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls ( P < 0.01 ) . In patients with primary biliary cirrhosis , serum 7alpha-hydroxycholesterol was slightly higher than in controls . 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls ( P < 0.05 ) and a significant linear correlation ( r = 0.771 ; P < 0.001 ) was found between 27-hydroxycholesterol and cholesterol . In contrast , in patients with primary biliary cirrhosis , high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol . Our data confirm that in patients with primary biliary cirrhosis , cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7alpha-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients . acids via the acidic pathway Phytosterol intake with natural foods , a measure of healthy dietary choices , increases plasma levels , but increased plasma phytosterols are believed to be a coronary heart disease ( CHD ) risk factor . To address this paradox , we evaluated baseline risk factors , phytosterol intake  , and  plasma noncholesterol sterol levels  in participants of a case control study nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) Spanish cohort who developed CHD ( n = 299 ) and matched controls ( n = 584 ) who remained free of CHD after a 10 year follow-up .  Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake ( P = 0.026 ) . HDL-cholesterol level increased , and adiposity measures , cholesterol/HDL ratios , and levels of glucose , triglycerides , and lathosterol , a cholesterol synthesis marker , decreased across plasma sitosterol tertiles ( P < 0.02 ; all ) . Compared with controls , cases had nonsignificantly lower median levels of phytosterol intake and plasma sitosterol . The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 ( 95 % confidence interval , 0.36–0.97 ) . Associations were weaker for plasma campesterol . The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols . The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort , a population with a high phytosterol intake Background Gallstone disease ( GD ) has been associated with low serum levels of plant sterols . We evaluated the impact of laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and non-alcoholic fatty liver disease ( NAFLD ) on the association of GD with low levels of serum plant sterols . Methods Two hundred forty-two consecutive morbidly obese patients were recruited to this prospect i ve study . Histological analysis of liver biopsy to diagnose NAFLD was performed . Bile sample was taken during the LRYGB . Associations of GD with serum non-cholesterol sterol to cholesterol ratios , measured using gas liquid chromatography and with mRNA expression of genes participating in the cholesterol , bile , and fatty acid metabolism in the liver , were analyzed . Results Out of the 242 participants , 95 had GD .  Lower weight ( p = 0.002 ) and female sex ( p = 0.0006 ) were associated with GD . Serum plant sterols , campesterol ( p = 0.003 ) , sitosterol ( p = 0.002 ) , and avenasterol ( p = 0.015 ) , were lower in patients with GD compared to those without GD . This association remained significant after adjustment for NAFLD , use of statin medication , and previous laparoscopic cholecystectomy ( LCC ) . Levels of sitosterol ( p = 0.001 ) and campesterol ( p = 0.001 ) remained lower in obese individuals with GD also after obesity surgery . Liver mRNA expression of genes regulating cholesterol synthesis and bile metabolism was increased in individuals with GD . Conclusions Serum plant sterols were lower in patients with GD independent of NAFLD , history of LCC , use of statin medication , and weight loss after LRYGB . Low serum plant sterols in patients with GD suggest potentially inherited alterations in sterol absorption and biliary transport in subjects susceptible for GD BACKGROUND / AIMS Cholesterol gallstone disease is often associated with an increased biliary secretion rate of cholesterol , which may be due to abnormalities in hepatic cholesterol metabolism . The aim of the present study was to investigate whether gallstone subjects may have an underlying defect in hepatic cholesterol and bile acid formation . METHODS In 41 asymptomatic gallstone subjects , r and omly selected from a population of both sexes 40 and 60 years of age , and in 72 age- and sex-matched controls , plasma levels of lathosterol ( reflecting hepatic HMG CoA reductase activity ) and 7alpha-hydroxy-4-cholesten-3-one ( reflecting cholesterol 7alpha-hydroxylase activity ) were analysed . In a subgroup of gallstone subjects and controls , plasma levels of 27-hydroxy cholesterol were also determined . RESULTS The gallstone subjects had normal plasma levels of cholesterol but displayed 20 - 25 % higher plasma levels of triglycerides compared with the controls . The plasma level of lathosterol was not significantly different between the two groups of subjects whereas the plasma level of 7alpha-hydroxy-4-cholesten-3-one was about 40 % higher in the gallstone subjects compared with the controls . Positive correlations were obtained between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and triglycerides in both groups of subjects . The plasma level of 27-hydroxy cholesterol was similar in gallstone subjects and controls . CONCLUSIONS The previously reported hypersecretion of cholesterol in gallstone patients is not due to a single metabolic defect leading to increased hepatic synthesis of cholesterol or decreased catabolism of cholesterol to bile acids via 7alpha-hydroxylation or 27-hydroxylation of cholesterol To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols , these noncholesterol sterols , fatty acids , and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a r and omly selected Finnish male population sample of 100 subjects , aged 50 years , who had normal dietary habits .  Serum levels of cholesterol precursors , desmosterol and lathosterol  ( in terms of micrograms/mg cholesterol ) , were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein ( HDL ) cholesterol , and positively related to overall cholesterol synthesis and serum very low density lipoprotein ( VLDL ) cholesterol . Serum levels of the plant sterols , campesterol and sitosterol , exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat , the linoleic acid contents of plasma and dietary lipids , the amount of dietary plant sterols ( as indicated by fecal output ) , fractional and absolute absorption of dietary cholesterol , and HDL cholesterol , but were inversely related to the overall cholesterol synthesis and VLDL cholesterol . Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption , dietary plant sterols , and biliary cholesterol secretion , and that of sitosterol with dietary plant sterols , cholesterol synthesis , fractional cholesterol absorption , and biliary cholesterol secretion . Thus , the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and , since gas liquid chromatographic determination of these sterols is quite simple , their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus ( GDM ) . Pregnant women at risk for GDM ( BMI > 30 kg/m2 ) were enrolled from maternity clinics in Finl and . GDM was determined from the results of an oral glucose tolerance test . Serum sample s were collected at six time-points , one in each trimester of pregnancy , and at 6 weeks , 6 months , and 12 months postpartum . Analysis of serum squalene and noncholesterol sterols  by gas-liquid chromatography revealed that in subjects with GDM ( n = 22 ) , the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher ( P < 0.05 ) than in the controls ( n = 30 ) in the first trimester , reflecting increased cholesterol synthesis . Also , subjects with GDM had an increased ratio of squalene to cholesterol ( 100 × μmol/mmol of cholesterol ) in the second ( 11.5 ± 0.5 vs. 9.1 ± 0.5 , P < 0.01 ) and third ( 12.1 ± 0.8 vs. 10.0 ± 0.7 , P < 0.05 ) trimester . In GDM , the second trimester maternal serum squalene concentration correlated with neonatal birth weight ( r = 0.70 , P < 0.001 ) . In conclusion , in obesity , GDM associated with elevated serum markers of cholesterol synthesis . Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM To gain further insight into the effects of insulin on cholesterol synthesis in humans , 19 newly insulin-treated diabetic patients were studied before any insulin treatment ( study day 1 ) and after a few days of optimized glycemic control with a continuous intravenous insulin infusion ( study day 2 ) . The patients were divided into two groups according to their clinical characteristics and laboratory disorders . Groups I and II consisted , respectively , of 10 newly diagnosed type I diabetic patients and nine type II diabetic patients with secondary failure to oral antidiabetic drugs .  Cholesterol synthesis was estimated from the determination of serum lathosterol , a metabolic precursor in the cholesterol pathway , and from the serum lathosterol to cholesterol ratio . Serum cholesterol ( millimolar , mean + /- SEM ) remained unchanged in both groups . After insulin therapy ( study day 2 ) , serum lathosterol ( micromolar ) and the serum lathosterol to cholesterol ratio ( molar ratio x 10(3 ) ) were significantly increased as compared with baseline ( study day 1 ) . Serum lathosterol levels were as follows : 9.9 + /- 2.0 versus 4.1 + /- 0.4 ( P < .02 ) in group I , and 9.9 + /- 0.8 versus 5.7 + /- 0.7 ( P < .005 ) in group II ; serum lathosterol to cholesterol ratios were 2.10 + /- 0.39 versus 0.86 + /- 0.11 ( P < .005 ) in group I , and 1.92 + /- 0.12 versus 0.98 + /- 0.10 ( P < .001 ) in group II . The data indicate that in newly insulin-treated diabetic patients , short-term intensive insulin therapy has a stimulatory effect on cholesterol synthesis and even results in cholesterol overproduction Results of previous studies have shown that ezetimibe ( 10 mg/day ) reduces LDL cholesterol in patients with mild hypercholesterolemia on a normal-cholesterol diet ( dietary intake of 200–500 mg/day ) by 16–22 % . However , the LDL cholesterol-lowering effect of ezetimibe in subjects with an extremely low dietary cholesterol intake ( vegetarians ) has not been studied . We conducted a r and omized , double-blind , placebo-controlled , two-phase crossover study in 18 healthy pure vegetarians to assess the effect of ezetimibe ( 10 mg/day ) on plasma lipids , cholesterol absorption , and its synthesis . Treatment periods lasted 2 weeks each , with an intervening 2 week washout period . Fractional cholesterol absorption was determined using the continuous dual stable isotope feeding method . Mean dietary cholesterol intake in the pure vegetarians was extremely low and averaged 29.4 ± 16.8 and 31.4 ± 14.4 mg/day during the placebo and ezetimibe administration phases , respectively . Fractional cholesterol absorption during the placebo phase was 48.2 ± 8.2 % and was decreased by 58 % during ezetimibe treatment to 20.2 ± 6.2 % ( P < 0.001 ) . This change in intestinal cholesterol absorption was followed by a significant reduction in LDL cholesterol of 17.3 % . In individuals with extremely low dietary cholesterol intake , treatment with ezetimibe ( 10 mg/day ) leads to a significant reduction of cholesterol absorption and a clinical ly relevant decrease of plasma LDL cholesterol , comparable to that of subjects with a normal dietary cholesterol intake . Thus , the lipid-lowering effect of ezetimibe is mediated mainly through a reduction of the absorption of endogenous ( biliary ) cholesterol Cholesterol homeostasis , defined as the balance between absorption and synthesis , influences circulating cholesterol concentrations and subsequent coronary heart disease ( CHD ) risk . Statin therapy targets the rate-limiting enzyme in cholesterol bio synthesis and is efficacious in lowering CHD events and mortality . Nonetheless , CHD events still occur in some treated patients . To address differences in outcome during pravastatin therapy ( 40 mg/day ) , plasma markers of cholesterol synthesis ( desmosterol , lathosterol ) and fractional cholesterol absorption ( campesterol , sitosterol ) were measured , baseline and on treatment , in the Prospect i ve Study of Pravastatin in the Elderly at Risk trial participants with ( cases , n = 223 ) and without ( controls , n = 257 ) a CHD event .  Pravastatin therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL-cholesterol concentrations to a similar extent in cases and controls . Decreased concentrations of the cholesterol synthesis markers desmosterol ( −12 % and −11 % ) and lathosterol ( −50 % and −56 % ) and increased concentrations of the cholesterol absorption markers campesterol ( 48 % and 51 % ) and sitosterol ( 25 % and 26 % ) were observed on treatment , but the magnitude of change was similar between cases and controls . These data suggest that decreases in cholesterol synthesis in response to pravastatin treatment were accompanied by modest compensatory increases in fractional cholesterol absorption . The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment BACKGROUND The rise in LDL with egg feeding in lean insulin-sensitive ( LIS ) participants is 2- and 3-fold greater than in lean insulin-resistant ( LIR ) and obese insulin-resistant ( OIR ) participants , respectively . OBJECTIVE We determined whether differences in cholesterol absorption , synthesis , or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis . DESIGN Plasma sterols were measured by gas chromatography-mass spectrometry in a r and om subset of 34 LIS , 37 LIR , and 37 OIR participants defined by the insulin sensitivity index ( S(I ) ) and by BMI criteria selected from a parent group of 197 participants . Cholestanol and plant sterols provide a measure of cholesterol absorption , and lathosterol provides a measure of cholesterol synthesis . RESULTS The mean ( ±SD ) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS , 3.25 ± 1.06 in LIR , and 2.82 ± 1.08 in OIR participants . After adjustment for age and sex , the relations of the absorption sterol-cholesterol ratios were as follows : LIS > OIR ( P < 0.001 ) , LIS > LIR ( P < 0.001 ) , and LIR > OIR ( P = 0.11 ) . Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants , 0.95 ± 0.47 in the LIR participants , and 1.29 ± 0.55 in the OIR participants . After adjustment for age and sex , the relations of lathosterol-cholesterol ratios were as follows : LIS < OIR ( P < 0.001 ) , LIS < LIR ( P = 0.03 ) , and LIR < OIR ( P = 0.002 ) . Total sterol concentrations were positively associated with S(I ) and negatively associated with obesity , whereas lathosterol correlations were the opposite . CONCLUSIONS Cholesterol absorption was highest in the LIS participants , whereas cholesterol synthesis was highest in the LIR and OIR participants . Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I ) and to decrease cholesterol overproduction in LIR and OIR persons Objective : The purpose of this study was to determine whether supplements of plant sterols and /or glucomannan improve lipid profile and cholesterol bio synthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments . Design : A r and omized , crossover study consisting of four phases of 21 days , with each phase separated by a 28-day washout . Setting : The Mary Emily Clinical Nutrition Research Unit of McGill University . Subjects : Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38–74 years . Interventions : Subjects were supplemented with plant sterols ( 1.8 g/day ) , glucomannan ( 10 g/day ) , a combination of glucomannan and plant sterols , and a placebo , provided in the form of bars . Results : Overall plasma cholesterol concentrations were lowered ( P<0.05 ) after combination treatment ( 4.72±0.20 mmol/l ) compared to control ( 5.47±0.18 mmol/l ) . Plasma low-density lipoprotein ( LDL ) cholesterol concentrations were decreased ( P<0.05 ) after glucomannan ( 3.16±0.14 mmol/l ) and combination treatments ( 2.95±0.16 mmol/l ) compared to control ( 3.60±0.16 mmol/l ) . The results of lipid profiles did not differ between subject groups . Overall plasma lathosterol concentrations , an index of cholesterol bio synthesis , were lowered ( P<0.05 ) after the combination treatment compared to the plant sterol treatment . Conclusions : The results suggest that glucomannan and a combination of glucomannan and plant sterols substantially improves plasma LDL cholesterol concentrations . Sponsorship : Forbes Medi-Tech Inc. , Vancouver , British Columbia , Canada To date , there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus ( T2DM ) . In this study , we recruited patients for hypercholesterolemic groups with T2DM ( n = 42 ; men/women = 24/18 ; HbA1c = 6.7 ± 5.4 % ) and without T2DM ( n = 21 ; men/women = 7/14 ; HbA1c = 5.3 ± 0.4 % ) . Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study . At baseline and after 12 weeks of treatment , several lipid parameters , including serum low-density-lipoprotein cholesterol ( LDL-C ) , non-high-density-lipoprotein cholesterol ( non-HDL-C ) , high-sensitivity C-reactive protein ( hs-CRP ) , and cholesterol synthesis /absorption-related markers , were measured . Compared with those at the baseline , the levels of LDL-C , non-HDL-C , campesterol , and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups . After adjusting for confounding factors , such as age , gender , smoking , and BMI , the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM ( -25.1 ± 13.6 % in LDL-C , -20.5 ± 11.2 % in non-HDL-C ) than those without T2DM ( -20.5 ± 7.8 % in LDL-C , P < 0.05 ; -17.4 ± 7.6 % in non-HDL-C , P < 0.05 ) . The reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM . Taken together , these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM BACKGROUND AND AIM Sitosterolemia , a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations , is associated with premature atherosclerosis in some individuals . This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events . METHODS AND RESULTS A nested case-control study using stored sample s from male participants in the Prospect i ve Cardiovascular Münster ( PROCAM ) study was performed . Each of 159 men who suffered a myocardial infa rct ion or sudden coronary death ( major coronary event ) within 10 years of follow-up in PROCAM was matched with 2 controls ( N = 318 ) by age , smoking status , and date of investigation . Analysis was performed using conditional logistic regression . Plasma sitosterol concentrations were elevated in cases compared with controls ( 4.94 + /- 3.44 micromol/L versus 4.27 + /- 2.38 micromol/L ; P = 0.028 ) . The upper quartile of sitosterol ( > 5.25 micromol/L ) was associated with a 1.8-fold increase in risk ( P < 0.05 ) compared with the lower three quartiles . Among men with an absolute  coronary risk > or = 20 % in 10 years as calculated using the PROCAM algorithm , high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events ( P = 0.032 ) ; a similar , significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk ( P = 0.030 ) . CONCLUSIONS Elevations in sitosterol concentrations and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease . Further evaluations are warranted to confirm these preliminary findings Some studies have suggested that a modest increase of plant sterol levels is a risk factor for coronary artery disease ( CAD ) . We studied the relationship between plant sterol levels and CAD risk in a prospect i ve nested case-control study consisting of 373 cases and 758 controls . Sitosterol and campesterol concentrations did not differ between cases and controls [ sitosterol , 0.21 vs. 0.21 mg/dl ( P = 0.1 ) ; campesterol , 0.31 vs. 0.32 mg/dl ( P = 0.5 ) ] . The sitosterol-to-cholesterol ratio was significantly lower in cases than in controls ( 1.19 vs. 1.29 μg/mg ; P = 0.008 ) , whereas the campesterol-to-cholesterol ratio did not differ significantly ( 1.78 vs. 1.88 μg/mg ; P = 0.1 ) . Plant sterol concentrations correlated positively with cholesterol levels and inversely with body mass index and triglyceride and lathosterol concentrations . Among individuals in the highest tertile of the sitosterol concentration , the unadjusted odds ratio ( OR ) for future CAD was 0.75 [ 95 % confidence interval ( CI ) = 0.56–1.01 ] . After adjustment for traditional risk factors , the OR was 0.79 ( 95 % CI = 0.56–1.13 ) . For the campesterol concentration , the unadjusted OR was 0.95 ( 95 % CI = 0.71–1.29 ) and the adjusted OR was 0.97 ( 95 % CI = 0.68–1.39 ) . In this large prospect i ve study , higher levels of plant sterols , at least in the physiological range , do not appear to be adversely related to CAD in apparently healthy individuals The differences in cholesterol metabolism after the 2 most common forms of obesity surgery , Roux-en-Y gastric bypass ( RYGB ) and gastric b and ing ( 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 nonr and omized 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
target: In general , markers for cholesterol absorption and synthesis displayed reciprocal patterns , showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis .
  Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified , suggesting that metabolic disorders can be classified as ' cholesterol absorbers or cholesterol synthesizers ' .
background: Non-cholesterol sterols are vali date d biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis .
  However , their use in metabolic disturbances has not been systematic ally explored .
  Therefore , we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders .