We have earlier demonstrated that muesli enriched with oat beta-glucan effectively lowered serum LDL cholesterol. Addition of plant stanols further lowered LDL cholesterol. Besides these hypocholesterolemic effects, beta-glucan and plant stanol esters (PSE) may also affect inflammatory processes. Forty-two mildly hypercholesterolemic subjects randomly consumed for 4 wk (crossover design) control muesli (4.8 g control fiber), beta-glucan muesli (4.8 g oat beta-glucan), or combination muesli (4.8 g oat beta-glucan plus 1.4 g stanol as PSE). Changes in cytokine production (IL-6, IL-8, and TNF-alpha) of LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood were evaluated, as well as changes in plasma high-sensitivity (hs)-CRP. Additionally, changes in expression profiles of 84 genes involved in atherosclerosis metabolism were assessed in isolated PBMC. IL-6, IL-8, and TNF-alpha production by PBMC and whole blood after LPS stimulation did not differ between the treatments. Also high-sensitivity C-reactive protein (hs-CRP) levels were similar. beta-Glucan consumption did not change gene expression, while only 3 genes (ADFP, CDH5, CSF2) out of the 84 genes from the atherosclerotic risk panel were differentially expressed (p < 0.05) after consumption of PSE. Consumption of beta-glucan with or without PSE did not influence inflammatory parameters in mildly hypercholesterolemic subjects.

Objective:To assess the effects of plant sterol or stanol ester consumption on their incorporation into erythrocytes and their effects on osmotic fragility of red blood cells.Design:Double-blind, randomized, placebo-controlled intervention trial.Subjects and intervention:Forty-one subjects on stable statin treatment - who already have increased serum plant sterol and stanol concentrations - first received for 4 weeks a control margarine. For the next 16 weeks, subjects were randomly assigned to one of three possible interventions. Eleven subjects continued with control margarine, 15 subjects with plant sterol ester enriched and 15 subjects with plant stanol ester-enriched margarine. Daily plant sterol or stanol intake was 2.5 g. Erythrocyte haemolysis was measured spectrophotometrically at five different saline concentrations.Results:Despite significant (P=0.004) increases of, respectively, 42 and 59% in cholesterol-standardized serum sitosterol and campesterol concentrations in the plant sterol group as compared to the control group, campesterol levels in the red blood cells did not change (P=0.196). Osmotic fragility did not change significantly (P=0.757) in the plant sterol and plant stanol groups as compared to the control group.Conclusion:We conclude that plant sterol and stanol ester consumption for 16 weeks does not change osmotic fragility of erythrocytes in statin-treated patients.Sponsorship:Netherlands Organisation for Health Research and Development (Program Nutrition: Health, Safety and Sustainability, Grant 014-12-010)European Journal of Clinical Nutrition advance online publication, 15 February 2006; doi:10.1038/sj.ejcn.1602409.

BACKGROUND: In obese subjects, chronic low-grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti-inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention. MATERIAL AND METHODS: Eleven obese men (BMI: 30-35 kg m(-2)) received daily fish oil (1.35 g n-3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9.4 kg. At the end of each experimental period a postprandial study was performed. RESULTS: Relative to fasting concentrations, interleukin-6 (IL-6) levels increased by 75% 2 h and by 118% 4 h after the meal (P < 0.001), when subjects consumed the control capsules. In contrast, C-reactive protein (C-RP) concentrations decreased slightly by 0.7% and 6.6%(P = 0.046), and those of plasminogen activator inhibitor-1 (PAI-1) antigen by, respectively, 26% and 53%(P < 0.001). Tumour necrosis factor-alpha (TNF-alpha; P = 0.330) and soluble TNF-receptor concentrations (sTNF-R55 and sTNF-R75; P = 0.451 and P = 0.108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL-6, C-RP, sTNF-R55, sTNF-R75, and PAI-1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. CONCLUSION: For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction.

BACKGROUND: Differences in genetic constitution may affect cholesterol metabolism and responses to diet. Identification of common variations in genes related to dietary responsiveness is therefore an attractive goal to be able to prescribe individually tailored diets for the treatment of dyslipidaemia. MATERIALS AND METHODS: We have examined relationships between serum lipids and lipoproteins, cholesterol-standardized campesterol and lathosterol concentrations with genetic variation, and the presence of a gene-diet interaction between plant stanol ester consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70 consumed 3.8-4.0 g plant stanol esters a day for 8 weeks. RESULTS: At baseline, high-density lipoprotein (HDL) concentrations of 1.56 +/- 0.36 mmol L(-1) in SR-BI-2 allele carriers tended to be lower compared to the 1.72 +/- 0.42 mmol L(-1) in SR-BI-1/1 subjects (P = 0.069). Cholesterol standardized lathosterol concentrations were also lower in the SR-BI-2 allele carriers (P = 0.002). Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2 subjects, were lower compared to the LDL cholesterol concentration in apoE3 group (P = 0.002) and apoE4 subjects (P < 0.001). No significant differences between the polymorphisms and dietary responsiveness to plant stanol ester consumption could be found, which indicates that it is unlikely that one of the single polymorphisms analysed in this study is a major factor in explaining the variation in serum LDL cholesterol responses. CONCLUSION: These findings suggest that all subjects who want to lower their cholesterol concentration, will benefit from plant stanol ester consumption, irrespective of their apoA-IV, SR-BI, HMG-CoA reductase, CETP, or apoE genotype.

Some oxidized forms of cholesterol (oxysterols) are thought to be atherogenic and cytotoxic. Because plant sterols are structurally related to cholesterol, we examined whether oxidized plant sterols (oxyphytosterols) could be identified in human serum and soy-based lipid emulsions. We first prepared both deuterated and nondeuterated reference compounds. We then analyzed by gas-liquid chromatography-mass spectrometry the oxyphytosterol concentrations in serum from patients with phytosterolemia or cerebrotendinous xanthomatosis, in a pool serum and in two lipid emulsions. 7-Ketositosterol, 7 beta-hydroxysitosterol, 5 alpha, 6 alpha-epoxysitosterol, 3 beta,5 alpha,6 beta-sitostanetriol, and probably also 7 alpha-hydroxysitosterol were present in markedly elevated concentrations in serum from phytosterolemic patients only. Also, campesterol oxidation products such as 7 alpha-hydroxycampesterol and 7 beta-hydroxycampesterol were found. Interestingly, sitosterol was oxidized for approximately 1.4% in phytosterolemic serum, which is rather high compared with the approximate 0.01% oxidatively modified cholesterol normally seen in human serum. The same oxyphytosterols were also found in two lipid emulsions in which the ratio of oxidized sitosterol to sitosterol varied between 0.038 and 0.041.In conclusion, we have shown that oxidized forms of plant sterols are present in serum from phytosterolemic patients and two frequently used soy-based lipid emulsions. Currently, it is unknown whether oxyphytosterols affect health, as has been suggested for oxysterols. However, 7 beta-hydroxycholesterol may be one of the more harmful oxysterols, and both sitosterol and campesterol were oxidized into 7 beta-hydroxysitosterol and 7 beta-hydroxycampesterol. The relevance of these findings therefore deserves further exploration.

The hypolipidemic and anti-atherosclerotic effects of vegetable oil- and wood-based dietary plant stanol esters were compared in female apoE*3-Leiden transgenic mice at relevant plasma cholesterol levels. The plant stanol esters derived from vegetable oil (sitostanol 65.7%, campestanol 30.1%) had different contents of sitostanol and campestanol than the plant stanol esters derived from wood (sitostanol 87.6%, campestanol 9.5%) or from a mixture of vegetable oil and wood (sitostanol 73.0%, campestanol 24.7%). The mice (10 per group) received for 38 weeks a control diet or diets containing 1.0%(w/w) plant stanol esters derived from either vegetable oil, wood or a mixture of both. Vegetable oil (-46%), wood (-42%) and vegetable oil/wood (-51%) plant stanol esters decreased the plasma cholesterol levels (P<0.0001) by reducing the cholesterol content in plasma very low density-, intermediate density- and to a lesser extent in low density-lipoprotein. Plant stanol ester feeding did not change plasma triglyceride levels. Dietary plant stanol esters reduced the atherosclerotic lesion area by 91+/-13%(vegetable oil), 97+/-4%(wood) and 78+/-34%(vegetable oil/wood)(P<0.0001) and the severity from regular intimal fatty streaks/mild plaques (on average type 2--3 lesions) in controls to individual intimal foam cells (<type 1 lesions) in the treatment groups (P<0.0001). Plant stanol esters had no effect on adherence of monocytes to the vessel wall. Feeding of plant stanol esters dramatically reduced, independent of its sources, the extent and severity of atherosclerotic lesions, by decreasing VLDL-, IDL- and to a lesser extent LDL-cholesterol in apoE*3-Leiden transgenic mice.

Dietary plant stanols lower serum cholesterol levels in humans and in hyperlipidemic rodents, mainly by inhibition of the intestinal cholesterol absorption. We used female apolipoprotein E*3-Leiden transgenic mice to investigate the consequences of this effect on serum lipid levels and hepatic lipid metabolism. Five groups of 6 or 7 mice received for 9 weeks a diet containing 0.25% cholesterol and 0.0%, 0.25%, 0.5%, 0.75%, or 1.0%(wt/wt) plant stanols (sitostanol 88%[wt/wt], campestanol 10%[wt/wt]) esterified to fatty acids. Compared with the control diet, plant stanol ester treatment dose-dependently reduced serum cholesterol levels by 10% to 33%(P<0.05), mainly in very low density lipoproteins (VLDLs), intermediate density lipoproteins, and low density lipoproteins. Furthermore, 1.0% of the dietary plant stanols significantly decreased the liver contents of cholesteryl esters (-62%), free cholesterol (-31%), and triglycerides (-38%) but did not change the hepatic VLDL-triglyceride and VLDL-apolipoprotein B production rates. However, plant stanol ester feeding significantly decreased the amounts of cholesteryl esters and free cholesterol incorporated in nascent VLDLs by 72% and 30%, respectively, resulting in a net 2-fold decreased VLDL cholesterol output. Liver mRNA levels of low density lipoprotein receptors, 3-hydroxy-3-methylglutaryl coenzyme A synthase, cholesterol 7alpha-hydroxylase, and sterol 27-hydroxylase were not changed by plant stanol ester feeding. Nevertheless, the serum lathosterol-to-cholesterol ratio was significantly increased by 23%, indicating that dietary plant stanol esters increased whole-body cholesterol synthesis. Plant stanol esters also significantly decreased the cholesterol saturation index in bile by 55%. In conclusion, in apolipoprotein E*3-Leiden transgenic mice, plant stanol ester feeding dose-dependently lowered serum cholesterol levels as a result of a reduced secretion of VLDL cholesterol. This was caused by a decreased hepatic cholesterol content that also resulted in a lowered biliary cholesterol output, indicative of a reduced lithogenicity of bile in these mice.

Functional foods enriched with plant sterols and stanols are on sale in many countries. Due to their structural similarity with cholesterol, these additives lower intestinal absorption of cholesterol, resulting in a 10-15% reduction in LDL-cholesterol when their daily intakes are 2-3 g. They are also effective as part of a cholesterol-lowering diet and in combination with cholesterol-lowering drugs. Estimates for the absorption of plant sterols (sitosterol and campesterol) and of campestanol are around 10%, and for sitostanol less than 5%. Lipid-standardized plasma levels are very low, but increase when statins are used. Extensive toxicological evaluation studies have not revealed any harmful side-effects. In human studies, side-effects were comparable to placebo treatment. However, lipid-standardized levels of the hydrocarbon carotenoids may decrease, without leaving the normal range. Together, these findings indicate that these functional foods have great potential in the prevention of coronary heart disease. However, post-marketing surveillance for example for functional foods in general is necessary to monitor possible adverse effects and describe consumers and consumption patterns.

Plant stanols lower intestinal cholesterol absorption. This causes a decrease in serum low-density lipoprotein (LDL)-cholesterol, despite a compensatory increase in cholesterol synthesis. We therefore hypothesized that plant stanols also change LDL-cholesterol-standardized concentrations of ubiquinol-10 (a side product of the cholesterol synthesis cascade) and of those fat-soluble antioxidants that are mainly carried by LDL. To examine this, 112 nonhypercholesterolemic subjects consumed low erucic acid rapeseed oil (LEAR)-based margarine and shortening for 4 weeks. For the next 8 weeks, 42 subjects consumed the same products, while the other subjects received products with vegetable oil-based stanols (2.6 g sitostanol plus 1.2 g campestanol daily, n = 36) or wood-based stanols (3.7 g sitostanol plus 0.3 g campestanol daily, n = 34). Consumption of both plant stanol ester mixtures increased cholesterol synthesis and lowered cholesterol absorption, as indicated by increased serum cholesterol-standardized lathosterol and decreased plant sterol concentrations, respectively. Compared with the control group, absolute plasma ubiquinol-10 concentrations were lowered by 12.3%+/- 18.9%(-0.14 microg/mL v. the control group; P =.004; 95% confidence interval [CI] for the difference in changes,-0.05 to -0.22 microg/mL) in the vegetable oil-based group and by 15.4%+/- 13.0%(-0.17 microg/mL v. the control group; P <.001; 95% CI for the difference,-0.08 to -0.27 microg/mL) in the wood-based group. Changes in LDL-cholesterol-standardized ubiquinol-10 concentrations were not significantly changed. The most lipophylic antioxidants, the hydrocarbon carotenoids (beta-carotene, alpha-carotene, and lycopene), decreased most, followed by the less lipophylic oxygenated carotenoids (lutein/zeaxanthin and beta-cryptoxanthin) and the tocopherols. These reductions were related to the reduction in LDL, which carry most of these antioxidants. The decrease in the hydrocarbon carotenoids, however, was also significantly associated with a decrease in cholesterol absorption. LDL-cholesterol-standardized antioxidant concentrations were not changed, except for beta-carotene, which was still, although not significantly, lowered by about 10%. We conclude that the increase in endogenous cholesterol synthesis during plant stanol ester consumption does not result in increased LDL-cholesterol-standardized concentrations of ubiquinol-10, a side product of the cholesterol synthesis cascade. Furthermore, decreases in absolute fat-soluble antioxidant concentrations are related to decreases in LDL-cholesterol. However, for the most lipophylic carotenoids, some of the reduction was also related to the decrease in cholesterol absorption.

Products enriched with plant sterol and stanol esters selectively lower LDL cholesterol. Consumption appears to be safe, and these functional foods thus have great potential for cardiovascular risk management. Although values remain within the normal range, one possible concern is that they lower lipid-standardized concentrations of the plasma carotenoids. Whether this affects health in the longer-term or in selected patient groups is not known. Therefore, especially in view of the increasing number of functional foods that will be on the market in the very near future, there is a clear need to establish an effective post-marketing safety net.

OBJECTIVE: To examine in humans the effects on serum lipids, lipoproteins and fat-soluble antioxidants of a daily consumption of 2.5 g plant stanols, consumed either once per day at lunch or divided over the three meals. DESIGN: A randomized, double-blind, placebo-controlled, cross-over design. SUBJECTS: Thirty-nine healthy normocholesterolemic or mildly hypercholesterolemic subjects participated. INTERVENTIONS: Each subject consumed in random order; no plant stanols; 2.5 g plant stanols at lunch; and 2.5 g plant stanols divided over the three meals (0.42 g at breakfast, 0.84 g at lunch and 1.25 g at dinner, which is proportional to dietary cholesterol intake). Each period lasted 4 weeks. Plant stanols were esterified with fatty acids from low erucic rapeseed oil (LEAR) and incorporated into margarines or shortenings. RESULTS: Consumption of 2.5 g plant stanols at lunch results in a similar low-density lipoprotein (LDL)-cholesterol-lowering efficacy compared to consumption of 2.5 g plant stanols divided over the three meals (-0. 29 mmol/l compared with the control period (P<0.001; 95% CI,-0.19 to -0.39 mmol/l) for the once per day diet and -0.31 mmol/l (P<0. 001; 95% CI,-0.20 to -0.41 mmol/l)) for the three times per day period). High-density Lipoprotein (HDL) cholesterol and triacylglycerol concentrations did not change. After standardization for LDL cholesterol, the sum of the most lipophylic hydrocarbon carotenoids (ie alpha-carotene, beta-carotene and lycopene) in particular was slightly, though not significantly, lowered by -0. 017+/-0.018 micromol/mmol LDL cholesterol (P=0.307) after the once per day period and by -0.032+/-0.016 micromol/mmol LDL cholesterol (P=0.049) after the three times per day period. CONCLUSIONS: Our findings suggest that for lowering LDL cholesterol concentrations it is not necessary to consume products rich in plant stanol ester at each meal or simultaneously with dietary cholesterol. SPONSORSHIP: Raisio Group, Raisio, Finland.

BACKGROUND & AIMS: Oxidative stress has a key role in atherosclerosis, cancer and other chronic diseases. Some bioactive compounds in nuts have been implicated in antioxidant activities. OBJECTIVE: We assessed how nut consumption affected several markers of oxidation and endothelial function (EF) in metabolic syndrome (MetS) patients. PATIENTS AND METHODS: A randomized, controlled, parallel feeding trial was conducted on 50 MetS adults who were recommended a healthy diet supplemented or not with 30 g of mixed nuts (Nut and Control groups, respectively) every day for 12 weeks. The plasma antioxidant capacity (AC), oxidized LDL (oxLDL), conjugated diene (CD) formation, urine 8-isoprostanes, DNA damage assessed by yield of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), and EF assessed by peripheral artery tonometry (PAT) and biochemical markers, were measured at baseline and the end of the intervention. RESULTS: No significant differences in changes between groups were observed in AC, oxLDL, CD, 8-isoprostanes or EF during the intervention, whereas the reduction in DNA damage was significant in the Nut group compared to Control group (P < 0.001). CONCLUSION: Nut consumption has no deleterious effect on lipid oxidation. The decrease in DNA damage observed in this study could contribute to explain the beneficial effects of regular nut consumption on some MetS features and several chronic diseases.

Evidence is accumulating that high serum concentrations of triacylglycerols (TAG) are, like LDL cholesterol, causally related to cardiovascular disease. A recent meta-analysis has indicated that plant stanol ester (PSE) intake not only lowered LDL cholesterol, but also serum TAG concentrations, especially in subjects with high baseline TAG concentrations. We therefore evaluated the effects of PSE supplementation on lipid metabolism in a population with elevated fasting TAG concentrations. In a randomized, placebo-controlled, parallel study, 28 subjects with elevated TAG concentrations (>1.7 mmol/L) were studied. After a 1-week run-in period during which a control margarine was used, subjects consumed for 3 weeks either control or PSE-enriched margarine (2.5 g/day of plant stanols). Serum plant stanol concentrations increased in all subjects receiving the PSE-enriched margarines, demonstrating good compliance. PSE supplementation significantly decreased serum total (6.7%, P = 0.015) and LDL cholesterol (9.5%, P = 0.041). A significant interaction between baseline TAG concentrations and PSE intake was found; PSE intake lowered TAG concentrations, particularly in subjects with high baseline TAG concentrations (>2.3 mmol/L; P = 0.009). Additionally, a significant interaction between baseline total number of LDL particles (LDL-P) and PSE intake was found (P = 0.020). PSE consumption lowered LDL-P, primarily in subjects with elevated baseline values; this was mainly due to a non-significant decrease in the number of atherogenic small LDL-P. Circulating levels of hs-CRP, glucose, and insulin were not changed after PSE intake. Taken together, PSE supplementation not only lowered LDL cholesterol, but also serum TAG concentrations, especially in subjects with overt hypertriglyceridemia.

A healthy diet and plant sterols (PS) are recommended for reducing low-density lipoprotein (LDL) cholesterol and, subsequently, the risk of premature cardiovascular disease. PS mediate a decrease in fat-soluble vitamin concentration, which can lead to a general impairment of antioxidative defenses and an increase in oxidative stress. Thus, we evaluated the effects of a healthy diet, including PS-enriched low-fat milk, on cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects. This was a randomized parallel trial employing 40 subjects and consisting of two 3-month intervention phases. After 3 months on a standard healthy diet, subjects were divided into two intervention groups: a diet group and a diet+PS group (2 g/day). Lipid profile, apolipoproteins, high-sensitivity C-reactive protein and oxidative stress parameters were analyzed. Diet significantly reduced total and LDL cholesterol (4.0% and 4.7%, respectively), produced an increase in the level of beta-carotene (23%) and improved the antioxidant capacity of LDL cholesterol particles (4.6%). PS induced a significant decrease in total cholesterol (6.4%), LDL (9.9%) and the apolipoprotein B100/apolipoprotein A1 ratio (4.9%), but led to a decrease in cryptoxanthin level (29%) without any change being observed in the antioxidant capacity of LDL cholesterol particles, total antioxidant status or lipid peroxidation. After 3 months, we observed the positive effect of including a PS supplement in dietary measures, as the lipoprotein-mediated risk of cardiovascular disease was reduced. Despite a decrease in the concentration of cryptoxanthin, no evidence of a global impairment of antioxidative defenses or an enhancement of oxidative stress parameters was found.

Abstract Sideritis euboea is a Greek plant that is traditionally consumed as a beverage (mountain tea). From in vitro studies, its extract has shown antioxidant and estrogenic activities. In our study we used S. euboea as an enriching food factor in order to produce a new functional food, a jelly dessert, in order to explore its antioxidant effects if consumed on a daily basis by healthy subjects. In this placebo-controlled clinical trial, 63 subjects were recruited for a 1-month nutritional intervention. Twelve subjects were excluded. The remaining 51 subjects were randomly classified in the intervention group (daily consumption of the jelly containing 0.3 g of S. euboea extract) or the placebo group (daily consumption of the same jelly without the enrichment). Vitamins C, A, and E, glutathione, coenzyme Q10, total nitrites, nitrates, total nitrogen oxide, nitrites/nitrates ratio, and total antioxidant status were measured in blood samples before and after the intervention. After the intervention, free glutathione and coenzyme Q10 increased, and nitrites decreased significantly in both groups. The other antioxidant markers were not altered. No statistical significant differences were observed between the two groups. The daily consumption of the functional food, for 30 days, had no effects on the antioxidant status of healthy volunteers.

Plant stanol esters not only lower low density lipoprotein cholesterol but also have previously been shown to lower serum triacylglycerol (TAG) concentrations, especially in subjects with elevated TAG concentrations. To find a possible explanation, we explored changes in serum lipoprotein profiles, as measured with nuclear magnetic resonance. For this, serum samples from two parallel-designed controlled studies were evaluated before and 8 weeks after the consumption of plant stanol esters. In the first study, dyslipidemic metabolic syndrome subjects participated and in the second study normolipidemic subjects. In metabolic syndrome subjects, plant stanol esters lowered concentrations of large (>60 nm) and medium (35-60 nm) VLDL particles as compared to controls. In normolipidemic subjects, the serum concentration of large VLDL-1 particles was also lowered, although less pronounced. Based on these findings, we hypothesize that the effect of plant stanol esters on serum TAG concentrations origins from a lowered hepatic production of large TAG-rich VLDL-1 particles.

BACKGROUND: Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. AIM OF THE STUDY: We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. METHODS: In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. RESULTS: When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17%(P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 mug/dL, staest: 37 +/- 2 mug/dL, serum campestanol during intervention, controls: 0.5 +/- 0 mug/dL, staest: 9 +/- 1 mug/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. CONCLUSIONS: Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.

Rapeseed oil (RSO) is a novel source of plant sterols, containing the unique brassicasterol in concentrations higher than allowed for plant sterol blends in food products in the European Union. Effects of RSO sterols and stanols on aortic atherosclerosis were studied in cholesterol-fed heterozygous Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n 18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma campestanol (P < 0.001) and sitostanol (P < 0.001) and aortic campestanol (P < 0.05) compared with controls. Feeding RSO sterol esters increased concentrations of plasma campesterol (P < 0.001), sitosterol (P < 0.001) and brassicasterol (P < 0.001) and aortic campesterol (P < 0.01). Significantly lower plasma cholesterol (P < 0.001) was recorded in the treated groups after 3 weeks and throughout the study. LDL-cholesterol was reduced 50 % in the high-dose RSO sterol ester (P < 0.01) and high-dose RSO stanol ester (P < 0.001) groups compared with controls. Atherosclerotic lesions were found in three rabbits in each of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P < 0.001) in response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration of brassicasterol were well tolerated. They were hypocholesterolaemic and inhibited experimental atherosclerosis in cholesterol-fed Hh-WHHL rabbits. A significant uptake of plant sterols into the blood and incorporation of campesterol and campestanol into aortic tissue was recorded.

BACKGROUND AND AIMS: Data comparing the impact of different sources of plant sterols on CVD risk factors and antioxidant levels is scarce. We evaluated the effects of plant sterols from rapeseed and tall oils on serum lipids, lipoproteins, fat-soluble vitamins and plant sterol concentrations. METHODS AND RESULTS: This was a double-blinded, randomized, crossover trial in which 59 hypercholesterolemic subjects consumed 25g/day of margarine for 4weeks separated by 1week washout periods. The two experimental margarines provided 2g/day of plant sterols from rapeseed or tall oil. The control margarine had no added plant sterols. The control margarine reduced LDL cholesterol by 4.5%(95% CI 1.4, 7.6%). The tall and rapeseed sterol margarines additionally reduced LDL cholesterol by 9.0%(95% CI 5.5, 12.4%) and 8.2%(95% CI 5.2, 11.4%) and apolipoprotein B by 5.3%(95% CI 1.0, 9.6%) and 6.9%(95% CI 3.6, 10.2%), respectively. Lipid-adjusted beta-carotene concentrations were reduced by both sterol margarines (P<0.017). alpha-Tocopherol concentrations were reduced by the tall sterol compared to the rapeseed sterol margarine (P=0.001). Campesterol concentrations increased more markedly with the rapeseed sterol versus tall sterol margarine (P<0.001). The rapeseed sterol margarine increased while the tall sterol margarine decreased brassicasterol concentrations (P<0.001). CONCLUSIONS: Plant sterols from tall and rapeseed oils reduce atherogenic lipids and lipoproteins similarly. The rapeseed sterol margarine may have more favorable effects on serum alpha-tocopherol concentrations.

Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P < 0.05). However, the consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P < 0.05). There was no significant effect of any type of oil consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.

Phytosterol and stanol (or phytosterols) consumption reduces intestinal cholesterol absorption, leading to decreased blood LDL-cholesterol levels and lowered cardiovascular disease risk. However, other biological roles for plant sterols and stanols have also been proposed. The objective of this review is to critically examine results from recent research regarding the potential effects and mechanisms of action of phytosterols on forms of cancer. Considerable emerging evidence supports the inhibitory actions of phytosterols on lung, stomach, as well as ovarian and breast cancer. Phytosterols seem to act through multiple mechanisms of action, including inhibition of carcinogen production, cancer-cell growth, angiogenesis, invasion and metastasis, and through the promotion of apoptosis of cancerous cells. Phytosterol consumption may also increase the activity of antioxidant enzymes and thereby reduce oxidative stress. In addition to altering cell-membrane structure and function, phytosterols probably promote apoptosis by lowering blood cholesterol levels. Moreover, consumption of phytosterols by healthy humans at the recommended level of 2 g per day does not cause any major health risks. In summary, mounting evidence supports a role for phytosterols in protecting against cancer development. Hence, phytosterols could be incorporated in diet not only to lower the cardiovascular disease risk, but also to potentially prevent cancer development.European Journal of Clinical Nutrition advance online publication, 3 June 2009; doi:10.1038/ejcn.2009.29.