Cholesterol Absorption Efficiency Research Articles

Efficiency of intestinal cholesterol absorption in humans is not related to apoE phenotype

The present study investigated the role of apolipoprotein E (apoE) phenotype on intestinal cholesterol absorption and cholesterol synthesis. Studies were carried out in eight subjects homozygous for the apoE4 and 12 subjects homozygous for the E2 allele (six normocholesterolemic volunteers and six patients with type III hyperlipoproteinemia). Cholesterol absorption did not differ between the three groups of subjects and averaged 38 +/- 2% (mean +/- SEM) in normolipemic E2/2, 37 +/- 4% in type III hyperlipemic E2/2, and 41 +/- 3% in E4/4 subjects, respectively. Dietary intake of fat and cholesterol had no influence on cholesterol absorption efficiency. A positive correlation between efficiency of cholesterol absorption and the ratio of campesterol to cholesterol in plasma, an indirect marker for cholesterol absorption, was observed after combining the results of the three groups (r = 0.504; P < 0.02). Bile acid and total cholesterol synthesis were also not affected by the different apoE alleles, but the well-known relationship between body weight and cholesterol synthesis was noticed (r = 0.574; P < 0.01). Thus, the present study provides evidence that the efficiency of intestinal absorption and synthesis of cholesterol in humans are not related to the apoE phenotype.

The intestinal absorption of biliary and dietary cholesterol as a drug target for lowering the plasma cholesterol level.

Elevated plasma low-density lipoprotein cholesterol levels constitute a major risk factor for coronary heart disease. The plasma low-density lipoprotein cholesterol concentration is dictated partly by the efficiency of intestinal cholesterol absorption. The efficacy of treatments designed to block cholesterol absorption is partially offset to the extent that the liver compensates for the interruption to the enterohepatic movement of cholesterol by increasing the rate at which it synthesizes cholesterol. Currently, the most widely-used treatment for hypercholesterolemia is based on a class of agents (statins) that partially inhibit cholesterol synthesis within the body. Recent clinical trials with a unique, potent, and selective cholesterol absorption inhibitor (ezetimibe) used in combination with lower doses of various statins showed an additive reduction in plasma low-density lipoprotein cholesterol levels which equaled the reduction achieved with maximal doses of statins given alone. Combination therapy using a statin and this novel cholesterol absorption inhibitor represents an efficacious new approach to the treatment of hypercholesterolemia in the general population.

Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons

Plant sterols, in various forms, have been shown to reduce total and LDL-cholesterol concentrations. Particularly controversial at present is the effect of the degree of hydrogenation of the plant sterols on cholesterol-lowering efficacy and the responsible mechanisms. Our goal was to examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentrations and cholesterol absorption, synthesis, and turnover. Fifteen otherwise healthy hypercholesterolemic subjects consumed each of 4 dietary treatments in a randomized crossover design. Unesterified sterols and stanols were blended into the butter component of the diet at a dosage of 1.8 g/d. The diets contained plant sterols (NS), plant stanols (SS), a 50:50 mixture of sterols and stanols (NSS), or cornstarch (control). Plasma total cholesterol concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS, and NSS groups, respectively, than in the control group. LDL-cholesterol concentrations were 11.3%, 13.4%, and 16.0% lower (P < 0.03) in the NS, SS, and NSS groups, respectively, than in the control group. Plasma triacylglycerols and HDL-cholesterol concentrations did not differ significantly across diets. Cholesterol absorption efficiency was 56.0%, 34.4%, and 48.9% lower (P < 0.001) in the NS, SS, and NSS groups, respectively, than in the control group. The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group. Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group. These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption.

Diabetes contributes to cholesterol metabolism regardless of obesity.

To investigate cholesterol metabolism in obesity with and without diabetes. We performed cross-sectional metabolic studies in obese individuals with and without type 2 diabetes. The study population consisted of 16 obese (BMI >30 kg/m(2)) diabetic subjects with a mean age of 52 +/- 2 years (SE) and 16 nondiabetic control subjects of similar age and weight. Cholesterol absorption efficiency was measured with peroral dual isotopes and cholesterol synthesis with sterol balance. Serum total cholesterol did not differ between the groups, but LDL and HDL cholesterol were significantly lower and VLDL cholesterol and serum total and VLDL triglycerides were higher in the diabetic group than in the control group. Cholesterol absorption efficiency was 29 +/- 1% in diabetic subjects vs. 42 +/- 2% in the control subjects (P < 0.01). Cholesterol synthesis was higher (17 +/- 1 vs. 14 +/- 1 mg. kg(-1). day(-1); P < 0.05) and neutral sterol and bile acid excretion and cholesterol turnover tended to be higher in the diabetic group than in the control group. Blood glucose was positively related to cholesterol synthesis in the diabetic group (r = +0.663, P < 0.01) and in the control group (r = +0.590, P < 0.05), suggesting that the higher blood glucose level, the higher the cholesterol synthesis. In addition, blood glucose was significantly positively related to fecal neutral sterol excretion in both groups. Cholesterol absorption efficiency was lower and cholesterol synthesis was higher in obese subjects with diabetes than in those without diabetes, suggesting that diabetes modulates cholesterol metabolism more than obesity alone.

Serum plant sterols and biliary cholesterol secretion in humans

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.

Acute effects of weight reduction on cholesterol metabolism in obese type 2 diabetes

Background: Weight reduction in obese type 2 diabetes increases the absorption efficiency of cholesterol and serum plant sterol levels from baseline. However, there is no information on the effects of acute restriction of calories and lack of dietary cholesterol and plant sterols on serum cholesterol precursor and plant sterols and on cholesterol metabolism. Thus, 10 obese (BMI>30 kg/m 2) type 2 diabetes subjects consumed very low energy diet virtually free of cholesterol, cholestanol and plant sterols for 3 months. Methods: Serum sterols were measured with gas–liquid chromatography. Results: Body weight was reduced by 15.5±1.7 kg ( p<0.001), serum cholesterol by 21±3%, triglycerides 45±5%, glucose 23±3%, insulin 59±5% and HbAIc by 8±2%, whereas serum sex hormone binding globulin increased by 108±25% ( p<0.05–0.001 for all). Serum desmosterol and lathosterol to cholesterol ratios (indicators of cholesterol synthesis) were significantly decreased by 20% suggesting that cholesterol synthesis was suppressed. Serum squalene ratio was unchanged. Despite lack of dietary plant sterols and cholestanol, serum campesterol and sitosterol ratios (indicators of cholesterol absorption efficiency) only tended to decrease, whereas serum cholestanol ratio, also an absorption indicator, was increased by 33±3% ( p<0.001), and its ratios to campesterol and sitosterol were increased by 60% and 31%, suggesting that sterol absorption efficiency might have been increased and their turnover reduced. Conclusions: In obese type 2 diabetes, restriction of calories and dietary sterols improved markedly control of diabetes, decreased serum cholesterol precursor sterols suggesting that cholesterol synthesis was decreased, but only tended to decrease serum values of plant sterols probably due to their release from the adipose tissues associated with their impaired turnover.

Genetic factors at the enterocyte level account for variations inintestinal cholesterol absorption efficiency among inbred strains of mice

Interindividual and interstrain variations in cholesterol absorptionefficiency occur in humans and animals. We investigated physiological biliaryand small intestinal factors that might determine variations in cholesterolabsorption efficiency among inbred mouse strains. We found that there weresignificant differences in cholesterol absorption efficiency measured by plasma,fecal, and lymphatic methods: <25% in AKR/J, C3H/J, and A/J strains;25–30% in SJL/J, DBA/2J, BALB/cJ, SWR/J, and SM/J strains; and31–40% in C57L/J, C57BL/6J, FVB/J, and 129/SvJ strains. In(AKR×C57L)F1 mice, the cholesterol absorption efficiency(31 ± 6%) mimicked that of the C57L parent (37 ± 5%) and wassignificantly higher than in AKR mice (24 ± 4%). Although biliary bilesalt compositions and small intestinal transit times were similar, C57L micedisplayed significantly greater bile salt secretion rates and pool sizes thanAKR mice. In examining lymphatic cholesterol transport in the setting of achronic biliary fistula, C57L mice displayed significantly higher cholesterolabsorption rates compared with AKR mice. Because biliary and intestinal transitfactors were accounted for, we conclude that genetic variations at theenterocyte level determine differences in murine cholesterol absorptionefficiency, with high cholesterol absorption likely to be a dominant trait. Thisstudy provides baseline information for identifying candidate genes thatregulate intestinal cholesterol absorption at the cellular level.—Wang, D. Q-H., B. Paigen, and M. C. Carey. Genetic factors atthe enterocyte level account for variations in intestinal cholesterol absorptionefficiency among inbred strains of mice.

Cholesterol absorption, synthesis, and fecal output in postmenopausal women with and without coronary artery disease.

Hypercholesterolemia is a prominent risk factor for coronary artery disease (CAD), yet cholesterol metabolism has not been evaluated in women with CAD. The objective of this study was to determine the interrelations of CAD, serum squalene and sterols, and cholesterol metabolism with each other in postmenopausal women. For this purpose, we measured serum squalene and sterols and fecal steroids (cholesterol and bile acids) and squalene by gas-liquid chromatography and evaluated cholesterol absorption and synthesis in postmenopausal women with CAD (n=29) and age-matched controls (n=20). On similar dietary lipid intake, the cholesterol absorption efficiency and mean serum cholesterol level were comparable, but the squalene-to-cholesterol ratio was higher in cases than in controls. The presence of CAD was inversely associated with fecal total steroids (logistic regression coefficient beta/SE=-2.11, P=0.04) and cholesterol synthesis (beta/SE=-2.14, P=0.04) and turnover (beta/SE=-2.19, P=0.03) after adjustment for dietary cholesterol, family history of CAD, smoking, low and high density lipoprotein cholesterol, and serum triglyceride levels. A high serum squalene ratio was not related to cholesterol synthesis but was inversely related to fecal squalene excretion, which was lower in cases than in controls. In conclusion, the presence of CAD in postmenopausal women is independently associated with altered cholesterol metabolism, as reflected by low synthesis and inefficient elimination of cholesterol.

Down-regulation of intestinal scavenger receptor class B, type I (SR-BI) expression in rodents under conditions of deficient bile delivery to the intestine

Scavenger receptor class B, type I (SR-BI) is expressed in the intestines of rodents and has been suggested to be involved in the absorption of dietary cholesterol. The aim of this study was to determine whether intestinal SR-BI expression is affected in animal models with altered bile delivery to the intestine and impaired cholesterol absorption. SR-BI protein and mRNA levels were determined in proximal and distal small intestine from control, bile-duct-ligated and bile-diverted rats and from control and bile-duct-ligated mice. Two genetically altered mouse models were studied: multidrug resistance-2 P-glycoprotein-deficient [Mdr2(−/−)] mice that produce phospholipid/cholesterol-free bile, and cholesterol 7α-hydroxylase-deficient [Cyp7a(−/−)] mice, which exhibit qualitative and quantitative changes in the bile-salt pool. Cholesterol-absorption efficiency was quantified using a dual-isotope ratio method. SR-BI was present at the apical membrane of enterocytes in control rats and mice and was more abundant in proximal than in distal segments of the intestine. In bile-duct-ligated animals, levels of SR-BI protein were virtually absent and mRNA levels were decreased by ≈ 50%. Bile-diverted rats, Mdr2(−/−) mice and Cyp7a(−/−) mice showed decreased levels of intestinal SR-BI protein while mRNA levels were unaffected. Cholesterol absorption was reduced by &amp;gt; 90% in bile-duct-ligated and bile-diverted animals and in Cyp7a(−/−) mice, whereas Mdr2(−/−) mice showed an ≈ 50% reduction. This study shows that SR-BI is expressed at the apical membrane of enterocytes of rats and mice, mainly in the upper intestine where cholesterol absorption is greatest, and indicates that bile components play a role in post-transcriptional regulation of SR-BI expression. Factors associated with cholestasis appear to be involved in transcriptional control of intestinal SR-BI expression. The role of SR-BI in the cholesterol-absorption process remains to be defined.

Down-regulation of intestinal scavenger receptor class B, type I (SR-BI) expression in rodents under conditions of deficient bile delivery to the intestine.

Scavenger receptor class B, type I (SR-BI) is expressed in the intestines of rodents and has been suggested to be involved in the absorption of dietary cholesterol. The aim of this study was to determine whether intestinal SR-BI expression is affected in animal models with altered bile delivery to the intestine and impaired cholesterol absorption. SR-BI protein and mRNA levels were determined in proximal and distal small intestine from control, bile-duct-ligated and bile-diverted rats and from control and bile-duct-ligated mice. Two genetically altered mouse models were studied: multidrug resistance-2 P-glycoprotein-deficient [Mdr2((-/-))] mice that produce phospholipid/cholesterol-free bile, and cholesterol 7alpha-hydroxylase-deficient [Cyp7a((-/-))] mice, which exhibit qualitative and quantitative changes in the bile-salt pool. Cholesterol-absorption efficiency was quantified using a dual-isotope ratio method. SR-BI was present at the apical membrane of enterocytes in control rats and mice and was more abundant in proximal than in distal segments of the intestine. In bile-duct-ligated animals, levels of SR-BI protein were virtually absent and mRNA levels were decreased by approximately 50%. Bile-diverted rats, Mdr2((-/-)) mice and Cyp7a((-/-)) mice showed decreased levels of intestinal SR-BI protein while mRNA levels were unaffected. Cholesterol absorption was reduced by >90% in bile-duct-ligated and bile-diverted animals and in Cyp7a((-/-)) mice, whereas Mdr2((-/-)) mice showed an approximately 50% reduction. This study shows that SR-BI is expressed at the apical membrane of enterocytes of rats and mice, mainly in the upper intestine where cholesterol absorption is greatest, and indicates that bile components play a role in post-transcriptional regulation of SR-BI expression. Factors associated with cholestasis appear to be involved in transcriptional control of intestinal SR-BI expression. The role of SR-BI in the cholesterol-absorption process remains to be defined.

Plasma cholesterol and CETP concentrations are lowered by dietary phytosterol ester but only the cholesterol variation related to the CETP 1405V polymorphism

Nutritional products containing fat-soluble phytosterol esters for serum cholesterol lowering have traditionally been oil-based. Their cholesterol-lowering efficacy when provided by low-fat vehicles with a diet of normal fat content is questionable. The aims of the present study were to find out whether 1-week consumption of plant stanol esters in pastilles alters absorption percentage of labeled esterified and free cholesterol and fecal elimination of sterols, including phytosterols (n = 9), and to define the impact of dietary fat on intestinal sterol ester hydrolysis (n = 8) in colectomized human subjects.Levels of lipoprotein cholesterol and triacylglycerols, non-cholesterol sterols and squalene in serum, neutral sterols, non-cholesterol sterols, fat and bile acids in feces, cholesterol absorption efficiency and cholesterol synthesis were analyzed at baseline and at the end of the treatment period. Analyses of esterified and free cholesterol and phytosterols were performed during diets with normal and low-fat content.Serum levels of total and low-density lipoprotein cholesterol decreased by 9% and 14%, respectively (P < 0.01 for both), and absorption of 3H-esterified and 14C-free cholesterol decreased in proportion to baseline values (r = −0.58, P < 0.05) by over 40% (P < 0.01) in colectomized patients with stanol ester pastilles. Fecal elimination of cholesterol was increased by about 35% and almost 60% of campestanol and sitostanol esters were hydrolyzed during their transit in gastrointestinal tract when consumed with a normal fat diet (mean daily fat 93 ± 13 g) for 1 week. The hydrolysis of plant stanol esters was more pronounced with a normal than with a low-fat diet (70% versus 40%, P < 0.001).We conclude that plant stanol esters provided in fat free milieu exert favourable effects on serum lipid profile by decreasing absorption of cholesterol in colectomized human subjects, even though the intestinal hydrolysis of plant stanol esters is weaker on low than normal fat diet.

Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A2-deficient mice

Numerous studies have suggested phospholipid inhibition of dietary cholesterol absorption through the gastrointestinal tract. This study addressed the importance of luminal phospholipid hydrolysis in this process. The effect of phospholipase inhibition on cholesterol transport from intestinal lumen to the lymphatics was evaluated in lymph fistula rats. Cholesterol and phospholipid absorption efficiency in intact animals was evaluated in control and phospholipase A(2) (PLA2) gene-targeted mice. The PLA2 inhibitor FPL 67047XX retarded cholesterol absorption in a lymph fistula rat model. Under basal chow-fed dietary conditions, cholesterol absorption efficiency from a single bolus meal, and plasma lipid levels, were similar among PLA2+/+, PLA2+/-, and PLA2-/- mice. Interestingly, the nonhydrolyzable phospholipid dioleoyl ether phosphatidylcholine suppressed cholesterol absorption by 10% to 18% in mice without regard to their PLA2 genotype. When 1-palmitoyl-2-[(14)C]oleoyl-phosphatidylcholine was used as the substrate, the radiolabeled phospholipid was found to be hydrolyzed and absorbed with equal efficiency in PLA2+/+, PLA2+/-, and PLA2-/- mice. These results suggested that although phospholipid digestion in the intestinal lumen is a prerequisite for efficient cholesterol absorption, additional enzyme(s) can compensate for pancreatic PLA2 in catalyzing phospholipid digestion and facilitating cholesterol absorption in PLA2 knockout mice.

Birth weight, subsequent growth, and cholesterol metabolism in children 8–12 years old born preterm

AIMSTo test the hypothesis that plasma lipids, lipoproteins, and markers of cholesterol biosynthesis (lathosterol) and absorption efficiency (campesterol) in children aged 8–12 years are related to birth size and subsequent...

Cholesterol absorption efficiency and sterol metabolism in obesity

Role of enterohepatic cholesterol metabolism in obesity-induced increase of cholesterol synthesis was studied in healthy lean (BMI <24) and overweight (BMI >31) subjects by measuring serum lipids (including plant sterols, cholestanol and cholesterol precursors), cholesterol absorption % (double-label method), sterol balance and biliary lipids. New aspects of sterol metabolism in obesity were as follows: low efficiency of cholesterol absorption, reduced ratios to cholesterol of serum and biliary plant sterols and cholestanol (5α-derivative of cholesterol), and a marked increase of serum and biliary cholesterol precursor sterols. Percent of cholesterol absorption was positively related to serum cholestanol and plant sterols, and negatively to cholesterol synthesis, measured by the sterol balance technique or cholesterol precursor sterols in serum or bile. Total and endogenous cholesterol fluxes into the intestine were increased, but owing to low absorption percent, mass of cholesterol absorption was within control limits in the obese subjects. Thus, per gram of their large liver tissue the entry of intestinal cholesterol may even be subnormal. Percent of cholesterol absorption was insignificantly negatively ( r=−0.256) related to intestinal cholesterol pool, but significantly to biliary concentrations of cholesterol ( r=−0.581), bile acids ( r=−0.513) and phospholipids ( r=−0.469). Thus, dilution of labeled dietary cholesterol by expanded intestinal cholesterol pool could have contributed to subnormal efficiency of cholesterol absorption, or transfer of labeled dietary cholesterol from intestinal oil phase to micellar phase may be competitively inhibited by expanded biliary secretion, resulting in reduced absorption of dietary cholesterol. These mechanisms could have contributed to changes in metabolism of non-cholesterol sterols, especially of cholestanol and plant sterols.

Regulation of plasma low density lipoprotein levels in postmenopausal women

To study the regulation of plasma low density lipoprotein (LDL) cholesterol in postmenopausal women ( n=79), fasting plasma lipids and lipoproteins, the fractional catabolic rate (FCR) and production rate for LDL apolipoprotein B (apo B), cholesterol absorption, apolipoprotein E phenotype and polymorphisms of the apo B and 7α-hydroxylase genes were determined. The level of LDL cholesterol was related to FCR ( r=−0.757, P<0.001) and the production ( r=0.531, P<0.001) of LDL apo B and body mass index ( r=0.265, P<0.05). In contrast, cholesterol absorption efficiency, apolipoprotein E phenotype, EcoRI and XbaI polymorphisms of the apo B gene and the polymorphism of 7α-hydroxylase gene were found to have no significance for the regulation of LDL cholesterol concentration in these postmenopausal women.

Introducing a new component of the metabolic syndrome: low cholesterol absorption

Weight reduction is the recommended treatment of obese type 2 diabetes, but the effects of weight reduction on cholesterol metabolism are poorly understood. We investigated glucose, cholesterol, and lipoprotein metabolism at baseline and 2 y after weight reduction in obese patients with type 2 diabetes consuming an isoenergetic diet. Sixteen subjects were randomly chosen to consume a very-low-energy or low-energy diet for 3 mo, after which they consumed a weight-maintenance diet for up to 2 y. Cholesterol absorption and metabolism, LDL and HDL kinetics, and variables of glucose metabolism were studied at baseline and 2 y. Baseline serum sex hormone binding globulin (SHBG) was significantly related to cholesterol absorption efficiency, and serum glucose and insulin concentrations were associated with cholesterol synthesis. After 2 y, body weight was reduced by 6 +/- 1 kg (P < 0.01), body mass index by 6% (P < 0.05), and blood glucose by 14% (P < 0.01); the ratio of serum SHBG to insulin increased by 66% (P < 0.05). Serum and VLDL, LDL, and HDL triacylglycerol were significantly reduced by 13-24%. Despite unchanged serum concentrations of cholesterol, cholesterol absorption efficiency and the ratio of serum plant sterols to cholesterol-indicators of cholesterol absorption-increased by 28% (P < 0.01) and 20-31% (P < 0. 05 for both), respectively; the fractional removal of LDL apolipoprotein B decreased. Fecal excretion of cholesterol as neutral sterols decreased significantly by 11%. Changes in body weight were significantly negatively correlated with changes in ratios of cholesterol to serum plant sterols and cholestanol. Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increased cholesterol absorption and improved variables of glucose metabolism. These results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.

Dietary Stearic Acid Reduces Cholesterol Absorption and Increases Endogenous Cholesterol Excretion in Hamsters Fed Cereal-Based Diets

The observation that dietary stearic acid does not raise plasma cholesterol concentration is well documented, although the regulating mechanisms are not completely understood. Therefore, we examined the effect of dietary stearic acid on cholesterol absorption and sterol balance using male Syrian hamsters fed modified NIH-07 cereal-based diets selectively enriched in palmitic acid (16:0), stearic acid (18:0), trans fatty acid (18:1t), cis oleic acid (18:1c) or linoleic acid (18:2). All diets contained 17 g/100 g total fat and 0.05 g/100 g cholesterol; the five fat blends were enriched 30% with the fatty acid of interest above a constant fatty acid background. Cholesterol absorption efficiency was 50-55% in all treatment groups except for the 18:0 group, in which cholesterol absorption was significantly reduced to 21%. Plasma total cholesterol concentration was significantly lower in the 18:0 group compared to the 16:0 group. Fecal neutral steroid excretion was significantly greater in hamsters fed the high 18:0 diet compared to the other treatment groups. After accounting for unabsorbed dietary cholesterol, endogenous cholesterol excretion was about 100% higher in the 18:0 group. Consequently, the calculated rate of whole body cholesterol synthesis was significantly increased by dietary 18:0. Bile acid excretion accounted for only 12-20% of total sterol output by the hamsters in this study. Thus, the data suggest that reduced plasma cholesterol concentration in hamsters fed high 18:0 diets may be influenced by reduced cholesterol absorption and increased excretion of endogenous cholesterol.

Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine

Cholesterol metabolic studies are simplified in colectomized patients because of rapid intestinal passage and reduced bacterial action. Our objective was to study the effect on cholesterol and plant sterol metabolism of feeding a margarine containing stanol ester to 11 colectomized patients. A margarine containing 2 g stanol was consumed for 7-18 d. Serum, biliary, and fecal lipids were measured before and during consumption of the margarine. Serum cholesterol concentrations and the ratio of plant sterol to cholesterol decreased after 1 d of consumption of stanol esters (P < 0.05). After 7 d, serum cholesterol decreased by 16% (P < 0.01), cholesterol absorption efficiency decreased by approximately 40%, and fecal output of cholesterol as neutral sterols (but not as bile acids) increased by 36%. Biliary bile acid composition and the molar percentage of biliary cholesterol were unchanged. Increased ratios of cholesterol precursor sterols in serum and bile indicated enhanced cholesterol synthesis during consumption of stanol esters; the percentage absorption of plant sterols and the ratios of plant sterols to cholesterol decreased, whereas serum and biliary plant stanols and their biliary secretion gradually increased. In feces, 95% of cholesterol and 90% of plant stanols were in unesterified form. In colectomized patients, effective inhibition of cholesterol absorption and lowering of serum cholesterol concentrations and plant sterol ratios occurs within 1 d of the start of consumption of stanol esters. The composition of major bile lipids is unchanged, indicating that gallstone formation is unlikely. Small amounts of plant stanols are recovered in serum and bile during consumption of stanol esters but effectively are secreted through bile, thereby balancing the intake-induced increase in their absorption.

Cholesterol absorption efficiency declines at moderate dietary doses in normal human subjects

While unphysiologically large cholesterol doses are known to reduce percent cholesterol absorption, smaller amounts are reported to have no effect in human subjects. To determine the dose–response relation between dietary cholesterol consumed and the efficiency of intestinal cholesterol absorption, we fed 18 normal subjects two test meals containing different amounts of natural cholesterol. In each test pentadeuterated cholesterol tracer was given orally, hexadeuterated cholesterol tracer was given intravenously, and the tracer ratio was measured in plasma 4 days later by gas chromatography/negative ion mass spectrometry. Baseline cholesterol absorption in the presence of 26 mg cholesterol tracer was 40.7 ± 2.3%. This decreased by 4.9 percentage points (P = 0.05) when a total of 188 mg cholesterol was included in the meal and by 15.6 percentage points (P = 0.006) when 421 mg cholesterol was given, showing that the efficiency of cholesterol absorption declines appreciably even with modest increases in cholesterol dose. Considerable variation was noted in the response of different subjects and, on the higher cholesterol dose, dietary cholesterol absorption varied 5-fold from 40 mg to 212 mg. Fasting plasma insulin was correlated with the ability to absorb higher cholesterol doses without loss of efficiency (rs = 0.700, P = 0.036).▪Percent cholesterol absorption in a single meal is significantly influenced by the amount of cholesterol in that meal, suggesting that acute dietary factors influencing cholesterol absorption need further study.—Ostlund, R. E., Jr., M. S. Bosner, and W. F. Stenson. Cholesterol absorption efficiency declines at moderate dietary doses in normal human subjects. J. Lipid Res. 1999. 40: 1453–1458.

Retinol, vitamin D, carotenes and α-tocopherol in serum of a moderately hypercholesterolemic population consuming sitostanol ester margarine

We have shown earlier that sitostanol ester margarine lowers serum cholesterol by inhibiting cholesterol absorption so that, theoretically, there could be interference with the absorption of fat-soluble vitamins. Accordingly, we investigated whether sitostanol ester margarine affects the serum levels of vitamin D, retinol, α-tocopherol and α- and β-carotenes during 1-year treatment in 102 subjects and 49 controls with moderate hypercholesterolemia. The vitamins were assayed at baseline on home diet, on margarine alone, after 1 year's consumption of sitostanol ester margarine and after an additional 2 months on home diet. In the sitostanol group, serum plant sterols, indicators of cholesterol absorption efficiency, were reduced up to −38% in relation to controls from home diet (P<0.01) indicating that cholesterol absorption was markedly reduced. Vitamin D and retinol concentrations and the ratio of α-tocopherol to cholesterol were unchanged by sitostanol ester. Serum β-carotenes and α-carotene concentration but not proportion were reduced in the sitostanol group from baseline and in relation to controls (P<0.01). Retinol and vitamin D were unassociated with serum cholesterol, plant sterols or other vitamins, whereas α-tocopherol and carotenes were significantly associated with serum plant sterols suggesting that the higher cholesterol absorption efficiency, the higher the α-tocopherol and carotene levels in serum. We conclude that sitostanol ester did not affect vitamin D and retinol concentrations and α-tocopherol/cholesterol proportion, but reduced serum β-carotene levels. α-Tocopherol and carotenes, but not vitamin D and retinol, were related to serum cholesterol and cholesterol absorption.