Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study.

BACKGROUND: Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). METHODS: In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585). RESULTS: Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ. CONCLUSIONS: In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.

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

BACKGROUND: 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. 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 = 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. RESULTS: 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. 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.

Consuming functional foods enriched with plant sterol or stanol esters for 85 weeks does not affect neurocognitive functioning or mood in statin-treated hypercholesterolemic individuals.

Recent animal and human studies have shown that plant sterols and stanols, which are used as functional food ingredients to lower increased LDL cholesterol concentrations, pass the blood-brain barrier. Whether this affects neurocognitive functioning and mental well-being in humans has, to our knowledge, never been investigated. The aim of the present study was therefore to examine the effects of long-term plant sterol or stanol consumption on neurocognitive functioning and mood in a randomized, double-blind, placebo-controlled dietary intervention trial. To this end, hypercholesterolemic individuals, aged 43-69 y, receiving stable statin treatment were randomly assigned to an 85-wk supplementation with margarines enriched with plant sterol esters (2.5 g/d), plant stanol esters (2.5 g/d), or placebo. At baseline and at the end of the intervention period, all participants underwent a cognitive assessment. In addition, subjective cognitive functioning and mood were assessed by means of questionnaires (Cognitive Failure Questionnaire and depression subscale of the Symptom Checklist 90, respectively). Long-term supplementation with plant sterol or stanol esters did not affect cognitive performance (memory, simple information processing speed, complex information processing speed, Letter-Digit Substitution test performance), subjective cognitive functioning, or mood. In conclusion, the present results indicate that long-term use of plant sterols or stanols at recommended intakes of 2.5 g/d does not affect neurocognitive functioning or mood in hypercholesterolemic individuals receiving statin treatment.

Effects of timing and extent of smoking, type of cigarettes, and concomitant risk factors on the association between smoking and subclinical atherosclerosis.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the effects of timing and extent of smoking, type of cigarettes, and concomitant vascular risk factors (VRFs) on the association between smoking and carotid intima-media thickness (C-IMT) in a lipid clinic population. METHODS: 1804 patients (869 men, age 21 to 85 year) participated in the study. Smoking habits were recorded and C-IMTs were measured by B-mode ultrasound. The associations of C-IMT with smoking status (never, former, and current) and with the cigarettes' content of tar, nicotine, and carbon monoxide (alone or combined to define "light" or "regular" cigarettes) as well as the interactions between smoking status, gender, and VRFs were evaluated before and after adjustment for confounders. RESULTS: C-IMT was highest in current smokers, lower in former, and lowest in never smokers. C-IMT of former and current smokers differed only after data adjustment for variables describing the extent and timing of smoking exposure. C-IMT was positively related to the number of pack-years (number of cigarettes smoked per day [cigarettes/d] multiplied by number of years smoked/20) in both former and current smokers. There were no differences in C-IMT between smokers of cigarettes with high or low nicotine, tar, or carbon monoxide content. Both diabetes and hypertension interacted positively with smoking in determining C-IMTs. CONCLUSIONS: In the present cross-sectional observational investigation, carried out in a cohort of patients attending a lipid clinic, consumption of light cigarettes does not reduce the atherogenic effect of smoking on C-IMT. The number of pack-years, cigarettes/d, and years of smoking are relevant covariates in evaluating the effects of smoking on vascular health. The presence of diabetes or hypertension strengthens the association between smoking and cardiovascular risk.

Long-term plant stanol and sterol ester-enriched functional food consumption, serum lutein/zeaxanthin concentration and macular pigment optical density.

Observational epidemiological studies have shown that low carotenoid intake and/or low carotenoid blood levels increase the risk of degenerative diseases like age-related macular degeneration. Functional foods enriched with plant sterol or stanol esters may lower serum concentrations of fat-soluble carotenoids. Theoretically, as a result the macular pigment optical density (MPOD), a marker for eye health, may change. We carried out a double-blind placebo-controlled human intervention trial with a duration of 18 months to evaluate the possible effects of plant stanol and sterol esters on serum lutein/zeaxanthin concentration in relation to the MPOD. Forty-seven subjects were randomly assigned to one of the three treatment groups: margarine without added plant sterols or stanols, plant sterol-enriched margarine, or plant stanol-enriched margarine. Serum cholesterol and lutein/zeaxanthine concentrations and the MPOD were evaluated at baseline and at study end. Changes in lipid-adjusted serum lutein/zeaxanthine concentrations between baseline and study end differed significantly between the three groups (P = 0.001). We found no differences in the MPOD between the three treatment groups, despite the differences in both absolute and cholesterol-standardized serum lutein/zeaxanthine concentrations. This shows that the observed reduction in serum carotenoid concentrations during 18 months consumption of these functional foods does not affect MPOD.

Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment.

Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3-7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n 18) or plant stanol (n 19) (2.5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0.28 mmol/l (or 8.7 %; P = 0.08) and 0.42 mmol/l (13.1 %; P = 0.006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7 alpha-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.

Preferential campesterol incorporation into various tissues in apolipoprotein E*3-Leiden mice consuming plant sterols or stanols.

Intestinal absorption of plant sterols and stanols is much lower as compared with that of cholesterol; and therefore, serum concentrations are low. Circulating plant sterols and stanols are incorporated into tissues. However, hardly any data are available about tissue distributions of individual plant sterols and stanols, particularly in relation to their serum concentrations. We therefore fed female apolipoprotein E*3-Leiden mice a control diet, a plant sterol-enriched diet (1g/100 g diet), or a plant stanol-enriched diet (1g/100 g diet) for 8 weeks. In the sterol group, serum cholesterol-standardized campesterol and sitosterol concentrations were, respectively, 8 and 7 times higher as compared with those in the control group. Consequently, the serum campesterol-sitosterol ratio remained essentially unchanged. Cholesterol-standardized plant sterol concentrations increased significantly in all analyzed tissues, except brain. However, the campesterol-sitosterol ratio also increased in all tissues (except in liver and spleen), suggesting that campesterol is preferentially incorporated over sitosterol in those tissues. For the stanol group, serum plant stanol concentrations also increased; but the increase was but less pronounced. We conclude that, in apolipoprotein E*3-Leiden mice, campesterol is preferentially incorporated into most tissues over sitosterol, which cannot be deduced from changes in serum concentrations.

Carotid intima-media thickness and markers of inflammation, endothelial damage and hemostasis.

BACKGROUND: Different soluble molecules involved in inflammation, endothelial damage, or hemostasis are recognized as potential cardiovascular risk markers. Studies to assess the role of these markers in the atherosclerotic process by evaluating their relationship to carotid intima-media thickness (C-IMT) tend to provide contrasting results. PURPOSE: To perform a review of studies addressing the association between C-IMT and soluble markers and to investigate whether the observed inconsistencies could be explained by the characteristics of the patients included in different studies, for example prevalence of atherosclerotic disease (atherosclerotic burden), gender, age, or occurrence of specific vascular risk factors (VRFs). DATA SOURCES: PubMed and Embase (January 1990 to March 2006). STUDY SELECTION: Articles in English reporting original cross-sectional studies. DATA EXTRACTION: Two authors independently extracted data on study design, population, sample size, ultrasonic methodology, and statistical approach. DATA SYNTHESIS: Despite the marked heterogeneity of results presented in the literature, meta-analysis established that studies showing positive associations between C-IMT and plasma levels of C-reactive protein (CRP) or fibrinogen are in the majority. Funnel plot analyses suggested the absence of an important publication bias. Data on the relationships between C-IMT and other soluble markers are by contrast scanty, contradictory, or unconfirmed by multivariate (as opposed to univariate) analyses, and the freedom from publication bias here cannot be vouched for. The degree of atherosclerotic burden in the population studied does not account for the heterogeneity of findings reported. Gender, noninsulin-dependent diabetes mellitus (NIDDM) and hypercholesterolemia influence the association between C-IMT and CRP. Blood pressure and hypercholesterolemia influence the association between C-IMT and fibrinogen. For all the other soluble markers considered, the number of groups was too small for this kind of statistical considerations. LIMITATIONS: Heterogeneity in ultrasound methodologies and in statistical approach limited comparability between studies. For most soluble markers, publication bias of positive results cannot be excluded. CONCLUSIONS: Only CRP and fibrinogen seem to be unequivocally related to C-IMT. For all the other soluble markers considered, no clear-cut conclusions can be drawn.

Performance in different proprioceptive tests does not correlate in ankles with recurrent sprain.

OBJECTIVE: To determine the relation between 2 proprioceptive tests, movement detection and movement discrimination, at the ankle. DESIGN: A cross-sectional descriptive study. SETTING: Research laboratory. PARTICIPANTS: Eighteen subjects with recurrent ankle inversion sprain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Threshold to detection of movement was tested for inversion and eversion movements at 3 velocities (0.1 degrees , 0.5 degrees , 2.5 degrees /s). Movement discrimination was tested for plantarflexion and inversion movements. The tests were performed in random order, and the velocity and movements were randomized within each test paradigm. Correlations (Pearson r) were calculated between movement detection and movement discrimination. RESULTS: Correlation within each proprioceptive paradigm was poor to moderate: for movement detection, correlations among movement directions at each velocity ranged from r equal to .53 to r equal to .54; for movement discrimination correlation was r equal to .49. There was poor correlation between the scores for the 2 tasks in 10 of the 12 comparisons (r range, -.02 to -.36). CONCLUSIONS: These findings show that performance in different proprioceptive tests is not well correlated and, therefore, that general proprioceptive status cannot be inferred from assessment of a single proprioceptive test.

Metabolic effects of plant sterols and stanols (Review).

High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated.