Stanol Research Articles

Comment on: “A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: Results of a meta-analysis of randomized, placebo controlled trials” by Musa-Veloso K et al., Prostagl. Leucot. Essential Fatty Acids 2011, 85, 9–28

Musa-Veloso et al. have recently published in your journal the results of a meta-analysis with the stated aim of determining whether plant sterols and plant stanols differ in their LDL-cholesterol lowering efficacy across a continuous dose range. This meta-analysis appears thorough in approach and includes data published subsequent to our own recent meta-analysis [ [1] Demonty I et al. J. Nutr. 2009; 139: 271-284 Crossref PubMed Scopus (384) Google Scholar ]. However, due to limitations in this type of meta-analysis as well as the amount of available data, we are concerned about the robustness of the conclusion they draw that the maximal LDL-cholesterol reduction achievable with plant stanols is twofold greater than that achievable with plant sterols. A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: Results of a meta-analysis of randomized, placebo-controlled trialsProstaglandins, Leukotrienes and Essential Fatty AcidsVol. 85Issue 1PreviewTo determine if plant stanols and plant sterols differ with respect to their low-density lipoprotein cholesterol (LDL-CH) lowering efficacies across a continuous dose range. Full-Text PDF

Role of plant sterols in lipid lowering--a safety issue

Sir, In their review Gupta et al .1 failed to emphasize enough the crucial difference between plant sterols and stanols, namely their contrasting effects on plasma levels of plant sterols. Consumption of plant sterol esters raises plasma plant sterols whereas plant stanol esters lower them, by blocking their absorption. Evidence for this differential effect of plant sterols and stanols is derived both from population studies2 and clinical trials. In the latter, serum plant sterol levels increased by 35–120% on consumption of plant sterol 1.6 g daily,3 whereas taking 1.6 g of plant stanol …

The influence of plant stanol on phospholipids monolayers – The effect of phospholipid structure

This work is aimed at investigating the influence of a plant stanol (β-sitostanol) on Langmuir monolayers from various phospholipids and comparing the effect of phytostanol versus its unsaturated analog – phytosterol (β-sitosterol). The studied phospholipids differed in the structure of polar head (phosphatidylcholine – PC, phosphatidylethanolamine – PE, phosphatidylserine – PS) as well as in the number of monounsaturated chains in PC molecule. It was found that the introduction of stanol into PC monolayers is thermodynamically favorable, contrary to its effect on PE and PS films. The magnitude of condensing and ordering effect of stanol depends both on the number of monounsaturated chains in PC molecule and on the composition of stanol-PC mixture. The analysis of BAM images evidenced phase separation of immiscible components in stanol/DPPS systems. The results of Langmuir monolayer studies for stanol/phospholipids mixtures compared with those for corresponding sterol/phospholipids systems proved quite a similar effect of both compounds on the investigated phospholipid monolayers, despite differences in the structure of tetracyclic ring skeleton.

Phytosterols and phytostanols: is it time to rethink that supplemented margarine?

The editorial refers to ‘Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE−/− mice’ by O. Weingartner et al., pp. 484–492, this issue. What are the pertinent questions with regard to dietary supplementation of phytosterols and -stanols? 1. Do they have beneficial effects? 2. Do they have adverse effects in the vessel wall or other organs? 3. Are there any differences between plant sterols and stanols? 4. Should we continue to buy phytosterol/stanol-supplemented food or should it be dropped from the market? For many years now it has generally been accepted that mechanisms leading to a decrease in serum cholesterol lead to a decrease in atherogenesis. Hence, for many years, the use of phytosterols and -stanols, molecules from plant cell membranes resembling cholesterol, has been advocated as a safe and efficient dietary adduct lowering serum LDL cholesterol.1 Just like zoosterols, phytosterols are taken up via the Niemann Pick C1-like 1 protein, thus competing for intestinal uptake. The standard western-type diet contains around 200–400 mg plant sterols, around 50 mg plant stanols, and about 300 mg cholesterol. Dietary addition of either phytosterols or phytostanols, the saturated form of plant sterols, leads to a comparable serum cholesterol …

Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol

Objective We investigated the effects of plant stanol esters (STAEST) on serum cholesterol and lipoprotein lipid concentrations and serum non-cholesterol sterols in patients with type 1 diabetes who were on statin treatment. Methods In a randomized, double-blind, parallel study the intervention group ( n = 12) consumed vegetable oil-based spread enriched with STAEST (3.0 g/d of plant stanols), and the control group ( n = 12) consumed the same spread containing no added plant stanols for 4 weeks. Results Serum total, LDL and non-HDL cholesterol concentrations were decreased by 9.6, 16.4 and 15.3% compared with the baseline concentrations in the STAEST group ( P < 0.05 for all). The respective reductions were 7.8, 14.8 and 12.2% compared with the controls ( P < 0.05 for all). No effects on HDL cholesterol or serum triglyceride concentrations were found. The STAEST consumption significantly decreased serum plant sterol concentrations and the ratios to cholesterol by 30–32 and 25–27% ( P < 0.05 for all) compared with the baseline levels, respectively. Cholesterol synthesis markers were not increased in the STAEST group, but serum lathosterol to campesterol ratio was significantly increased by 57% compared with the baseline levels indicating increased cholesterol synthesis at least to some extent in compensation for decreased cholesterol absorption. However, cholesterol homeostasis, intact at baseline and in the control group also during the intervention was lost in the STAEST group. Conclusion STAEST significantly decreased serum total, LDL and non-HDL cholesterol concentrations and thus offers an additional benefit to cholesterol lowering in patients with type 1 diabetes who are on statin treatment.

Cholesterol-Lowering Effects of Plant Steryl and Stanyl Laurate by Oral Administration in Mice

The present study was conducted to investigate the efficacy of synthesized plant steryl and stanyl laurate in lowering the cholesterol level and to further examine the cholesterol-lowering potential of the free plant sterols and stanols dissolved in liquid emulsion on serum and liver lipids in mice by oral administration. Experimental results showed that both plant steryl and stanyl laurate could significantly decrease the serum levels of TC, LDL-C, LDL-C/HDL-C, and liver cholesterol contents and markedly increase fecal cholesterol concentrations but have no effect on serum TAG level, indicating that the produced plant steryl and stanyl laurate retained the cholesterol-lowering potential of natural plant sterols and stanols. However, no statistical difference in cholesterol-lowering efficacy was observed between plant steryl laurate and plant stanyl laurate, and free plant sterols and stanols dissolved in liquid emulsion could also significantly decrease serum cholesterol levels and markedly increase fecal cholesterol excretion. These results suggested that the esterified plant sterols/stanols had comparable effects to the free plant sterols/stanols in lowering serum TC levels but that they did gain a solubility advantage from the free plant sterols/stanols. Therefore, plant steryl/stanyl laurate could be considered as a potential nutraceutical or functional ingredient to reduce or prevent atherosclerosis and its related complications.

Plant Sterols and Stanols in the Treatment of Dyslipidemia: New Insights into Targets and Mechanisms Related to Cardiovascular Risk

Plant sterols and stanols are naturally occurring constituents of plants and as such normal components of our daily diet. The consumption of foods enriched in plant sterols and stanols may help to reduce low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analyses have shown that consuming approximately 2.5 g plant sterols or stanols per day lowers serum LDL-C concentrations up to 10%, with little additional benefit achieved at higher intakes. However, recent studies evaluating plant stanol intakes up to 9 g/d have indicated that LDL-C concentrations can be reduced up to 17%, which suggests that more pronounced reductions can be achieved at higher intakes. Studies describing effects of high plant sterol intakes on serum LDL-C concentrations are not consistent. Besides the effects of higher than advocated intakes on serum LDL-C concentrations, several topics will be discussed in this review. First, besides the well-characterized effect of plant sterols and stanols on serum LDL-C concentrations, evidence is now emerging of their effects on triacylglycerol metabolism, which makes them highly attractive for interventions in metabolic syndrome-like populations. Secondly, there is an ongoing debate whether increased plant sterol concentrations are associated with an increased cardiovascular disease risk or not. For this there are at least two possible explanations. First, the potential atherogenicity of increased plant sterol concentrations might be ascribed to the formation of plant sterol oxidation products (so-called oxyphytosterols) or secondly, elevated serum plant sterol concentrations should only be seen as surrogate markers for characterizing subjects with high intestinal cholesterol absorption. Finally, we discuss recent studies, which suggest that plant sterols and stanols can improve endothelial dysfunction in subjects at risk, although evidence is limited and more research is needed.

A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: Results of a meta-analysis of randomized, placebo-controlled trials

Purpose To determine if plant stanols and plant sterols differ with respect to their low-density lipoprotein cholesterol (LDL-CH) lowering efficacies across a continuous dose range. Methods Dose-response relationships were evaluated separately for plant stanols and plant sterols and reductions in LDL-CH, using a first-order elimination function. Results Altogether, 113 publications and 1 unpublished study report (representing 182 strata) complied with the pre-defined inclusion and exclusion criteria and were included in the assessment. The maximal LDL-CH reductions for plant stanols (16.4%) and plant stanol ester (17.1%) were significantly greater than the maximal LDL-CH reductions for plant sterols (8.3%) and plant sterol ester (8.4%). These findings persisted in several additional analyses. Discussion and conclusions Intakes of plant stanols in excess of the recommended 2 g/day dose are associated with additional and dose-dependent reductions in LDL-CH, possibly resulting in further reductions in the risk of coronary heart disease (CHD).

Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice.

Aims‘Functional foods’ supplemented with plant sterol esters (PSE) and plant stanol esters (PSA) are therapeutic options for the management of hypercholesterolaemia. However, their effects on blood monocytes, endothelial function, atherogenesis, and sterol tissue concentrations are poorly understood.Methods and resultsMale apoE−/− mice (n= 30) were randomized to three different diets for 6 weeks (n= 10 per group): high-cholesterol (1.25%) western-type diet (WTD), WTD + 2% PSE, and WTD + 2% PSA. Both supplements reduced serum cholesterol. WTD + PSE resulted in increased plant sterol serum concentrations and increased inflammatory Ly-6C(high) monocyte numbers. WTD + PSA increased plant stanol serum concentrations and Ly-6C-monocyte numbers, but decreased vascular superoxide release, lipid hydroperoxides, and inflammatory cytokines in aortic tissue, in plasma, and in circulating monocytes. Despite reduced serum cholesterol concentrations, both supplements impaired endothelial vasodilation compared with WTD. WTD + PSA reduced the development of atherosclerotic lesions compared with WTD alone (12.7 ± 3.7 vs. 28.3 ± 3.5%), and WTD + PSE was less effective (17.5 ± 3.7%). WTD + PSE and WTD + PSA reduced the cholesterol content in the liver, but not in the brain. However, WTD + PSE and WTD + PSA increased plant sterol and plant stanol concentrations in the liver as well as in the brain.ConclusionPSE and PSA supplementation reduced serum cholesterol, but increased plant sterol and plant stanol concentrations. Elevated levels of PSE and PSA were associated with endothelial dysfunction and increased central nervous system depositions. Atherosclerotic lesion retardation was more pronounced in WTD + PSA, coinciding with higher regenerative monocyte numbers, decreased oxidative stress, and decreased inflammatory cytokines compared with WTD + PSE.

Dietary supplementation with phytosterol and ascorbic acid reduces body mass accumulation and alters food transit time in a diet-induced obesity mouse model

Previous research indicates that animals fed a high fat (HF) diet supplemented with disodium ascorbyl phytostanyl phosphate (DAPP) exhibit reduced mass accumulation when compared to HF control. This compound is a water-soluble phytostanol ester and consists of a hydrophobic plant stanol covalently bonded to ascorbic acid (Vitamin C). To provide insight into the mechanism of this response, we examined the in vivo effects of a high fat diet supplemented with ascorbic acid (AA) in the presence and absence of unesterified phytosterols (PS), and set out to establish whether the supplements have a synergistic effect in a diet-induced obesity mouse model. Our data indicate that HF diet supplementation with a combination of 1% w/w phytosterol and 1% w/w ascorbic acid results in reduced mass accumulation, with mean differences in absolute mass between PSAA and HF control of 10.05%; and differences in mass accumulation of 21.6% (i.e. the PSAA group gained on average 21% less mass each week from weeks 7-12 than the HF control group). In our previous study, the absolute mass difference between the 2% DAPP and HF control was 41%, while the mean difference in mass accumulation between the two groups for weeks 7-12 was 67.9%. Mass loss was not observed in animals supplemented with PS or AA alone. These data suggest that the supplements are synergistic with respect to mass accumulation, and the esterification of the compounds further potentiates the response. Our data also indicate that chronic administration of PS, both in the presence and absence of AA, results in changes to fecal output and food transit time, providing insight into the possibility of long-term changes in intestinal function related to PS supplementation.

Plant stanol consumption for cardiovascular health: what do we know about efficacy and safety?

Plant stanol ester enriched with different food products has proven to be effective and safe as a dietary hypocholesterolemic tool in approximately 60 published clinical studies during 15 years on the market. In addition to LDL-C lowering by 10% with 2 g of plant stanols/day, it effectively reduces serum plant sterols, and some studies suggest, also serum triglycerides. Increasing the plant stanol dose up to 9 g/day, LDL-C lowering is dose dependent and a 17% LDL-C reduction can be reached with the maximal dose, similar to that of ezetimibe. Plant stanol ester consumption reduces the plant sterol content of arterial walls, and in some, but not all studies, it improves endothelial function, a surrogate marker of preclinical atherosclerosis. However, hard end point studies both for plant stanol and plant sterol consumption are not available.

Effects of long term plant sterol and -stanol consumption on the retinal vasculature: A randomized controlled trial in statin users

As sitosterolemic patients have an increased cardiovascular risk, there is concern that reducing serum LDL-cholesterol concentrations by plant sterols enriched functional foods might adversely affect vascular function. Whether increased concentrations of plant sterols truly affect vascular function and whether these effects are exclusive to the larger vessels remains unknown. We compared the effects of long-term plant sterol and -stanol consumption on changes in retinal vessels diameter which reflex alterations in the microcirculation. Three randomized groups were studied at baseline and after 85-weeks. Group one (N=11) consumed plant sterol enriched margarine (2.5g/day), the second (N=8) plant stanol enriched margarine (2.5g/day), and the control group (N=11) non-enriched margarine (2.5g/day). Serum cholesterol-standardized campesterol and sitosterol concentrations increased by 354.84±168.22·102μmol/mmol and 84.36±48.26·102μmol/mmol (p<0.001), respectively in the sterol group, while decreasing non-significantly in the plant stanol group. Serum LDL-cholesterol concentrations decreased significantly in both the plant sterol (−0.33±0.33mmol/L, p=0.016) and -stanol groups (−0.38±0.34mmol/L, p=0.018) compared to the increase in the controls (0.29±0.34mmol/L). The mean change in venular diameters for the plant sterol group (2.3±3.1μm), plant stanol groups (−0.8±3.4μm) and control group (−0.8±5.1μm) did not reach significance but the change in cholesterol-standardized campesterol concentrations correlated positively with the change in venular diameter independent of changes in serum LDL-cholesterol concentrations (r=0.39, N=30, p=0.033). Increased serum campesterol concentration correlated positively with increased retinal venular diameter, independent from changes in serum LDL-cholesterol concentrations. This may constitute an explanation for the suggested effects of plant sterols on vascular function. However, this novel finding needs confirmation and further study.

Scientific Opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations (ID 549, 550, 567, 713, 1234, 1235, 1466, 1634, 1984, 2909, 3140), and maintenance of normal pr

Scientific Opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations (ID 549, 550, 567, 713, 1234, 1235, 1466, 1634, 1984, 2909, 3140), and maintenance of normal pr

High-Dose Plant Stanols

High-Dose Plant Stanols

Phytosterol Ester Constituents Affect Micellar Cholesterol Solubility in Model Bile

Plant sterols and stanols (phytosterols) and their esters are nutraceuticals that lower LDL cholesterol, but the mechanisms of action are not fully understood. We hypothesized that intact esters and simulated hydrolysis products of esters (phytosterols and fatty acids in equal ratios) would differentially affect the solubility of cholesterol in model bile mixed micelles in vitro. Sodium salts of glycine- and taurine-conjugated bile acids were sonicated with phosphatidylcholine and either sterol esters or combinations of sterols and fatty acids to determine the amount of cholesterol solubilized into micelles. Intact sterol esters did not solubilize into micelles, nor did they alter cholesterol solubility. However, free sterols and fatty acids altered cholesterol solubility independently (no interaction effect). Equal contents of cholesterol and either campesterol, stigmasterol, sitosterol, or stigmastanol (sitostanol) decreased cholesterol solubility in micelles by approximately 50% compared to no phytosterol present, with stigmasterol performing slightly better than sitosterol. Phytosterols competed with cholesterol in a dose-dependent manner, demonstrating a 1:1 M substitution of phytosterol for cholesterol in micelle preparations. Unsaturated fatty acids increased the micelle solubility of sterols as compared with saturated or no fatty acids. No differences were detected in the size of the model micelles. Together, these data indicate that stigmasterol combined with saturated fatty acids may be more effective at lowering cholesterol micelle solubility in vivo.

Lipase-catalyzed synthesis of phytostanyl esters in non-aqueous media

Stanols are more effective and safer than sterols in lowering plasma total cholesterol, while stanol esters are advantageous since this compound has a better solubility than the free stanols, which contribute to the practical application in foods. The current work focuses on the synthesis of phytostanyl esters from plant stanols and fatty acid such as lauric acid, including screening of various source lipases and selecting solvents of different Log P values. Among lipases from different origins, the immobilized Novozym 435 lipase from microorganism was found to be the best biocatalyst, while plant lipase from Carica papaya and animal lipase from Porcine pancreas are quite ineffective as biocatalyst for the esterification of plant stanols with fatty acid. The highest phytostanyl laurate esterification degree of 79.3% was obtained under the selected conditions: 25 μmol/mL plant stanols, 100 μmol/mL lauric acid, 80 mg/mL 3 Å molecular sieves and 40 mg/mL Novozym 435 at 150 rpm and 55 °C for 96 h in 10 mL of n-hexane. The chemical structure of sitostanyl laurate was confirmed by FT-IR, MS and NMR. The comparison of solubility of plant stanols and phytostanyl laurate in plant oil was done.

Plant stanols dose-dependently decrease LDL-cholesterol concentrations, but not cholesterol-standardized fat-soluble antioxidant concentrations, at intakes up to 9 g/d

It is unclear whether plant stanols lower serum LDL-cholesterol concentrations and cholesterol-standardized fat-soluble antioxidant concentrations dose-dependently when consumption exceeds the recommended daily intakes of 2.0-3.0 g. The objective was to study the relation between plant stanols provided as plant stanol esters on changes in serum concentrations of LDL cholesterol and fat-soluble antioxidants. Healthy subjects (n = 93) with slightly elevated serum total cholesterol concentrations (5.0-8.0 mmol/L) received, after a 3-wk run-in period, control products (n = 22) or products (margarine and soy-based yogurt) providing 3 g (n = 24), 6 g (n = 22), or 9 g (n = 25) plant stanols provided as fatty acid esters for 4 wk. Serum LDL cholesterol decreased dose-dependently. Compared with control, decreases in the 3-g group were 0.32 mmol/L (7.4%; P = 0.005 after adjustment for multiple comparisons). An intake of 6 g plant stanols caused an additional decrease of 0.18 mmol/L (4.5%; P = 0.100 compared with the 3-g group). In the 9-g group, a further decrease of 0.22 mmol/L (5.4%) was observed (P = 0.048 compared with the 6-g group). Serum LDL-cholesterol concentrations were lowered by 17.4% in the 9-g group compared with the control group. No effects on cholesterol-standardized beta-carotene concentrations were observed. Even the change of -0.01 mumol/mmol cholesterol (or -9.2%; P = 0.341) in the 3-g group compared with the control group was not statistically significant because of the large variation in response. Serum HDL-cholesterol and triacylglycerol concentrations, cholesterol-standardized alpha-tocopherol and lutein concentrations, and plasma markers reflecting liver and renal function were not affected. Daily consumption of plant stanols up to 9 g reduces serum LDL-cholesterol concentrations linearly up to 17.4%. For cholesterol-standardized fat-soluble antioxidant concentrations, such a relation could not be ascertained.

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.

Abstract 4374: Plant stanols induce the formation of intestinal adenomas and activate ERK1 signaling in the ApcMin/+ mouse

Abstract Introduction The incidence of colorectal cancer (CRC) has been increasing in many Western countries for several decades. Diet rich in plant foods is known to decrease CRC risk, whereas high intake of fat and cholesterol is associated with an increased risk. Plant sterols have been shown to inhibit colon cancer cell growth in vitro (Awad et al. 1996, Choi et al. 2003). The ApcMin/+ mouse carries a heterozygous germ line mutation in the Apc tumour suppressor gene. The homologous gene is mutated in patients with hereditary colon cancer (FAP, familial adenomatosis polyposis). In the ApcMin/+ mouse, the loss of heterozygosity in Apc allele activates the Wnt/Tcf-pathway which leads to accumulation of β-catenin in the cytosol and its translocation to the cell nucleus. β-Catenin acts as a transcription factor for several genes (e.g. cyclin D1, c-myc) and enhances cell proliferation. ApcMin/+ mice develop dozens of adenomas in the small intestine. The aim of this study was to investigate the effect of plant stanol feeding on adenoma formation and cell signaling in ApcMin/+ mice. The sterol composition of the intestinal mucosa was also analyzed. Materials and methods ApcMin/+ mice were fed either a 0.8% (w/w) plant stanol diet (n=14) or a control diet without plant stanols (n=14). Plant stanols were added to the experimental diet in the form of freeze-dried products with plant stanol ester enrichment. The level of cyclin D1, phosphorylated and total ERK1/2 (extracellular signal regulated kinase) were analyzed from the normal appearing intestinal mucosa by Western blot. Cholesterol, plant sterols (sitosterol, campesterol) and stanols (sitostanol, campestanol) were isolated from the intestinal mucosa by direct saponification method and analyzed by gas chromatography. Results The number of small intestinal adenomas was significantly increased by plant stanol feeding (p=0.002). Plant stanols induced adenoma formation by over 60% compared to the control group. No difference in the size of intestinal adenomas was seen. Plant stanol feeding increased the level of activated ERK1 (the ratio of phosphorylated p44 to total p44) and nuclear cyclin D1 in the intestinal mucosa (p=0.024 and p=0.038, respectively). The level of mucosal cholesterol was not affected by plant stanol feeding; however, the level of sitosterol and campesterol were decreased (p&amp;lt;0.001 for both) and sitostanol and campestanol increased (p&amp;lt;0.001 for both) in the intestinal mucosa of plant stanol fed ApcMin/+ mice. The number of intestinal adenomas and the level of mucosal plant sterols appear to have a negative correlation (rs=-0.517; p=0.007). References Awad et al. Anticancer Res 1996;16:2797-2804. Choi et al. Int J Oncol 2003;23:1657-62. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4374.

Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial

Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (beta = 0.020, P = 0.587 for campesterol/TC and beta<0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.