Customary use of plant sterol and plant stanol enriched margarine is associated with changes in serum plant sterol and stanol concentrations in humans

The consumption of products enriched with plant sterol or stanol esters lowers serum total and LDL-cholesterol concentrations, thereby most likely reducing the risk of coronary heart disease. However, using plant sterol (not plant stanol) enriched products elevates serum plant sterol concentrations in humans. This may be unwanted because health effects of elevated serum plant sterol concentrations are still controversial. Within postlaunch monitoring of functional foods, we compared serum plant sterol and plant stanol concentrations among users of plant sterol (n = 67) or plant stanol (n = 13) enriched margarines with those of matched nonusers (n = 81) in the ongoing Dutch Doetinchem cohort study. Subjects (aged 29-67 y) were examined in 1994-1998 (before the introduction of enriched margarines) and re-examined in 1999-2003. Serum concentrations of plant sterols and stanols were measured in samples from nonfasting subjects by GLC-MS. Intake of plant sterols was 1.1 +/- 0.6 g/d and was associated with a decrease of serum total cholesterol concentration of 0.25 +/- 0.91 mmol/L (4%, P < 0.05), a change that differed (P < 0.05) from the nonsignificant increase in nonusers (+2%, 0.12 +/- 0.78 mmol/L, P = 0.16). Cholesterol-standardized serum sitosterol and campesterol increased in plant sterol users by 22% (P < 0.0001) and 103% (P < 0.0001), respectively. Cholesterol-standardized serum sitostanol and campestanol increased in plant stanol users by 197% (P = 0.02) and 196% (P = 0.01). To our knowledge, these data are the first to show changes in serum cholesterol, plant sterol, and plant stanol concentrations after (long-term) consumption of plant sterol and stanol enriched margarines in a free-living population in a nonexperimental setting. Whether the increased serum sterol concentrations result in adverse side effects needs to be investigated in future postlaunch monitoring studies.     

Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters

Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC-MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood-brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system.     

Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet

Background

Phytosterols in natural foods are thought to inhibit cholesterol absorption. The Mediterranean diet is rich in phytosterol-containing plant foods.

Aim of the study

To assess whether increasing phytosterol intake from natural foods was associated with a cholesterol-lowering effect in a substudy of a randomized trial of nutritional intervention with Mediterranean diets for primary cardiovascular prevention (PREDIMED study).

Methods

One hundred and six high cardiovascular risk subjects assigned to two Mediterranean diets supplemented with virgin olive oil (VOO) or nuts, which are phytosterol-rich foods, or advice on a low-fat diet. Outcomes were 1-year changes in nutrient intake and serum levels of lipids and non-cholesterol sterols.

Results

Average phytosterol intake increased by 76, 158 and 15 mg/day in participants assigned VOO, nuts and low-fat diets, respectively. Compared to participants in the low-fat diet group, changes in outcome variables were observed only in those in the Mediterranean diet with nuts group, with increases in intake of fibre, polyunsaturated fatty acids and phytosterols (P < 0.020, all) and significant (P < 0.05) reductions of LDL-cholesterol (0.27 mmol/l or 8.3%) and the LDL/HDL-cholesterol ratio (0.29 mmol/l or 11.5%). Variations in saturated fat, cholesterol or fibre intake were unrelated to LDL-cholesterol changes. In the whole group, changes in serum sitosterol-to-cholesterol, which reflect those of dietary phytosterol intake and absorption, correlated inversely to LDL-cholesterol changes (r = ?0.256; P = 0.008). In multivariate analyses, baseline LDL-cholesterol, increases in serum sitosterol ratios and statin use were independently associated with LDL-cholesterol reductions.

Conclusions

Small amounts of phytosterols in natural foods appear to be bioactive in cholesterol lowering.     

Safety of long-term consumption of plant sterol esters-enriched spread

OBJECTIVE: To evaluate both efficacy and safety in humans of long-term consumption of spreads containing plant sterol esters. DESIGN: Randomized double-blind placebo-controlled parallel trial. SUBJECTS:: Hundred and eighty-five healthy volunteers (35-64 y). INTERVENTION: Volunteers daily consumed 20 g spread enriched with 1.6 g plant sterols as fatty acid esters or a control spread for 1 y. They continued their habitual diet and lifestyle. Outcome measures included efficacy markers such as total and LDL-cholesterol, a large range of safety parameters, and reporting of adverse events. RESULTS: Consumption of the plant sterol ester-enriched spread consistently lowered total and LDL cholesterol during the 1 y period on average by 4 and 6%, respectively (0.01 < P < 0.05). Plant sterols intake did on average not result in a lower carotenoid concentration (when expressed per LDL-cholesterol) after 52 weeks (P>0.05). However, carotenoid concentrations changed over time. Plant sterols intake reduced lipid adjusted alpha- and beta-carotene-concentrations by only 15-25% after 1 y, relative to control. Lipid-adjusted fat-soluble vitamin concentrations remained unchanged. Plant sterol concentrations in serum were increased from 2.76 to 5.31 ( micro mol/mmol total cholesterol) for campesterol (P<0.0001) and from 1.86 to 2.47 ( micro mol/mmol total cholesterol) for beta-sitosterol (P<0.0001). The increase in total plant sterol concentration in red blood cells (5.29-9.62 micro g/g) did not affect red blood cell deformability. Hormone levels in males (free and total testosterone) and females (luteinizing hormone, follicle stimulating hormone, beta-estradiol and progesterone) as well as all clinical chemical and hematological parameters measured were unaffected. Adverse events reported were not different between subjects consuming control spread and subjects consuming plant sterol esters-enriched spread. CONCLUSION: Consumption of a plant sterol esters-enriched spread is an effective way to consistently lower blood cholesterol concentrations and is safe to use over a long period of time.     

Cost-benefit analysis of a plant sterol containing low-fat margarine for cholesterol reduction

For decreasing the risk of coronary heart disease (CHD) it has been proposed to enrich food such as margarine with plant sterol esters which have been shown to reduce total and LDL cholesterol concentrations, two of the major risk factors. A Markov model was developed to assess the costs and benefits of consuming a low-fat plant sterol containing margarine (PS margarine). A health insurer's perspective was taken with a time frame of 10 years. Transition probabilities for CHD and CHD-related death were calculated on the basis of the Framingham risk equations. These were applied to a representative sample of the German population. The alteration in cholesterol levels after intake of PS margarine was estimated based on a meta-analysis of ten randomized controlled trials with parallel or crossover design that found a reduction of 5.7% in total cholesterol. Average annual costs of CHD were assumed to be at 3,000 euro. Costs for "no CHD" and "CHD-related death" were set to 0 euro since the intervention would solely be paid by the consumers. Sensitivity analyses were performed with regard to annual costs, risk estimation, PS margarine reduction in total cholesterol, discount factor, and risk of CHD-related death. The 10-year CHD risks are 6.1% (PS margarine) vs. 6.5% (control). Thus expected 10-year CHD costs are 696 euro (PS margarine) vs. 748 euro (control). The cost savings of 52 euro varied between 32 euro and 74 euro in the sensitivity analysis. A projection at the level of the population for which evidence (randomized controlled trials) exists that plant sterols lower cholesterol (25.35 million) leads to a reduction of 117,000 CHD cases over 10 years and a cost reduction of 1.3 billion euro for this time period (sensitivity analysis 0.8-1.9 billion euro).     

The lipid lowering effect of plant sterol ester capsules in hypercholesterolemic subjects

Background  

Foods enriched with phytosterols have been proven to be an effective therapy to improve blood lipid profiles. However, none of the studies have investigated the efficacy in lipid lowering of plant sterol esters (PSE) in capsule form. The objective of this study is to determine if the plant sterol esters (PSE) in capsule form (1.3 grams of PSE/day) lowered plasma cholesterol levels and lipid ratios in free-living hypercholesterolemic subjects during a 4-week intervention period.     

Tocopherol,tocotrienol and plant sterol contents of vegetable oils and industrial fats

The tocopherol and tocotrienol (i.e. tocol) and plant sterol contents of 14 vegetable and 9 industrial fats and oils available on the Finnish market in 2005 were determined using NP-HPLC with fluorescence detection (tocols) and GC-FID (plant sterols). Best sources of α-tocopherol were wheat germ (192 mg/100 g) and sunflower oil (59 mg/100 g). Oils richest in γ-tocopherol were camelina (72 mg/100 g), linseed (52 mg/100 g) and organic rapeseed oil (51 mg/100 g). Total tocol contents were between 4.2 mg/100 g (coconut fat) and 268 mg/100 g (wheat germ oil). Plant sterol contents ranged from 69 mg/100 g in a frying fat to 4240 mg/100 g in wheat germ oil. Organic rapeseed oil, the second best source of plant sterols, contained 887 mg/100 g. The variations of the total tocol and sterol contents in 10 rapeseed oil sub-samples analysed separately were 9.7% for tocols and 9.9% for sterols in refined rapeseed oil, and 6.3% for tocols and 4.2% for sterols, respectively, in cold-pressed rapeseed oil. In addition to the target compounds, plastochromanol-8 could be determined in all plant-based samples with contents ranging from 0.13 (walnut oil) to 18 mg/100 g (linseed oil). The lignans sesamin and sesamolin could be identified in sesame oil.     

Soy protein enhances the cholesterol-lowering effect of plant sterol esters in cholesterol-fed hamsters

This study aimed to investigate whether the combination of plant sterol esters (PSE) with soy protein or soy isoflavones may have extra cholesterol-lowering effects. Male hamsters (n=20/group) were fed diets containing (g/100 g diet) (A) 20 casein (control), (B) 0.24 PSE, (C) 20 intact soy protein (replacing casein), (D) 0.02 soy isoflavones, (E) 0.24 PSE plus 20 soy protein (replacing casein), or (F) 0.24 PSE plus 0.02 soy isoflavones, for 5 wk. All diets contained 0.08 g cholesterol/100 g diet. Compared with the control diet, the PSE and soy protein diets significantly lowered the plasma total cholesterol concentration by 13% (P<0.05) and 9% (P<0.05), respectively, whereas the isoflavone diet (D) had no effect. The combination of PSE and soy protein (diet E) decreased plasma total cholesterol by 26% (P<0.05). The decrease in plasma cholesterol concentration was mainly in the non-HDL fraction. In addition, the combination of PSE and soy protein significantly decreased plasma triacylglycerol concentration (37%, P<0.05) and reduced cholesterol accumulation in the liver. The abundance of hepatic LDL-receptors was not influenced by any of the test diets. PSE selectively increased fecal excretion of neutral sterols by 190% (P<0.05), whereas soy protein increased fecal excretion of neutral sterols and bile acids by 66% (P<0.05) and 130% (P<0.05), respectively. The combination of PSE and soy protein increased the fecal excretion of neutral sterols and bile acids compared with PSE and soy protein alone. In conclusion, the combination of PSE and soy protein more dramatically lowers plasma lipids than the individual ingredients.     

Reduction in cholesterol absorption is enhanced by stearate-enriched plant sterol esters in hamsters

Consumption of plant sterol esters reduces plasma LDL cholesterol concentration by inhibiting intestinal cholesterol absorption. Commercially available plant sterol esters are prepared by esterifying free sterols to fatty acids from edible plant oils such as canola, soybean, and sunflower. To determine the influence of the fatty acid moiety on cholesterol metabolism, plant sterol esters were made with fatty acids from soybean oil (SO), beef tallow (BT), or purified stearic acid (SA) and fed to male hamsters for 4 wk. A control group fed no plant sterol esters was also included. Hamsters fed BT and SA had significantly lower cholesterol absorption and decreased concentrations of plasma non-HDL cholesterol and liver esterified cholesterol, and significantly greater fecal sterol excretion than SO and control hamsters. Cholesterol absorption was lowest in hamsters fed SA (7.5%), whereas it was 72.9% in control hamsters. Cholesterol absorption was correlated with fecal sterol excretion (r = -0.72, P < 0.001), liver cholesterol concentration (r = 0.88, P < 0.001), and plasma non-HDL cholesterol concentration (r = 0.85, P < 0.001). A multiple regression model that included each sterol ester type vs. cholesterol absorption indicated that intake of steryl stearate was the only dietary component that contributed significantly to the model (R2 = -0.75, P < 0.001). Therefore, our results demonstrate that BT and SA are more effective than SO in reducing cholesterol absorption, liver cholesterol, and plasma non-HDL cholesterol concentration, suggesting that cardioprotective benefits can be achieved by consuming stearate-enriched plant sterol esters.     

Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP Study). Special Turku Coronary Risk Factor Intervention Project.

Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant sterol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from vegetable oil or margarine in early childhood affect serum concentrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (Delta-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We measured the serum sterol concentrations using gas liquid chromatography in 20 healthy 13-mo-old intervention children in a randomized, prospective study designed to decrease exposure of the children to known environmental atherosclerosis risk factors and in 20 control children. The diet of the intervention children was rich in plant sterols due to replacement of milk fat with vegetable fat, whereas the diet of the control children contained only small amounts of plant sterols. The intervention children consumed twice as much plant sterols as the control children (P < 0.001). Their serum concentrations of campesterol and sitosterol were 75% and 44% higher, respectively, than those in the control children (P < 0.001 for both), but serum cholesterol precursor sterol concentrations did not differ between the two groups. We conclude that doubling dietary plant sterol intake almost doubles serum plant sterol concentrations in 13-mo-old children, but has no effect on endogenous cholesterol synthesis. Relative intestinal absorption of natural plant sterols from the diet in early childhood is similar to that in adults.     

植物固醇对高脂膳食大鼠血脂及脂质过氧化物的影响

目的:研究植物固醇对高脂膳食大鼠的降血脂作用。方法:将50只大鼠随机分为五组,分别为正常对照组、高脂对照组、植物固醇高、中、低剂量组。除正常对照组外,其余各组先喂饲高脂饲料,制作高血脂动物模型;待高脂动物模型成功后,采用植物固醇灌胃进行干预。植物固醇低、中、高剂量分别为0.3、0.6和0.9 g/(kg.d),每天灌胃一次,高脂对照组灌胃同体积豆油,连续4周。测定血脂、肝脂和丙二醛(MDA)等相关指标。结果:与高脂对照组比,植物固醇各剂量组血清三酰甘油(TG)水平显著下降(P<0.05),其中植物固醇高剂量组血清总胆固醇(TC)水平下降极显著(P<0.01)。肝脂水平亦明显下降。植物固醇高剂量组的抗动脉硬化指数和致动脉硬化指数均下降明显。中、低剂量组血清MDA含量显著降低;各植物固醇剂量组肝中MDA含量亦显著下降。结论:植物固醇有显著的降脂、抗氧化和抗动脉硬化作用。     

Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal

OBJECTIVE: To measure the relative effects of each of four phytosterol ester-enriched low-fat foods (bread, breakfast cereal, milk and yoghurt) on serum lipids, plasma phytosterols and carotenoids. DESIGN:: Three research centres undertook a randomised, incomplete crossover, single-blind study consisting of four treatment periods of 3 weeks each, one of which was a control period. Each sterol-enriched test food provided 1.6 g/day of phytosterols as sterol esters. SETTING: General Community. SUBJECTS: In all 58, free-living men and women with mean age (s.d.) 54 (8) y, moderately elevated plasma total cholesterol 6.2 (0.7) mmol/l and body mass index 26.2 (3.0) kg/m(2). MAIN OUTCOME MEASURES: Serum lipids, plasma phytosterols and carotenoids. RESULTS: Serum total and LDL cholesterol levels were significantly lowered by consumption of phytosterol-enriched foods: milk (8.7 and 15.9%) and yoghurt (5.6 and 8.6%). Serum LDL cholesterol levels fell significantly by 6.5% with bread and 5.4% with cereal. They were both significantly less efficacious than sterol-enriched milk (P<0.001). Plasma sitosterol increased by 17-23% and campesterol by 48-52% with phytosterol-enriched milk and bread. Lipid-adjusted beta-carotene was lowered by 5-10% by sterols in bread and milk, respectively. CONCLUSIONS: This is the first study to demonstrate that cholesterol-lowering effects of plant sterol esters may differ according to the food matrix. Plant sterols in low-fat milk was almost three times more effective than in bread and cereal. Despite phytosterol-enriched cereal products resulting in lower serum cholesterol reductions compared to sterol-enriched milk, the detection of similar changes in plasma phytosterols demonstrated that such products still delivered and released phytosterols to the gut.     

Dose-dependent cholesterol-lowering effect of a mayonnaise-type product with a main component of diacylglycerol-containing plant sterol esters

OBJECTIVE: The objective of this study was to investigate the effective dose of plant sterol ester (PSE)-enriched diacylglycerol (DAG) oil for healthy subjects with mild hypercholesterolemia. METHODS: A randomized, placebo-controlled, double-blind, parallel study was performed in patients with mild hypercholesterolemia; 0.0, 0.3, 0.4, and 0.5 g of PSE was dissolved in 15 g of a DAG-containing mayonnaise-type product; and 15 g/d of the product was administered 4 wk. RESULTS: Total serum cholesterol levels were significantly decreased as a result of the ingestion of at least 0.4 g/d of PSE, and serum low-density lipoprotein cholesterol levels were significantly decreased by the ingestion of at least 0.3 g/d of PSE. CONCLUSIONS: Daily ingestion of 15 g of DAG plus mayonnaise containing at least 0.4 g/d of PSE for 4 wk may significantly decrease cholesterol.     

Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread

OBJECTIVE: To study the compliance and changes in plasma lipids, plant sterols, fat-soluble vitamins and carotenoids in children and parents with familial hypercholesterolemia (FH) consuming a plant sterol ester-enriched (PSE) spread. DESIGN: A 26-week open-label follow-up of children who had previously been studied in a controlled cross-over design. The parents were also included in the open-label arm of the study. SETTING: Outpatient clinic for treatment of hyperlipidemia. SUBJECTS: A total of 37 children (7-13 y) and 20 parents (32-51 y) diagnosed with 'definite' or 'possible' heterozygous FH. In all, 19 of the parents, but no children, used statins. All were patients at the Lipid Clinic, National Hospital in Oslo. INTERVENTIONS: Subjects were recommended to eat 20 g/day of PSE spread as part of their lipid-lowering diet. RESULTS: The mean intake of PSE spread was 13.7 and 16.5 g/days in the children and parents, respectively, corresponding to 1.2 and 1.5 g of plant sterols. Plasma total cholesterol decreased by 9.1% in both children (P<0.001) and parents (P=0.002). The corresponding decreases in LDL cholesterol were 11.4% (P<0.001) and 11.0% (P=0.012). Increases in serum lathosterol, campesterol and sitosterol, adjusted for total cholesterol, were observed in the children (31, 96, 48%, respectively, P<0.001) at the end of the controlled cross-over period. In the parents, serum campesterol and sitosterol, adjusted for total cholesterol, increased by 92 and 39%, respectively (P< 0.001). Lipid-adjusted serum alpha- and beta-carotene decreased by 17.4% (P=0.008) and 10.9% (P=0.018), respectively, in the children at the end of the controlled PSE period, but increased again during the follow-up. In the parents, serum alpha- and beta-carotene concentrations were unchanged, while serum lutein and lycopene decreased by 7.3% (P=0.037) and 14.6% (P=0.044), respectively. CONCLUSIONS: Sustained efficacy of cholesterol reduction and long-term compliance of PSE intake were demonstrated in this study.     

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

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