The -250G/A polymorphism in the hepatic lipase gene promoter influences the postprandial lipemic response in healthy men

Background and aimThe −250G/A promoter polymorphism of the hepatic lipase gene has been associated with changes in the activity of the enzyme. We investigated whether this polymorphism modifies the postprandial response of triacylglycerol-rich lipoproteins (TRL) in young normolipemic males.Methods and resultsFifty-one healthy apolipoprotein (apo) E3/E3 male volunteers (30 G/G and 21 carriers of the A allele) underwent a vitamin A fat-loading test and blood samples were drawn every hour until the 6th, and every 2 h and 30 min until the 11th. Total plasma cholesterol and triacylglycerols (TG), as well as cholesterol, TG and retinyl palmitate (RP) in TRL, isolated by ultracentrifugation, were determined.Carriers of the A allele showed a higher response (P = 0.008), a higher area under the curve (AUC; P = 0.022) and a lower RP peak time (P = 0.029) in small TRL during the postprandial response, as well as a lower peak time in total plasma TG levels (P = 0.034) and large TRL-TG (P = 0.033) than subjects who were homozygous for the G allele.ConclusionOur data indicate that the presence of the A allele in the −250G/A promoter polymorphism of the hepatic lipase gene is associated with a higher postprandial lipemic response.     

Decreased lipoprotein lipase activity and increased postprandial concentrations of triglyceride-rich lipoproteins in offspring of elderly survivors of myocardial infarction

Background and aimA family history of myocardial infarction (MI) is an independent risk factor for future coronary events. Decreased plasma lipoprotein lipase (LPL) activity is associated with delayed clearance of triglyceride-rich lipoproteins (TRL) and low fasting HDL cholesterol. The aim of the study was to investigate the relations between plasma LPL activity, postprandial TRL and HDL cholesterol in offspring of MI patients.Methods and resultsA case-control study was performed in 17 healthy middle-aged offspring of MI patients and 13 healthy age-and sex-matched controls. Fasting blood samples were collected and each subject was given a standardized oral fat load (1 g fat/kg body weight) with subsequent blood samples collected for an 8-h period. Offspring of MI patients had significantly lower postheparin LPL activity (62.9 mU/ml ± 22.8 mU/ml) (mean ± SD) than healthy controls (93.0 mU/ml ± 21.7 mU/ml) (p = 0.002). Decreased postheparin LPL activity was accompanied by significantly increased and delayed clearance of postprandial TRL and subsequent lower fasting HDL cholesterol in offspring of MI patients. Postheparin LPL activity was associated with HDL cholesterol (r = 0.40, p = 0.036) and trend analysis revealed a decrease in incremental area under the curve (AUCi) for chylomicrons with increasing LPL activity (p = 0.013).ConclusionsOffspring of MI patients had decreased postheparin LPL activity accompanied by increased postprandial TRL and subsequent decreased HDL cholesterol, an unfavourable lipid profile which may contribute to their increased risk for future coronary events.     

The Mediterranean and CHO diets decrease VCAM-1 and E-selectin expression induced by modified low-density lipoprotein in HUVECs

Background and AimThe oxidative modifications of low-density lipoprotein (LDL) are crucial for the atherosclerosis process. The aim of this study was to determine if the minimally modified LDL, obtained after the ingestion of three different diets, produce differential effects on the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression in human umbilical endothelial cells (HUVECs).Methods and ResultsTwenty healthy young males were exposed to three dietary periods. Each period lasted four weeks. During the first period, all subjects consumed a saturated fat (SFA) enriched diet (38% fat, 20% SFA). The second and third dietary periods were administered following a randomized crossover design: a low fat high carbohydrates diet (CHO diet) and a Mediterranean diet. LDL particles, isolated during each dietary period, were oxidized by exposure to UV light and incubated for 48 h with HUVEC. Thereafter, 100 U/mL of TNF-α was added and incubation continued for 6 h. Cellular ELISA determined adhesion molecules expression. Lag time, propagation rate and total amounts of formed conjugated dienes were calculated in LDL incubated with 10 μmol/L Cu²⁺. When compared to the SFA diet, LDL isolated from the Mediterranean and CHO diets induced a lower expression of VCAM-1 and E-selectin in HUVECS (P < 0.007). There were no differences between both lipid lowering diets. However, lag time of LDL from the Mediterranean diet was higher than with the CHO diet (P < 0.042). This parameter was inversely correlated with E-selectin expression (r = − 0.497; P < 0.04).ConclusionOur results suggest that both the Mediterranean and CHO diets may decrease the pro-inflammatory environment induced by modified LDL in endothelial cells.     

Effects of a low-calorie diet associated with weight loss on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in healthy obese women

IntroductionPlatelet-activating factor acetylhydrolase (PAF-AH or Lp-PLA₂) is a Ca²⁺-independent phospholipase A₂ primarily associated in plasma with low density lipoproteins (LDL), especially with small dense LDL (sdLDL) particles. Increased plasma Lp-PLA₂ levels have been associated with increased cardiovascular risk in large clinical trials.AimTo assess the effects of weight loss on Lp-PLA₂ activity and to examine the association of Lp-PLA₂ activity changes with the alterations of sdLDL, the primary carrier of Lp-PLA₂ in plasma.MethodsTwenty-eight obese, non-diabetic women participated in a weight reduction program. Anthropometric parameters were assessed and parameters of glucose metabolism, lipid profile, Lp-PLA₂ activity, and LDL phenotype (using a 3% polyacrylamide gel-tube electrophoresis method), were determined at baseline and after 4 months of weight loss.ResultsA 10% diet-induced weight loss resulted in significant improvement in most parameters of lipid and glucose metabolism. Moreover, Lp-PLA₂ activity was significantly reduced (−10.2%, p < 0.01). Mean LDL particle diameter did not change after the weight loss program. The cholesterol levels of very low-density lipoprotein (VLDL) and large-buoyant LDL particles were significantly reduced, but neither the cholesterol levels of sdLDL particles nor the % proportion of the sdLDL-cholesterol over the total LDL-cholesterol were changed after the intervention program. Interestingly, the changes in Lp-PLA₂ activity were correlated with the changes of VLDL-cholesterol (r = 0.39, p < 0.05), but not with the changes of anthropometric or other lipid variables.ConclusionsA low-calorie diet associated with weight loss in obese women resulted in the significant reduction of the plasma levels of Lp-PLA₂, the potentially new predictor for incident atherosclerotic disease.     

Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus

ObjectiveThe effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial. We thus determined the concentration of atherogenic small, dense LDL (sdLDL) in patients with type 2 diabetes and an elevated cardiovascular risk profile.Research design and methodsMulticenter, randomized, open-label 6-week study investigating the effect of ezetimibe 10 mg (E), simvastatin 20 mg (S) and the combination of ezetimibe-/simvastatin 10/20 mg (C) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes (NCT01384058).ResultsFifty-six patients were screened for sdLDL, 41 were randomized, and 40 patients (12 E, 14 S and 14 C) completed the study. Total and LDL cholesterol fell by 14% (p = 0.004) and 15% (p = 0.006) with E, 22% (p < 0.001) and 32% (p < 0.001) with S, and 32% (p < 0.001) and 44% (p < 0.001) with C, respectively. E reduced the concentration of sdLDL by 20% (p = 0.043) whereas S and C reduced sdLDL by 24% (p = 0.020) and 33% (p = 0.003), respectively, and non-sdLDL by 28% (p = 0.004) and 42% (p < 0.001), respectively. However, the further drop in sdLDL by adding E to S was not significant.ConclusionEzetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes.     

Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment

Background and aimsDietary therapy using phytosterols can reinforce statin treatment; however the value of a low-dose combination of those agents remains to be investigated. Plant sterols (PS), dissolved in diacylglycerol (DAG) oil, (PS/DAG) can be effective at a relatively low dose. The objective of the present study was to examine the effect of PS/DAG oil on blood cholesterol concentrations in hypercholesterolemic outpatients on low-dose pravastatin (10 mg/day).Methods and resultsThe patients (n = 61) were randomly assigned to one of three groups, who consumed TAG (control), DAG or PS/DAG oil. The average intake of PS from the PS/DAG oil during the test period was significantly higher than that for TAG and DAG oils (502 vs. 49 and 38 mg/day, P < 0.05). Significant cholesterol-lowering effects from the baseline were observed in the case of the PS/DAG oil treatment alone. Changes in low-density lipoprotein (LDL) cholesterol were inversely correlated with baseline serum campesterol concentrations (r = −0.560, P < 0.05), but not baseline LDL cholesterol concentrations. In addition, serum apolipoprotein B concentrations were reduced to a greater extent in subjects with high versus low levels of baseline campesterol (−13.2 mg/dL vs. −3.1 mg/dL, P < 0.05). Furthermore, there was a mild, but significant reduction in serum lipoprotein (a) concentration from the baseline (−5.9 mg/dL), which was correlated with the reduction in serum apolipoprotein B concentration (r = 0.596, P < 0.05).ConclusionA low-dose combination of PS/DAG oil and pravastatin may be a useful strategy for further ameliorating blood cholesterol and lipoprotein (a) concentrations for hypercholesterolemic patients with a low response to pravastatin.     

Effect of an oral astaxanthin prodrug (CDX-085) on lipoprotein levels and progression of atherosclerosis in LDLR(-/-) and ApoE(-/-) mice

Oxidative stress and inflammation are key promoters of atherosclerosis and myocardial damage. When orally administered, the novel astaxanthin prodrug CDX-085 delivers high levels of the xanthophyll antioxidant astaxanthin that protects LDL from oxidation and reduces primary thrombosis. In this study, we analyzed whether delivery of astaxanthin from administration of the CDX-085 prodrug reduces plasma lipoprotein levels and the progression of atherosclerosis in low-density lipoprotein receptor negative (LDLR^?/?) and apolipoprotein E deficient (ApoE^?/?) mice.MethodsRelative circulating levels of astaxanthin derived from CDX-085 administration compared to administration of pure astaxanthin was initially evaluated in a canine model. In mouse Study #1, 16 wild-type and 16 LDLR^?/? mice on 0.5% cholesterol diet supplemented with either 0.0%, 0.08%, 0.2% and 0.4% CDX-085 were used to assess plasma levels and lipoprotein biodistribution measured by FPLC after 4 weeks treatment. In Study #2, 36 male LDLR^?/? mice were randomized to a 0.5% cholesterol chow diet (CHOW group, n = 12) or 0.5% cholesterol chow fortified with 0.08% CDX-085 (n = 12) or 0.5% cholesterol chow with 0.4% CDX-085 (n = 12) for 12 weeks. In Study #3, 34 male ApoE^?/? mice were randomized in the same fashion as the Study #2 and fed similar diets for 9 weeks.ResultsCDX-085 administration was shown to result in significantly higher levels of circulating astaxanthin (p < 0.001 ANOVA) over a 72 h period compared to pure, non-esterified astaxanthin in a single-dose pharmacokinetic study in beagles. In Study #1, plasma astaxanthin levels were 5–9-fold higher in LDLR^?/? mice compared to wild-type mice. Astaxanthin was highly distributed among all lipoprotein fractions, generally reflecting cholesterol content of lipoproteins. In Study #2, administration of CDX-085 resulted in significantly lower total cholesterol levels (528 ± 68 mg/dL vs. 550 ± 67 mg/dL vs. 602 ± 80 mg/dL, p = 0.047) and aortic arch atherosclerosis (9.0 ± 4.2% vs. 9.8 ± 3.5% vs. 13.2 ± 3.6%, p = 0.023) in the 0.4% CDX-085 group compared to the 0.08% CDX-085 and CHOW groups, respectively. In ApoE^?/? mice, a 72% reduction in triglycerides in the 0.4% CDX-085 group and 50% reduction in the 0.08% CDX-085 groups was noted compared to CHOW group (final levels 17 ± 11 mg/dL vs. 30 ± 15 mg/dL vs. 60 ± 32 mg/dL, respectively, p = 0.001).ConclusionOral administration of the novel astaxanthin prodrug CDX-085 shows that it distributes among lipoproteins. CDX-085 lowers total cholesterol and aortic arch atherosclerosis in LDLR^?/? mice and triglyceride levels in ApoE^?/? mice and shows promise for further evaluation in human studies.     

Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome

Background and aimsCarbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS.Methods and results39 subjects (15 men/24 women) were randomly allocated to a CR diet [20–25% energy from carbohydrate (CHO)] for 12 wk (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the American Heart Association diet (50–55% CHO, AHA group) for an additional 6 wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P < 0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12 wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P < 0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P < 0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only.ConclusionsThese results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.     

Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults

Background and aimsPostprandial lipemia predicts the evolution of cardiovascular disease. Obesity is associated with an increase in the magnitude of postprandial lipemia. Our objective was to evaluate the influence of body mass index (BMI) on the effects of acute ingestion of different types of fat on the postprandial lipemic response.Methods and resultsTwenty-one healthy men followed a 4-week baseline diet and then consumed three fat-loaded meals that included 1 g fat/kg body wt (65%fat) according to a randomized crossover design. The compositions of the three meals were olive oil meal (22% saturated fatty acids (SFA), 38% monounsaturated fatty acids (MUFA), 4% polyunsaturated fatty acids (PUFA)); butter meal (35% SFA, 22% MUFA, 4% PUFA); walnuts meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Higher-weight (HW) subjects (BMI greater than the median 26.18 kg/m², n = 11) presented higher incremental area under the curve (iAUC) for triglycerides (TG), both in large- and small-TG rich lipoproteins (TRL) than lower-weight (LW) subjects (BMI < 26.18 kg/m², n = 10) (p < 0.05), and a similar trend for plasma TG (p = 0.084). Moreover, HW subjects presented higher concentrations for small TRL-cholesterol and small TRL-TG in different timepoints of the postprandial lipemia after the intake of enriched walnuts or butter meals compared with the olive oil-enriched meal (p < 0.05) No significant differences were observed between the three types of meals in the postprandial response of LW subjects.ConclusionHW subjects present a greater postprandial response than LW subjects, and they benefit from the consumption of monounsaturated fatty acids from olive oil, to lower their levels of TRL particles during the postprandial state.     

A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women

High hepatic lipase (HL) activity is associated with an atherogenic lipoprotein profile of small, dense LDL particles and lower HDL(2)-C. Intra-abdominal fat (IAF) is positively associated with HL activity. A hepatic lipase gene (LIPC) promoter variant (G-->A(-250)) is associated with lower HL activity, higher HDL(2)-C, and less dense LDL particles. To determine whether the LIPC promoter polymorphism acts independently of IAF to regulate HL, 57 healthy, premenopausal women were studied. The LIPC promoter A allele was associated with significantly lower HL activity (GA/AA=104+/-34 versus GG=145+/-57 nmoles x mL(-1) x min(-1), P=0.009). IAF was positively correlated with HL activity (r=0.431, P<0.001). Multivariate analysis revealed a strong relationship between both the LIPC promoter genotype (P=0. 001) and IAF (P<0.001) with HL activity. The relationship between IAF and HL activity for carriers and noncarriers of the A allele was curvilinear with the carriers having a lower apparent maximum level of plasma HL activity compared with noncarriers (138 versus 218 nmoles x mL(-1) x min(-1), P<0.001). In addition, the LIPC A allele was associated with a significantly higher HDL(2)-C (GA/AA=16+/-7 versus GG=11+/-5 mg/dL, P=0.003). We conclude that the LIPC promoter A allele attenuates the increase in HL activity due to IAF in premenopausal women.     

Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study

Background and aimsPlant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant β-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved.Methods and resultsThe effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated in a multicenter, randomized double blind study. Hypercholesterolemic patients consumed a FM daily for 6 weeks. Subjects were randomized to receive either 1.6 g of plant sterol-enriched FM (n = 60) or control FM product (n = 56). After 6 weeks of plant sterol-enriched FM consumption, LDL cholesterol was reduced from 166.2 ± 2.0 to 147.4 ± 2.8 mg/dL (p = 0.01). A significant reduction was observed for total cholesterol (from 263.5 ± 2.6 to 231.0 ± 3.2 mg/dL, p = 0.01). There was greater LDL cholesterol lowering among hypercholesterolemic patients with higher LDL cholesterol at baseline. We found a reduction of plasma 8-isoprostane in patients taking plant sterol-enriched FM (from 43.07 ± 1.78 to 38.04 ± 1.14 pg/ml, p = 0.018) but not in patients taking the control product (from 42.56 ± 2.12 to 43.19 ± 2.0 pg/ml, p = NS). Campesterol and β-sitosterol levels were not influenced by phytosterol consumption.ConclusionsDaily consumption of low-fat plant sterol dairy product favourably changes lipid profile by reducing LDL-cholesterol, and may also have an anti-oxidative effect through a reduction of plasma isoprostanes.     

Relationship of plasma apolipoprotein M with proprotein convertase subtilisin-kexin type 9 levels in non-diabetic subjects

PurposeApolipoprotein M (apoM) retards atherosclerosis development in murine models, and may be regulated by pathways involved in LDL metabolism. Proprotein convertase subtilisin–kexin type 9 (PCSK9) plays a key role in LDL receptor processing. We determined the extent to which plasma apoM is related to PCSK9 levels in subjects with varying degrees of obesity.MethodsWe sought correlations between plasma apoM and PCSK9, measured using recently developed ELISAs, in 79 non-diabetic subjects.ResultsApoM and PCSK9 levels were both correlated positively with total cholesterol, non-HDL cholesterol, LDL cholesterol and apoB (P < 0.05 to P < 0.001). ApoM correlated positively with PCSK9 in lean individuals (n = 37, r = 0.337, P = 0.041), but not in overweight subjects (n = 32, r = 0.125, P = 0.50) and in obese subjects (n = 10, r = ?0.055, P = 0.88).ConclusionsThe PCSK9 pathway may contribute to plasma apoM regulation in humans. The influence of PCSK9 on circulating apoM appears to be modified by adiposity.     

Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients

PurposeProprotein convertase subtilisin–kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus.MethodsA 24 h moderately hyperinsulinemic glucose clamp (30 mU/kg/h) was performed in 8 healthy men and 8 male type 2 diabetic patients. Plasma PCSK9 was measured using a sandwich enzyme-linked immunosorbent assay.ResultsPlasma LDL cholesterol and apolipoprotein B were lowered by insulin in healthy subjects and diabetic patients (P < 0.01 for all), whereas triglycerides were also decreased in healthy subjects (P < 0.01). Plasma PCSK9 levels remained unchanged in healthy subjects (median (interquartile range) change, ?23 (?63 to 25) %, P = 0.50) and in diabetic patients (change, 4 (?17 to 44) %, P = 0.20). Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24 h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all).ConclusionPlasma PCSK9 levels are not increased by exposure to moderate 24 h hyperinsulinemia in healthy and type 2 diabetic individuals.     

Glycation of LDL in non-diabetic people: Small dense LDL is preferentially glycated both in vivo and in vitro

ObjectiveLDL atherogenicity is frequently attributed to oxidative modification, but glycated LDL, which can participate in many of the cellular processes leading to atherosclerosis, generally circulates at higher concentration even in non-diabetic people. We tested the hypothesis that small-dense LDL, known to be most closely associated with coronary heart disease, undergoes more glycation than other LDL sub-fractions.Methods and resultsThe concentration of glycated apolipoprotein B (apo B) was measured in serum, LDL and its sub-fractions from 44 non-diabetic subjects. By ELISA serum glycated apoB concentration was 3.0 ± 1.1 mg/dl (mean ± S.D.) of which 84.6 ± 13.6% was in LDL. Of the glycated apo B in LDL 67.8 ± 21.9% was in small dense LDL (LDL3; D1.044-1.063 g/ml) whereas only 32.2 ± 21.9% was in more buoyant LDL subfractions (LDL1 and 2; D1.019–1.044 g/ml). The percentage of apo B present in LDL1 and 2 which was glycated was 1.8 ± 1.8% whereas in LDL3 it was 17.4 ± 18.5% (P < 0.001). Furthermore when LDL sub-fractions from non-diabetics (n = 29) were incubated with glucose (30–80 mmol/l) glycation of apo B in the denser LDL3 subfraction was significantly more pronounced than in less dense LDL subfractions.ConclusionSmall-dense LDL is more susceptible to glycation and this may contribute to the atherogenicity of small-dense LDL, even in non-diabetic people.     

The effect of high-fiber rye bread enriched with nonesterified plant sterols on major serum lipids and apolipoproteins in normocholesterolemic individuals

Background and aimsPlant sterols are naturally occurring cholesterol-lowering compounds which are industrially incorporated in various foods. A novel food carrier is rye bread, the intake of which can be monitored in trials utilizing newly defined plasma biomarkers. Our aim was to determine the effects of plant sterols incorporated into high-fiber rye bread on serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios and lipophilic (pro)vitamins in healthy free-living normocholesterolemic individuals.Methods and resultsIn this double-blind, dietary intervention trial the subjects (n = 68) were randomized to receive a rye bread (9.3 g/d fiber) with added plant sterols (2 g/d) (active) or without (control). In the second phase of the study the amount of rye bread was doubled providing 18.6 g/d fiber and in the active group 4 g/d plant sterols. Compliance was monitored utilizing 3-day food diaries and a novel rye fiber-derived biomarker in plasma. Intake of rye bread enriched with 2 g/d of plant sterols during two weeks reduced significantly serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios by 5.1%, 8.1%, 8.3% and 7.2%, respectively, compared to controls. Correspondingly, the following two-week treatment with 4 g/d of plant sterols resulted in 6.5%, 10.4%, 5.5% and 3.7% difference compared to controls, being most pronounced for LDL (0.33 mmol/L). The treatments did not affect lipophilic (pro)vitamin levels.ConclusionRye bread enriched with 2–4 g/d of nonesterified plant sterols beneficially modifies cardiovascular lipid risk factors in normocholesterolemic subjects compared to controls.     

Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Effect of Lactobacillus fermentum on serum lipids in subjects with elevated serum cholesterol

Background and AimsThere is increasing interest in the use of natural therapies to reduce elevated low density lipoprotein (LDL) cholesterol. This study assessed the effects of PCC^® Lactobacillus fermentum on LDL cholesterol and other lipid fractions.Methods and resultsThis was a single centre, double blind, placebo-controlled, parallel design trial in volunteers having total cholesterol ≥4 mmol/L. Subjects (n = 46) were randomised to receive either Lactobacillus fermentum 2 capsules twice daily (each capsule containing 2 × 10⁹ colony forming units) or matching placebo for a period of 10 weeks. Main outcome measures were percentage changes in LDL cholesterol and other lipids, changes in liver enzymes and other safety tests. Two subjects withdrew early in the study, 1 for personal reasons and 1 because of bowel discomfort. Three other subjects experienced some bowel discomfort but still completed the study. LDL cholesterol showed a modest downward trend on both Lactobacillus fermentum and placebo of 7.0% and 5.2% respectively. This trend did not reach statistical significance over time, nor was there a significant difference between the treatment arms. There were no significant changes over time or between treatments noted in total cholesterol, high density lipoprotein cholesterol or triglycerides. There were no significant changes in liver enzymes or other safety parameters with time or between treatments.ConclusionLactobacillus fermentum did not appear to produce a major change in serum lipid fractions, but a small effect cannot be excluded.     

Apolipoprotein E enrichment of immuno-separated chylomicron and chylomicron remnants following saturated fatty acids

AimWe examined the effect of meal fatty acids on lipid and apolipoprotein concentrations of very low density lipoprotein (VLDL) and chylomicron/chylomicron remnants in lipid fractions with a Svedberg flotation rate (S_f) 60–400 and S_f 20–60.Methods and resultsSix healthy middle-aged men received in random order mixed meals enriched with saturated (SFA), polyunsaturated (PUFA) or monounsaturated (MUFA) fatty acids on 3 occasions. VLDL and chylomicron/chylomicron remnants in the lipid fractions were separated by immunoaffinity chromatography against apo B-100. In the S_f 60–400 chylomicron/chylomicron remnants, triacylglycerol and cholesterol concentrations were significantly lower following PUFA compared with SFA and MUFA (P ≤ 0.05). Apolipoprotein (apo) E responses were significantly higher after SFA in chylomicron/chylomicron remnants and VLDL compared with PUFA and MUFA (P < 0.007). However, apo B responses (particle number) were higher following MUFA than SFA (P = 0.039 for chylomicron/chylomicron remnants). Composition of the chylomicron/chylomicron remnants (expressed per particle) revealed differences in their triacylglycerol and apo E contents; in the S_f 60–400 fraction, SFA-rich chylomicron/chylomicron remnants contained significantly more triacylglycerol than MUFA (P = 0.028), more apo E than PUFA- and MUFA-rich particles (P < 0.05) and in the S_f 20–60 fraction, more apo E than MUFA (P = 0.009).ConclusionThere are specific differences in the composition of chylomicron/chylomicron remnants formed after saturated compared with unsaturated fatty acid-rich meals which could determine their metabolic fate in the circulation and subsequent atherogenicity.     

Effects of plant stanol esters supplied in a fat free milieu by pastilles on cholesterol metabolism in colectomized human subjects

Background and aimNutritional products containing fat-soluble phytosterol esters for serum cholesterol lowering have traditionally been oil-based. Their cholesterol-lowering efficacy when provided by low-fat vehicles with a diet of normal fat content is questionable. The aims of the present study were to find out whether 1-week consumption of plant stanol esters in pastilles alters absorption percentage of labeled esterified and free cholesterol and fecal elimination of sterols, including phytosterols (n = 9), and to define the impact of dietary fat on intestinal sterol ester hydrolysis (n = 8) in colectomized human subjects.Methods and resultsLevels of lipoprotein cholesterol and triacylglycerols, non-cholesterol sterols and squalene in serum, neutral sterols, non-cholesterol sterols, fat and bile acids in feces, cholesterol absorption efficiency and cholesterol synthesis were analyzed at baseline and at the end of the treatment period. Analyses of esterified and free cholesterol and phytosterols were performed during diets with normal and low-fat content.Serum levels of total and low-density lipoprotein cholesterol decreased by 9% and 14%, respectively (P < 0.01 for both), and absorption of ³H-esterified and ¹⁴C-free cholesterol decreased in proportion to baseline values (r = −0.58, P < 0.05) by over 40% (P < 0.01) in colectomized patients with stanol ester pastilles. Fecal elimination of cholesterol was increased by about 35% and almost 60% of campestanol and sitostanol esters were hydrolyzed during their transit in gastrointestinal tract when consumed with a normal fat diet (mean daily fat 93 ± 13 g) for 1 week. The hydrolysis of plant stanol esters was more pronounced with a normal than with a low-fat diet (70% versus 40%, P < 0.001).ConclusionsWe conclude that plant stanol esters provided in fat free milieu exert favourable effects on serum lipid profile by decreasing absorption of cholesterol in colectomized human subjects, even though the intestinal hydrolysis of plant stanol esters is weaker on low than normal fat diet.     

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients

Background and aimType 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients.Methods and resultsWe studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (−108C > T, 55T > A, and 192A > G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P = 0.016), OxLDL/HDL (18%; P = 0.024) and OxLDL-Ab (12%; P = 0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P < 0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (−108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P = 0.040) in patients with atherosclerosis.ConclusionOxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.