Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Dietary sitostanol related to absorption, synthesis and serum level of cholesterol in different apolipoprotein E phenotypes. Exercise enhances whole-body cholesterol turnover in mice. Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity. Serum Plant Sterols Associate with Gallstone Disease Independent of Weight Loss and Non-Alcoholic Fatty Liver Disease Effects of soybean protein and very low dietary cholesterol on serum lipids, biliary lipids, and fecal sterols in humans. Dietary squalene increases cholesterol synthesis measured with serum non-cholesterol sterols after a single oral dose in humans. Efficacy of ezetimibe as monotherapy or combination therapy in hypercholesterolemic patients with and without diabetes. Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in hypercholesterolemic type 2 diabetic and nondiabetic persons. Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters in hypercholesterolaemic subjects. The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia. Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid. Optimizing the effect of plant sterols on cholesterol absorption in man. Decreased Plasma Cholesterol Concentrations After PUFA-Rich Diets are not Due to Reduced Cholesterol Absorption/Synthesis Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant women: effects on serum cholestanol and other non-cholesterol sterols. The role of soluble fiber intake in patients under highly effective lipid-lowering therapy Serum cholestanol, cholesterol precursors, and plant sterols during placebo-controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine. Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels. Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway. Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds Cholesterol absorption decreases after Roux-en-Y gastric bypass but not after gastric banding. Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes
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 Effects of small amounts of sitosterol , sitostanol and sitostanol esters ( < 1 g/day of free sterols ) dissolved in rapeseed oil ( RSO ) were studied on serum lipids and cholesterol metabolism in patients with primary hypercholesterolemia and different apolipoprotein E phenotypes on an RSO diet . One of the four groups was an RSO-fed control .  Serum total and LDL cholesterol reductions were small in different plant sterol-fed groups , tended to be highest in the sitostanol ester group ( -7 % ) , but were significantly reduced by about 5 % in the combined plant sterol groups . The reductions were -8 % in the subjects with epsilon 4 allele and insignificant in those with apo E3/3 phenotype . Cholesterol precursor sterols in serum , markers of cholesterol synthesis , were increased only in the subjects with epsilon 4 allele . Cholesterol absorption was reduced by 7 % , being 31 % in the subjects with epsilon 4 allele , and fecal elimination of cholesterol was increased , a finding also indicating increased cholesterol synthesis . The changes in cholesterol absorption were related to those in fecal plant sterols ( change in dietary intake ) and serum total and LDL cholesterol ( P = 0.04 , 0.01 and 0.05 , respectively ) . Thus , small amounts of dietary plant sterols ( < 1 g/day ) , especially sitostanol esters dissolved in dietary fats , decrease serum total and LDL cholesterol by a proportional decrease in cholesterol absorption which , in turn , is associated with a compensatory increase in cholesterol synthesis . The effects are most consistent in subjects with epsilon 4 allele , but for effective hypocholesterolemic treatment dietary amount of sitostanol ester should exceed 1 g/day PURPOSE Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels , but the underlying mechanisms have not been fully explored . Exercise might provoke changes in cholesterol and bile acid metabolism and thereby reduce cardiovascular risk . We examined whether voluntary wheel running in mice modulates cholesterol and bile acid metabolism . METHODS Male mice ( 10 wk old ) were r and omly assigned to have access to a voluntary running wheel for 2 wk ( RUN group ) or remained sedentary ( SED group ) . Running wheel activity was recorded daily . In a first experiment , fecal sterol outputs , fecal bile acid profiles , plasma parameters , and expression levels of genes involved in cholesterol and bile acid metabolism were determined . In a second experiment , bile flow , biliary bile acid profile , and biliary secretion rates of cholesterol , phospholipids , and bile acids were determined . RESULTS The RUN group ran an average of 10 km.d and displayed lower plasma cholesterol compared with SED ( P = 0.030 ) . Fecal bile acid loss was induced by approximately 30 % in running mice compared with SED ( P = 0.0012 ) . A approximately 30 % increase in fecal cholesterol output in RUN ( P = 0.014 ) was consistent with changes in parameters of cholesterol absorption , such as reduced plasma plant sterol-cholesterol ratio ( P = 0.044 ) and decreased jejunal expression of Npc1l1 ( P = 0.013 ) . Supportive of an increased cholesterol synthesis to compensate for fecal sterol loss were increased hepatic mRNA levels of HMGCoA reductase ( P = 0.006 ) and an increased plasma lathosterol-cholesterol ratio ( P = 0.0011 ) in RUN . CONCLUSIONS Voluntary wheel running increased cholesterol turnover in healthy mice owing to an increased fecal bile acid excretion and a decreased intestinal cholesterol absorption . Enhanced cholesterol turnover may contribute to the established reduction of cardiovascular risk induced by regular exercise 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 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 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 Soy-base texturized vegetable protein ( TVP ; Archer Daniels Midl and , Decatur , IL ) has been used to decrease serum cholesterol and as a substitute for animal protein to achieve very low levels of dietary cholesterol . The effect of very low dietary cholesterol and of TVP on biliary lipids and fecal sterols is unclear . The study objective was to determine the effects of very low intake of dietary cholesterol , as well as TVP itself , on serum lipids , biliary lipids , and fecal sterols . We studied eight normal subjects living on a metabolic ward during three r and omly ordered 6- to 7-week periods : ( 1 ) st and ard cholesterol diet ( 190 to 550 mg/d ) , ( 2 ) TVP-low-cholesterol diet ( 17 to 30 mg/d ) , and ( 3 ) TVP-st and ard cholesterol diet .  By analysis of covariance ( ANCOVA ) , reducing dietary cholesterol to these very low levels significantly decreased serum low-density lipoprotein ( LDL ) cholesterol ( P=.048 ) but did not affect high-density lipoprotein ( HDL ) cholesterol or triglyceride . TVP result ed in a borderline significant reduction in LDL cholesterol ( P=.058 ) with a highly significant reduction in HDL cholesterol ( P=.004 ) and an increase in serum triglyceride ( P=.010 ) . During TVP ingestion , there was a highly significant increase in the output of fecal neutral sterols ( P=.005 ) and a tendency for a higher output of fecal acidic sterols ( P=.100 ) . Fecal sterol balance was significantly more negative ( indicating increased cholesterol synthesis ) during TVP ingestion ( P=.016 ) . Neither TVP nor the very-low-cholesterol diet appreciably affected the gallbladder bile molar percent cholesterol or saturation index . The data are consistent with the hypothesis that to the extent TVP decreases serum LDL cholesterol ( an effect of borderline significance in this study ) , the effect occurs via a reduction in the absorption of cholesterol and perhaps bile acid . However , the potential benefit of decreasing LDL cholesterol in this way seems to be at least partially offset by a concomitant reduction in HDL cholesterol and an increase in serum triglycerides Studies considering long-term squalene consumption have revealed no consistent effects on serum cholesterol levels but the immediate effect of dietary squalene on cholesterol synthesis has not been studied . Thus , the effect of a single dose of dietary squalene on postpr and ial lipid metabolism was studied in 16 male volunteeers aged 22 - 79 years .  Two oral fat meals a week apart were administered to every subject , one without ( control ) and the other with 500 mg of squalene . Lipids , retinyl palmitate , squalene and non-cholesterol sterols  were measured at baseline and after 3 , 4 , 6 , 9 , 12 and 24 h postpr and ially in plasma , chylomicron , VLDL and VLDL bottom and , in six r and omly chosen subjects , also in IDL , LDL and HDL . In the fasting sample s , squalene was mainly transported in LDL and HDL , whereas in squalene-supplemented postpr and ium most of squalene was carried in the triglyceride-rich lipoproteins . Postpr and ial squalene and retinyl palmitate curves closely resembled each other . After the squalene-enriched dietary fat load , squalene was significantly increased compared to control fat loads in plasma , chylomicrons , VLDL and IDL . Squalene addition increased significantly lathosterol/campesterol ratio in chylomicrons and VLDL at 12 h and in VLDL bottom at 9 - 12 h , and increased significantly VLDL lanosterol/campesterol ratio at 12 h , indicating enhanced cholesterol synthesis caused by squalene . Plasma plant sterol levels remained unchanged . In conclusion , a single oral dose of squalene representing a potential daily dietary amount increases cholesterol synthesis within 9 - 12 h detected in chylomicrons , VLDL and VLDL bottom Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone ( monotherapy ) and along with common lipid-regulating agents ( combination therapy ) . To evaluate the effect of ezetimibe therapy on the lipid profile , glucose metabolism , and levels of cholesterol absorption and synthesis markers , we administered 10 mg ezetimibe to 50 hypercholesterolemic patients with or without diabetes . The serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly reduced at 4 and 12 weeks of ezetimibe therapy in diabetic patients of both the monotherapy and combination-therapy groups and in nondiabetic patients of the combination-therapy group . The serum levels of the cholesterol absorption markers were significantly reduced , while those of the cholesterol synthesis markers were significantly increased at 12 weeks of ezetimibe therapy . No significant differences were noted in the values of the parameters of glucose metabolism in all patients . We also investigated the clinical characteristics of patients who exhibited a good response to ezetimibe  ( ezetimibe responders ) ; however , multivariate regression analysis did not reveal a correlation between ezetimibe efficacy and patient characteristics such as gender , age , BMI , diabetic condition , method of ezetimibe administration , and the initial absolute values of cholesterol absorption/ synthesis markers levels . In conclusion , ezetimibe therapy significantly improved the lipid profile without disturbing glucose metabolism . We were unable to identify the specific characteristics of ezetimibe responders among our subjects . However , we may interpret this result as suggesting that ezetimibe can be used in any population to lower low-density lipoprotein cholesterol levels 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 1 . Serum cholesterol reduction and changes in cholesterol metabolism were studied during rapeseed oil feeding without and with increasing amounts of sitostanol trans-esterified with rapeseed oil fatty acids and dissolved in rapeseed oil mayonnaise .  Fifteen mildly hypercholesterolaemic subjects replaced 50 g of their usual dietary fat by 50 g of rapeseed oil fat mayonnaise for 6 weeks followed by r and omization so that eight subjects continued on rapeseed oil mayonnaise alone ( control group ) for 15 weeks and seven on rapeseed oil mayonnaise with a small dose of sitostanol ester ( 800 mg/day of sitostanol ) for 9 weeks followed by 6 weeks with higher dose of sitostanol ester ( 2000 mg/day of sitostanol ) . 2 . During the rapeseed oil period the reduction in serum low-density lipoprotein cholesterol was 14 % from the home diet . The control-adjusted reduction by the low sitostanol ester dose was 7.4 % ( not significant ) and by the higher dose it was 15.7 % . 3 . The low dose of sitostanol ester had no consistent effect on cholesterol precursors or cholestanol in serum , reduced serum levels of campesterol and sitosterol by 28.2 % and 23.6 % , respectively , and reduced cholesterol absorption efficiency significantly from 28.7 % to 23.4 % . In accordance , faecal excretion of neutral and particularly endogenous neutral sterols increased ( 16.7 % and 19.7 % , respectively ) , but faecal cholesterol elimination and cholesterol synthesis were only insignificantly increased . 4 . During the high dose of sitostanol ester the high-density lipoprotein-to low-density lipoprotein-cholesterol ratio increased . ( ABSTRACT TRUNCATED AT 250 WORDS AIM To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption , we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis , lipid and glucose metabolism , and markers of obesity and inflammation . METHODS A total of 120 patients with dyslipidemia ( 46 men ; mean age 66.5 years ) , who had not achieved the low density lipoprotein cholesterol ( LDL-C ) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy , were enrolled and additionally treated with ezetimibe ( 10 mg/day ) for 12 weeks . RESULTS Compared to the baseline , LDL-C was reduced by 19.2 % ( p<0.001 ) after ezetimibe monotherapy and by 24.7 % ( p<0.001 ) after co-administration with ezetimibe and any statin . Ezetimibe therapy decreased cholesterol absorption markers and increased a cholesterol synthesis marker . Treatment with ezetimibe reduced the fasting serum insulin level ( p<0.05 ) and HbA1c ( p<0.05 ) , increased serum adiponectin ( p<0.01 ) , and showed a significant decrease of high-sensitive C-reactive protein ( hsCRP , p<0.01 ) . No adverse events occurred during the study . CONCLUSION Thus , cholesterol absorption inhibition by ezetimibe is an important therapeutic strategy since LDL-C and cholesterol absorption markers had a positive correlation . Ezetimibe not only reduced the serum LDL-C level but also improved glucose metabolism as well as obesity and inflammation markers . These findings support the benefit of ezetimibe as a new option for the treatment of dyslipidemia Ratios of cholestanol , campesterol , and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency . Here , a possible link between these ratios and biliary secretion rates of cholesterol was investigated . Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones . Seven were treated with ursodeoxycholic acid ( UDCA ) ( 1,000 mg/d ) . Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers , who received either placebo or UDCA ( 750 mg/d ) .  Biliary cholesterol secretion was significantly lower , whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA .  A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed . In volunteers , administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios . Even 4 weeks after discontinuing UDCA administration , campesterol and sitosterol were still significantly higher than pretreatment levels , which was also true for the campesterol-cholesterol ratio after 8 weeks . The results suggest that the ratios of cholestanol , campesterol , and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates During three experimental periods , nine adults were hospitalized on a metabolic ward and fed a meal containing 500 mg of cholesterol as a component of scrambled eggs . In addition , the meal contained : 1 ) no additive , 2 ) 1 g beta-sitosterol , or 3 ) 2 g beta-sitosteryl oleate . Stools for the succeeding 5 days were analyzed to determine the percentage of the cholesterol in the test meal that was absorbed . The addition of beta-sitosterol result ed in a 42 % decrease in cholesterol absorption ; the beta-sitosteryl oleate caused a 33 % reduction . These results indicate that the judicious addition of beta-sitosterol or beta-sitosteryl oleate to meals containing cholesterol-rich foods will result in a significant decrease in cholesterol absorption , with a consequent decrease in plasma cholesterol Plasma cholesterol concentrations increase with consumption of high saturated fatty acid ( SFA ) and decrease with high polyunsaturated fatty acid ( PUFA ) diets , leading to shifts in lipid levels consistent with reduction in heart disease risk . Direct measurements of cholesterol absorption , one of the key regulators of plasma cholesterol levels , have not been performed in humans after consumption of high PUFA diets . Thus , cholesterol absorption and fractional synthesis rates ( FSRs ) were measured in 16 healthy adults ( 8 males and 9 females ) using a r and omized cross-over study with a diet containing high ( PUFA/SFA ) P/S ratio ( 2:1 ) and a low P/S ratio ( 0.5:1 ) . Cholesterol absorption and fractional cholesterol synthetic rates were measured using stable isotopes after 20 days of dietary intervention . Diet did not affect cholesterol absorption or synthesis . There was a significant decrease in plasma cholesterol concentrations ( P < 0.02 ) , specifically LDL-cholesterol ( P < 0.02 ) , without a change in HDL-cholesterol or triacylglycerol concentrations . Intraluminal cholesterol solubilization and plasma sterol ( cholesterol biosynthetic intermediates and plant sterols ) levels were not affected by diet . Thus , consumption of diets with a high P/S ratio reduces plasma total and LDL-cholesterol concentrations independent of shifts in cholesterol absorption or synthesis 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 Background It has been demonstrated that statins can increase intestinal sterol absorption . Augments in phytosterolemia seems related to cardiovascular disease . Objective We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy . Design In an open label , r and omized , parallel- design study with blinded endpoints , subjects with primary hypercholesterolemia ( n = 116 ) were assigned to receive during 12 weeks , a daily dose of 25 g of fiber ( corresponding to 6 g of soluble fibers ) plus rosuvastatin 40 mg ( n = 28 ) , rosuvastatin 40 mg alone ( n = 30 ) , sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber ( n = 28 ) , or sinvastatin 40 mg plus ezetimibe 10 mg ( n = 30 ) alone . Results The four assigned therapies produced similar changes in total cholesterol , LDL-cholesterol , and triglycerides ( p < 0.001 vs. baseline ) and did not change HDL-cholesterol . Fiber intake decreased plasma campesterol ( p < 0.001 vs. baseline ) , particularly among those patients receiving ezetimibe ( p < 0.05 vs. other groups ) , and β-sitosterol ( p = 0.03 vs. baseline ) , with a trend for lower levels in the group receiving fiber plus ezetimibe ( p = 0.07 ) . Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol ( p = 0.003 vs. other groups ) . Compared to non-fiber supplemented individuals , those treated with fibers had weight loss ( p = 0.04 ) , reduced body mass index ( p = 0.002 ) and blood glucose ( p = 0.047 ) . Conclusion Among subjects treated with highly effective lipid-lowering therapy , the intake of 25 g of fibers added favorable effects , mainly by reducing phytosterolemia . Additional benefits include improvement in blood glucose and anthropometric parameters A r and omized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis ( PBC ) on serum lipids during ursodeoxycholic acid ( URSO ) and colchicine treatments .  In addition to serum bilirubin and alkaline phosphatase ( AFOS ) , two variables considered to reflect liver function , serum lipoproteins , cholesterol precursors ( squalene , delta 8-cholestenol , lathosterol and desmosterol ) , markers of cholesterol synthesis , cholestanol and plant sterols ( campesterol and sitosterol ) , markers of liver function and cholesterol absorption , were studied before and during the treatments . Serum bilirubin was inconsistently improved by URSO , whereas improvement of AFOS values was better by URSO than colchicine , especially in patients with initially more advanced PBC . Serum total cholesterol was reduced by both drugs , very low-density lipoprotein ( VLDL ) and high-density lipoprotein ( HDL ) cholesterol by URSO .  Cholesterol precursor sterols were increased by both URSO and colchicine mainly in patients with initially less severe PBC . On the other h and , the cholestanol values were markedly increased initially , and the values were related to bilirubin during the 2-year period , were further increased in the placebo group , and reduced in the URSO and colchicine groups , so that the improvement was highest in the URSO-treated patients with the severe form of PBC . The increase of the serum plant sterols , particularly that of sitosterol , was retarded by the two drugs so that the campesterol/sitosterol ratio , which was related to serum bilirubin , was increased especially in the cases with initially more advanced PBC . ( ABSTRACT TRUNCATED AT 250 WORDS Obesity and dietary plant sterols were negatively associated with fractional absorption of dietary cholesterol in a r and om population of 63 middle-aged men . Absorbed dietary cholesterol increased linearly with the increase of dietary cholesterol intake . The higher the fractional and absolute absorption of dietary cholesterol the lower the rates of biliary secretion , fecal elimination , and cholesterol synthesis . The findings also revealed that high serum levels of total , LDL , and HDL cholesterol were associated with high cholesterol absorption and that of HDL cholesterol was associated also with low synthesis and fecal elimination of cholesterol . Thus , cholesterol absorption efficiency and absorbed dietary cholesterol significantly regulate cholesterol synthesis and elimination and are important determinants of within- population variation in the serum levels of total , LDL , and HDL cholesterol 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 Background Consumption of a cholesterol lowering dietary portfolio including plant sterols ( PS ) , viscous fibre , soy proteins and nuts for 6 months improves blood lipid profile . Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption . Objective The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins . Methods Using a parallel design study , 351 hyperlipidemic participants from 4 centres across Canada were r and omized to 1 of 3 groups . Participants followed dietary advice with control or portfolio diet . Participants on routine and intensive portfolio involved 2 and 7 clinic visits , respectively , over 6 months . Results No changes in plasma concentrations of α and γ tocopherol , lutein , lycopene and retinol , but decreased β-carotene concentrations were observed with intensive ( week 12:p = 0.045 ; week 24:p = 0.039 ) and routine ( week 12:p = 0.031 ; week 24:p = 0.078 ) portfolio groups compared to control . However , cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control . Plasma PS concentrations were increased with intensive ( campesterol : p = 0.012 ; β-sitosterol : p = 0.035 ) and routine ( campesterol : p = 0.034 ; β-sitosterol : p = 0.080 ) portfolio groups compared to control . Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated ( p < 0.001 ) with total and LDL-C levels . Conclusion Results demonstrate that consuming a portfolio diet  reduces serum total and LDL-C levels while increasing PS values , without altering fat soluble compounds concentrations . The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health . Results indicate portfolio diet as one of the best options for CVD risk reduction . Trial registration clinical trials.gov Identifier : 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 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
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 ' .
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 .