Non-esterified plant sterols solubilized in low fat milks inhibit cholesterol absorption--a stable isotope double-blind crossover study

Summary. Background: The cholesterol absorption inhibiting properties of plant sterols in milks are unknown. The milk fat globule membrane components may enhance the absorption of cholesterol and could make plant sterols less efficient in this complex matrix. Aim of the study: To evaluate in hypercholesterolemic men the cholesterol absorption inhibiting properties of verified properly solubilized, non-esterified plant sterols in partly vegetable oil containing milks. Methods: The plant sterols in milk were determined to be properly solubilized, and to have effective in vitro functionality. Sixteen hypercholesterolemic adult men (initial total cholesterol 5.8–8.6 mM) then consumed milk containing sterols (1.8 g of non-esterified pure plant sterols/d) and control milk, alternatively, during two 6-day periods in a double blind cross over design. During the trial, cholesterol absorption was evaluated from the ratio of plasma isotopic enrichment of [26, 26, 26, 27, 27, 27–²H₆]cholesterol from oral intake (35.6 ± 0.2 μmol, ± SEM) over enrichment of [23, 24, 25, 26, 27–¹³C₅]cholesterol from intravenous injection (77.9 ± 0.5 μmol). Results: Plant sterols in low fat milks contained very few crystals > 11 μm in the presence and absence of bile salts and lysophospholipids, and inhibited cholesterol uptake in Caco-2 cell. This assured that the sterols were properly solubilized prior to the clinical trial. In the clinical study, compliance of volunteers was excellent. After tracer injections (72 h), the plasma [²H] and [¹³C] isotopic enrichments changed from 0.024 ± 0.001 and 0.072 ± 0.003 MPE (control) to 0.015 ± 0.001 and 0.074 ± 0.002 MPE during sterol treatment, respectively. Cholesterol absorption was reduced from 70.1 ± 4.2 % with control to 41.1 ± 4.0 % with milks containing plant sterol (P < 0.001). Conclusions: These results demonstrate that properly solubilized non-esterified plant sterols in milks significantly inhibit cholesterol absorption in mildly hypercholesterolemic men. Received: 10 October 2002, Accepted: 8 January 2003 Correspondence to: Etienne B. Pouteau     

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

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: 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). RESULTS: 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. CONCLUSION: These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption.     

Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized,placebo-controlled crossover trial

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol ? control) were significant (p < 0.05) for LDL-C ( ? 4.9%), non-HDL-C ( ? 3.6%) and TC ( ? 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia.     

The hypocholesterolemic effect of lemon peels,lemon pectin,and the waste stream material of lemon peels in hybrid F<Subscript>1</Subscript>B hamsters

Summary Background We found in preliminary studies with hamsters that citrus peels have a cholesterol lowering effect comparable to that of pectin extracted from these peels. Aim of the study We wanted to examine whether the cholesterol lowering effect of the peels could be completely accounted for by the pectin in the peels. Methods We fed cholesterol enriched (0.1 %,w/w) semipurified diets containing 3 % (w/w) of cellulose, lemon peels, lemon pectin, and the waste stream material of the lemon peels to hybrid F₁B hamsters for a period of 8 weeks. The waste stream of the lemon peels is the left over after extraction of the lemon pectin. Results Feeding the semipurified diets resulted in an increase of plasma cholesterol levels in all the dietary groups after 2 and 4 weeks on the diets. Cholesterol concentrations in the cellulose fed hamsters continued to increase after 4 weeks on the diet, whereas cholesterol levels in the other groups had reached a plateau. As a consequence, the plasma cholesterol levels in the hamsters fed the peels (5.59 ± 0.74 mmol/L, mean ± SD, n = 14), pectin (5.19 ± 0.48 mmol/L), or waste stream (5.53 ± 0.94 mmol/L) were lower than those in the hamsters fed cellulose (6.71 ± 1.52 mmol/L) after 8 weeks on the diets. Differences in total plasma cholesterol were reflected in differences in both VLDL and LDL cholesterol concentration, but this effect was more distinct for the VLDL. There was no effect of the type of fiber on HDL cholesterol levels. Liver cholesterol concentrations paralleled the concentrations of plasma cholesterol and the liver cholesterol concentrations in the hamsters fed the peels (3.57 ± 1.01 μmol/g liver, mean ± SD, n = 14), pectin (4.86 ± 1.42), and the waste stream (4.96 ± 1.89) were lower than those in the cellulose group (7.19 ± 2.32). The hamsters fed the peels, pectin, or waste stream tended to have a higher excretion of fecal bile acids and neutral sterols then the cellulose fed hamsters. Conclusion The results of this study suggest that lemon peels and the waste stream of the lemon peels are as effective in lowering plasma and liver cholesterol in hamsters as the pectin extracted from the peels and that also compounds other than pectin are probably responsible for the cholesterol lowering effect of the citrus peels. Received: 20 September 2001, Accepted: 17 December 2001     

Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter

Dietary supplementation with plant sterols, stanols, and their esters reduces intestinal cholesterol absorption, thus lowering plasma LDL cholesterol concentration in humans. It was suggested that these beneficial effects are attributable in part to induction of genes involved in intestinal cholesterol transport, e.g., Abcg5 and Abcg8, via the liver X receptor (LXR), but direct proof is lacking. Male C57BL/6J mice were fed a purified diet (control), diets containing cholesterol (0.12 g/100 g) only, or in combination with either plant sterols or stanols (0.5 g/100 g) for 4 wk. Plant sterols and stanols dramatically increased neutral fecal sterol excretion (2.2 and 1.4-fold, respectively, compared with cholesterol-fed mice; P < 0.05). Cholesterol and cholesterol ester concentrations were higher in livers of mice fed cholesterol compared with controls (+135% and +925%; P < 0.05). Plant sterols and stanols completely prevented cholesterol accumulation as well as induction of LXR target genes in liver. Feeding plant sterols and stanols did not alter intestinal expression of Abcg5, Abcg8, or other LXR target genes nor of Npc1l1. Fractional cholesterol absorption in Abcg5-/- mice was reduced to the same extent by dietary plant sterols (49%) as in wild-type littermates (44%). Plant sterol and stanol-induced reduction of cholesterol absorption in mice is not associated with upregulation of intestinal LXR target genes nor is it influenced by Abcg5-deficiency. Our data indicate that dietary plant sterols and stanols inhibit cholesterol absorption within the intestinal lumen independently of LXR.     

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.     

Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects

Summary Background Plant sterols have been shown to reduce serum lipid concentrations. The effectiveness is highly dependent on the physical state of the plant sterols. By means of a new crystallizing method, plant sterols can be added into dietary fats and oils homogeneously. In this fat ingredient, plant sterols are in a microcrystalline form. Aims of the study We investigated the cholesterol-lowering effect and possible side effects of vegetable oil-based spreads fortified with two different doses of microcrystalline plant sterols. Methods: This double-blind randomized, placebo-controlled study consisted of a 6-wk run-in and a 6-month experimental period. During the run-in period, all 155 hypercholesterolemic subjects received rapeseed oil-based control spread. In the beginning of the experimental period subjects were randomly assigned into one of three experimental groups. The control group continued to use control spread, and the two test groups used spreads with added plant sterols of either 1.5 g/d or 3.0 g/d. The subjects consumed test spreads as a part of their normal diet without any restrictions in lifestyle and diet. Results Plasma total- and LDL-cholesterol concentrations were significantly reduced by 7.5–11.6 % (0.46–0.62 mmol/l) in groups consuming margarine enriched with free plant sterols, compared with the control group. The effects were similar between the two groups consuming either 1.5 g or 3.0 g plant sterols per day. No effect on HDL-cholesterol or triacylglycerol concentrations occurred. The test spreads did not induce any adverse effects in blood clinical chemistry, hematology or decreases in serum concentrations of lipid soluble vitamins. Conclusions Microcrystalline plant sterols are effective in lowering serum total- and LDL-cholesterol concentrations without obvious side effects. The daily dose of 1.5 g plant sterols is enough to reach the maximum effect. Received: 5 December 2000 / Accepted: 14 March 2001     

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.     

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.     

Unesterified plant sterols and stanols do not affect LDL electrophoretic characteristics in hypercholesterolemic subjects

The extent to which sterols and stanols modulate LDL particle size is unknown. We examined the effects of supplementation with unesterified plant sterols and stanols on several LDL electrophoretic characteristics. Healthy hypercholesterolemic subjects (n = 14) consumed each of four experimental diets contained plant sterols (S), plant stanols (SN), a 50:50 mixture of sterols and stanols (SSN), or cornstarch (control) in a randomized crossover design. The butter component of the diet was blended with unesterified sterols and stanols at a dose of 1.8 g/d. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis of whole plasma. LDL cholesterol (LDL-C) concentrations decreased by 8.8, 13.6, and 13.1% in the S, SN, and SSN groups, respectively (P < 0.01) with a significant increase of 4.3% in the control group. None of the treatments with sterols and stanols induced significant changes in LDL peak particle diameter or in the cholesterol levels of the small LDL subfraction (<25.5 nm). The reduction in plasma LDL-C levels with SN consumption was due mainly to a decrease (P < 0.05) in the concentration of cholesterol in the large subfraction (>26.0 nm). The significant reduction in plasma LDL-C concentrations by sterol and stanol consumption in subjects was not paralleled by any beneficial changes in LDL electrophoretic characteristics.     

Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods.

OBJECTIVES: To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine. DESIGN: Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g)-containing foods were eaten during 4 week test periods of cross-over design following a 4 week control food period. In Study 2, in a random order cross-over design, a 50% dairy fat spread with or without 2.4 g sterol esters daily was tested. SUBJECTS: Hypercholesterolaemic subjects; 22 in study 1 and 15 in study 2. MAIN OUTCOME MEASURES: Plasma lipids, plasma sterols, plasma carotenoids and tocopherols. RESULTS: Study 1-median LDL cholesterol was reduced by the sterol esters (-13.6%; P<0.001 by ANOVA on ranks; P<0.05 by pairwise comparison) and by stanols (-8.3%; P=0.003, ANOVA and <0.05 pairwise comparison). With sterol esters plasma plant sterol levels rose (35% for sitosterol, 51% for campesterol; P<0.001); plasma lathosterol rose 20% (P=0.03), indicating compensatory increased cholesterol synthesis. With stanols, plasma sitosterol fell 22% (P=0.004), indicating less cholesterol absorption. None of the four carotenoids measured in plasma changed significantly. In study 2, median LDL cholesterol rose 6.5% with dairy spread and fell 12.2% with the sitosterol ester fortified spread (P=0.03 ANOVA and <5% pairwise comparison). CONCLUSION: 1. Plant sterol esters and non-esterified stanols, two-thirds of which were incorporated into low-fat foods, contributed effectively to LDL cholesterol lowering, extending the range of potential foods. 2. The LDL cholesterol-raising effect of butter fat could be countered by including sterol esters. 3. Plasma carotenoids and tocopherols were not reduced in this study. SPONSORSHIP: Meadow Lea Foods, Australia.     

A Softgel Dietary Supplement Containing Esterified Plant Sterols and Stanols Improves the Blood Lipid Profile of Adults with Primary Hypercholesterolemia: A Randomized,Double-Blind,Placebo-Controlled Replication Study

A well-controlled clinical trial previously demonstrated the efficacy of a novel softgel dietary supplement providing 1.8 g/day esterified plant sterols and stanols, as part of the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to improve the fasting lipid profile of men and women with primary hypercholesterolemia (fasting low-density lipoprotein [LDL] cholesterol ≥130 and <220 mg/dL [≥3.37 and <5.70 mmol/L]). The purpose of this randomized, double blind, placebo-controlled crossover study (conducted July 2011 to January 2012) was to support these previous findings in a similar, but independent, sample with a different lead investigator and research site. Repeated measures analysis of covariance was used to compare outcomes for sterol/stanol and placebo treatment conditions using the baseline value as a covariate. Forty-nine subjects were screened and 30 (8 men and 22 women) were randomized to treatment (all completed the trial). Baseline (mean±standard error of the mean) plasma lipid concentrations were: total cholesterol 236.6±4.2 mg/dL (6.11±0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8±3.0 mg/dL (1.47±0.08 mmol/L), LDL cholesterol 151.6±3.3 mg/dL (3.92±0.09 mmol/L), non-HDL cholesterol 179.7±4.6 mg/dL (4.64±0.12 mmol/L), and triglycerides 144.5±14.3 mg/dL (1.63±0.16 mmol/L). Mean placebo-adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL cholesterol (–4.3%), non-HDL cholesterol (–4.1%), and total cholesterol (–3.5%), but not for triglycerides or HDL cholesterol. These results support the efficacy of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to augment reductions in atherogenic lipid levels in individuals with hypercholesterolemia.     

Effects of insulin and amino acids on leucine metabolism in young and middle-aged humans

Summary Background Aging is characterized by loss of muscle mass. In healthy subjects this process is associated with hormone and nutritional changes which take place over many decades. Aim of the study To investigate the effects of insulin and amino acids on amino acid metabolism in middle-aged humans. Methods We evaluated leucine kinetics by means of the intravenous infusion of [1-¹⁴C]leucine, in 8 young (age 24±2 yr, BMI 21±2 kg/m²) and in 6 middle-aged (age 53±4 yr, BMI 26±1 kg/m²) healthy subjects. Studies were performed under fasting conditions (basal), and after 180 min of euglycemic hyperinsulinemic clamp (study I), or 180 min of euglycemic hyperinsulinemia in combination with an intravenous amino acid infusion (study II). Results In the basal state endogenous leucine flux (ELF, an index of proteolysis), normalized for IBW, averaged 1.71±0.12 and 1.66±0.14 μmol/kg·min in young and middle-aged subjects, respectively. Basal leucine oxidation (0.22±0.03 vs 0.28±0.03 μmol/kg·min, p < 0.05) was lower in middle-aged with respect to young subjects. Non-oxidative leucine disposal (NOLD, an index of protein synthesis: 1.44±0.11 vs 1.43±0.11 μmol/kg·min) was similar in young and middle-aged subjects, respectively. In response to insulin (study I) the absolute and percent decline of ELF and LOX were similar in young and middle-aged subjects: ELF declined to 1.05±0.06 μmol/kg·<,min (−M39±5 %) and 1.07±0.14 μmol/kg·min (−36±4 %), in young and middle-aged, respectively (both p < 0.01 vs basal); LOX declined to 0.21±0.02 μmol/kg·min (−35±3 %), and 0.18±0.05 μmol/kg·min (−28±3 %, p < 0.05 vs basal) in young and middle-aged individuals respectively (both p < 0.01 vs basal). In contrast, insulin-mediated whole-body glucose uptake was lower in middle-aged subjects (6.6±1.4 mg/kg·min) with respect to young individuals (8.1±1.7 mg/kg·min, p < 0.05). During study II (insulin plus AA) a significant rise in NOLD was obtained in both young (1.72±0.10 μmol/kg·min, p < 0.01 vs basal) and middle-aged subjects (1.76±0.25 μmol/kg·min, p < 0.01 vs basal). Similarly, net leucine balance rose significantly in both young (+0.62±0.13 vs −0.25±0.02 μmol/kg·min, p < 0.01 vs basal) and middle-aged subjects (+0.37±0.08 vs −0.22±0.03 μmol/kg·min, p < 0.01 vs basal) suggesting that the anabolic response to amino acids is preserved in middle-aged subjects. Conclusions In middle-aged subjects we observed 1) a moderate decline in basal leucine oxidation; 2) a normal antiproteolytic response to insulin and a reduction in glucose uptake; and 3) a normal anabolic response to AA plus insulin. In conclusion, the data provide evidence for a normal regulation of protein anabolism and an early dissociation between the metabolic effects of insulin on glucose uptake and proteolysis in middle-aged subjects. Received: 6 September 2000, Accepted: 10 July 2001     

Adaption of Sprague Dawley rats to long-term feeding of high fat of high fructose diets

Summary Background Present animal models used to emulate type 2 diabetes may not accurately reflect the metabolic changes that occur in humans. Aims of the study The purpose of this research was to evaluate diets reported to induce insulin resistance and impaired glucose metabolism in rats as a potentially useful model for studying type 2 diabets. Methods Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. Glucose tolerance tests were carried out in week 3 and week 9 of the experiment. At the termination of the experiment, serum insulin, glucose, cholesterol and triacylglycerols were measured. Glucose incorporation into glycogen and glycogen synthase activity were measured in soleus muscles. Results Similar weight gain was observed for all three groups of rats. Glucose tolerance curves and fasting glucose levels were not significantly different at any time point in the experiment. Insulin levels were unchanged for the controls (171±21 pM), high fructose (164±16 pM) and high fat (181±30 pM) diets. Fasting serum triacylglycerols and cholesterol levels were not significantly elevated by dietary treatment. In soleus muscles, rats on all three diets had a significant increase in glycogen synthesis in response to insulin, but synthesis was similar in all three groups. Glycogen synthase activity was also not significantly affected by long-term dietary intervention. Conclusions In this study, healthy Sprague Dawley rats fed high fat or high fructose diets for 3 months adapted to the nutritional intervention without developing classical signs of insulin resistance and impaired glucose tolerance. Received: 17 May 2000, Accepted: 31 August 2000     

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.     

The Comparative Efficacy of Plant Sterols and Stanols on Serum Lipids: A Systematic Review and Meta-Analysis

Background

Plant sterols and stanols are plant steroids with a similar chemical structure and cellular function to human cholesterol, and are recommended as dietary modifiers of serum lipids. Plant sterols have a higher degree of absorption than plant stanols, suggesting differential efficacy between the two.

Design

A meta-analysis of randomized controlled trials was performed to summarize direct comparisons between the effect of plant sterols vs plant stanols on serum lipid levels in healthy patients and patients with hypercholesterolemia.

Methods

A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from January 1950 through January 2009. Trials were included in the analysis if they were randomized controlled trials evaluating the effect of plant sterols vs plant stanols in healthy patients or patients with hypercholesterolemia who reported efficacy data on total, low-density lipoprotein, and high-density lipoprotein cholesterols or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval was calculated as the difference between the means in the plant sterol and plant stanol groups using a random-effects model.

Results

Fourteen studies (n=531 patients) met the inclusion criteria. Upon meta-analysis, the results showed that there is no statistically or clinically significant difference between plant sterols and plant stanols in their abilities to modify total cholesterol (WMD −1.11 mg/dL [−0.0286 mmol/L], 95% confidence interval [CI] −4.12 to 1.90, P=0.47), low-density lipoprotein cholesterol (WMD −0.35 mg/dL [−0.0091 mmol/L], 95% CI −2.98 to 2.28, P=0.79), high-density lipoprotein cholesterol (WMD −0.28 mg/dL [-0.00073 mmol/L], 95% CI −1.18 to 0.62, P=0.54), or triglycerides (WMD −1.80 mg/dL [−0.0203 mmol/L], 95% CI −6.80 to 3.21, P=0.48).

Conclusions

Plant sterols and plant stanols do not have statistically or clinically relevant differing effects on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels. The selection of plant sterols vs plant stanols should then be based on potential differences in safety parameters and further study is required to elucidate such differences.     

Plant sterols in vegetables and fruits commonly consumed in Sweden

Summary Plant sterols are known to have serum cholesterol lowering effects. A high dietary intake might therefore have a positive impact on health. All food items of vegetable origin contain some amount of plant sterols. The aim of this study was to analyse the plant sterol content of vegetables and fruits commonly consumed in Sweden, and to compare fresh and cooked samples of the same items. Altogether 20 different vegetables and 14 fruits were analysed. All vegetables and fruits were purchased in two shops in the city of Gothenburg, Sweden. Lyophilization was performed within one month of the items being purchased. The samples were frozen at −20 (C and analysed within six months, with a GLC method after acid hydrolysis, alkaline hydrolysis and silylation with tri-methylsilylether. The acid hydrolysis was done in order to detect the fraction of glycosylated plant sterols, which are split during boiling with HCl. The median plant sterol content of vegetables was 14 (3.8–50) mg/100 g edible portion. The highest concentrations were found in broccoli, Brussels sprouts, cauliflower and olives. The median plant sterol content of fruits was 16 (3–44) mg/100 g edible portion. The highest concentrations were found in oranges and passion fruits. The plant sterol concentrations were thus low in vegetables and fruits commonly consumed in Sweden. A serum cholesterol lowering effect attributed to the plant sterols in vegetables and fruits would therefore be of limited significance. Received: 25 September 1998, Accepted: 10 February 1999     

Fecal steroids and colorectal cancer

The fecal steroid profiles of healthy subjects were compared with those of colorectal cancer (CRC) patients. The multicomponent profiles did not differ qualitatively in that CRC patients, like control subjects, had similar fecal steroids. The major bile acids detected in fecal extracts were lithocholic acid (LCA) and deoxycholic acid (DCA). The major sterol of animal origin was cholesterol and its bacterial metabolite coprostanol, whereas the major plant sterols were ß‐sitosterol, stigmasterol, campesterol, and their corresponding bacterial metabolites. CRC patients excreted higher amounts of total major bile acids (LCA and DCA) than did the control group, but this difference was not significant. However, the LCA‐to‐DCA ratio was much higher in the CRC group [(1.43, p < 0.01) compared with the control group (0.72)]. The control group excreted significantly higher amounts of total neutral sterols (p < 0.001), sterols of animal origin (p < 0.001), and plant sterols (p < 0.001) compared with the CRC group; the plant sterols represented a much lower proportion of excreted total neutral sterols in the CRC group (p > 0.001) compared with the control group.

We propose the following hypotheses. 1) The LCA‐to‐DCA ratio may be an important discriminant market for CRC susceptibility. 2) The fecal LCA‐to‐DCA ratio may depend on the differential hepatic synthesis of their respective precursors chenodeoxycholic acid (CDCA) and cholic acid. 3) Hepatic synthesis of CDC A may be increased by more efficient conservation of dietary cholesterol because it has been shown that cholesterol of exogenous origin is the main precursor of this bile acid. 4) Cholesterol absorption may be augmented in CRC patients because of the low intake of plant sterols, which are known to suppress cholesterol absorption.     

The Role of Dietary Supplementation with Plant Sterols and Stanols in the Prevention of Cardiovascular Disease

Several studies have shown that increased levels of low-density lipoprotein (LDL) cholesterol predict cardiovascular events. The Adult Treatment Panel II (ATP II) introduced the principle of therapeutic lifestyle changes, including plant sterols/stanols for the management of LDL cholesterol. Plant sterols and stanols in fat matrices effectively lower LDL cholesterol levels in hypercholesterolemic, diabetic, and healthy human volunteers. Recent studies also show that sterols (2 g/d) lower LDL cholesterol even when incorporated in nonfat matrices. In addition, they may reduce biomarkers of oxidative stress and inflammation. Plant sterols and stanols exert their hypocholes-terolemic effects possibly by interfering with the uptake of both dietary and biliary cholesterol from the intestinal tract. Present evidence is accumulating to promote their use for lowering LDL cholesterol levels, as a first line of therapy (as well as adjunctive therapy) in patients on statin therapy.