Stanol Research Articles

Low-Fat Formulations of Plant Stanols and Sterols

Clinical trials have shown that an intake of 2 to 3 g/day of esterified plant stanol--when incorporated in margarines or spreads--significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations without affecting serum high-density lipoprotein cholesterol or triglyceride levels. There is also a growing interest in incorporating cholesterol-lowering ingredients into low-fat foods. Esterification of stanols with long-chain fatty acids increases fat solubility by 10-fold and enables the incorporation of plant stanols into different food products, even low-fat foods. It provides a means of introducing an adequate daily amount of stanol for optimal reduction of cholesterol absorption, while maintaining a high-quality food product. Recent clinical trials show that esterified plant stanols effectively reduce serum total and LDL cholesterol levels, even when used in food vehicles with a low-fat content.

History and Development of Plant Sterol and Stanol Esters for Cholesterol-Lowering Purposes

Plant stanol esters provide a novel approach to lowering plasma low-density lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by a long period of research into the cholesterol-lowering properties of plant sterols and, recently, plant stanols. Both classes of compound competitively inhibit the absorption of cholesterol and thus lower its level in plasma. Initial impressions were that stanols were more effective and safer than sterols, but the negative outcome of a study led to the recognition that the lipid solubility of free stanols was very limited. This was overcome by esterifying them with fatty acids, with the resultant stanol esters being freely soluble in fat spreads. This led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995. The coincident publication of the year-long North Karelia study conclusively demonstrated the long-term LDL-lowering efficacy of plant stanol esters. Variables that might influence the efficacy of stanol esters include dose, frequency of administration, food vehicle in which the stanol ester is incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol by 6% to 15%. This effect is maintained, appears to be similar with once-daily or divided dosage, and is independent of the fat content of the food vehicle. Short-term studies suggest that equivalent amounts of plant sterol and stanol esters are similarly effective in lowering LDL, the main difference being that plasma plant sterol levels increase on plant sterols and decrease on plant stanols. The clinical significance of these changes remains to be determined.

Responsiveness of Plasma Lipids and Lipoproteins to Plant Stanol Esters

Plant stanols have been shown to reduce serum levels of low-density lipoprotein (LDL) cholesterol, and they are an attractive adjunct in dietary therapy for elevated LDL cholesterol. This investigation addressed 3 questions through metabolic studies in human subjects: (1) whether plant stanol esters given at higher doses than the 2-g/day dose recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) will provide additional LDL-lowering efficacy (study 1); (2) whether substantial reduction in LDL cholesterol can be obtained in postmenopausal women with hypercholesterolemia by addition of plant stanol esters to the diet (study 2); and (3) whether ATP III goals can be obtained by adding plant stanol esters to an LDL-lowering regimen in high-risk patients who retain LDL cholesterol levels in the above-optimal range (ie, 2.6 to 3.3 mmol/L [100 to 129 mg/dL]), despite ongoing statin therapy (study 3). Study 1 showed that maximal LDL lowering with plant stanols in the form of esters can be achieved at a dose of 2 g/day. Higher doses do not provide additional efficacy. Study 2 demonstrated that stanol esters can reduce LDL cholesterol levels in postmenopausal women by about 13%, which makes use of stanol esters attractive as a component of nondrug therapy in these women who generally are at relatively low risk for coronary heart disease. Finally, study 3 found that plant stanols provide additional lowering of LDL cholesterol when added to ongoing statin therapy. This makes plant stanols an attractive dietary component to help to achieve the goals of LDL-lowering therapy in patients requiring an LDL-lowering drug.

Additive Effects of Plant Sterol and Stanol Esters to Statin Therapy

Plant sterol and stanol esters each have similar additive effects in lowering low-density lipoprotein cholesterol when combined with statins. They differ in that plasma plant sterols increase when plant sterol esters are used for this purpose, especially in patients with familial hypercholesterolemia, but decrease when plant stanol esters are used.

Comparison of Efficacy of Plant Stanol Ester and Sterol Ester: Short-Term and Longer-Term Studies

Published data suggest that the cholesterol-lowering effect of dietary plant sterol esters is less marked in longer-term than in short-term studies, whereas plant stanol esters maintain their efficacy. To investigate this further, healthy subjects and patients with familial hypercholesterolemia (FH) receiving statins were randomized to receive plant sterol ester 1.6 g/day or plant stanol ester 1.6 g/day or 2.6 g/day for 2 months. There was no difference among the 3 groups in the pooled low-density lipoprotein (LDL)-lowering response of FH patients and healthy subjects, but the effect of plant sterol diminished at 2 months and was not significantly different from baseline. This was accompanied by increases in serum plant sterols and a significant decrease in 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, especially in FH patients not taking bile acid sequestrants. In contrast, plant stanol esters lowered significantly both LDL cholesterol and plant sterols at 2 months and had no effect on bile acid synthesis. Slight decreases in serum lipid-soluble antioxidants occurred with both plant sterol and stanol esters. Our findings suggest that absorption of dietary plant sterols downregulates bile acid synthesis, which attenuates their cholesterol-lowering efficacy. We conclude that plant stanol esters are preferable for the long-term management of hypercholesterolemia.

Plant Stanol and Sterol Esters in the Control of Blood Cholesterol Levels: Mechanism and Safety Aspects

Incorporation of plant stanol esters into margarine is among the first examples of a functional food with proven low-density lipoprotein (LDL) cholesterol-lowering effectiveness. Recently, there have been many studies on the effects of plant stanols/sterols on cholesterol metabolism. It has been found that the serum LDL cholesterol-lowering effect of plant stanols/sterols originates from reduced intestinal cholesterol absorption, a process in which changes in micellar composition are thought to play a major role. However, recent findings suggest that there is an additional process in which plant stanols/sterols actively influence cellular cholesterol metabolism within intestinal enterocytes. Furthermore, in response to the reduced supply of exogenous cholesterol, receptor-mediated lipoprotein cholesterol uptake is probably enhanced, as shown by increased LDL receptor expression. At recommended intakes of about 2 to 2.5 g/day, products enriched with plant stanol/sterol esters lower plasma LDL cholesterol levels by 10% to 14% without any reported side effects. Thus, plant stanols/sterols can be considered to be effective and safe cholesterol-lowering functional food ingredients.

Effects Of Dietary Plant Stanol Ester Margarine And Aerobic Exercise Training On Blood Lipid Concentrations

PURPOSE To determine the independent and combined effects of dietary plant stanol ester (PSE) margarine and aerobic exercise training on blood lipid concentrations in 26 healthy sedentary, middle-aged men and postmenopausal women (Age = 53 + 8, BMI = 27±1.0, %FAT= 28.5 ±2). METHOD In a stratified, double blind manner, participants were randomly assigned to either a stanol ester (SEM, n = 17) or a placebo (CON, n = 9) margarine group. Participants supplemented their daily diets with 42 g of a commercially available margarine spread (SEM, PSE = 3 g; CON, PSE = 0 g) for approximately 9 weeks. During the last 4 weeks of margarine supplementation, participants expended 400 kcals on a motor driven treadmill 5 days/week at 65% of VO reserve (2000 kcals/week). Fasting blood samples were obtained prior to initiating and after 4 weeks of margarine supplementation and after exercise training. All blood samples were analyzed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL -C) and HDL-C subfractions (HDL2&3-C). A 2 (Group) × 3 (Time) ANOVA, repeated for the second factor was used to analyze changes in blood lipid concentrations. RESULTS Baseline physiological characteristics and blood lipid concentrations were not different between groups. TC (−10%), LDL-C (−13%) and TG (−18%) concentrations decreased significantly after 4 weeks of margarine supplementation in the SEM group (p <0.05 for all), but not in the CON group. Four weeks of aerobic exercise did not alter TC, LDL-C or TG concentrations in either group; however, a 10 mg/dL increase in HDL-C in the CON group was significant, whereas, a 2 mg/dL increase in the SEM group did not reach statistical significance. The TC/HDL-C ratio decreased significantly in the SEM group but did not change in the CON group. HDL23-C were not altered with either PSE or exercise. DISCUSSION The combined effects of dietary PSE and exercise is reflected in the modest change in the TC/HDL-C ratio observed in the SEM group and suggest that the combination of these therapeutic lifestyle interventions may be an effective strategy for ameliorating dyslipidemia in healthy middle-age men and women.

W09-P-016 Plant sterols and stanols retard lesion progression and induce lesion regression in heterozygous LDL receptor deficient mice as well as atorvastatin

W09-P-016 Plant sterols and stanols retard lesion progression and induce lesion regression in heterozygous LDL receptor deficient mice as well as atorvastatin

W16-P-088 The effects of a simultaneous intake of dietary fiber plus plant stanol esters on serum lipids in slightly hypercholesterolemic subjects

W16-P-088 The effects of a simultaneous intake of dietary fiber plus plant stanol esters on serum lipids in slightly hypercholesterolemic subjects

W16-P-019 Plant stanol consumption stimulates postprandial TH1 immunity in type 2 diabetic patients

W16-P-019 Plant stanol consumption stimulates postprandial TH1 immunity in type 2 diabetic patients

W16-P-054 Plant stanol consumption reduces markers of chronic low-grade inflammation in the postprandial state in type 2 diabetic patients

W16-P-054 Plant stanol consumption reduces markers of chronic low-grade inflammation in the postprandial state in type 2 diabetic patients

Opinion of the NDA Panel related to a notification from Raisio Life Sciences on plant stanol esters produced from soybean oil sterols pursuant to Article 6 paragraph 11 of Directive 2000/13/EC

Opinion of the NDA Panel related to a notification from Raisio Life Sciences on plant stanol esters produced from soybean oil sterols pursuant to Article 6 paragraph 11 of Directive 2000/13/EC

Eficacia hipocolesterolemiante de un yogur que contiene ésteres de estanol vegetal

This clinical trial was carried out with the objective of a preliminar evaluation of the hypocholesteremic effectiveness of a dietary dairy product currently marketed in Spain in the form of drinkable yogurt. Thirty-two adult male and female patients with LDL cholesterol higher than 120 mg/dl were recruited in a pilot, randomized as parallel groups, double-blind, and placebo-controlled clinical trial. Patients consumed during 3 weeks (a bottle a day) Kaiku's Benecol containing 2 g/bottle of plant stanol esters, or a placebo consisting of the same product without plant stanol. Furthermore, all participants carried out some dietary standards. At the beginning and the end of the treatment LDL cholesterol, total cholesterol, and HDL cholesterol were assessed; LDL/HDL index was also calculated. At the end of the treatment in the active group a significant decline (p < 0.01) with regard to the initial levels was observed in LDL cholesterol (157 +/- 30 to 140 +/- 34, mg/dl, mean +/- SD) levels, total cholesterol (235 +/- 34 to 219 +/- 35) levels, and LDL/HDL index (3,2 +/- 1,0 to 3,0 +/- 1,2), without significant changes in HDL cholesterol (48 +/- 15 to 53 +/- 29); in the placebo group there were no significant changes (LDL cholesterol: 168 +/- 25 to 164 +/- 23; total cholesterol: 245 +/- 31 to 237 +/- 23; HDL cholesterol: 51 +/- 12 to 51 +/- 12; LDL/HDL index: 3,4 +/- 0,6 to 3,3 +/- 0,8). In short, consumption of a yogurt a day containing 2 g of stanol reduces significantly the cholesterol levels and this effect is not observed with the placebo.

Phosphatidylinositol increases HDL-C levels in humans

Studies have shown that phosphatidylinositol (PI) can stimulate reverse cholesterol transport by enhancing the flux of cholesterol into HDL and by promoting the transport of high density lipoprotein-cholesterol (HDL-C) to the liver and bile. The goal of this study was to determine the safety and therapeutic value of PI after oral administration to normolipidemic human subjects. We performed a randomized 2 week study in 16 normolipidemic subjects. Subjects received either 2.8 or 5.6 g of PI, with or without food. PI was well tolerated by all subjects. PI significantly affected the levels of HDL-C and triglyceride in the plasma of subjects receiving PI with food. The lower dose showed a 13% increase in HDL-C, whereas the high dose showed an increase of 18% over the 2 week period. Both low- and high-dose groups showed significant increases in plasma apolipoprotein A-I. The high dose of PI also decreased plasma triglycerides by 36% in the fed subjects. These data suggest that after only 2 weeks, PI may have a comparable therapeutic value to niacin, with negligible side effects.

Meta-Analysis of Natural Therapies for Hyperlipidemia: Plant Sterols and Stanols versus Policosanol

To compare the efficacy and safety of plant sterols and stanols as well as policosanol in the treatment of coronary heart disease, as measured by a reduction in low-density lipoprotein cholesterol (LDL) levels. Systematic review and meta-analysis of randomized controlled trials. A total of 4596 patients from 52 eligible studies. We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. Reduction of LDL levels was the primary end point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end points. Weighted estimates of percent change in LDL were -11.0% for plant sterol and stanol esters 3.4 g/day (range 2-9 g/day [893 patients]) versus -2.3% for placebo (769 patients) in 23 eligible studies, compared with -23.7% for policosanol 12 mg/day (range 5-40 mg/day [1528 patients]) versus -0.11% for placebo (1406 patients) in 29 eligible studies. Cumulative p values were significantly different from placebo for both (p<0.0001). The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p<0.0001). Policosanol also affected total cholesterol, high-density lipoprotein cholesterol (HDL), and triglyceride levels more favorably than plant sterols and stanols. Policosanol caused a clinically significant decrease in the LDL:HDL ratio. Pooled withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (95% confidence interval [CI] 0.36-1.95, p=0.69), for plant sterols and stanols across 20 studies versus 0.86% and 0.31, respectively (95% CI 0.20-0.48, p<0.0001), for policosanol across 28 studies. Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy.

Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers

Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations. It is not known whether these polymorphisms are also associated with variations in serum plant sterol concentrations during interventions affecting plant sterol metabolism. We therefore decided to study changes in serum plant sterol concentrations with ABCG5/G8 polymorphisms after consumption of plant stanol esters, which decrease plasma plant sterol concentrations. Cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8 T400K genotype, as were changes in serum plant sterol concentrations after consumption of plant stanols. The reduction of -57.1 +/- 38.3 10(2) x micromol/mmol cholesterol for sitosterol in TT subjects was significantly greater compared with the -36.0 +/- 18.7 reduction in subjects with the TK genotype (P = 0.021) and the -16.9 +/- 13.0 reduction in subjects with the KK genotype (P = 0.047). Changes in serum campesterol concentrations showed a comparable association. No association with serum LDL cholesterol was found. Genetic variation in ABCG8 not only explains cross-sectional differences in serum plant sterol concentrations but also determines a subject's responsiveness to changes in serum plant sterols during interventions known to affect plant sterol metabolism.

Nutritional Supplements Modulating Metabolic Syndrome Risk Factors and the Prevention of Cardiovascular Disease

Metabolic syndrome risk factors (MSRF) can lead to cardiovascular disease (CVD) and its prevalence is increasing at an alarming rate in the United States and worldwide. Pathways leading directly from visceral adiposity to the genesis of free fatty acids and lipid accumulation are mediators of insulin resistance and hypertension. These conditions lead to a proinflammatory and prothrombotic state that can potentiate cardiovascular disease. Metabolic syndrome risk factors are interrelated and associated with predisposition to diabetes, obesity, hypertension and dyslipidemia and, thus, ultimately can lead to CVD. In this review, the authors focused on seven research-supported nutrients available as dietary supplements that offer potential benefits for people with MSRF. For the past two decades, a number of studies have evaluated the role of nutritional supplementation in the prevention of atherogenic and abnormal glucose risk factors. It is, therefore, important to identify strategies that favorably impact MSRF and disease conditions. This review focuses on nutritional compounds such as policosanol, soy proteins, plant stanols, plant esters and isoflavones, omega-3 fatty acids and chromium. These ingredients can beneficially modulate MSRF and, thus, potentially improve disease risk factors and related sequelae. Although the benefits of dietary supplements in general have not been comprehensively elucidated or established, it seems plausible, given available data, that non-pharmacological compounds exhibit the ability to measurably reduce MSRF and, consequently, provide potential protection against CVD and its associated complications. Keywords: metabolic syndrome, insulin resistance and cardiovascular disease

Non-cholesterol sterols in serum, lipoproteins, and red cells in statin-treated FH subjects off and on plant stanol and sterol ester spreads

Background Serum plant sterol levels are increased by consumption of statins and dietary plant sterols, and decreased by dietary plant stanols, but little is known about combination therapy of statin and plant sterols. Methods We measured plant sterols in serum, lipoproteins, and red cells in subjects with familial hypercholesterolemia (FH) ( n=18) treated with variable doses of statins off and on plant stanol (STA) and sterol ester (STE) spreads. Results STA and STE spreads lowered LDL cholesterol ∼15%. Plant sterols were decreased in serum, lipoproteins, and red cells by ∼25% with STA and increased from 37% to 80% with STE, especially with high statin doses. The changes in serum were related to those in red cells. The baseline levels of serum plant sterols were negatively ( r-range −0.639 to −0.935) and positively ( r-range 0.526 to 0.598) correlated with the respective changes evoked by the STA and STE spreads. Conclusions STE reduces LDL cholesterol, but increases serum, lipoprotein, and red cell plant sterol levels in statin-treated FH subjects, while all the respective values are decreased with STA. Recent predictions that elevated serum plant sterols pose an increased coronary risk suggest that increases of serum plant sterol levels should be avoided, especially in atherosclerosis-prone individuals, such as subjects with FH.

Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick C1-like 1 protein gene expression

Possible mechanisms for the cholesterol-lowering effects of plant stanol esters were addressed by feeding hamsters diets containing stanol esters, cholesterol, or cholestyramine/lovastatin. ABCA1, ATP binding cassette G1 (ABCG1), ABCG5, ABCG8, and Niemann-Pick C1-like 1 (NPC1L1) mRNA levels were then estimated in duodenum, jejunum, and ileum. Plasma cholesterol was decreased by 36% and 94% in animals fed stanol esters and cholestyramine/lovastatin, respectively. Cholesterol feeding increased plasma cholesterol by 2.5-fold. Plasma plant sterols were unchanged by stanol ester feeding but became undetectable by feeding cholestyramine/lovastatin. Cholesterol and stanols accumulated in enterocytes of animals fed cholesterol and stanol esters, respectively. ABCG5 and ABCG8 mRNA levels were decreased by stanol esters and cholestyramine/lovastatin. Cholesterol feeding markedly increased ABCA1 and ABCG1 expression and modestly increased ABCG5/ABCG8. NPC1L1 mRNA was not significantly altered by any of the diets. ABCG1, ABCG5, ABCG8, and NPC1L1 mRNAs were highest in cells of the upper villus, whereas ABCA1 mRNA was highest in cells of the lower villus. The results suggest that cholesterol lowering effect of stanol esters is unrelated to changes in mRNA levels of intestinal ABC sterol transporters or NPC1L1. Cholesterol flux regulates ABC expression but not NPC1L1. The different localization of ABCA1 suggests a different function for this protein than for ABCG1, ABCG5, ABCG8, and NPC1L1.

Caracterização físico-química de creme vegetal enriquecido com ésteres de fitosteróis

Atualmente, esteróis e estanóis têm sido adicionados a margarinas especiais, comercialmente disponíveis como alimentos funcionais, com o intuito de reduzir os níveis de colesterol. Como parte de uma dieta saudável, é cientificamente comprovado que esse tipo de produto reduz o colesterol LDL em aproximadamente 10-15%. A literatura disponível sobre os efeitos dos fitosteróis/fitostanóis na redução do colesterol no organismo, bem como a forma como estes componentes são metabolizados, é muito vasta. Porém, informações sobre as propriedades físicas e químicas destas substâncias e os efeitos de sua aplicação em alimentos, do ponto de vista tecnológico, dificilmente são encontradas. Este trabalho tem como objetivo caracterizar um creme vegetal enriquecido com fitosteróis e comparar suas propriedades físicas com as de margarinas comuns disponíveis comercialmente. As composições em ácidos graxos e em esteróis foram determinadas por cromatografia gasosa. Foram, também, analisados ponto de amolecimento, textura, composição química e estrutura cristalina. O creme vegetal enriquecido é composto de 49,3% de umidade, 49,6% de lipídios e 1,1% de sólidos. O b-sitosterol é o esterol mais abundante, constituindo 36,1% do total de esteróis. O ácido linoléico (C18:2 n-6) corresponde a 45,3% do total de ácidos graxos e é o que está presente em maior quantidade. Em geral, as propriedades de textura da base gordurosa e do creme vegetal apresentaram correlação linear significativa. Embora um pouco mais duro que as margarinas cremosas comerciais, o creme vegetal com fitosteróis apresenta plasticidade satisfatória na faixa de temperatura entre a de refrigeração e a ambiente e maior resistência à temperatura do que as margarinas cremosas. Em geral, os ésteres de fitosteróis apresentaram comportamento de fusão e cristalização diferentes dos óleos e gorduras comestíveis.