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Helena Gylling - One of the best experts on this subject based on the ideXlab platform.
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are Plant sterols and Plant Stanols a viable future treatment for dyslipidemia
Expert Review of Cardiovascular Therapy, 2016Co-Authors: Helena Gylling, Piia SimonenAbstract:Plant sterols and Plant Stanols are normal components of Plants present in all vegetable foods, especially in vegetable oils (corn oil, rapeseed oil, soybean oil, and sunflower oil), seeds, nuts, a...
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dietary Plant Stanols or sterols neither accumulate in stenotic aortic valves nor influence their structure or inflammatory status
Clinical Nutrition, 2015Co-Authors: Piia Simonen, Helena Gylling, Petri T. Kovanen, Jaakko I Lommi, Maarit Hallikainen, Satu Helskesuihko, Kalervo Werkkala, Markku KupariAbstract:Summary Background & aims Consumption of Plant Stanols and Plant sterols decreases LDL cholesterol level and increases serum concentrations of Plant Stanols/sterols, but it is practically unexplored whether also their tissue concentrations increase. Thus, the aim of this study was to assess whether consuming Plant Stanols/sterols increases their concentrations in stenotic aortic valves and affect the valvular structure (collagen and elastin) or inflammation (macrophages and mast cells). Methods In a randomized, double-blind controlled intervention patients with severe aortic stenosis consumed margarine without (n = 11) or with 2 g of Plant Stanols (n = 12) or sterols (n = 13) until valve replacement surgery (2.6 months, on average). The effects of sitostanol and sitosterol on the expression and secretion of proinflammatory cytokines by cultured aortic valve myofibroblasts were also assessed. Results Control-related LDL-cholesterol was diminished by 16% (p Conclusions In this study, Plant stanol/sterol consumption did not affect cholesterol, Plant stanol or sterol levels in stenotic aortic valves; neither did they influence the structure or the inflammatory status of the valves. However, these findings need to be confirmed in a larger-scale intervention. ClinicalTrials.govRegister # NCT00738933 .
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serum proprotein convertase subtilisin kexin type 9 concentration is not increased by Plant stanol ester consumption in normo to moderately hypercholesterolaemic non obese subjects the blood flow intervention study
Clinical Science, 2015Co-Authors: Piia Simonen, Ulf-håkan Stenman, Helena GyllingAbstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant Stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (Plant stanol group, n =46) or not (control group, n =46) with Plant Stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant Stanols reduced LDL-C by 10% from controls ( P <0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with Plant stanol esters did not affect serum PCSK9 concentration. Thus, Plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal. * BMI, : body mass index; CAD, : coronary artery disease; HDL, : high-density lipoprotein; hs-CRP, : high sensitive C-reactive protein; LDL, : low-density lipoprotein; LDL-C, : LDL cholesterol; PCSK9, : proprotein convertase subtilisin/kexin type 9; SREBP-2, : sterol response element-binding protein 2; VLDL, : very-low-density lipoprotein
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Plant sterols and Plant Stanols in the management of dyslipidaemia and prevention of cardiovascular disease
Atherosclerosis, 2014Co-Authors: Helena Gylling, Jogchum Plat, Dieter Lutjohann, Stephen D Turley, Henry N Ginsberg, Lars Ellegard, Wendy Jessup, Peter J H Jones, Winfried MaerzAbstract:Abstract Objective This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added Plant sterols and/or Plant Stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. Methods and results Plant sterols/Stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/Stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of Plant sterols/Stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of Plant sterols/Stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, Plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6–9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. Conclusion Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with Plant sterols/Stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of Plant sterols or Plant Stanols.
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Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol.
Atherosclerosis, 2011Co-Authors: Maarit Hallikainen, Tatu A. Miettinen, Sudhir Kurl, Markku Laakso, Helena GyllingAbstract:Abstract 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 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.
Jogchum Plat - One of the best experts on this subject based on the ideXlab platform.
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Beneficial Effects of Sitostanol on the Attenuated Immune Function in Asthma Patients: Results of an In Vitro Approach
2016Co-Authors: Ronald P. Mensink, Constanze Husche, Geertjan Wesseling, Y F. Steinbusch, Jogchum PlatAbstract:Background: In vitro and animal studies have suggested that Plant sterols and Stanols increase cytokine production by T-helper-1 cells. This may be beneficial for patient groups characterized by a T-helper-2 dominant immune response, e.g. asthma patients. (1) to evaluate whether sitostanol induces a T-helper-1 shift in peripheral blood mononuclear cells (PBMCs) from asthma patients, and (2) to unravel the role of regulatory T-cells in this respect. Methodology/Principal Findings: PBMCs from 10 asthma patients and 10 healthy subjects were isolated and incubated with 1.2 mM sitostanol, while stimulated with 5 mg/ml PHA. Similar amounts of cholesterol were used to determine whether effects were specific for Plant Stanols or for sterols in general. Changes in cytokine production were measured using antibody arrays and ELISAs. Changes in regulatory T-cell population size were measured by flow cytometry, using intracellular Foxp3 staining. Sitostanol increased production of IFNc by 6.5 % and IL-2 by 6.0 % compared to cholesterol (p,0.01). No changes in IL-4 and IL-13 were found. Interestingly, this effect was only present in PBMCs from asthma patients. The number of Foxp3+ cells tended to increase and their activity, measured by IL-10 production, increased after sitostanol treatment in PBMCs from asthma patients compared to controls by 32.3 % (p = 0.077) and 13.3 % (p,0.05), respectively. Conclusions/Significance: Altogether, the sitostanol-induced Thelper-1 shift in PBMCs from asthma patients and th
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Effects of Plant stanol ester consumption on fasting plasma oxy(phyto)sterol concentrations as related to fecal microbiota characteristics.
The Journal of steroid biochemistry and molecular biology, 2016Co-Authors: Sabine Baumgartner, Ronald P. Mensink, Els De Smet, Maurice Konings, Susana Fuentes, Willem M. De Vos, Jogchum PlatAbstract:Abstract Information regarding dietary effects on plasma oxyphytosterol concentrations as well as on the origin of oxyphytosterols is scarce. We hypothesized that Plant sterols are oxidized in the intestinal lumen, mediated by microbial activity, followed by uptake into the circulation. To address this hypothesis, we carried out, a randomized, double blind, crossover study in 13 healthy subjects, who consumed for 3 weeks control and Plant stanol ester enriched margarines (3.0 g/d Plant Stanols) separated by a 4-week wash-out period. Plasma oxy(phyto)sterols were determined via GC–MS/MS, while microbiota analyses were performed on fecal DNA using a phylogenetic microarray to assess microbial composition and diversity. Plasma Plant sterol concentrations did not correlate with plasma oxyphytosterols concentrations at baseline. Plant stanol consumption reduced serum sitosterol and campesterol concentrations (-37% and -38%), respectively ( p p p p
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Plant sterols and Plant Stanols in the management of dyslipidaemia and prevention of cardiovascular disease
Atherosclerosis, 2014Co-Authors: Helena Gylling, Jogchum Plat, Dieter Lutjohann, Stephen D Turley, Henry N Ginsberg, Lars Ellegard, Wendy Jessup, Peter J H Jones, Winfried MaerzAbstract:Abstract Objective This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added Plant sterols and/or Plant Stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. Methods and results Plant sterols/Stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/Stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of Plant sterols/Stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of Plant sterols/Stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, Plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6–9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. Conclusion Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with Plant sterols/Stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of Plant sterols or Plant Stanols.
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Effect of Plant Stanols on macrophages in vitro.
2014Co-Authors: Jogchum Plat, Els De Smet, Maurice Konings, Tim Hendrikx, Veerle Bieghs, Mike L. J. Jeurissen, Sofie M. A. Walenbergh, Patrick J. Van Gorp, Anita C. E. Vreugdenhil, Yasmin Dias GuichotAbstract:Changes in Tnf-α concentrations in supernatant and LXR target gene expression of bone marrow derived macrophages after incubation with sitostanol (0.6 and 1.2 µm) or desmosterol (0.25, 0.5 and 1.0 µm) and 4 h LPS stimulation. (A) Tnf-α concentrations, (B) LXRα mRNA, (C) Abca1 mRNA, and (D) Abcg1 mRNA expression after sitostanol exposure, (E) Tnf-α mRNA, (F) LXRα mRNA, (G) Abca1 mRNA, and (H) Abcg1 mRNA expression after desmosterol exposure. Data were set relative to cells incubated with cyclodextrin (carrier control). *P
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Composition of the experimental and chow diets.
2014Co-Authors: Jogchum Plat, Els De Smet, Maurice Konings, Tim Hendrikx, Veerle Bieghs, Mike L. J. Jeurissen, Sofie M. A. Walenbergh, Patrick J. Van Gorp, Anita C. E. Vreugdenhil, Yasmin Dias GuichotAbstract:1HFD: high fat diet;2Vitamin mix: vitamins premix, trace elements premix;3Mineral mix: calcium hydrogen phosphate, calcium carbonate, potassium chloride, potassium dihydrogen phosphate, magnesium sulphate heptahydrate, sodium chloride, magnesium oxide;4This added amount of 0.2% cholesterol together with the 0.015% cholesterol from beef fat makes that the diet contains 0.22% cholesterol;5The small amounts of olive oil, soybean oil and linseed oil were added to the HFD and not to the HFD + sterol or stanol esters to make the amount and type of fatty acids in the three HF diets comparable since the fatty acids in the sterol and stanol esters (rapeseed oil fatty acids) become available during digestion.6The 3.1% Plant sterol or stanol esters correspond to ±2% free Plant sterols or Stanols. The Plant Stanols used are a mixture of mainly sitostanol and campestanol 85/15 and the Plant sterols used are a mixture of mainly sitosterol and campesterol 70/30.The chow diet contains ±10.2 en% fat, whereas the HFD contains ±41.5 en% fat.Composition of the experimental and chow diets.
Piia Simonen - One of the best experts on this subject based on the ideXlab platform.
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Lowering Low-Density Lipoprotein Cholesterol Concentration with Plant Stanol Esters to Reduce the Risk of Atherosclerotic Cardiovascular Disease Events at a Population Level: A Critical Discussion.
Nutrients, 2020Co-Authors: Timo E. Strandberg, Petri T. Kovanen, Piia SimonenAbstract:Atherosclerotic cardiovascular diseases (ASCVDs) cause every fifth death worldwide. However, it is possible to prevent the progression of ASCVDs by reducing circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Recent large meta-analyses demonstrated that by reducing the dietary intake of saturated fat and cholesterol, it is possible to reduce the risk of ASCVD events. Plant Stanols, as fatty-acid esters, were developed as a dietary adjunct to reduce LDL-C levels as part of a heart-healthy diet. They reduce cholesterol absorption so that less cholesterol is transported to the liver, and the expression of LDL receptors is upregulated. Ultimately, LDL-C concentrations are reduced on average by 9-12% by consuming 2-3 g of Plant stanol esters per day. In this review, we discuss recent information regarding the prevention of ASCVDs with a focus on dietary means. We also present new estimates on the effect of Plant stanol ester consumption on LDL-C levels and the risk of ASCVD events. Plant stanol esters as part of a heart-healthy diet plausibly offer a means to reduce the risk of ASCVD events at a population level. This approach is not only appropriate for subjects with a high risk of ASCVD, but also for subjects at an apparently lower risk to prevent subclinical atherosclerosis.
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are Plant sterols and Plant Stanols a viable future treatment for dyslipidemia
Expert Review of Cardiovascular Therapy, 2016Co-Authors: Helena Gylling, Piia SimonenAbstract:Plant sterols and Plant Stanols are normal components of Plants present in all vegetable foods, especially in vegetable oils (corn oil, rapeseed oil, soybean oil, and sunflower oil), seeds, nuts, a...
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dietary Plant Stanols or sterols neither accumulate in stenotic aortic valves nor influence their structure or inflammatory status
Clinical Nutrition, 2015Co-Authors: Piia Simonen, Helena Gylling, Petri T. Kovanen, Jaakko I Lommi, Maarit Hallikainen, Satu Helskesuihko, Kalervo Werkkala, Markku KupariAbstract:Summary Background & aims Consumption of Plant Stanols and Plant sterols decreases LDL cholesterol level and increases serum concentrations of Plant Stanols/sterols, but it is practically unexplored whether also their tissue concentrations increase. Thus, the aim of this study was to assess whether consuming Plant Stanols/sterols increases their concentrations in stenotic aortic valves and affect the valvular structure (collagen and elastin) or inflammation (macrophages and mast cells). Methods In a randomized, double-blind controlled intervention patients with severe aortic stenosis consumed margarine without (n = 11) or with 2 g of Plant Stanols (n = 12) or sterols (n = 13) until valve replacement surgery (2.6 months, on average). The effects of sitostanol and sitosterol on the expression and secretion of proinflammatory cytokines by cultured aortic valve myofibroblasts were also assessed. Results Control-related LDL-cholesterol was diminished by 16% (p Conclusions In this study, Plant stanol/sterol consumption did not affect cholesterol, Plant stanol or sterol levels in stenotic aortic valves; neither did they influence the structure or the inflammatory status of the valves. However, these findings need to be confirmed in a larger-scale intervention. ClinicalTrials.govRegister # NCT00738933 .
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serum proprotein convertase subtilisin kexin type 9 concentration is not increased by Plant stanol ester consumption in normo to moderately hypercholesterolaemic non obese subjects the blood flow intervention study
Clinical Science, 2015Co-Authors: Piia Simonen, Ulf-håkan Stenman, Helena GyllingAbstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant Stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (Plant stanol group, n =46) or not (control group, n =46) with Plant Stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant Stanols reduced LDL-C by 10% from controls ( P <0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with Plant stanol esters did not affect serum PCSK9 concentration. Thus, Plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal. * BMI, : body mass index; CAD, : coronary artery disease; HDL, : high-density lipoprotein; hs-CRP, : high sensitive C-reactive protein; LDL, : low-density lipoprotein; LDL-C, : LDL cholesterol; PCSK9, : proprotein convertase subtilisin/kexin type 9; SREBP-2, : sterol response element-binding protein 2; VLDL, : very-low-density lipoprotein
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abstract 15438 serum proprotein convertase subtilisin kexin type 9 levels are not increased by Plant stanol ester consumption
Circulation, 2014Co-Authors: Piia Simonen, Ulf-håkan StenmanAbstract:Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating cholesterol metabolism mainly by binding to LDL receptors targeting them for degradation. Statins, inhibitors of cholesterol synthesis, increase the serum PCSK9 concentration limiting the potential of statins to reduce LDL cholesterol (C) concentration, whereas ezetimibe, an inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant Stanols lower LDL-C by inhibiting cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Hypothesis: We assessed the hypothesis that consumption of Plant stanol esters lowers LDL-C without increasing circulating PCSK9 levels. Methods: Ninety-two normo- and mildly hypercholesterolemic subjects, 35 men and 57 women (mean age 50.8±1.0 (SE) years) were randomly divided into Plant stanol ester (STANOL) (n=46) and control (n=46) groups. They consumed spread enriched with (STANOL group) and without (control group) plan...
Ronald P. Mensink - One of the best experts on this subject based on the ideXlab platform.
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Beneficial Effects of Sitostanol on the Attenuated Immune Function in Asthma Patients: Results of an In Vitro Approach
2016Co-Authors: Ronald P. Mensink, Constanze Husche, Geertjan Wesseling, Y F. Steinbusch, Jogchum PlatAbstract:Background: In vitro and animal studies have suggested that Plant sterols and Stanols increase cytokine production by T-helper-1 cells. This may be beneficial for patient groups characterized by a T-helper-2 dominant immune response, e.g. asthma patients. (1) to evaluate whether sitostanol induces a T-helper-1 shift in peripheral blood mononuclear cells (PBMCs) from asthma patients, and (2) to unravel the role of regulatory T-cells in this respect. Methodology/Principal Findings: PBMCs from 10 asthma patients and 10 healthy subjects were isolated and incubated with 1.2 mM sitostanol, while stimulated with 5 mg/ml PHA. Similar amounts of cholesterol were used to determine whether effects were specific for Plant Stanols or for sterols in general. Changes in cytokine production were measured using antibody arrays and ELISAs. Changes in regulatory T-cell population size were measured by flow cytometry, using intracellular Foxp3 staining. Sitostanol increased production of IFNc by 6.5 % and IL-2 by 6.0 % compared to cholesterol (p,0.01). No changes in IL-4 and IL-13 were found. Interestingly, this effect was only present in PBMCs from asthma patients. The number of Foxp3+ cells tended to increase and their activity, measured by IL-10 production, increased after sitostanol treatment in PBMCs from asthma patients compared to controls by 32.3 % (p = 0.077) and 13.3 % (p,0.05), respectively. Conclusions/Significance: Altogether, the sitostanol-induced Thelper-1 shift in PBMCs from asthma patients and th
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Effects of Plant stanol ester consumption on fasting plasma oxy(phyto)sterol concentrations as related to fecal microbiota characteristics.
The Journal of steroid biochemistry and molecular biology, 2016Co-Authors: Sabine Baumgartner, Ronald P. Mensink, Els De Smet, Maurice Konings, Susana Fuentes, Willem M. De Vos, Jogchum PlatAbstract:Abstract Information regarding dietary effects on plasma oxyphytosterol concentrations as well as on the origin of oxyphytosterols is scarce. We hypothesized that Plant sterols are oxidized in the intestinal lumen, mediated by microbial activity, followed by uptake into the circulation. To address this hypothesis, we carried out, a randomized, double blind, crossover study in 13 healthy subjects, who consumed for 3 weeks control and Plant stanol ester enriched margarines (3.0 g/d Plant Stanols) separated by a 4-week wash-out period. Plasma oxy(phyto)sterols were determined via GC–MS/MS, while microbiota analyses were performed on fecal DNA using a phylogenetic microarray to assess microbial composition and diversity. Plasma Plant sterol concentrations did not correlate with plasma oxyphytosterols concentrations at baseline. Plant stanol consumption reduced serum sitosterol and campesterol concentrations (-37% and -38%), respectively ( p p p p
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effects of Plant sterol or stanol enriched margarine on fasting plasma oxyphytosterol concentrations in healthy subjects
Atherosclerosis, 2013Co-Authors: Sabine Baumgartner, Ronald P. Mensink, Dieter Lutjohann, Constanze Husche, Jogchum PlatAbstract:Abstract Background Consumption of Plant sterols and Plant Stanols reduces low-density lipoprotein cholesterol (LDL-C) concentrations. At the same time, plasma Plant sterol concentrations will increase after Plant sterol consumption, but decrease after Plant stanol consumption. In contrast to Plant Stanols, Plant sterols can undergo oxidation and form oxyphytosterols. Findings from in vitro and animal studies suggest that oxyphytosterols might be atherogenic. Objective The objective was to examine whether Plant sterol and stanol consumption changes fasting plasma oxyphytosterol concentrations. Design A randomized, double blind, cross-over study was performed in which 43 healthy subjects (18–70 years) consumed for 4 weeks a Plant sterol-enriched (3.0 g/d of Plant sterols), a Plant stanol-enriched (3.0 g/d of Plant Stanols), and a control margarine separated by wash-out periods of 4 weeks. Oxyphytosterol concentrations were determined in BHT-enriched plasma via GC–MS. Results Compared to control, serum LDL-C concentrations were reduced after Plant sterol (−8.1%; p p p p p Conclusions Daily consumption of a Plant sterol-enriched margarine does not increase oxyphytosterol concentrations, while Plant stanol consumption may reduce the concentrations of the oxidative Plant sterol metabolites 7β-OH-campesterol and 7-keto-campesterol. This trial is registered at clinicaltrials.gov as NCT01559428.
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beneficial effects of sitostanol on the attenuated immune function in asthma patients results of an in vitro approach
PLOS ONE, 2012Co-Authors: Florence Brull, Ronald P. Mensink, Dieter Lutjohann, Mandy M F Steinbusch, Constanze Husche, Geertjan Wesseling, Jogchum PlatAbstract:BACKGROUND: In vitro and animal studies have suggested that Plant sterols and Stanols increase cytokine production by T-helper-1 cells. This may be beneficial for patient groups characterized by a T-helper-2 dominant immune response, e.g. asthma patients. (1) to evaluate whether sitostanol induces a T-helper-1 shift in peripheral blood mononuclear cells (PBMCs) from asthma patients, and (2) to unravel the role of regulatory T-cells in this respect. METHODOLOGY/PRINCIPAL FINDINGS: PBMCs from 10 asthma patients and 10 healthy subjects were isolated and incubated with 1.2 microM sitostanol, while stimulated with 5 microg/ml PHA. Similar amounts of cholesterol were used to determine whether effects were specific for Plant Stanols or for sterols in general. Changes in cytokine production were measured using antibody arrays and ELISAs. Changes in regulatory T-cell population size were measured by flow cytometry, using intracellular Foxp3 staining. Sitostanol increased production of IFNgamma by 6.5% and IL-2 by 6.0% compared to cholesterol (p<0.01). No changes in IL-4 and IL-13 were found. Interestingly, this effect was only present in PBMCs from asthma patients. The number of Foxp3+ cells tended to increase and their activity, measured by IL-10 production, increased after sitostanol treatment in PBMCs from asthma patients compared to controls by 32.3% (p = 0.077) and 13.3% (p<0.05), respectively. CONCLUSIONS/SIGNIFICANCE: Altogether, the sitostanol-induced Thelper-1 shift in PBMCs from asthma patients and the stimulating effects of sitostanol on Treg cell numbers and activity indicate a possible novel approach for Plant stanol ester enriched functional foods in the amelioration of asthmatic symptoms. Functional effects, however, require further evaluation.
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Plant Stanols dose dependently decrease ldl cholesterol concentrations but not cholesterol standardized fat soluble antioxidant concentrations at intakes up to 9 g d
The American Journal of Clinical Nutrition, 2010Co-Authors: Ronald P. Mensink, Dieter Lutjohann, Arienne De Jong, Guido R M M Haenen, Jogchum PlatAbstract:Background: It is unclear whether Plant Stanols lower serum LDLcholesterol concentrations and cholesterol-standardized fat-soluble antioxidant concentrations dose-dependently when consumption exceeds the recommended daily intakes of 2.0–3.0 g. Objective: 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. Design: Healthy subjects (n ¼ 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 ¼ 22) or products (margarine and soy-based yogurt) providing 3 g (n ¼ 24), 6 g (n ¼ 22), or 9 g (n ¼ 25) Plant Stanols provided as fatty acid esters for 4 wk. Results: Serum LDL cholesterol decreased dose-dependently. Compared with control, decreases in the 3-g group were 0.32 mmol/L (7.4%; P ¼ 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 ¼ 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 ¼ 0.048 compared with the 6-g group). Serum LDLcholesterol concentrations were lowered by 17.4% in the 9-g group compared with the control group. No effects on cholesterolstandardized b-carotene concentrations were observed. Even the change of 20.01 lmol/mmol cholesterol (or 29.2%; P ¼ 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, cholesterolstandardized a-tocopherol and lutein concentrations, and plasma markers reflecting liver and renal function were not affected. Conclusions: 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. Am J Clin Nutr doi: 10.3945/ajcn.2009.29143.
Ulf-håkan Stenman - One of the best experts on this subject based on the ideXlab platform.
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serum proprotein convertase subtilisin kexin type 9 concentration is not increased by Plant stanol ester consumption in normo to moderately hypercholesterolaemic non obese subjects the blood flow intervention study
Clinical Science, 2015Co-Authors: Piia Simonen, Ulf-håkan Stenman, Helena GyllingAbstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant Stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (Plant stanol group, n =46) or not (control group, n =46) with Plant Stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant Stanols reduced LDL-C by 10% from controls ( P <0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with Plant stanol esters did not affect serum PCSK9 concentration. Thus, Plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal. * BMI, : body mass index; CAD, : coronary artery disease; HDL, : high-density lipoprotein; hs-CRP, : high sensitive C-reactive protein; LDL, : low-density lipoprotein; LDL-C, : LDL cholesterol; PCSK9, : proprotein convertase subtilisin/kexin type 9; SREBP-2, : sterol response element-binding protein 2; VLDL, : very-low-density lipoprotein
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abstract 15438 serum proprotein convertase subtilisin kexin type 9 levels are not increased by Plant stanol ester consumption
Circulation, 2014Co-Authors: Piia Simonen, Ulf-håkan StenmanAbstract:Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating cholesterol metabolism mainly by binding to LDL receptors targeting them for degradation. Statins, inhibitors of cholesterol synthesis, increase the serum PCSK9 concentration limiting the potential of statins to reduce LDL cholesterol (C) concentration, whereas ezetimibe, an inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant Stanols lower LDL-C by inhibiting cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Hypothesis: We assessed the hypothesis that consumption of Plant stanol esters lowers LDL-C without increasing circulating PCSK9 levels. Methods: Ninety-two normo- and mildly hypercholesterolemic subjects, 35 men and 57 women (mean age 50.8±1.0 (SE) years) were randomly divided into Plant stanol ester (STANOL) (n=46) and control (n=46) groups. They consumed spread enriched with (STANOL group) and without (control group) plan...