Effectiveness and easiness of adherence to behavioural guidelines for diet and lifestyle changes for cholesterol-lowering: the Increasing Adherence of Consumers to Diet & Lifestyle Changes to Lower (LDL) Cholesterol (ACT) randomised controlled trial.

BACKGROUND: The present study aimed to assess perceived effectiveness and easiness of behavioural diet and lifestyle changes related to dyslipidaemia given by physicians or dieticians as a result of diet and lifestyle modifications being difficult to maintain. METHODS: One-hundred hypercholesterolaemic individuals were enrolled in a parallel, randomised 6-week study. Fifty were advised by dietitians (dietitian group: DG) in six weekly face-to-face behavioural therapy sessions and 50 received standard advice from physicians (physician group: PG). All individuals were followed-up for another 6 weeks under real-life conditions. Questionnaires regarding perceived effectiveness, easiness of adhering, forecasted and actual adherence to specific cholesterol-lowering advice were completed. RESULTS: Scores of perceived effectiveness of advice for sufficient exercise, limiting saturated fat (SFA) intake, eating fish twice a week, consuming plenty of fresh fruit and vegetables, and limiting salt intake different scientifically (all P < 0.05) in PG and DG between study phases. Scores of the individuals' perception of effectiveness at all study phases were higher in the DG compared to PG for sufficient exercise, limiting SFA intake, eating fish twice a week, eating plenty of fruits and vegetables, and limiting salt intake, whereas scores of easiness were significant only for fish consumption (P = 0.008) and using foods with added plant sterols (all P < 0.05). DG and PG significantly differed in forecasted (week 6) versus actual adherence (week 12) to various chances, with DG reporting higher adherence. CONCLUSIONS: Lifestyle and dietary changes related to dyslipidaemia can be achieved with continuous education, monitoring and follow-ups by dieticians, as well as potentially other trained healthcare professionals.

Plant-based sterols and stanols in health & disease: "Consequences of human development in a plant-based environment?"

Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question "What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?" What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols.

Structured advice provided by a dietitian increases adherence of consumers to diet and lifestyle changes and lowers blood low-density lipoprotein (LDL)-cholesterol: the Increasing Adherence of Consumers to Diet & Lifestyle Changes to Lower (LDL) Cholesterol (ACT) randomised controlled trial.

BACKGROUND: Evidence from healthcare professionals suggest that consumer compliance to healthy diet and lifestyle changes is often poor. The present study investigated the effect of advice provided by a physician or dietitian on consumer adherence to these measures combined with consuming foods with added plant sterols (PS) with the aim of lowering low-density lipoprotein cholesterol (LDL-C). METHODS: One hundred mildly-to-moderately hypercholesterolaemic individuals were enrolled into a parallel, randomised, placebo-controlled study. Dietitians (dietitian group; DG) advised 50 individuals in six weekly face-to-face behavioural therapy sessions, whereas the other 50 received standard advice from physicians (physician group, PG). Both groups consumed foods with added PS (three servings a day) for 6 weeks. Subsequently, all individuals were followed-up for another 6 weeks under real-life conditions. Blood lipids were measured at baseline and weeks 6 and 12 and 3-day diet diaries were taken at weeks 1, 6 and 12. RESULTS: Individuals in the DG significantly improved their dietary habits, physical activity and increased PS intake compared to the PG. After 6 weeks, LDL-C decreased in both groups compared to baseline without any significant differences between groups. At week 12, LDL-C was further significantly improved only in the DG (P = 0.006) compared to week 6. Total cholesterol, LDL-C and triglycerides were significantly lower in the DG compared to the PG at week 12 after adjusting for levels at week 6 (P < 0.001, P < 0.001 and P = 0.009, respectively). CONCLUSIONS: Although structured counselling by dietitians and common standard advice by physicians were equally effective with respect to improving blood cholesterol after 6 weeks, dietitians were more effective in the longer-term (i.e. 6 weeks after the end of the intervention period).

Increases in plasma plant sterols stabilize within four weeks of plant sterol intake and are independent of cholesterol metabolism.

BACKGROUND AND AIMS: Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, the impact of cholesterol synthesis and absorption on changes in plasma PS is explored. METHODS AND RESULTS: The study was a double-blind, randomized, placebo-controlled, parallel-group study with the main aim to investigate the effects of PS on vascular function (clinicaltrials.gov: NCT01803178). Hypercholesterolemic but otherwise healthy men and women (n = 240) consumed low-fat spreads without or with added PS (3 g/d) for 12 weeks after a 4-week run-in period. Blood sampling was performed at week 0, 4, 8 and 12. Basal cholesterol-standardized concentrations of lathosterol and sitosterol + campesterol were used as markers of cholesterol synthesis and absorption, respectively. In the PS group, plasma sitosterol and campesterol concentrations increased within the first 4 weeks of intervention by 69% (95%CI: 58; 82) starting at 7.2 µmol/L and by 28% (95%CI: 19; 39) starting at 11.4 µmol/L, respectively, and remained stable during the following 8 weeks. Placebo-corrected increases in plasma PS were not significantly different between high and low cholesterol synthesizers (P-values >0.05). Between high and low cholesterol absorbers, no significant differences were observed, except for the cholesterol-standardized sum of four major plasma PS (sitosterol, campesterol, brassicasterol and stigmasterol) showing larger increases in low absorbers (78.3% (95%CI: 51.7; 109.5)) compared to high absorbers (40.8% (95%CI: 19.9; 65.5)). CONCLUSIONS: Increases in plasma PS stabilize within 4 weeks of PS intake and do not seem impacted by basal cholesterol synthesis or absorption efficiency. This study was registered at clinicaltrials.gov (NCT01803178).

Effect of a plant sterol-enriched spread on biomarkers of endothelial dysfunction and low-grade inflammation in hypercholesterolaemic subjects.

Plant sterols (PS) lower LDL-cholesterol, an established risk factor for CHD. Endothelial dysfunction and low-grade inflammation are two important features in the development of atherosclerosis. Whether PS affect biomarkers of endothelial function and low-grade inflammation is not well studied. The aim of the present study was to investigate the effect of regular intake of PS on biomarkers of endothelial dysfunction and low-grade inflammation. In a double-blind, randomised, placebo-controlled, parallel-group study, which was primarily designed to investigate the effect of PS intake on vascular function (clinicaltrials.gov: NCT01803178), 240 hypercholesterolaemic but otherwise healthy men and women consumed a low-fat spread with added PS (3 g/d) or a placebo spread for 12 weeks. Endothelial dysfunction biomarkers (both vascular and intracellular adhesion molecules 1 and soluble endothelial-selectin) and low-grade inflammation biomarkers (C-reactive protein, serum amyloid A, IL-6, IL-8, TNF-α and soluble intercellular adhesion molecule-1) were measured using a multi-array detection system based on electrochemiluminescence technology. Biomarkers were combined using z-scores. Differences in changes from baseline between the PS and the placebo groups were assessed. The intake of PS did not significantly change the individual biomarkers of endothelial dysfunction and low-grade inflammation. The z-scores for endothelial dysfunction (-0·02; 95 % CI -0·15, 0·11) and low-grade inflammation (-0·04; 95 % CI -0·16, 0·07) were also not significantly changed after PS intake compared with placebo. In conclusion, biomarkers of endothelial dysfunction and low-grade inflammation were not affected by regular intake of 3 g/d PS for 12 weeks in hypercholesterolaemic men and women.

Baseline plasma plant sterol concentrations do not predict changes in serum lipids, C-reactive protein (CRP) and plasma plant sterols following intake of a plant sterol-enriched food.

BACKGROUND/OBJECTIVES: Plant sterol (PS) consumption lowers serum cholesterol levels, while modestly increasing plasma PS concentrations. Plasma PS concentrations may reflect sterol absorption, thus individuals with high plasma plant sterol (HPS) concentrations may show greater changes in circulating cholesterol and PS than individuals with low plasma plant sterol (LPS) concentrations. The objective of this study was to examine whether HPS and LPS concentrations are related to subsequent changes in plasma PS, serum lipid and C-reactive protein (CRP) concentrations, following dietary PS intake in otherwise healthy hypercholesterolemic men. SUBJECTS/METHODS: This single-blinded, randomized, diet-controlled study consisted of two 4-week phases, separated by a 4-week washout, where a diet with a placebo or the 2.0 g per day PS-enriched spread was consumed during the phases. RESULTS: At baseline, men with HPS possessed higher (P<0.01) mean serum cholesterol concentration, while those with LPS had higher (P<0.05) body mass index. Following PS intake, plasma sum of campesterol plus sitosterol concentrations were elevated from 34.6+/-4.2 to 46.2+/-3.3 micromol l(-1) (mean+/-SE) and 16.5+/-0.9 to 20.8+/-1.2 micromol l(-1) after PS intake in men with HPS and LPS, respectively. Changes in plasma PS concentrations, however, were not different between individuals with either HPS or LPS baseline concentrations. Total cholesterol and low-density lipoprotein cholesterol levels were decreased (P<0.0001) by 6.3 and 7.8%, respectively, with PS consumption for all individuals. Changes in lipid parameters were not different between individuals with HPS or LPS baseline concentrations. No changes in CRP were apparent subsequent to PS intervention. CONCLUSIONS: Baseline plasma PS concentrations are not associated or predictive of changes in serum cholesterol or plasma PS concentrations after PS intervention. Thus, individuals with HPS show similar increases in PS concentrations as individuals with LPS following PS supplementation. Plasma PS remained in the range of previously reported concentrations.

Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols.

OBJECTIVE: To test the dose-response effect on low-density lipoprotein cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat spread. METHODS: Dose responses of soybean oil (BO), tall oil (TO) and a mix of tall oil and rapeseed oil (TO/RP) as fatty acid esters were tested in a parallel design in free-living subjects recruited from the general community who had elevated cholesterol concentrations. Subjects received either control for 6 weeks or 1.6 g PS per day for 3 weeks, then 3.0 g/day for 3 weeks. RESULTS: LDL-c was lowered significantly by consumption of 1.6 g/day of PS (-10.4%, range -7.3 to -11.4%). Increasing the dose to 3.0 g/day modestly reduced LDL-c concentrations further to -14.7%. TO, containing 78% sitosterol, produced an increase in serum sitosterol of 6.5 nmol/ml, while BO, containing only 27% campesterol, produced an increase in serum campesterol of 9.5 nmol/ml in 6 weeks. After PS withdrawal, serum sterols declined by 50% within 2 weeks. CONCLUSION: Different PS sources were equally effective in lowering serum LDL-c concentrations. The decrease in absolute concentrations of LDL-c was dependent on the baseline concentrations.

Long-term effects of a plant-based dietary portfolio of cholesterol-lowering foods on blood pressure.

OBJECTIVE: To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio). METHODS: For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study. RESULTS: Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and -2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=-0.34, n=50, P=0.017; diastolic: r=-0.29, n=50, P=0.041). CONCLUSIONS: A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

Preferential efflux of phytosterols over cholesterol from macrophages.

Phytosterols are structurally similar to cholesterol. Increased dietary intake of phytosterols effectively lowers LDL-cholesterol. Since phytosterols are incorporated in a growing number of foods and some of the ingested phytosterols reach the circulation, accumulation of phytosterols in foam-cell-prone cells such as macrophages might occur. Therefore we examined the influx and efflux of phytosterols by human THP-1 macrophages. The influx rates of methyl-beta-cyclodextrin delivered phytosterols did not significantly differ from that of cholesterol (approximately 3.8 pmol/min per mg cellular protein), neither did the total influx of oxidised LDL delivered phytosterols differ from that of cholesterol. The efflux of beta-sitosterol and sitostanol from preloaded THP-1 cells to HDL was more efficient than the efflux of campesterol and cholesterol (rate constants of 0.41 +/- 0.04/h, 0.62 +/- 0.08/h, 0.23 +/- 0.05/h and 0.29 +/- 0.03/h, respectively). The efflux of beta-sitosterol was not associated with a dominant transfer to ApoA-I, nor did ABCA1 induction-promoted cholesterol efflux to the level observed for beta-sitosterol. Our data show that THP-1 macrophages take up phytosterols, but have efficient mechanisms to remove phytosterols from their cellular compartments. Consequently, it is less likely that macrophages preferentially accumulate phytosterols over cholesterol and hence promote foam-cell formation in vivo.

Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet.

BACKGROUND: A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods. METHODS: For 12 months, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (23 g/1000 kcal). Fifty-five subjects completed the study. RESULTS: Over the 1 year, data on completers indicated small but significant reductions in hemoglobin (-1.5+/-0.6 g/l, P=0.013), hematocrit (-0.007+/-0.002 l/l, P<0.001), red cell number (-0.07+/-0.02 10(9)/l, P<0.001) and neutrophils (-0.34+/-0.13 10(9)/l, P=0.014). Mean platelet volume was also increased (0.16+/-0.07 fl, P=0.033). The increase in red cell osmotic fragility (0.05+/-0.03 g/l, P=0.107) did not reach significance. CONCLUSIONS: These small changes in hematological indices after a cholesterol-lowering diet are in the direction, which would be predicted to reduce CHD risk. Further research is needed to clarify whether the changes observed will contribute directly or indirectly to cardiovascular benefits beyond those expected from reductions previously seen in serum lipids and blood pressure.

Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects.

OBJECTIVE: To determine the impact of intake occasion (with or without a meal), and product fat level on the cholesterol-lowering efficacy of a plant sterol (PS)-enriched (3 g/day) single-dose yoghurt drink. DESIGN: Double-blind, randomized, placebo-controlled, parallel study with a 4 weeks run-in and 4 weeks intervention period. SETTING: Subjects recruited from the general community. SUBJECTS: A total of 184 moderate hypercholesterolaemic subjects (81 men and 103 women) (age 57+/-2 years) completed the study. INTERVENTIONS: The study product was a 100-g single-dose yoghurt drink with or without added PS in the form of PS esters. The subjects were randomly assigned to one of five 4-week treatments: (i) drink A (0.1% dairy fat, 2.2% total fat) with a meal, (ii) drink A without a meal, (iii) drink B (1.5% dairy fat, 3.3% total fat) with a meal, (iv) drink B without a meal and (v) placebo drink with a meal. RESULTS: LDL-cholesterol (LDL-C) was significantly lowered when the single-dose drink was taken with a meal independent of its fat content (drink A: -9.5% (P<0.001, 95% CI: -13.8 to -5.2); drink B: -9.3% (P<0.001, 95% CI: -13.7 to -4.9)) as compared to placebo. When consumed without a meal, LDL-C was also significantly decreased (drink A: -5.1% (P<0.05, 95% CI: -9.4 to -0.8); drink B: -6.9% (P<0.01, 95% CI: -11.3 to -2.5) as compared to placebo, however the effect was significantly smaller as compared to the intake with a meal. CONCLUSION: These results indicate that a PS-ester-enriched single-dose yoghurt drink effectively reduces LDL-C irrespective of the fat content of the product. A substantially larger decrease in serum cholesterol concentration was achieved when the single-dose drink was consumed with a meal emphasizing the importance of the intake occasion for optimal cholesterol-lowering efficacy. SPONSORSHIP: Unilever Research and Development, Vlaardingen, The Netherlands.

Modern fat technology: what is the potential for heart health?

Saturated and trans-fatty acids raise total cholesterol and LDL-cholesterol and are known to increase the risk of CHD, while dietary unsaturated fatty acids play important roles in maintaining cardiovascular health. Replacing saturated fats with unsaturated fats in the diet often involves many complex dietary changes. Modifying the composition of foods high in saturated fat, particularly those foods that are consumed daily, can help individuals to meet the nutritional targets for reducing the risk of CHD. In the 1960s the Dutch medical community approached Unilever about the technical feasibility of producing margarine with a high-PUFA and low-saturated fatty acid composition. Margarine is an emulsion of water in liquid oil that is stabilised by a network of fat crystals. In-depth expertise of fat crystallisation processes allowed Unilever scientists to use a minimum of solid fat (saturated fatty acids) to structure a maximum level of PUFA-rich liquid oil, thus developing the first blood-cholesterol-lowering product, Becel. Over the years the composition of this spread has been modified to reflect new scientific findings and recommendations. The present paper will briefly review the developments in fat technology that have made these improvements possible. Unilever produces spreads that are low in total fat and saturated fat, virtually free of trans-fatty acids and with levels of n-3 and n-6 PUFA that are in line with the latest dietary recommendations for the prevention of CHD. Individuals with the metabolic syndrome have a 2-4-fold increased risk of developing CHD; therefore, these spreads could make a contribution to CHD prevention in this group. In addition, for individuals with the metabolic syndrome the spreads could be further modified to address their unique dyslipidaemia, i.e. elevated blood triacylglycerols and low HDL-cholesterol. Research conducted in the LIPGENE study and other dietary intervention studies will deliver the scientific evidence to justify further modifications in the composition of spreads that are healthy for the heart disease risk factors associated with the metabolic syndrome.

Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis.

BACKGROUND: Differences in isoflavone content of soy protein may explain the absence of a dose-response relation between soy protein intake and blood cholesterol concentrations. OBJECTIVE: To study specifically the effect of soy-associated isoflavones on cholesterol concentrations in well-controlled trials substituting soy protein with dairy or animal protein. DESIGN: Studies were identified by MEDLINE searches (1995 - 6 June 2002) and reviewing reference lists. Studies were included if they had a control group or treatment, experimental diets only differed in the amounts of soy protein and isoflavones and were each fed for at least 14 days. A total of 10 studies met these criteria, providing 21 dietary comparisons. SUBJECTS: : Studies comprised 959 subjects (336 men and 623 women), average age ranged from 41 to 67 y and baseline cholesterol concentration from 5.42 to 6.60 mmol/l. INTERVENTIONS: The intake of soy-associated isoflavones increased by 1-95 mg/day and the intake of soy protein increased by 19-60 g/day. RESULTS: Feeding daily 36 g soy protein with 52 mg soy-associated isoflavones on average decreased low-density lipoprotein (LDL) cholesterol by -0.17+/-0.04 mmol/l (mean+/-s.e.) and increased high-density lipoprotein (HDL) cholesterol by 0.03+/-0.01 mmol/l. There was no dose-response relation between soy-associated isoflavones and changes in LDL cholesterol (R=-0.33, P=0.14) (Pearson correlation coefficient) or HDL cholesterol (R=-0.07, P=0.76) or their ratio. CONCLUSIONS: Consumption of soy-associated isoflavones is not related to changes in LDL or HDL cholesterol.

A case-control study of the effect of infant feeding on celiac disease.

AIMS: The aim of this study was to investigate the association between the duration of breast-feeding and the age at the first gluten introduction into the infant diet and the incidence and age at onset of celiac disease. METHODS: In a case-control study, 143 children with celiac disease and 137 randomly recruited gender- and age-matched control children were administered a standardized questionnaire. Multivariate-adjusted odds ratios (OR) as estimates of the relative risk and corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: The risk of developing celiac disease decreased significantly by 63% for children breast-fed for more than 2 months (OR 0.37, 95% CI 0.21-0.64) as compared with children breast-fed for 2 months or less. The age at first gluten introduction had no significant influence on the incidence of celiac disease (OR 0.72, 95% CI 0.29-1.79 comparing first gluten introduction into infant diet >3 months vs. < or =3 months). CONCLUSIONS: A significant protective effect on the incidence of celiac disease was suggested by the duration of breast-feeding (partial breast-feeding as well as exclusive breast-feeding). The data did not support an influence of the age at first dietary gluten exposure on the incidence of celiac disease. However, the age at first gluten exposure appeared to affect the age at onset of symptoms.

Characterization of the bile acid profile in developing male and female hamsters in response to dietary cholesterol challenge.

The Syrian golden hamster is a frequently used model to study cholesterol and bile acid metabolism as well as cholesterol-induced cholelithiasis. However, diet-induced gallstones seem limited to young male hamsters of certain strains that develop depressed cholate/chenodeoxycholate bile acid ratios. To further elucidate gender and age specific aspects of cholesterol and bile acid metabolism, i.e. a possible age-related bile acid/gallstone relationship, plasma and biliary lipids and bile acid composition were analyzed in male and female hamsters under various physiological conditions of age and diet, the latter formulated with and without dietary cholesterol. During normal development (no cholesterol challenge) the percentage of cholic acid decreased while chenodeoxycholate increased, the shift being more pronounced in males. Furthermore, female hamsters had higher total plasma cholesterol than in males, while hepatic and biliary lipids did not differ. When challenged with excessive dietary cholesterol, female hamsters again developed significantly higher total plasma and hepatic cholesterol concentrations. Biliary lipids and cholesterol gallstone incidence revealed a significant gender effect with male hamsters developing a higher lithogenic index and more gallstones (cholesterol and pigment stones) than females. Female hamsters revealed a lower percentage of chenodeoxycholate and a higher percentage of cholate resulting in a more protective, higher cholate/cheno ratio (1.5 +/- 1.0) than in males (1.0 +/- 0.2). In summary, the bile acid pattern in developing and cholesterol-fed hamsters renders females less susceptible to gallstones, in part because they maintain more favorable biliary lipid and bile acid profiles, characterized by lower molar percentages of biliary cholesterol and chenodeoxycholate.

Replacing saturated fat with PUFA-rich (sunflower oil) or MUFA-rich (rapeseed, olive and high-oleic sunflower oil) fats resulted in comparable hypocholesterolemic effects in cholesterol-fed hamsters.

Recent studies have suggested that monounsaturated fatty acid (MUFA)-rich dietary fats do not have the same plasma cholesterol-lowering effects whereby rapeseed oil was more effective than olive oil. This phenomenon could be explicable by the content of other fatty acids or plant sterols. To further evaluate the effects of different MUFA-rich oils (18:1-rich sunflower oil, rapeseed oil, olive oil) in comparison to polyunsaturated (PUFA)-rich oils (18:2-rich sunflower oil) and saturated fat (palm stearin) on cholesterol and bile acid metabolism, male Syrian golden hamsters were fed semipurified diets containing 5% fat and 0.2% cholesterol for 5 weeks. To test whether oil refining would have an impact on the cholesterol-lowering potential, unrefined and refined varieties of rapeseed and olive oil were included. After 5 weeks, plasma total cholesterol (TC) was highest with palm stearin (10.0 +/- 2.6 mmol/l) while the MUFA- or PUFA-rich fats significantly lowered TC. The lowest TC concentrations were found with refined rapeseed, cold pressed rapeseed and 18:2-rich sunflower oil (6.7 +/- 1.2; 7.1 +/- 0.7 and 7.1 +/- 0.7 mmol/l, respectively), whereas TC was 10-15% higher (not significant) with 18:1-rich sunflower, virgin and refined olive oil. Liver cholesterol concentrations were lowest in hamsters fed palm stearin or 18:2-rich sunflower oil while MUFA-rich fats increased hepatic cholesteryl ester accumulation, especially of cholesteryl oleate. There were no significant differences in the fecal neutral sterol and bile acid excretion. These data demonstrate that MUFA-rich dietary fats, e.g. rapeseed, olive and 18:1-rich sunflower oil, are comparable in their hypocholesterolemic potential and cause similar effects on plasma cholesterol as 18:2-rich sunflower oil in hamsters when the dietary cholesterol intake is moderate.

Increased fecal bile acid excretion and changes in the circulating bile acid pool are involved in the hypocholesterolemic and gallstone-preventive actions of psyllium in hamsters.

The lipid-lowering effect of psyllium (PSY) is well established. Enhanced fecal bile acid excretion and a stimulation of hepatic bile acid synthesis are discussed as primary mechanisms of this action. To further examine the effect of bile acid excretion and specifically of compositional alterations in the bile acid pool on the cholesterol-lowering and gallstone-preventing action of PSY, male golden Syrian hamsters were fed lithogenic diets containing 5 g/100 g fat, 0.4 g/100 g cholesterol and 0 (control), 4 or 6% PSY or 1% cholestyramine (CHY). PSY significantly lowered plasma total cholesterol and triacylglycerol at a magnitude comparable to that induced by CHY. Although hepatic cholesteryl ester accumulation was completely inhibited by CHY, PSY did not prevent the hepatic storage of esterified cholesterol. PSY and CHY caused distinct alterations in the bile acid profile. PSY caused a selective reduction of taurine-conjugated bile acids, especially of taurochenodeoxycholate. As a result, the glycine:taurine conjugation and the cholate:chenodeoxycholate ratios were significantly higher in PSY-fed hamsters. PSY and CHY normalized the lithogenic index and prevented cholesterol gallstone formation compared with controls. Daily fecal bile acid excretion was approximately 400% greater in hamsters fed 6% PSY, whereas CHY caused an 11-fold increase. Daily neutral sterol excretion did not differ in PSY-fed hamsters but was >100% greater in those fed CHY than in controls. These data emphasize the potent lipid-lowering effect of PSY. Increased fecal bile acid excretion and alterations of the circulating bile acid pool by removal of dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators of the hypocholesterolemic action of PSY by leading to an up-regulation of hepatic bile acid synthesis.

Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters.

To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of beta-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by -75% and -44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. beta-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta-cyclodextrin and 19-times with 1% cholestyramine compared to control. beta-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of beta-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol excretion is most likely the primary mechanism responsible for the lipid-lowering action of beta-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.

Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters.

The mechanisms by which inulin may elicit its lipid-lowering effect are not well elucidated. To examine the lipid-lowering potential of inulin and especially its effect on bile acid metabolism, male golden Syrian hamsters were fed semipurified diets containing 20 g/100 g fat, 0.12 g/100 g cholesterol and 0 (control), 8, 12 or 16% inulin for 5 wk. Plasma total cholesterol concentrations were significantly lowered by 18, 15 and 29% in hamsters fed 8, 12 and 16% inulin, respectively. Dietary inulin specifically decreased VLDL cholesterol, which was significantly lower in hamsters fed 16% inulin compared with controls (1.1 +/- 0.3 vs. 2.9 +/- 0.6 mmol/L). LDL and HDL cholesterol were not significantly affected by dietary inulin. Plasma triacylglycerol was significantly reduced by 40 and 63% in hamsters fed 12 and 16% inulin, respectively. Hepatic total cholesterol and particularly esterified cholesterol accumulation were significantly lower in hamsters fed 8% inulin compared with controls. All three levels of dietary inulin caused distinct alterations in the bile acid profile of gallbladder bile. Taurochenodeoxycholic acid was significantly lower, whereas glycocholic and glycodeoxycholic acid were greater in hamsters fed inulin. Daily fecal bile acid excretion (micromol/d) tended to be greater (P = 0.056) in inulin-fed hamsters compared with controls, whereas daily neutral sterol excretion was not affected. These data demonstrate that the lipid-lowering action of inulin is possibly due to several mechanisms, including altered hepatic triacylglycerol synthesis and VLDL secretion and impaired reabsorption of circulating bile acids.

Effect of different varieties of pectin and guar gum on plasma, hepatic and biliary lipids and cholesterol gallstone formation in hamsters fed on high-cholesterol diets.

The effect of high- (hePE) and low- (lePE) esterification pectin and high- (hvGG) and low-(lvGG) viscosity guar gum on plasma, hepatic and biliary lipids and on prevention of cholesterol gallstones was investigated in male golden Syrian hamsters (Mesocricetus auratus). Hamsters were fed on cholesterol-rich (4 g/kg), gallstone-inducing diets for 6 weeks. The diets were supplemented with 80 g hePE, lePE, hvGG or lvGG/kg or 80 g additional cellulose/kg. No significant differences in plasma total cholesterol and triacylglycerol concentrations between hvGG and lvGG and the gallstone-inducing or cellulose-enriched diets were observed. The hePE diet produced a 16% (non-significant) reduction in total plasma cholesterol but significantly decreased the plasma triacylglycerol level by 45%. The lePE diet caused only minor changes in plasma lipids. Hepatic cholesterol concentrations were significantly higher in hamsters fed on hvGG, lvGG, hePE or lePE primarily due to the accumulation of esterified cholesterol. Supersaturated bile samples, with lithogenic indices ranging from 1.6 to 2.0, were determined with all diets. The hePE and lePE diets slightly altered the bile acid profile by increasing glycocholic acid and decreasing taurochenodeoxycholic acid concentrations resulting in a higher cholic:chenodeoxycholic acid ratio. Cholesterol gallstone formation was not substantially inhibited by the two varieties of pectin and guar gum. The hvGG, lvGG, hePE and lePE diets did not alter faecal weight and caused only minor increases in faecal bile acid excretion. In general, the present findings demonstrate that dietary pectins and guar gums had only minor effects on cholesterol metabolism and did not prevent cholesterol gallstone formation in this hamster model. Possible explanations for this lack of a distinct response to pectin and guar gum are discussed.