Effects of low-fat hard cheese enriched with plant stanol esters on serum lipids and apolipoprotein B in mildly hypercholesterolaemic subjects

OBJECTIVE: To investigate the cholesterol-lowering effects of a low-fat cheese enriched with plant stanol esters in mildly hypercholesterolaemic subjects, as part of their normal diet. DESIGN: A randomized double-blind parallel-group study. SETTING: Valio Ltd, Helsinki. SUBJECTS: Sixty-seven mildly hypercholesterolaemic volunteers (24 men, 43 women) participated in the study, which all of them completed. INTERVENTIONS: The subjects were randomly assigned to the plant stanol ester group or the control group. During the 5-week intervention, the subjects in the stanol group consumed a cheese enriched with 2 g of plant stanols per day, and the subjects in the control group, a control cheese with no plant stanols. RESULTS: In the stanol ester group, as compared to the control group, both serum total and low-density lipoprotein (LDL) cholesterol decreased significantly, that is, by 5.8% (-0.32 mmol/l, 95% CI -0.50 to -0.15 mmol/l, P < 0.001) and 10.3% (-0.36 mmol/l, 95% CI -0.53 to -0.18 mmol/l, P < 0.001), respectively. There were no significant changes in high-density lipoprotein cholesterol (HDL), triglycerides or apolipoprotein B concentrations between the groups. CONCLUSION: Cheese enriched with 2 g of plant stanol in the form of fatty acid esters decreases serum total and LDL cholesterol significantly.     

Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment

Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3-7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n 18) or plant stanol (n 19) (2.5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0.28 mmol/l (or 8.7 %; P = 0.08) and 0.42 mmol/l (13.1 %; P = 0.006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7 alpha-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.     

Simultaneous intake of beta-glucan and plant stanol esters affects lipid metabolism in slightly hypercholesterolemic subjects

Intake of food products rich in water-soluble fiber beta-glucan and products enriched with plant stanol esters lower serum cholesterol. Combining 2 functional food ingredients into one food product may achieve additional reductions of serum cholesterol. Our objective was to investigate the effects of a simultaneous intake of beta-glucan plus plant stanol esters on lipid metabolism in mildly hypercholesterolemic volunteers. In a randomized, controlled, 3-period crossover study, 40 mildly hypercholesterolemic men and women received muesli in random order twice a day for 4 wk, which provided, in total, 5 g control fiber from wheat (control muesli), 5 g oat beta-glucan (beta-glucan muesli), or 5 g oat beta-glucan plus 1.5 g plant stanols (combination muesli). beta-Glucan muesli decreased serum LDL cholesterol by 5.0% compared with control muesli (P = 0.013). Combination muesli reduced LDL cholesterol by 9.6% compared with control muesli (P < 0.001), and by 4.4% compared with beta-glucan muesli (P = 0.036). Serum HDL cholesterol and triacylglycerol concentrations did not differ after the 3 treatments. Compared with control muesli, beta-glucan muesli increased bile acid synthesis (P = 0.043) and decreased cholesterol absorption (P = 0.011). Addition of plant stanols did not influence bile acid synthesis but decreased cholesterol absorption (P < 0.001) and raised cholesterol synthesis (P = 0.016) compared with control muesli, and the plant stanols decreased cholesterol absorption compared with beta-glucan muesli (P = 0.004). The combination muesli decreased serum concentrations of sitostanol compared with control muesli (P = 0.010). Plasma concentrations of lipid-soluble antioxidants did not differ after the 3 treatments. beta-Glucan muesli effectively lowered serum LDL cholesterol concentrations. The addition of plant stanol esters to beta-glucan-enriched muesli further lowered serum LDL cholesterol, although effects were slightly less than predicted.     

Influence of polymorphisms for apolipoprotein B (ins/del,Xbal, EcoRI)and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population

A total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del, XbaI, and EcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09; X⁺, 0.1; and R^?, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy-Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between the ins/del and XbaI site polymorphisms of apo B (χ₄² = 25.3; P < 0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except for XabI, which appeared to be associated with serum TG (as the log transform: R² = 8.3; F = 4.8; P < 0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F = 5.4; P < 0.01). © 1994 Wiley-Liss, Inc.     

Carotid artery compliance in users of plant stanol ester margarine

OBJECTIVE: To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. DESIGN: Case-control study comparing regular stanol ester margarine users to non-users. SETTING: Occupational health service clinic. SUBJECTS: We recruited 50 cases and 50 controls (mean age 51+/-8, range 26-65 years). All subjects were non-smokers and the study groups were matched for age and sex. As cases, we invited subjects who had been using regularly (daily) plant stanol ester margarine for a period of 2 years or longer. Non-invasive ultrasound was used to measure carotid artery compliance, carotid intima-media thickness and brachial artery flow-mediated endothelial dependent vasodilatation. RESULTS: The carotid artery compliance was non-significantly higher in cases compared with controls, 1.84+/-1.02 vs 1.58+/-0.76 %/10 mm Hg (P=0.13). The difference in compliance became statistically significant (P=0.04) when the unbalance between the groups in family history of coronary artery disease and years of education were taken into account. There was also a significant dose-response relationship between stanol margarine use and carotid compliance, longer use being associated with higher compliance. Serum lipoproteins, blood pressure, flow-mediated dilation and intima-media thickness values did not differ between cases and controls. CONCLUSION: These data raise the possibility that regular stanol ester margarine use may be associated with beneficial changes in arterial compliance. Intervention studies are needed to test this hypothesis and to reveal possible mechanisms.     

Independent and interactive effects of apolipoprotein E phenotype and cardiorespiratory fitness on plasma lipids

PURPOSE: To examine whether the association Apolipoprotein E (Apo E) phenotype with plasma lipids is influenced by physical fitness level. Also, to explore the interactive and independent relative contributions of Apo E phenotype, fitness (or physical activity), and other modifiable factors to variation in plasma low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) levels at baseline and over a seven-year follow-up. METHODS: Physical fitness (duration of a graded treadmill test), Apo E phenotype, plasma LDL-C and HDL-C, and covariates were measured at baseline and seven years later in a bi-racial cohort of young adults, aged 18-30 years at baseline in 1985-86, from the Coronary Artery Risk Development In Young Adults (CARDIA) study. RESULTS: Fitness did not influence the associations of Apo E and LDL-C or HDL-C. The independent effects of several modifiable variables (changes in Keys' score, smoking, oral contraceptive use, education, body weight, alcohol intake, and fitness), when combined, contributed considerably more than Apo E to the variance in LDL-C changes (6.74% or 8.71% for combined modifiable variables vs. 1.27% or 0.90% for ApoE, in women or men, respectively) and HDL-C changes (13.11% or 12.66% for combined modifiable variables vs. 0.12% or 0.02% for ApoE, in women or men, respectively). The pattern of findings was similar when self-reported physical activity was substituted for fitness. CONCLUSIONS: Changes in modifiable factors, including fitness, may be stronger correlates of changes in LDL-C and HDL-C over time than the immutable factor, Apo E phenotype.     

A controlled study on the effect of beta-glucan-rich oat bran on serum lipids in hypercholesterolemic subjects: relation to apolipoprotein E phenotype.

The effects of beta-glucan-rich oat bran on serum lipids and lipoproteins were examined in a randomized 8-week study. After a 4-week run-in phase, subjects with mild to moderate hypercholesterolemia [serum total cholesterol (TC) 5.5-8.5 mmol/l] on cholesterol-lowering diets were randomly allocated to an oat bran (10.3 g beta-glucan/day) or wheat bran group. Thirty-six subjects (20 in the oat bran group, 16 in the wheat bran group) completed the study. The diet was identical in both groups during the trial and no significant changes in body weight were found. Serum TC and low-density lipoprotein cholesterol (LDL-C) significantly declined in the oat bran group during the first 4 weeks from 7.03 +/- 0.81 to 6.72 +/- 0.97 (p = 0.028) and from 4.90 +/- 0.69 to 4.61 +/- 0.89 mmol/l (p = 0.038), respectively, but at 8 weeks the values were not significantly different from baseline. Changes in serum TC were mainly confined to those who ate at least two-thirds of the planned daily dose of oat bran. In wheat bran group no changes were observed in serum TC or LDL-C levels. Apolipoprotein A1 and B did not change significantly in either group. Only subjects with apolipoprotein E 3/3 phenotype (n = 12) had hypocholesterolemic response to oat bran at 4 weeks, but no change was found in those with apolipoprotein E 4/4 or 4/3 (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet

OBJECTIVE: To investigate cholesterol-lowering effects of stanol ester (STAEST) and sterol ester (STEEST)-enriched margarines as part of a low-fat diet. DESIGN: According to a Latin square model randomized double-blind repeated measures design with three test margarines and three periods. SETTING: Outpatient clinical trial with free-living subjects. SUBJECTS: Thirty-four hypercholesterolaemic subjects completed the study. Interventions: Subjects consumed three rapeseed oil-based test margarines (STAEST, STEEST and control (no added stanols or sterols)) as part of a low-fat diet each for 4 weeks. RESULTS: Mean daily intake of total plant sterols plus stanols was 2.01-2.04 g during the two test margarine periods. In reference to control, serum total cholesterol was reduced by 9.2 and 7.3% with the STAEST and STEEST margarine, respectively (P<0.001 for both). The respective reductions for low-density lipoprotein (LDL) cholesterol were 12.7 and 10.4% (P<0. 001). The cholesterol-lowering effects of the test margarines did not differ significantly. The presence of apolipoprotein E4 allele had a significant effect on LDL cholesterol response during the STAEST margarine only. Serum sitosterol and campesterol increased by 0.83 and 2.77 mg/l with the STEEST (P<0.001), respectively and decreased by 1.18 and 2.60 mg/l with the STAEST margarine (P<0.001). Increases of serum sitostanol and campestanol were 0.11 and 0.19 mg/l with the STAEST margarine (P<0.001), repsectively. No significant changes were found in serum fat-soluble vitamin and carotenoid concentrations when related to serum total cholesterol. CONCLUSIONS: STAEST and STEEST margarines reduced significantly and equally serum total and LDL cholesterol concentrations as part of a low-fat diet. SPONSORSHIP: Grant to the University of Kuopio by Raisio Benecol Ltd, Raisio, Finland.     

Serum and lipoprotein sitostanol and non-cholesterol sterols after an acute dose of plant stanol ester on its long-term consumption

Purpose

Chronic inhibition of cholesterol absorption with large doses of plant stanol esters (staest) alters profoundly cholesterol metabolism, but it is unknown how an acute inhibition with a large staest dose alters the postprandial serum and lipoprotein cholesterol precursor, plant sterol, and sitostanol contents.

Methods

Hypercholesterolemic subjects, randomly and double-blind divided into control (n?=?18) and intervention groups (n?=?20), consumed experimental diet without and with staest (plant stanols 8.8?g/day) for 10?weeks. Next morning after a fasting blood sample (0 h), the subjects had a breakfast without or with staest (4.5?g of plant stanols). Blood sampling was repeated 4?h later. Lipoproteins were separated with ultracentrifugation, and sterols were measured with gas–liquid chromatography.

Results

In 0-h chylomicrons and VLDL, plant sterols were lower in staest than in controls. Postprandially, cholestenol (cholesterol synthesis marker) was reduced in chylomicrons in staest compared with controls (?0.13?±?0.04?μg/dL vs. 0.01?±?0.08?μg/dL, P?P?Conclusions Chronic cholesterol absorption inhibition with large amount of plant stanol esters decreases plant sterols in triglyceride-rich lipoproteins. Acute plant stanol ester consumption increases sitostanol content in triglyceride-rich lipoproteins but suggests to decrease the risk of plant sterol and plant stanol accumulation into vascular wall by chylomicrons.     

Brazil nut ingestion increased plasma selenium but had minimal effects on lipids,apolipoproteins, and high-density lipoprotein function in human subjects

The Brazil nut (Bertholletia excelsa) of the Amazon region is consumed worldwide. It is rich in both monounsaturated fatty acids and polyunsaturated fatty acids and is known for its high selenium content. This study tested the hypothesis whether the consumption of this nut could affect the plasma lipids and apolipoproteins and some functional properties of the antiatherogenic high-density lipoprotein (HDL). Fifteen normolipidemic subjects aged 27.3 ± 3.9 years and with body mass index of 23.8 ± 2.8 kg/m² consumed 45 g of Brazil nuts per day during a 15-day period. On days 0 and 15, blood was collected for biochemical analysis, determination of HDL particle size, paraoxonase 1 activity, and lipid transfer from a lipoprotein-like nanoparticle to the HDL fraction. Brazil nut ingestion did not alter HDL, low-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I, or apolipoprotein B concentrations. HDL particle diameter and the activity of antioxidative paraoxonase 1, mostly found in the HDL fraction, were also unaffected. Supplementation increased the reception of cholesteryl esters (P < .05) by the HDL yet did not alter the reception of phospholipids, free cholesterol, or triacylglycerols. As expected, plasma selenium was significantly increased. However, the consumption of Brazil nuts for short duration by normolipidemic subjects in comparable amounts to those tested for other nuts did not alter serum lipid profile. The only alteration in HDL function was the increase in cholesteryl ester transfer. This latter finding may be beneficial because it would improve the nonatherogenic reverse cholesterol transport pathway.     

Apolipoprotein-E phenotype and basal activity of low-density lipoprotein receptor are independent of changes in plasma lipoprotein subfractions after cholesterol ingestion in Japanese subjects

We investigated whether the apolipoprotein-E (apoE) phenotype and the basal activity of low-density lipoprotein (LDL) receptor, which were reported to be the major determinants for increase in plasma LDL levels by cholesterol ingestion, have the same role in Japanese subjects whose diet is low in fat and cholesterol. Cholesterol (750 mg/d) was added to the ordinary diet as a dried egg-yolk supplement for 4 wk to 110 subjects. Plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions were measured at the beginning and end of the test period. Phenotyping of apoE was determined by an isoelectric focusing-immunoblotting method, and LDL receptor activity in lymphocytes was determined by flow cytometry. Plasma levels of cholesterol in less-dense LDL (LDL(1)) and less-dense high-density lipoprotein (HDL(2)) were slightly but significantly increased, 3.4% and 4.1%, respectively, by cholesterol ingestion, but the increases were not statistically significant in any of E2, E3, and E4 groups. The distribution of the apoE phenotype was equivalent in all three LDL-cholesterol groups (no change, increase, and decrease by cholesterol ingestion). Plasma levels of LDL, LDL(1), and LDL(2) cholesterol were not significantly increased in the three groups of subjects with lymphocyte LDL-receptor activities (low, medium, and high). As with apoE phenotype, LDL-receptor activities were the same in all three LDL-cholesterol groups. In addition, there were no significant correlations between LDL-receptor activity and changes in plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions. Therefore, we concluded that cholesterol ingestion significantly increases plasma levels of less-dense LDL and HDL, but neither apoE phenotype nor basal LDL-receptor activity explain the variability in changes in plasma lipoprotein subfractions by cholesterol ingestion in Japanese subjects.     

Plant stanol ester and bran fiber in childhood: effects on lipids, stool weight and stool frequency in preschool children

OBJECTIVES: The objective of the study was to evaluate the effects of plant stanol esters and bran fiber on lipids, stool weight and stool frequency in preschool children. METHODS: The present study was a 13 week open cross-over study designed to evaluate the effects of plant stanol ester in healthy two to five year old preschool children. After a one week lead-in, eligible children were randomly assigned to begin with either Diet Phase A (plant stanol ester) or Phase B (wheat bran fiber). Each diet phase was four weeks long, followed by a two-week wash-out, and then cross-over to the alternate diet. During Diet Phase A children consumed three eight-gram servings of a spread, each containing one gram of plant stanols, for total daily dose of three grams. During Diet Phase B, children added five grams of dietary fiber to their diet for the first two weeks and then ten grams for the second two weeks. RESULTS: Overall, for the whole study group, plant-stanol-ester spread use yielded a decrease in total cholesterol of 19.9 mg/dL (12.4% reduction from baseline) and a 14.6 mg/dL decrease in LDL cholesterol (15.5% reduction from baseline). There were no significant changes in HDL-cholesterol or triglyceride levels. A predominately insoluble dietary fiber supplement derived from wheat bran, as expected, yielded a small but non-significant decrease in total cholesterol of 6.1 mg/dL, a four percent reduction from baseline. CONCLUSIONS: Results demonstrated that preschool age children could adhere to a program requiring consumption of three daily servings of spread containing plant stanol ester and that this level of consumption resulted in a significant decrease in total cholesterol and LDL cholesterol after a four week period. In addition, consumption of plant stanol ester was not associated with any short-term adverse health effects.     

Effects of low-fat stanol ester enriched margarines on concentrations of serum carotenoids in subjects with elevated serum cholesterol concentrations

OBJECTIVE: To investigate the effects of low-fat stanol ester margarines on concentrations of serum carotenoids. DESIGN: A randomized parallel double-blind study design consisting of a 4-week run-in (high-fat diet) and an 8-week experimental (low-fat, low-cholesterol diet) period. During the experimental diet period subjects consumed low-fat wood stanol ester (WSEM), vegetable oil stanol ester (VOSEM) or control (no stanol esters) margarine daily. The daily mean total stanol intake was 2.31 and 2.16 g in the WSEM and VOSEM groups, respectively. SETTING: Outpatient clinical trial with free-living subjects. SUBJECTS: Altogether, 60 hypercholesterolaemic subjects were selected for the study out of 91 originally screened. The study was completed by 55 subjects. MAIN OUTCOMES MEASURES: Serum alpha- and beta-carotene and lycopene determined by the HPLC. RESULTS: Serum alpha-carotene concentration did not change significantly in either of the experimental groups, whereas beta-carotene concentration decreased significantly in the WSEM and VOSEM groups (P<0.01), and the change differed significantly (P<0.05 and P <0.01, respectively) from that of the control group. Decrease in alpha+beta-carotene concentration was significantly greater (P <0.05) in both experimental groups than in the control group. However, the change in alpha-, beta- or alpha+beta-carotene/total cholesterol ratio did not differ significantly among the groups. No significant changes were found in serum lycopene or lycopene/total cholesterol ratio in both experimental groups. CONCLUSIONS: Low-fat stanol ester margarines appeared to have little effect on serum concentrations of alpha-, beta- or alpha + beta-carotene, or lycopene. SPONSORSHIP: Grant to the University of Kuopio by Raisio Benecol Ltd, Raisio, Finland.     

Customary use of plant sterol and plant stanol enriched margarine is associated with changes in serum plant sterol and stanol concentrations in humans

The consumption of products enriched with plant sterol or stanol esters lowers serum total and LDL-cholesterol concentrations, thereby most likely reducing the risk of coronary heart disease. However, using plant sterol (not plant stanol) enriched products elevates serum plant sterol concentrations in humans. This may be unwanted because health effects of elevated serum plant sterol concentrations are still controversial. Within postlaunch monitoring of functional foods, we compared serum plant sterol and plant stanol concentrations among users of plant sterol (n = 67) or plant stanol (n = 13) enriched margarines with those of matched nonusers (n = 81) in the ongoing Dutch Doetinchem cohort study. Subjects (aged 29-67 y) were examined in 1994-1998 (before the introduction of enriched margarines) and re-examined in 1999-2003. Serum concentrations of plant sterols and stanols were measured in samples from nonfasting subjects by GLC-MS. Intake of plant sterols was 1.1 +/- 0.6 g/d and was associated with a decrease of serum total cholesterol concentration of 0.25 +/- 0.91 mmol/L (4%, P < 0.05), a change that differed (P < 0.05) from the nonsignificant increase in nonusers (+2%, 0.12 +/- 0.78 mmol/L, P = 0.16). Cholesterol-standardized serum sitosterol and campesterol increased in plant sterol users by 22% (P < 0.0001) and 103% (P < 0.0001), respectively. Cholesterol-standardized serum sitostanol and campestanol increased in plant stanol users by 197% (P = 0.02) and 196% (P = 0.01). To our knowledge, these data are the first to show changes in serum cholesterol, plant sterol, and plant stanol concentrations after (long-term) consumption of plant sterol and stanol enriched margarines in a free-living population in a nonexperimental setting. Whether the increased serum sterol concentrations result in adverse side effects needs to be investigated in future postlaunch monitoring studies.     

Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters

Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC-MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood-brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system.     

Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment

OBJECTIVE: The present study was designed to examine for the first time, side-by-side, the effects of plant sterol and stanol consumption on lipid metabolism and markers of antioxidant status, oxidative stress, endothelial dysfunction and low-grade inflammation in subjects on stable statin-treatment. DESIGN: Double-blind, randomized, placebo-controlled, intervention trial. SETTING: University. SUBJECTS: Forty-five patients on current statin treatment were recruited via newspaper advertisements. Data of 41 patients were used in statistical analysis. INTERVENTION: Subjects consumed margarine with no added plant sterols or stanols for 4 weeks and were then divided into three groups of 15 subjects. For the next 16 weeks, one group continued with the control margarine and the other two groups with either a plant sterol- or stanol (2.5 g/day)-enriched margarine. Blood was sampled at the end of the run-in and intervention periods. RESULTS: Plant sterol and stanol consumption significantly (P=0.026) reduced low-density lipoprotein (LDL) cholesterol by 0.34 mmol/l (95% confidence interval (CI), -0.67 to -0.04 mmol/l). No effects were shown on enzymatic and non-enzymatic antioxidants and markers of oxidative modification of lipids and DNA. In addition, no effect was found on soluble adhesion molecules, C-reactive protein and monocyte chemotactic protein-1 concentrations. CONCLUSIONS: We conclude that 16 weeks of plant sterol or stanol consumption did not affect markers of antioxidant status, oxidative stress, endothelial dysfunction and low-grade inflammation in patients on stable statin treatment, despite a significant reduction of LDL cholesterol.     

Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on lipids and insulin

OBJECTIVE: To assess the interaction between apolipoprotein (apo) E polymorphism, alcohol consumption, and BMI on insulin, lipid, and lipoprotein levels in men. RESEARCH METHODS AND PROCEDURES: Cross-sectional study of 266 healthy men without hypolipidemic or antidiabetic drug treatment. BMI, apo E polymorphisms, insulin, and lipid and lipoprotein levels were assessed. Alcohol consumption was assessed by questionnaire. epsilon2/epsilon4 carriers were excluded from the analysis. RESULTS: On bivariate analysis, epsilon2 carriers had lower levels of total and low-density lipoprotein cholesterol and higher levels of apo E and lipoparticle B:E than epsilon3 carriers, the opposite being found for epsilon4 carriers compared with epsilon3 carriers; epsilon4 carriers also had significantly higher insulin levels. On multivariate analysis, significant interactions (p < 0.04) between apo E alleles and increased BMI were found for total and low-density lipoprotein cholesterol and insulin levels, the increase in those parameters with BMI being stronger among epsilon4 carriers than among epsilon3 or epsilon2 carriers. Significant interactions (p < 0.02) between apo E alleles and alcohol consumption were also found for apo B levels, which increased in epsilon2 carriers but remained relatively stable in epsilon3 and tended to decrease in epsilon4 carriers. DISCUSSION: These data suggest that effects of apo E alleles on lipids and insulin levels are partly dependent on environmental variables such as BMI and alcohol intake. These findings highlight the importance of gene x environment interactions on the deleterious effect of obesity on cardiovascular risk factors.     

Decrease in plasma low-density lipoprotein cholesterol,apolipoprotein B,cholesteryl ester transfer protein,and oxidized low-density lipoprotein by plant stanol ester-containing spread: a randomized,placebo-controlled trial

OBJECTIVE: The ester of plant stanols significantly reduces plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in Western people. Effects of plant stanol ester-containing spread on plasma levels of TC, LDL-C, and apolipoprotein B (apoB) were studied in a randomized, placebo-controlled trial in Japanese subjects whose diet is low in fat and cholesterol. The effects of plant stanol ester on plasma levels of arteriosclerosis-promoting factors, namely remnants of triacylglycerol (TG)-rich lipoproteins, cholesteryl ester transfer protein (CETP), and oxidized LDL (Ox-LDL), were also studied. The assessment of safety was also made. METHODS: One hundred and five healthy volunteers were assigned randomly to one of three groups: placebo spread (n = 35), 2 g/d of plant stanol (3.4 g of stanol ester; n = 34), and 3 g/d of plant stanol (5.1 g of stanol ester; n = 36). Plasma levels of lipids were measured at start of the study, at 2 and 4 wk (end of trial), and at 8 wk (+4 wk). Plasma apoproteins, cholesterol in remnant-like particles which are equivalent to remnants of TG-rich lipoproteins (RLP-C), CETP mass, and Ox-LDL were measured at the beginning and the end of the trial. Plasma levels of plant steroids and fat-soluble vitamins were also measured for the assessment of safety. RESULTS: Background and dietary composition did not differ among groups. Plasma levels of TC, LDL-C, apoB, apoE, CETP mass, and Ox-LDL were reduced significantly by 6.5%, 9.6%, 8.3%, 4.5%, 6.1%, and 20%, respectively, in the 2 g/d plant stanol group. Plasma levels of TC, LDL-C, apoB, CETP mass, and Ox-LDL were decreased significantly by 5.5%, 7.3%, 5.6%, 3.3%, and 19%, respectively, in the 3 g/d plant stanol group. Plasma levels of plant stanols, plant sterols, retinol, beta-carotene, and alpha-tocopherol did not change in any group, but levels of campestanol increased and alpha-tocopherol decreased slightly in the sitostanol groups. CONCLUSION: Plasma levels of TC and LDL-C were significantly reduced by the plant stanol ester-containing spread. The smaller reduction than in Western studies and the lack of dose dependency in this study might be due to the different basal diets. We concluded that plant stanol ester-containing spread is efficacious in reducing plasma LDL-C, apoB, CETP, and Ox-LDL and that 2 g/d plant stanol is adequate for Japanese people. No significant side effects were observed in any group.     

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

BACKGROUND: Cholesterol metabolic studies are simplified in colectomized patients because of rapid intestinal passage and reduced bacterial action. OBJECTIVE: Our objective was to study the effect on cholesterol and plant sterol metabolism of feeding a margarine containing stanol ester to 11 colectomized patients. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.