human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
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 ' .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    