The effects of acceptance and commitment therapy on eating behavior and diet delivered through face-to-face contact and a mobile app: a randomized controlled trial.

BACKGROUND: Internal motivation and good psychological capabilities are important factors in successful eating-related behavior change. Thus, we investigated whether general acceptance and commitment therapy (ACT) affects reported eating behavior and diet quality and whether baseline perceived stress moderates the intervention effects. METHODS: Secondary analysis of unblinded randomized controlled trial in three Finnish cities. Working-aged adults with psychological distress and overweight or obesity in three parallel groups: (1) ACT-based Face-to-face (n = 70; six group sessions led by a psychologist), (2) ACT-based Mobile (n = 78; one group session and mobile app), and (3) Control (n = 71; only the measurements). At baseline, the participants' (n = 219, 85% females) mean body mass index was 31.3 kg/m2 (SD = 2.9), and mean age was 49.5 years (SD = 7.4). The measurements conducted before the 8-week intervention period (baseline), 10 weeks after the baseline (post-intervention), and 36 weeks after the baseline (follow-up) included clinical measurements, questionnaires of eating behavior (IES-1, TFEQ-R18, HTAS, ecSI 2.0, REBS), diet quality (IDQ), alcohol consumption (AUDIT-C), perceived stress (PSS), and 48-h dietary recall. Hierarchical linear modeling (Wald test) was used to analyze the differences in changes between groups. RESULTS: Group x time interactions showed that the subcomponent of intuitive eating (IES-1), i.e., Eating for physical rather than emotional reasons, increased in both ACT-based groups (p = .019); the subcomponent of TFEQ-R18, i.e., Uncontrolled eating, decreased in the Face-to-face group (p = .020); the subcomponent of health and taste attitudes (HTAS), i.e., Using food as a reward, decreased in the Mobile group (p = .048); and both subcomponent of eating competence (ecSI 2.0), i.e., Food acceptance (p = .048), and two subcomponents of regulation of eating behavior (REBS), i.e., Integrated and Identified regulation (p = .003, p = .023, respectively), increased in the Face-to-face group. Baseline perceived stress did not moderate effects on these particular features of eating behavior from baseline to follow-up. No statistically significant effects were found for dietary measures. CONCLUSIONS: ACT-based interventions, delivered in group sessions or by mobile app, showed beneficial effects on reported eating behavior. Beneficial effects on eating behavior were, however, not accompanied by parallel changes in diet, which suggests that ACT-based interventions should include nutritional counseling if changes in diet are targeted. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01738256 ), registered 17 August, 2012.

High perceived stress is associated with unfavorable eating behavior in overweight and obese Finns of working age.

Stress-related eating may be a potential factor in the obesity epidemic. Rather little is known about how stress associates with eating behavior and food intake in overweight individuals in a free-living situation. Thus, the present study aims to investigate this question in psychologically distressed overweight and obese working-aged Finns. The study is a cross-sectional baseline analysis of a randomized controlled trial. Of the 339 study participants, those with all the needed data available (n = 297, 84% females) were included. The mean age was 48.9 y (SD = 7.6) and mean body mass index 31.3 kg/m(2) (SD = 3.0). Perceived stress and eating behavior were assessed by self-reported questionnaires Perceived Stress Scale (PSS), Intuitive Eating Scale, the Three-Factor Eating Questionnaire, Health and Taste Attitude Scales and ecSatter Inventory. Diet and alcohol consumption were assessed by 48-h dietary recall, Index of Diet Quality, and AUDIT-C. Individuals reporting most perceived stress (i.e. in the highest PSS tertile) had less intuitive eating, more uncontrolled eating, and more emotional eating compared to those reporting less perceived stress (p < 0.05). Moreover, individuals in the highest PSS tertile reported less cognitive restraint and less eating competence than those in the lowest tertile (p < 0.05). Intake of whole grain products was the lowest among those in the highest PSS tertile (p < 0.05). Otherwise the quality of diet and alcohol consumption did not differ among the PSS tertiles. In conclusion, high perceived stress was associated with the features of eating behavior that could in turn contribute to difficulties in weight management. Stress-related way of eating could thus form a potential risk factor for obesity. More research is needed to develop efficient methods for clinicians to assist in handling stress-related eating in the treatment of obese people.

Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

BACKGROUND: The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. METHODS: We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. RESULTS: The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. CONCLUSIONS: Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved. TRIAL REGISTRATION: Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117].

The effects of plant stanol ester consumption on arterial stiffness and endothelial function in adults: a randomised controlled clinical trial.

BACKGROUND: The hypocholesterolemic effect of plant stanol ester consumption has been studied extensively, but its effect on cardiovascular health has been less frequently investigated. We studied the effects of plant stanol esters (staest) on arterial stiffness and endothelial function in adults without lipid medication. METHODS: Ninety-two asymptomatic subjects, 35 men and 57 women, mean age of 50.8±1.0 years (SEM) were recruited from different commercial companies. It was randomized, controlled, double-blind, parallel trial and lasted 6 months. The staest group (n=46) consumed rapeseed oil-based spread enriched with staest (3.0 g of plant stanols/d), and controls (n=46) the same spread without staest. Arterial stiffness was assessed via the cardio-ankle vascular index (CAVI) in large and as an augmentation index (AI) in peripheral arteries, and endothelial function as reactive hyperemia index (RHI). Lipids and vascular endpoints were tested using analysis of variance for repeated measurements. RESULTS: At baseline, 28% of subjects had a normal LDL cholesterol level (≤3.0 mmol/l) and normal arterial stiffness (<8). After the intervention, in the staest group, serum total, LDL, and non-HDL cholesterol concentrations declined by 6.6, 10.2, and 10.6% compared with controls (p<0.001 for all). CAVI was unchanged in the whole study group, but in control men, CAVI tended to increase by 3.1% (p=0.06) but was unchanged in the staest men, thus the difference in the changes between groups was statistically significant (p=0.023). AI was unchanged in staest (1.96±2.47, NS) but increased by 3.30±1.83 in controls (p=0.034) i.e. the groups differed from each other (p=0.046). The reduction in LDL and non-HDL cholesterol levels achieved by staest was related to the improvement in RHI (r=-0.452, p=0.006 and -0.436, p=0.008). CONCLUSIONS: Lowering LDL and non-HDL cholesterol by 10% with staest for 6 months reduced arterial stiffness in small arteries. In subgroup analyses, staest also had a beneficial effect on arterial stiffness in large arteries in men and on endothelial function. Further research will be needed to confirm these results in different populations. TRIAL REGISTRATION: Clinical Trials Register # NCT01315964.

Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose and lipoprotein metabolism. However, the metabolism of cholesterol in NAFLD remains unexplored. We investigated how fatty liver influences cholesterol metabolism in 242 non-diabetic subjects. METHODS: Liver fat content was measured with proton magnetic resonance spectroscopy. Cholesterol metabolism was assayed with serum non-cholesterol sterols, surrogate markers of cholesterol synthesis and absorption. The analyses were performed with gas-liquid chromatography. RESULTS: A total of 114 subjects had NAFLD and 128 subjects had normal liver fat content. Non-cholesterol sterols reflecting cholesterol synthesis (cholestenol, desmosterol, and lathosterol) were higher, and those reflecting cholesterol absorption (cholestanol and plant sterols) were lower in subjects with NAFLD than in controls, independent of body mass index. Liver fat content was positively associated with markers of cholesterol synthesis (r = from 0.262 to 0.344, p < 0.001 for all) and inversely associated with markers of cholesterol absorption (r = from -0.299 to -0.336, p < 0.001 for all). In the entire study group, synthesis and absorption markers were interrelated, indicating that the homeostasis of cholesterol metabolism was maintained. LDL cholesterol was similar in the two groups. CONCLUSIONS: We demonstrated that although LDL cholesterol concentrations are unchanged, cholesterol metabolism in NAFLD is characterized by increased synthesis and diminished absorption of cholesterol. These changes are associated with liver fat content independent of body weight.

Sleep-time physiological recovery is associated with eating habits in distressed working-age Finns with overweight: secondary analysis of a randomised controlled trial.

BACKGROUND: Association of physiological recovery with nutrition has scarcely been studied. We investigated whether physiological recovery during sleep relates to eating habits, i.e., eating behaviour and diet quality. METHODS: Cross-sectional baseline analysis of psychologically distressed adults with overweight (N = 252) participating in a lifestyle intervention study in three Finnish cities. Recovery measures were based on sleep-time heart rate variability (HRV) measured for 3 consecutive nights. Measures derived from HRV were 1) RMSSD (Root Mean Square of the Successive Differences) indicating the parasympathetic activation of the autonomic nervous system and 2) Stress Balance (SB) indicating the temporal ratio of recovery to stress. Eating behaviour was measured with questionnaires (Intuitive Eating Scale, Three-Factor Eating Questionnaire, Health and Taste Attitude Scales, ecSatter Inventory™). Diet quality was quantified using questionnaires (Index of Diet Quality, Alcohol Use Disorders Identification Test Consumption) and 48-h dietary recall. RESULTS: Participants with best RMSSD reported less intuitive eating (p = 0.019) and less eating for physical rather than emotional reasons (p = 0.010) compared to those with poorest RMSSD; participants with good SB reported less unconditional permission to eat (p = 0.008), higher fibre intake (p = 0.028), higher diet quality (p = 0.001), and lower alcohol consumption (p < 0.001) compared to those with poor SB, although effect sizes were small. In subgroup analyses among participants who reported working regular daytime hours (n = 216), only the associations of SB with diet quality and alcohol consumption remained significant. CONCLUSIONS: Better nocturnal recovery showed associations with better diet quality, lower alcohol consumption and possibly lower intuitive eating. In future lifestyle interventions and clinical practice, it is important to acknowledge sleep-time recovery as one possible factor linked with eating habits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01738256 , Registered 17 August 2012.

Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study.

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 +/- 7 vs. 136 +/- 3 10(2) mumol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = -0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.

Very high plant stanol intake and serum plant stanols and non-cholesterol sterols.

BACKGROUND: Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. AIM OF THE STUDY: We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. METHODS: In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. RESULTS: When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 microg/dL, staest: 37 +/- 2 microg/dL, serum campestanol during intervention, controls: 0.5 +/- 0 microg/dL, staest: 9 +/- 1 microg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. CONCLUSIONS: Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.

Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation.

Polymorphisms of the ABCG5 and ABCG8 genes interfere with cholesterol absorption and synthesis. We determined whether common polymorphisms of these genes regulate the responses of serum cholesterol and vascular function during long-term inhibition of cholesterol absorption. Mildly to moderately hypercholesterolaemic subjects (n 282) completed a 1-year study consuming plant stanol or sterol ester (2 g stanol or sterol) or control spread. Serum cholesterol and non-cholesterol sterols, markers of cholesterol absorption and synthesis, and variables of vascular function and structure were analysed in relation to common polymorphisms of ABCG5 and ABCG8. At baseline, subjects with the 54K allele of ABCG8 had higher brachial endothelial-dependent flow-mediated dilatation than those without it (5.79 (se 0.31) v. 4.46 (se 0.44) %; P = 0.049), and subjects with the 632V allele of ABCG8 had larger brachial artery diameter than those without it. Polymorphisms of ABCG5 and ABCG8 were neither associated with serum cholesterol reduction nor changes in cholesterol metabolism or in vascular function. However, in subjects with the 400K allele of ABCG8, intima media thickness (IMT) was increased in all groups more than in those without it (P < 0.05). In conclusion, serum cholesterol lowering with absorption inhibition was not associated with polymorphic sites of ABCG5 and ABCG8. However, regulation of baseline cholesterol metabolism and vascular function and structure, and IMT progression during 1 year seemed to share some of the common polymorphic sites of these genes, suggesting a gene-regulated interaction between cholesterol metabolism and vascular function and structure.

Effect of parenteral serum plant sterols on liver enzymes and cholesterol metabolism in a patient with short bowel syndrome.

Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially available solutions contains plant sterols. It is not known whether plant sterols in parenteral nutrition interfere with hepatic function in adults. We detected how different amounts of plant sterols in parenteral nutrition solution affected serum plant sterol concentrations and liver enzymes during a 1.5-year follow-up in a patient with short bowel syndrome. Serum lipid, plant sterol, and liver enzyme levels were measured regularly during the transition from Intralipid (100% soy-based intravenous fat emulsion) to ClinOleic (an olive oil-based intravenous fat emulsion with 80% olive oil, 20% soy oil and lower plant sterols); the lipid supply was also gradually increased from 20 to 35 g/d. Plant sterols in parenteral nutrition solution and serum were measured with gas-liquid chromatography. During infusion of soy-based intravenous fat emulsion (30 g/d, total plant sterols 87 mg/d), the concentrations of sitosterol, campesterol, and stigmasterol were 4361, 1387, and 378 microg/dL, respectively, and serum liver enzyme values were >or= 2.5 times above upper limit of normal. After changing to olive oil-based intravenous fat emulsion (20-35 g/d, plant sterols 37-65 mg/d), concentrations decreased to 2148 to 2251 microg/dL for sitosterol, 569-297 microg/dL for campesterol, and 95-55 microg/dL for stigmasterol. Concomitantly, liver enzyme values decreased to 1.4 to 1.8 times above upper limit of normal at the end of follow-up. The nutrition status of the patient improved. The amount of plant sterols in lipid emulsion affects serum liver enzyme levels more than the amount of lipid.

Serum adipokines are associated with cholesterol metabolism in the metabolic syndrome.

BACKGROUND: The purpose of this study was to investigate whether cholesterol metabolism is associated with serum adipokines and inflammatory markers. METHODS: In fifty-eight subjects with impaired fasting glucose or impaired glucose tolerance and features of the metabolic syndrome cholesterol metabolism was assayed with serum non-cholesterol sterol ratios to cholesterol, surrogate markers of synthesis (cholesterol precursors) and dietary absorption % of cholesterol (cholestanol and plant sterols) and related them to serum adiponectin, leptin, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Adiponectin was negatively related to synthesis markers (e.g. desmosterol r=-0.371, P<0.01), and positively to absorption markers (e.g. cholestanol r=0.269, P<0.05). Leptin was associated with synthesis markers (e.g. desmosterol r=0.271, P<0.05) and negatively with absorption markers (e.g. sitosterol r=-0.278, P<0.05). Hs-CRP was negatively associated with absorption markers (e.g. sitosterol r=-0.407, P<0.001). IL-6 and TNF-alpha were not related to cholesterol metabolism. When dividing the subjects into tertiles by the serum desmosterol/cholestanol ratio, the I tertile (high synthesis/low absorption) was associated with low adiponectin concentrations, high BMI and serum leptin concentrations (P<0.05 for all). CONCLUSIONS: Adiponectin, leptin and hs-CRP were associated with variables of cholesterol metabolism. A high ratio of cholesterol synthesis to absorption is characterized by high serum leptin and low adiponectin concentrations.

Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome.

BACKGROUND: Carbohydrate modification based on rye bread and pasta enhances early insulin secretion in subjects with the metabolic syndrome. OBJECTIVE: Because the actions of insulin and cholesterol metabolism are interrelated, the question is raised of whether it is possible to alter cholesterol metabolism by means of dietary carbohydrate modification. DESIGN: We investigated the 12-wk effects of dietary carbohydrate modification on cholesterol synthesis and absorption by measuring the ratios of surrogate markers of precursor (cholestenol, desmosterol, and lathosterol) and absorption (cholestanol and plant sterols) sterols to cholesterol and their association to glucose metabolism in 74 subjects with the metabolic syndrome. The subjects were randomly assigned to diets with rye bread and pasta (RPa) or oat, wheat bread, and potato (OWPo) as the main carbohydrate source (34% and 37% of energy intake, respectively). RESULTS: During the study, serum cholesterol concentrations remained unchanged. Cholesterol synthesis was lower (6-10% for cholestenol and lathosterol; P < 0.05) and absorption higher (9%; P < 0.05 for sitosterol) with the OWPo diet than at baseline. With the RPa diet, cholesterol absorption was lower and synthesis higher than with the OWPo diet. The increment in the glucose area under the curve with the RPa diet was positively related to baseline cholesterol synthesis (eg, lathosterol; r = 0.480, P < 0.05) and negatively to absorption (for cholestanol; r = -0.520, P < 0.05). In the combined group, the changes in the cholestanol ratio and the insulinogenic index were interrelated (r = -0.464, P < 0.001). CONCLUSIONS: Carbohydrate modifications had dissimilar effects on cholesterol metabolism. Consumption of RPa, as compared with OWPo, may be clinically more favorable because it seems to inhibit the absorption of cholesterol, a factor crucial in the development of arterial atherosclerosis.

Endothelial function in hypercholesterolemic subjects: Effects of plant stanol and sterol esters.

We investigated the effects of stanol (STAEST) and sterol esters (STEEST) on endothelial function in hypercholesterolemic subjects. In addition, associations of variables of cholesterol metabolism with endothelial function were investigated. In a double-blind randomized cross-over study (n=39) with age-matched parallel control group (n=37) the subjects consumed STAEST or STEEST spread (total plant sterols and stanols 1.93-1.98g/day) for 10 weeks each. Controls consumed the spread without sterols or stanols for 20 weeks. At baseline, brachial artery diameter was positively correlated with serum triglycerides (r=0.375, p=0.001) and glucose (r=0.420, p<0.001) and with cholesterol synthesis marker ratios to cholesterol (e.g. desmosterol r=0.540, p<0.001) and negatively with HDL cholesterol (r=-0.309, p=0.008) and absorption marker ratios (e.g. campesterol r=-0.332, p=0.004). During the intervention, LDL cholesterol was reduced by 6-9% from baseline with STAEST and STEEST spreads (p<0.05), and by 9-12%, respectively, from controls (p<0.05). Flow-mediated dilatation did not change during the investigation. Brachial artery diameter was unchanged in controls and during STAEST periods, but it was reduced during STEEST by 2.2% (p=0.012) from STAEST. In conclusion, variables of cholesterol metabolism are associated with brachial artery diameter at baseline. STEEST diminishes brachial artery diameter, but its clinical relevance remains unclear.

Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial.

BACKGROUND: HMG-CoA reductase inhibitors ('statins') have been associated with a decrease in ubidecarenone (ubiquinone) levels, a lipophilic enzyme also known as coenzyme Q10 (CoQ10), due to inhibition of mevalonate synthesis. There is speculation that a decrease in CoQ10 levels may be associated with statin-induced myopathy. The cholesterol absorption inhibitor ezetimibe increases endogenous cholesterol synthesis. The purpose of this study was to examine (i) the effects of ezetimibe and simvastatin on plasma CoQ10 levels and (ii) whether ezetimibe coadministered with simvastatin abrogates the suggested statin-induced decrease in the CoQ10 plasma levels. METHODS: Seventy-two healthy male subjects were enrolled in a single-centre, randomised, parallel-group study with three arms. Subjects received ezetimibe 10 mg/day, simvastatin 40 mg/day or the combination of ezetimibe 10 mg/day plus simvastatin 40 mg/day for 14 days. RESULTS: Baseline CoQ10 (0.99 +/- 0.30 mg/L) levels for the combined groups remained unchanged in the ezetimibe group (0.95 +/- 0.24 mg/L), and significantly decreased in the simvastatin and combination groups (0.82 +/- 0.18 mg/L, p = 0.0002 and 0.7 +/- 0.22 mg/L, p < 0.0001, respectively). There was a correlation between the percentage change in the levels of low-density lipoprotein-cholesterol (LDL-C) and the percentage change in CoQ10 levels in all treatment groups (correlation coefficient [R] = 0.67, p < 0.0001). The ratios of CoQ10 levels to LDL-C levels were significantly increased in all treatment groups (p < 0.0001). CoQ10 level was independent of cholesterol synthesis or absorption markers. CONCLUSIONS: Simvastatin and the combination of simvastatin and ezetimibe significantly decrease plasma CoQ10 levels whereas ezetimibe monotherapy does not. There is a significant correlation between the CoQ10 level decrease and the decrease in total and LDL-C levels in all three treatment groups, suggesting that the CoQ10 decrease may reflect the decrease in the levels of its lipoprotein carriers and might not be statin-specific. The statin-associated CoQ10 reduction is not abrogated through ezetimibe coadministration. Changes of CoQ10 levels are independent of cholesterol synthesis and absorption.

Postprandial lipemic response and lipoprotein composition in subjects with low or high cholesterol absorption efficiency.

BACKGROUND: The purpose of this study was to investigate the effect of differences in cholesterol absorption efficiency on the postprandial lipemia and lipoprotein composition. METHODS: Fifteen healthy subjects were divided into low and high cholesterol absorbers on the basis of serum cholestanol to cholesterol ratio. A high-performance liquid chromatographic method with evaporative light scattering detection was developed for quantitation of free and esterified cholesterol, triglycerides and major phospholipids from the same lipid extract in two runs utilizing the same internal standard. RESULTS: The free cholesterol to phosphatidylcholine ratio of chylomicrons was higher in the high cholesterol absorption group. The total increase of cholesterol in combined chylomicron and very low density lipoprotein (VLDL) fraction was also higher in this group. Chylomicron free cholesterol and cholesterol ester responses correlated with fasting low density lipoprotein (LDL) cholesterol. VLDL and VLDL1 triglyceride responses correlated inversely with fasting insulin and homeostasis model assessment of insulin resistance. CONCLUSIONS: High cholesterol absorption efficiency was seen in chylomicrons as higher cholesterol to phosphatidylcholine ratio during the postprandial peak. Chylomicron cholesterol response was linked to fasting LDL cholesterol and low VLDL triglyceride response to fasting insulin.

Dietary plant stanols or sterols neither accumulate in stenotic aortic valves nor influence their structure or inflammatory status.

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 < 0.05) by plant stanol and by 11% (NS) by plant sterol consumption, respectively. In the resected valves, cholesterol, plant stanol and sterol levels were similar in all groups. Consumed plant stanols or sterols had no effect on valvular structure or mast cell or macrophage numbers in valves. Incubation of cultured myofibroblasts derived from stenotic valves with sitostanol or sitosterol decreased mRNA expression of the monocyte chemotactic protein-1 (p < 0.05) and interleukin-1 beta (p < 0.05). 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.

Short-term LDL cholesterol-lowering efficacy of plant stanol esters.

BACKGROUND: The short-term cholesterol-lowering efficacy of plant stanol esters has been open to debate, and the data from different clinical studies with hypercholesterolemic subjects are variable, partly due to lack of systematic studies. Therefore, we investigated the time in days needed to obtain the full cholesterol-lowering effect of stanol esters in hypercholesterolemic subjects. METHODS: Eleven mildly to moderately hypercholesterolemic subjects consumed stanol ester margarine (2.0 g/day of stanols) as a part of their habitual diet for 14 days and the changes in serum lipid values were measured three times at 4, 8 and 15 days after the initiation of test margarine consumption (0 day). The returning of serum lipid concentrations to baseline was measured two times after 2 or 3 days and after 7 days of the end of the test margarine consumption. RESULTS: Serum LDL cholesterol concentrations were reduced from 0 day (4.51 +/- 0.66 mmol/l) by 3.5% (P = ns), 9.9% (p < 0.05) and 10.2% (P < 0.05) at 4, 8 and 15 days, respectively. Serum campesterol/total cholesterol ratio, an indirect marker of intestinal cholesterol absorption, was significantly reduced on day 4 already. After ending the stanol ester use serum cholesterol concentrations began to return rapidly and after 7 days serum LDL cholesterol was 5.3% less than the initial value (P = ns). CONCLUSION: The specific effect of plant stanol esters on serum LDL cholesterol can fully be obtained within 1-2 weeks of the use of plant stanol ester-enriched margarine.

Low-Fat Nondairy Minidrink Containing Plant Stanol Ester Effectively Reduces LDL Cholesterol in Subjects with Mild to Moderate Hypercholesterolemia as Part of a Western Diet.

The cholesterol-lowering efficacy of plant stanol ester (STAEST) added to fat- or milk-based products is well documented. However, their efficacy when added to nondairy liquid drinks is less certain. Therefore, we have investigated the cholesterol-lowering efficacy of STAEST added to a soymilk-based minidrink in the hypercholesterolemic subjects. In a randomized, double-blind, placebo-controlled parallel study, the intervention group (n = 27) consumed 2.7 g/d of plant stanols as the ester in soymilk-based minidrink (65 mL/d) with the control group (n = 29) receiving the same drink without added plant stanols once a day with a meal for 4 weeks. Serum total, LDL, and non-HDL cholesterol concentrations were reduced by 8.0, 11.1, and 10.2% compared with controls (P < 0.05 for all). Serum plant sterol concentrations and their ratios to cholesterol declined by 12-25% from baseline in the STAEST group while the ratio of campesterol to cholesterol was increased by 10% in the controls (P < 0.05 for all). Serum precursors of cholesterol remained unchanged in both groups. In conclusion, STAEST-containing soymilk-based low-fat minidrink consumed once a day with a meal lowered LDL and non-HDL cholesterol concentrations without evoking any side effects in subjects consuming normal Western diet. The clinical trial registration number is NCT01716390.

Diet and cardiovascular health in asymptomatic normo- and mildly-to-moderately hypercholesterolemic participants - baseline data from the BLOOD FLOW intervention study.

BACKGROUND: For decades in Finland, intensive population strategies and preventive activities have been used to lower the risk of atherosclerotic coronary heart disease (CHD). Lifestyle changes, with the emphasis on diet, play an important role in preventive strategies. The aim of this study was to evaluate arterial stiffness and endothelial function in asymptomatic free-living adults and to relate the results to CHD risk factors and lifestyle habits with the emphasis on diet. METHODS: Ninety-four asymptomatic participants were recruited by advertisements in four large companies and two research institutes employing mainly office workers. Arterial stiffness was assessed as the cardio-ankle vascular index in large arteries, and endothelial function as the reactive hyperemia index with peripheral arterial tonometry. The systematic Cardiovascular Risk Estimation (SCORE) was calculated. RESULTS: The data was collected in the spring of 2011. Anthropometric, dietary, and lipid data was available from 92 participants, blood pressure from 85 and vascular measurements from 86-88 subjects (38% males; 62% females; mean age of all 51). The majority (72%) had an elevated low density lipoprotein (LDL) cholesterol concentration and over half were overweight or obese. SCORE stated that 49% of the participants had a moderate risk of cardiovascular disease. When compared to general recommendations, half of the participants had too high intake of total fat and in 66% the consumption of saturated fat was too high. In contrast, the intake of carbohydrates was too low in 90% of the participants and for fiber 73% were below recommendations. There was evidence of borderline or increased arterial stiffness in 72% of the participants and endothelial function was impaired in 8%. Arterial stiffness was associated with LDL cholesterol concentration (p = 0.024), dietary cholesterol intake (p = 0.029), and SCORE (p < 0.001). CONCLUSIONS: In a cross-sectional study of asymptomatic middle-aged participants, the half had a moderate risk for cardiovascular diseases manifested as increased arterial stiffness, elevated LDL cholesterol concentration, and poor dietary habits. The new observation that arterial stiffness was associated with dietary cholesterol intake and SCORE emphasizes the urgency of adequate lifestyle and dietary interventions to prevent future coronary events even in asymptomatic participants. TRIAL REGISTRATION: Clinical Trials Register # NCT01315964.

Cholesterol metabolism and weight reduction in subjects with mild obstructive sleep apnoea: a randomised, controlled study.

To evaluate whether parameters of obstructive sleep apnoea (OSA) associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention (N = 23) or to control group (N = 18) with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols) and synthesis (cholestenol, desmosterol, and lathosterol) at baseline and after 1-year intervention. At baseline, arterial oxygen saturation (SaO2 ) was associated with serum campesterol (P < 0.05) and inversely with desmosterol ratios (P < 0.001) independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR). Apnoea-hypopnoea index (AHI) was not associated with cholesterol metabolism. Weight reduction significantly increased SaO2 and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (P < 0.05). In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.