Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet

We previously reported that carbohydrate restriction (CR) (10–15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.001). However, those subjects with a higher intake of cholesterol provided by eggs (640 mg additional cholesterol, EGG group) had higher concentrations of high-density lipoprotein (HDL) cholesterol (P<.0001) than the individuals consuming lower amounts (0 mg of additional cholesterol, SUB group). The objectives of the present study were to evaluate whether CR and egg intake (1) modulate circulating carotenoids and (2) affect the concentrations of plasma apolipoproteins (apo), lipoprotein size and subfraction distribution. CR decreased the number of large and medium very low-density lipoprotein cholesterol subclasses (P<.001), while small low-density lipoprotein (LDL) were reduced (P<.001). In agreement with these observations, a decrease in apo B (P<.01) was observed. In addition, CR resulted in a 133% increase in apo C-II and a 65% decrease in apo C-III (P<.0001). Although an increase of the larger LDL subclass was observed for all subjects, the EGG group had a greater increase (P<.05). The EGG group also presented a higher number of large HDL particles (P<.01) compared to the SUB group. Regarding carotenoids, CR resulted in no changes in dietary or plasma α- or β-carotene and β-cryptoxanthin, while there was a significant reduction in both dietary and plasma lycopene (P<.001). In contrast, dietary lutein and zeaxanthin were increased during the intervention (P<.05). However, only those subjects from the EGG group presented higher concentrations of these two carotenoids in plasma, which were correlated with the higher concentrations of large LDL observed in the EGG group. These results indicate that CR favorably alters VLDL metabolism and apolipoprotein concentrations, while the components of the egg yolk favor the formation of larger LDL and HDL leading to an increase in plasma lutein and zeaxanthin.     

TaqIB polymorphism in the CETP gene modulates the impact of HC/LF diet on the HDL profile in healthy Chinese young adults

The aim of this study was to investigate the interactions of genetic variants in the genes of cholesterol ester transfer protein (CETP) and low-density lipoprotein receptor (LDLR) with high carbohydrate and low fat (HC/LF) diet on lipid profiles in a young and healthy Chinese Han population. Fifty-six healthy subjects (22.89±1.80 years) were given washout diets of 31% fat and 54% carbohydrate for 7 days, followed by HC/LF diets of 15% fat and 70% carbohydrate for 6 days, with no total energy restriction. Serum lipid profiles at baseline, after washout and following HC/LF diets, as well as CETP and LDLR polymorphisms were analyzed. Carriers of B2 allele of CETP TaqIB polymorphism had significantly higher levels of high density lipoprotein cholesterol (HDL-C) and apo A-I in the whole study population after the diet intervention. Notably, males with CETP TaqIB B1B1 experienced significantly increased HDL-C and apo A-I after HC/LF diet. Regarding the LDLR Pvu II polymorphism, both P1P1 subjects and P2 carriers experienced decreased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels after HC/LF diet with no statistically significant differences between the genotypes. Our results demonstrate that the elevated HDL-C levels after HC/LF diet in healthy Chinese Han youth are associated with CETP TaqI B2 allele while males with B1B1 genotype are more susceptible to the influence of HC/LF diet on their HDL-C levels. The decreased TC and LDL-C levels after HC/LF diet are not associated with LDLR Pvu II polymorphism.     

One-year effects of increasingly fat-restricted, carbohydrate-enriched diets on lipoprotein levels in free-living subjects

Restriction of all dietary fat is a popular strategy for restricting saturated fat intake to lower LDL cholesterol. Some authorities advise the restriction of fat intake to the extreme of less than 10% of daily energy on the assumption that more fat restriction is better. The two studies described herein address questions relating to whether increasing fat restriction produces proportionally increasing benefit on cardiovascular risk factors in hyperlipidemic subjects.The first study is the Dietary Alternatives Study (DAS). The DAS was conducted in 531 male Boeing employees over a 2-year period. Subjects were defined as hypercholesterolemic (HC) or combined hyperlipidemic (CHL) based on age-specific 75th percentiles for plasma LDL-C and triglyceride levels. Hypothesis test analyses were performed at 1 year. HC subjects were randomized to diets taught to attain fat intakes of 30, 26, 22, and 18% (Diets levels 1-4, respectively). CHL subjects (slightly fewer in number) were randomized to Diets 1-3. After 1 year, subjects' total fat intakes were 27, 26, 25, and 22% of energy (en%), resulting in saturated fat intakes of 8, 7, 7, and 6%, respectively. In HC subjects the greatest LDL-C decrease was with Diet 2 (mean of 13.4%) and in CHL subjects with Diet 1 (7.0%). Surprisingly, plasma triglyceride concentrations rose in HC subjects 20% and 40% above baseline on Diets 3 and 4, respectively, with reciprocal reductions in HDL cholesterol of 2.5% and 3%, respectively. Furthermore, apo B reductions were attenuated below Diet 2 in HC subjects and Diet 1 in CHL subjects, and no further reductions were seen in plasma glucose and insulin concentrations, blood pressure, or body weight. Measurements of plasma total fatty acid composition showed a slight increase in plasma palmitate, whereas stearate decreased slightly, supporting the idea that de novo synthesis of palmitic acid was increased in the chronic high-carbohydrate feeding condition. The second study asked if the most effective diet in HC subjects, Diet 2, has an equivalent effect in women and men. To answer this question, men and women Boeing employees were taught the closely similar National Cholesterol Education Program (NCEP) Step II diet. After 6 and 12 months, equivalent reductions in LDL cholesterol were observed in women compared with men. HDL cholesterol levels in men were unchanged from baseline at 6 and 12 months, but were reduced 8% in HC women, with accompanying decreases of 18% in HDL2-cholesterol and 5% in apoprotein A-I (all P < 0.01). These data indicate that intakes of fat below about 25 en% and carbohydrate intake above approximately 60 en% yield no further LDL-C lowering in HC and CHL male subjects and can be counterproductive to triglyceride, HDL-C, and apo B levels. This lack of benefit appears to be explained by an enhanced endogenous synthesis of palmitic acid, which negates the benefit of further saturated fat restriction. The HDL-C decrease in HC women may have a similar cause and points to an underlying male-female difference. Alternative dietary approaches to limit saturated fat intake deserve intensive study.     

Effect of Kluyveromyces marxianus YIT 8292 Crude Cell Wall Fraction on Serum Lipids in Normocholesterolemic and Mildly Hypercholesterolemic Subjects

The hypocholesterolemic effects of Kluyveromyces marxianus YIT 8292 crude cell wall (KM-CW) were examined. In pilot studies, KM-CW tablets were administered to mildly hypercholesterolemic subjects at doses of 8.0, 4.0, 2.0, or 1.0 g/d for 4 weeks. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) decreased at doses above 2.0 and 4.0 g/d, respectively. Further, we examined the effect of intake of yogurt containing 3.0 or 4.0 g of KM-CW/d for 8 weeks in normal and hypercholesterolemic subjects in a double-blind placebo-controlled study. The intake of either of the KM-CW-containing yogurts was associated with significantly improved TC and LDL-C in hypercholesterolemic subjects, but had no effect on these levels in normal subjects. TC was significantly lower at week 8 in the hypercholesterolemic subjects who ingested yogurt containing 3.0 or 4.0 g of KM-CW than in those who consumed placebo yogurt. Intake of KM-CW might contribute to the prevention of hypercholesterolemia.     

Effect of Kluyveromyces marxianus YIT 8292 crude cell wall fraction on serum lipids in normocholesterolemic and mildly hypercholesterolemic subjects

The hypocholesterolemic effects of Kluyveromyces marxianus YIT 8292 crude cell wall (KM-CW) were examined. In pilot studies, KM-CW tablets were administered to mildly hypercholesterolemic subjects at doses of 8.0, 4.0, 2.0, or 1.0 g/d for 4 weeks. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) decreased at doses above 2.0 and 4.0 g/d, respectively. Further, we examined the effect of intake of yogurt containing 3.0 or 4.0 g of KM-CW/d for 8 weeks in normal and hypercholesterolemic subjects in a double-blind placebo-controlled study. The intake of either of the KM-CW-containing yogurts was associated with significantly improved TC and LDL-C in hypercholesterolemic subjects, but had no effect on these levels in normal subjects. TC was significantly lower at week 8 in the hypercholesterolemic subjects who ingested yogurt containing 3.0 or 4.0 g of KM-CW than in those who consumed placebo yogurt. Intake of KM-CW might contribute to the prevention of hypercholesterolemia.     

Pectin and psyllium decrease the susceptibility of LDL to oxidation in guinea pigs

These studies were undertaken to determine whether pectin (PE) and psyllium (PSY) intake affect the circulating levels of alpha-tocopherol and the susceptibility of low density lipoprotein (LDL) to oxidation. For that purpose, male Hartley guinea pigs were fed 19 g/100 g of a fat mix with a 2:1:1 ratio of saturated:polyunsaturated:monounsaturated fatty acids and 35 g/100 g total carbohydrate with 80% of the carbohydrate energy contributed by sucrose. Diets were identical in composition except for the fiber source: cellulose (control diet), PE, or PSY. Guinea pigs fed PE or PSY had 36% and 67% lower plasma cholesterol concentrations, respectively, compared with controls (P < 0.001). This plasma cholesterol lowering was associated with both very low density lipoproteins and LDL cholesterol fractions. Intake of PE or PSY resulted in 54% lower plasma triacylglycerol (TAG) concentrations compared with the control group (P < 0.001). LDL from PE and PSY fed guinea pigs contained fewer molecules of cholesteryl ester, and alpha-tocopherol concentrations in this particle were 49% and 66% higher, respectively, compared with controls. In addition, LDL from guinea pigs fed soluble fiber exhibited less susceptibility to oxidation than those from the control group, as determined by thiobarbituric acid-reactive substances formation. Hepatic free and esterified cholesterol were 32% lower and hepatic TAG was 25% lower in guinea pigs fed PE and PSY compared with controls. The data from these studies confirm that PE and PSY reverse the hyperlipidemia associated with high fat-sucrose diets and demonstrate a potential antioxidant effect of soluble fiber on circulating LDL.     

Effects of R219K polymorphism of ATP-binding cassette transporter 1 gene on serum lipids ratios induced by a high-carbohydrate and low-fat diet in healthy youth

Background

Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1^st, 8^th and 14^th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method.

Results

The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1^st, 8^th and 14^th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1^st and 14^th days, and higher LDL-C/HDL-C on the 14^th day. When compared with that on the 8^th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14^th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype.

Conclusions

These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.     

Apolipoprotein E gene polymorphism and serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations

Hei Yi Zhuang is an isolated subgroup of the Zhuang minority in China. Little is known about the distribution of apolipoprotein (apo) E genetic variations and its role in lipid metabolism in this population. The present study was undertaken to compare the effect of apoE gene polymorphism on serum lipid levels between the Guangxi Hei Yi Zhuang and Han populations. A total of 873 subjects of Hei Yi Zhuang and 867 participants of Han Chinese were surveyed by a stratified randomized cluster sampling. Genotyping of apoE was performed using polymerase chain reaction and restriction fragment length polymorphism. The frequencies of 2, 3, and 4 alleles were 15.23%, 79.84%, and 4.93% in Hei Yi Zhuang, and 9.23%, 81.43%, and 9.34% in Han (P < 0.001); respectively. The frequencies of 2/ 2, 2/ 3, 2/ 4, 3/ 3, 3/ 4, and 4/ 4 genotypes were 4.70%, 17.86%, 3.21%, 68.16%, 5.50%, and 0.57% in Hei Yi Zhuang, and 2.54%, 9.23%, 4.15%, 70.70%, 12.23%, and 1.15% in Han (P < 0.001); respectively. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apoB levels were lower in Hei Yi Zhuang than in Han (P < 0.01-0.001), but high-density lipoprotein cholesterol (HDL-C) levels and the ratio of apoA-I to apoB were higher in Hei Yi Zhuang than in Han (P < 0.001 for each). There were significant differences in TC, HDL-C, LDL-C, and apoB levels among the six genotypes in both ethnic groups (P < 0.01-0.001). Hyperlipidemia was positively correlated with age, body mass index, hypertension, alcohol consumption, and apoE allele in both populations (P < 0.05-0.001). TC, LDL-C, and apoB levels were positively correlated, and HDL-C levels were negatively associated with apoE genotypes in both ethnic groups (P < 0.001 for all). The differences in the lipid profiles between Hei Yi Zhuang and Han Chinese might partly attribute to the differences in apoE genotypic and allelic frequencies.     

实验性高脂血症恒河猴模型的初步建立及分析

目的建立实验性高脂血症恒河猴模型,为人类高脂血症研究提供理想动物模型。方法设计高脂实验饲料配方并检测常规营养成分,用高脂饲料诱导实验性高脂血症恒河猴模型,分别在2个月、4个月、6个月后监测体重、血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL—C）、低密度脂蛋白（LDL—C）等指标,对其血脂指标的变化趋势进行分析。结果模型组在实验2个月、4个月时的日采食量和摄入能量均低于对照组（P（0．05）,但体重则无明显变化（P〉0．05）;而在实验6个月时日采食量和摄入能量与对照组无显著性差异（P〉0．05）,体重有显著性差异（P〈0．05）;模型组与对照组的TC、TG、HDL—C、LDL—C在实验前和2个月比较无显著性差异（P〉0．05）;在4个月比较时TC、TG、LDL—C有显著性差异（P〈0．05）,而HDL无显著性差异（P〉0．05）;在6个月比较时TC、LDL—C有显著性差异（P〈0．05）,并且TC、LDL—C远远高于恒河猴血脂的正常参考值水平,而TG、HDL—C则无显著性差异（P〉0．05）;变化趋势分析结果为,模型组TC和LDL-C水平有递增趋势、TG水平则出现了先递减后逐渐恢复的趋势、HDL—C水平未出现明显变化趋势。结论模型组恒河猴具有高胆固醇血症和高低密度脂蛋白血症的特征,已经初步建立了实验性恒河猴高脂血症动物模型。     

CD45: a leukocyte-specific member of the protein tyrosine phosphatase family.

In a recent study from this laboratory, rhesus monkeys fed a 90% palm oil/10% soybean oil-containing diet (PS), rich in 16:0 and 18:1 fatty acids, had decreased total and LDL cholesterol concentrations compared to monkeys fed a 90% coconut oil/10% soybean oil-containing diet (CS), rich in 12:0 and 14:0 fatty acids. To investigate the metabolic basis of these changes, homologous 125I-VLDL and 131I-LDL were injected simultaneously into eight monkeys (four per dietary group). Analysis of apo B specific activity curves revealed that PS monkeys had an increased pool size of VLDL apo B (P less than 0.02), a 3-fold increase in the total VLDL apo B transport rate (P less than 0.001), a decreased pool size of LDL apo B (P less than 0.01) and a 2-fold decrease in the total transport rate of LDL apo B (P less than 0.001), while the irreversible FCR for VLDL apo B and LDL apo B was similar between dietary groups. PS monkeys derived a greater percentage of LDL apo B from VLDL catabolism resulting in a greater transport rate of LDL apo B from VLDL catabolism (P less than 0.055), in comparison to CS monkeys. For CS monkeys the proportion as well as the amount of LDL apo B derived from VLDL-independent catabolism (i.e., LDL apo B derived from sources other than VLDL catabolism) was higher (P less than 0.001) than the values obtained in PS monkeys. In both dietary groups the proportion of VLDL apo B converted to LDL apo B was similar, although the absolute amount was higher for the PS monkeys (P less than 0.06). The proportion of VLDL apo B directly removed from the circulation was similar for both dietary groups, with the absolute amount being higher for the PS monkeys (P less than 0.001). Consistent with the lower pool size of LDL apo B and the higher pool size of VLDL apo B observed in PS monkeys, plasma and LDL cholesterol concentrations tended to be lower, whereas plasma triacylglycerol and VLDL cholesterol concentrations tended to be higher, but these changes were not statistically significant. Although total apo B and VLDL apo B transport rates were increased 2-3-fold in PS monkeys, LDL apo B concentration was reduced by 40% (P less than 0.02) attributed to a significant reduction in the mass and proportion of LDL apo B derived independent of VLDL catabolism.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dietary carbohydrate and cholesterol influence the number of particles and distributions of lipoprotein subfractions in guinea pigs

Guinea pigs (n=10/group) were fed one of three diets: a high carbohydrate (CHO) (42% energy), low cholesterol (0.04%) diet (LChHC), a diet with the same amount of CHO but with 0.25% cholesterol (HChHC) or a diet with 11% of energy from CHO and 0.25% cholesterol (HChLC) for 12 weeks. VLDL- and LDL cholesterol (LDL-C) were higher in the HChLC and HChHC groups than in the LChHC group (P<.0001). Lipoprotein subclasses and size were analyzed by nuclear magnetic resonance. Dietary cholesterol (HChHC and HChLC groups) resulted in larger VLDL particles (71.1+/-6.9, 78.9+/-3.33 nm, respectively) than those in the LChHC group (44.3+/-10.8 nm). In addition, there were higher concentrations of the large VLDL (>60 nm) and the medium VLDL (>35 nm) in the high cholesterol groups (P<.01). Similarly, the concentration of the medium (>8.2 nm) and small HDL (>7.2 nm) was higher in the HChHC and HChLC groups (P<.001). In contrast, CHO restriction affected the concentrations of LDL subfractions. The number of total LDL particles was lower in the HChLC (291.3+/-85.0 nmol/L) than in the HChHC group (467.6+/-113.1 nmol/L), indicating that the cholesterol in LDL was distributed in less particles in the former group. The concentrations of medium LDL (>19.8 nm) (98.4+/-90.8) and small LDL (>18 nm) (29.3+/-24.9 nmol/L) were lower in the HChLC group than in the HChHC group (261.8+/-105.8 and 64.9+/-27.9 nmol/L, respectively). These results indicate that dietary cholesterol increased the atherogenicity of both VLDL and HDL while CHO restriction increased the number of large LDL and decreased the concentrations of the more atherogenic smaller LDL subfractions.     

Increased beef consumption increases apolipoprotein A-I but not serum cholesterol of mildly hypercholesterolemic men with different levels of habitual beef intake

The objective of this research was to compare the effects of a lean beef enriched in oleic acid to a beef that is typical of the commercial beef consumed in the United States. Ten mildly hypercholesterolemic men, ages 34-58 years old, were selected from the Texas A&M University faculty and staff. Subjects were randomly assigned to one of two diets for a 6-week duration followed by a crossover after a 4-week habitual diet washout period. Diets were consumed daily for a 6-week study period. Participants substituted lean beef obtained from Wagyu bullocks or commercial beef for the meat typically consumed. Total cholesterol, apolipoproteins A-I and B, triacylglycerols, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured in serum samples collected weekly. Beef type had no effect on any measured variable. There were no significant differences between baseline HDL or LDL cholesterol concentrations after the consumption of the beef test diets. Apolipoprotein A-I, serum glucose, and uric acid concentrations were elevated by the additional dietary beef. Analysis of records of customary diets indicated that one group consumed 160 g of beef daily, whereas the other group consumed only 26 g of beef daily. Therefore, post hoc analyses tested the habitual beef intake x treatment time interaction. LDL cholesterol concentration was markedly higher in the group with low habitual beef intake (180 vs 144 mg/dl), and HDL cholesterol was slightly higher (44 vs 40 mg/dl; post-test values) than for the group with high habitual beef intake, but there were no habitual intake x time interactions for LDL or HDL cholesterol. Creatinine and blood urea nitrogen concentrations also were greater in the individuals habitually consuming less beef. This study had three important findings: i) a lean beef source enriched with oleic acid was no different from commercial beef in its effect on lipoprotein fractions; ii) neither previous level of beef intake nor baseline LDL cholesterol concentration influenced the serum cholesterol response to added dietary beef, which was negative; and iii) apolipoprotein A-I, but not HDL or LDL cholesterol, was sensitive to the additional dietary beef.     

Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy.

Pregnancy is associated with increases in plasma total cholesterol (TC) and triglycerides (TG). Individuals with decreased LPL activity have a mild form of hypertriglyceridemia. Variations in the apolipoprotein E (apoE) gene have been associated with increases in plasma TG in addition to differences in plasma TC, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). Because of the overproduction of TG-rich VLDL, normal pregnancy challenges the lipolytic capacity of LPL and the clearance of remnants particles. During pregnancy, LPL and apoE polymorphisms may contribute to hypertriglyceridemia. This study investigated the impact of three LPL polymorphisms and the apoE genotypes on lipid levels during pregnancy. Fasting plasma lipids were measured and analyses of the LPL and apoE polymorphisms were performed in 250 women in the third trimester of pregnancy. S447X carriers had lower TG (P = 0.003), and N291S carriers had lower HDL-C (P < 0.02) and higher fractional esterification rate of HDL (FER(HDL)) (P = 0.007), a measure of HDL particle size, than the noncarriers. The E2 allele was associated with lower TC, LDL-C, and FER(HDL) (P < 0.05) compared to the E3/E3 genotype. These findings support that LPL and apoE polymorphisms play an important role in lipid metabolism in pregnancy. The relationship of these polymorphisms to risk of coronary heart disease in women requires further study.     

青少年家族性高胆固醇血症患者血浆同型半胱氨酸和高敏C 反应蛋白水 平的临床价值及与血脂相关性研究

目的:探讨血浆同型半胱氨酸(Homocysteine,Hcy)、高敏C反应蛋白(Hypersensitive C-reactive protein,hs-CRP)在家族性高胆固醇血症(FH)的纯合子和杂合子患者中的水平及其与临床生化指标的相关性。方法:入选在2013.10~2015.7期间在动脉硬化门诊随访、确诊的家族性高胆固醇患者34人(纯合子14例,杂合子20例)。根据FH纯合子、杂合子、健康体检者分成三组,分别测定其总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(Glu)、Hcy、hs-CRP水平,并比较FH患者血浆LDL-C、非高密度脂蛋白(non-HDL)水平Hcy、hs-CRP水平的相关性。结果:FH组的TC、LDL-C、non-HDL、Hcy水平显著高于正常对照组(P0.05)。FH根据基因型亚组分析中,青少年纯合子组HDL-C[(0.78±0.21)vs(1.25±0.40)mmol/L]小于杂合子组(P0.001),而TC[(16.11±2.66)vs(7.30±2.54)mmol/L]、LDL-C[(14.06±2.22)vs(5.25±2.16)mmol/L]、non-HDL[(15.33±2.60)vs(6.05±2.61)mmol/L]、Hcy[(19.3±11.58)vs(11.29±3.42)μmol/L]水平显著高于杂合子组(P0.05)。Pearson相关性分析显示,FH患者血浆LDL-C、non-HDL水平与Hcy水平呈正相关(P0.05),而与hs-CRP无相关性。结论:FH患者,特别是青少年的纯合子患者,与对照组相较,具有较高的TC、LDL-C和Hcy水平,并且与血浆LDL-C、non-HDL水平呈正相关。FH患者hs-CRP的水平高于健康人,但差异无统计学意义,与血浆LDL-C、non-HDL水平也无明显相关性。     

Association of methylenetetrahydrofolate (MTHFR) and apolipoprotein E (apo E) genotypes with homocysteine, vitamin and lipid levels in carotid stenosis

The aim of the study was to investigate the association between methylenetetrahydrofolate (MTHFR) genotypes and levels of homocysteine (Hcy), folate, vitamin B12 and lipids as well as the association between apolipoprotein E (apo E) genotypes and levels of lipids in a Croatian healthy control group and a group of patients with > 70% carotid stenosis (CS). The study included 98 Croats, 38 patients with > 70% carotid stenosis and 60 age- and sex-matched controls. The MTHFR and apo E genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Hcy by enzyme immunoassay, vitamins by immunochemiluminiscence, and lipids by spectrophotometric method. There was no difference between control subjects and CS patients in the distribution of C677T MTHFR genotypes (p=0. 786) and alleles (p=0.904), however, differences in the frequencies of apo E genotypes (p=0.012) and alleles (p=0.029) were statistically significant. The odds ratio for apo E 3/4 genotype was 3.93 (95% CI 1.23-12.61). Hyperhomocysteinemia (> or =15 micromol/L) was found in 11% of CS patients and 5% of control subjects. Total cholesterol, triglycerides, vitamin B12 and folate were statistically different in "all MTHFR genotypes" (p<0.001, p<0.01, p=0.044 and p=0.036, respectively), and in TC/TT (p<0.001, p=0.003, p=0.030 and p=0.032, respectively) groups. The levels of total cholesterol, LDL cholesterol and triglycerides in the apo E 3/3, and total cholesterol in the apo E 3/4 group yielded statistical difference. An association was found of apo E 3/4 genotype but not of MTHFR genotypes with the risk of CS. MTHFR and apo E affect blood lipid levels, which was statistically confirmed. An association was also recorded between hyperhomocysteinemia and patients with CS. Vitamin status in CS showed a statistically verified association with TC/TT MTHFR genotype. In the group of patients with TC/TT MTHFR genotype, lower vitamin B12 and higher folate values were recorded. The results of multiple logistic analysis showed that there was no statistical significance of Hcy levels (OR 2.403, p=0.334) or conventional vascular risk factors such as smoking habit (OR 0.505, p=0.149), age (OR 1.048, p=0.087) or sex (OR 2.037, p=0.112) in predicting CS.     

Effects of Coffee Consumption on Oxidative Susceptibility of Low-Density Lipoproteins and Serum Lipid Levels in Humans

Since little is known about how coffee intake affects low-density lipoprotein (LDL) oxidative susceptibility and serum lipid levels, we conducted an in vivo study in 11 healthy male students of Wakayama Medical University aged between 20 and 31 years fed an average Japanese diet. On days 1-7 of the study, the subjects drank mineral water. On day 7, the subjects began drinking coffee, 24 g total per day, for one week. This was followed by a one week "washout period" during which mineral water was consumed. Fasting peripheral venous blood samples were taken at the end of each one-week period. LDL oxidation lag time was approximately 8% greater (p < 0.01) after the coffee drinking period than the other periods. Serum levels of total cholesterol and LDL-cholesterol (LDL-C) and malondialdehyde (MDA) as thiobarbituric acid reactive substances (TBARS) were significantly decreased after the coffee drinking period. Finally, regular coffee ingestion may favorably affect cardiovascular risk status by modestly reducing LDL oxidation susceptibility and decreasing LDL-cholesterol and MDA levels.     

Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial

Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (β = 0.020, P = 0.587 for campesterol/TC and β<0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.     

Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk

The PPARγ2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. The RISCK Study investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low-fat (LF) diet. At recruitment, there were no significant associations between genotype and plasma lipids; however, P:S × genotype interaction influenced plasma total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and triglyceride (TG) (P = 0.02) concentrations. At P:S ratio ≤ 0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with increasing P:S (respectively, ≤0.33 to >0.65; 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and noncarriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they are not dependent on a reduction in SFA intake.     

Carbohydrate restriction and dietary cholesterol distinctly affect plasma lipids and lipoprotein subfractions in adult guinea pigs

To evaluate the effects of carbohydrate restriction (CR) and dietary cholesterol on lipoprotein metabolism, adult male guinea pigs (10 guinea pigs/diet) were fed either low (0.04 g/100 g) or high (0.25 g/100 g) amounts of dietary cholesterol, in combination with either low (10% total energy) or high (54.2% total energy) dietary carbohydrate (control groups) for a total of four groups: high carbohydrate–low cholesterol (control-L), high carbohydrate–high cholesterol (control-H), low carbohydrate–low cholesterol (CR-L) and low carbohydrate–high cholesterol (CR-H). Plasma triglyceride concentrations were lower (P<.01%), while high-density lipoprotein cholesterol concentrations were higher (P<.05) in the CR groups compared to the control groups. In contrast, high dietary cholesterol (CR-H and control-H) resulted in higher concentrations of total and low-density lipoprotein (LDL) cholesterol compared to those guinea pigs fed the low-cholesterol diets (P<.01). Dietary cholesterol significantly increased the total number of LDL particles (P<.001) and the number of small LDL (P<.001), as determined by nuclear magnetic resonance. In contrast, carbohydrate restriction (CR-L and CR-H) resulted in lower concentrations of medium very-low-density lipoprotein and small LDL particles compared to the high-carbohydrate groups. Plasma lecithin:cholesterol acyltransferase (LCAT) activity was decreased and cholesterol ester transfer protein activity was increased by dietary cholesterol, whereas carbohydrate restriction increased LCAT activity (P<.05). These findings are similar to those observed in humans, thus validating the use of adult guinea pigs to study lipid responses to carbohydrate restriction. The results also indicate that the atherogenicity of lipoproteins induced by high dietary cholesterol is attenuated by carbohydrate restriction in guinea pigs.