Alterations in the High Density Lipoprotein Phenotype and HDL-Associated Enzymes in Subjects with Metabolic Syndrome

Patients with metabolic syndrome (MetS) usually have low high density lipoprotein cholesterol (HDL-C) levels. We determined the HDL distribution profile as well as the HDL-related lipoprotein associated phospholipase A₂ (HDL-LpPLA₂) and paraoxonase-1 (PON1) activities in subjects with MetS (n = 189) but otherwise healthy. Age and sex-matched individuals (n = 166) without MetS served as controls. The lower HDL-C concentration in MetS patients was due to a reduction in both large and small HDL subclasses (P < 0.001 and P < 0.05, respectively). As the number of MetS components increased, the HDL phenotype comprised of a greater percentage of small HDL-3 and less large HDL-2 subclasses, resulting in a decreased HDL-2/HDL-3 ratio (P < 0.001 for all trends). Multivariate analysis revealed that HDL-2 levels and the HDL-2/HDL-3 ratio significantly and independently correlated with HDL-C (positively) and TG (negatively) levels. HDL-3 concentration significantly and independently positively correlated with HDL-C and TG levels. HDL-LpPLA₂ activity was decreased in MetS patients (P < 0.01), a phenomenon that may contribute to the defective antiatherogenic activity of HDL in MetS. PON1 activity did not differ between groups. We conclude that MetS, in addition to the decrease in HDL-C concentration, is associated with alterations in the HDL phenotype, which is comprised of a greater percentage of small HDL subclasses. Furthermore, HDL-LpPLA₂ activity is decreased in MetS patients.     

Serum Oxidized-LDL is Associated with Diabetes Duration Independent of Maintaining Optimized Levels of LDL-Cholesterol

Oxidized low-density lipoprotein (ox-LDL) plays a key role in the progression of atherosclerosis and diabetes complications. The aim of this study was first, to evaluate the association between ox-LDL and diabetes duration, and second, to examine serum level of ox-LDL in patients with prolonged diabetes and a desirable LDL-cholesterol level. A total of 36 type-2 diabetic patients with a diabetes duration of more than 5 years, 36 newly diagnosed diabetic patients, and 36 age-, sex- and BMI-matched healthy participants were recruited. Healthy participants and newly diagnosed patients were not receiving any treatment. All patients with prolonged diabetes had desirable LDL-cholesterol levels (<100 mg/dL), according to the adult treatment panel-III guidelines. While LDL-cholesterol was significantly lower in patients with diabetes duration >5 years, in comparison to newly diagnosed patients (P < 0.01), ox-LDL was significantly higher in patients with prolonged diabetes (P < 0.001). The ox-LDL-to-LDL ratio was dramatically higher in patients with diabetes duration >5 years in comparison to newly diagnosed patients and healthy participants (P < 0.001). Ox-LDL was significantly associated with diabetes duration (r = 0.519, P = 0.001). In multivariate analysis, this association remained significant (β = 0.501, P = 0.003) after adjustment for potential confounders. In conclusion, this study showed that the serum ox-LDL level increases with the length of diabetes, even though the patients’ LDL-cholesterol level is maintained at a desirable level. Our findings highlight that possibly more attention should be focused on markers of oxidative stress in the management of lipids in diabetic patients.     

A High Legume Low Glycemic Index Diet Improves Serum Lipid Profiles in Men

Clinical studies have shown that fiber consumption facilitates weight loss and improves lipid profiles; however, the beneficial effects of high fermentable fiber low glycemic index (GI) diets under conditions of weight maintenance are unclear. In the Legume Inflammation Feeding Experiment, a randomized controlled cross-over feeding study, 64 middle-aged men who had undergone colonoscopies within the previous 2 years received both a healthy American (HA) diet (no legume consumption, fiber consumption = 9 g/1,000 kcal, and GI = 69) and a legume enriched (1.5 servings/1,000 kcal), high fiber (21 g/1,000 kcal), low GI (GI = 38) diet (LG) in random order. Diets were isocaloric and controlled for macronutrients including saturated fat; they were consumed each for 4 weeks with a 2–4 week break separating dietary treatments. Compared to the HA diet, the LG diet led to greater declines in both fasting serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (P < 0.001 and P < 0.01, respectively). Insulin-resistant (IR) subjects had greater reductions in high density lipoprotein cholesterol (HDL-C; P < 0.01), and triglycerides (TAG)/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. Insulin-sensitive (IS) subjects had greater reductions in TC (P < 0.001), LDL-C (P < 0.01), TC/HDL-C (P < 0.01), and LDL-C/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. In conclusion, a high legume, high fiber, low GI diet improves serum lipid profiles in men, compared to a healthy American diet. However, IR individuals do not achieve the full benefits of the same diet on cardiovascular disease (CVD) lipid risk factors.     

The HMG-CoA Reductase Gene and Lipid and Lipoprotein Levels: the Multi-Ethnic Study of Atherosclerosis

HMG-CoA reductase (HMGCR) is an enzyme involved in cholesterol synthesis. To investigate the contribution of the HMGCR gene to lipids and lipoprotein subfractions in different ethnicities, we performed an association study in the Multi-Ethnic Study of Atherosclerosis (MESA). In total, 2,444 MESA subjects [597 African-Americans (AA), 627 Chinese-Americans (CHA), 612 European-Americans (EA), and 608 Hispanic-Americans (HA)] without statin use were included. Participants had measurements of blood pressure, anthropometry, and fasting blood samples. Subjects were genotyped for 10 single nucleotide polymorphisms (SNPs). After excluding SNPs with minor allele frequency <5%, a single block was constructed. The most frequent haplotype was H1 (41–56%) in all ethnic groups except AA (H2a, 44.9%). Lower triglyceride level was associated with the H2a haplotype in AA and H2 in HA. In HA, H4 carriers had higher levels of triglyceride and small low-density lipoprotein (s-LDL), and lower high-density lipoprotein cholesterol (HDL-c), while carriers with H7 or H8 had associations with these traits in the opposite direction. No significant association was discovered in both CHA and EA. The total variation for triglyceride that could be explained by H2 alone was 2.6% in HA and 1.4% in AA. In conclusion, HMGCR gene variation is associated with multiple lipid/lipoprotein traits, especially with triglyceride, s-LDL, and HDL-c. The impact of the genetic variance is modest and differs greatly among ethnicities.     

Effects of policosanols and phytosterols on lipid levels and cholesterol biosynthesis in hamsters

The current study was carried out to examine the effects of policosanols and phytosterols, alone and in combination, on lipid profiles, cholesterol biosynthesis, and tissue histopathological changes in hamsters. Fifty male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 wk before being randomly assigned into 5 groups of 10 animals each fed semisynthetic diets for 4 wk. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a PUFA to saturated FA ratio of 0.4. Groups 2 to 5 were fed the control diet and given Octa-6 [a policosanol mixture from sugar cane was, 25 mg/kg body weight (BW)], Ricewax (a policosanol mixture from rice wax with 50% being converted to the corresponding acids, 50 mg/kg BW), phytosterols (Cholestatin^TM; 1,000 mg/kg BW), and Ricewax (50 mg/kg BW) plus phytosterols (1,000 mg/kg BW), respectively. The results showed that there was no difference between Octa-6 and Ricewax treatments in any of the lipid parameters measured, and both had similar levels of triglyceride (TG), total cholesterol (T-C), and HDL cholesterol (HDL-C) as the control. Octa-6 but not Ricewax increased (P=0.03) non-HDL-C as compared with the control. Phytosterols reduced T-C (P<0.0003) and HDL-C (P<0.004) without a significant effect on TG and non-HDL-C as compared to the control. Ricewax plus phytosterols had effects similar to those with phytosterols alone. Free cholesterol synthetic rates were not different among the treatments. Policosanols or phytosterols did not show any toxic effects in liver, heart, brain, or kidney. Results suggest that, although phytosterols reduce T-C and HDL-C levels, policosanols have no significant favorable effect in changing lipid levels in hamsters.     

Sugar Cane Policosanols do not Reduce LDL Oxidation in Hypercholesterolemic Individuals

Sugar cane policosanols (SCP) have been shown to exert antioxidant properties in various studies conducted in Cuba. Independent studies have since reported no significant effect of SCP consumption on oxidized LDL levels. The objective of the present study was to confirm the effects of Cuban SCP on LDL oxidation using a high-precision capture ELISA procedure in hypercholesterolemic individuals. Twenty-one otherwise healthy hypercholesterolemic men and post-menopausal women participated in a randomized double blind crossover study where they received 10 mg/day of policosanol or a placebo incorporated in margarine as an evening snack for a period of 28 days. Subjects maintained their usual dietary and exercise habits throughout the duration of the study. Blood was collected on the first as well as the last 2 days of the trial. LDL oxidation was measured from plasma using a solid phase two-site enzyme immunoassay. A lack of effect of SCP was observed on LDL cholesterol levels, as well as no difference in LDL oxidation between the SCP treatment and placebo at the end of the intervention period. Subject body weights remained stable throughout the study and showed no significant correlation with LDL oxidation levels. Absolute levels of plasma LDL cholesterol were significantly (P < 0.05) correlated with plasma concentrations of oxidized LDL. The findings of the present study suggest that SCP do not significantly affect LDL oxidation. Our results align with results of recent policosanol research questioning the efficacy of these natural extracts as cardio-protective agents.     

A high-saturated fat diet enriched with phytosterol and pectin affects the fatty acid profile in guinea pigs

This paper presents the results of a study whose aim was to test the effects of several doses of pectin and phytosterols on the body weight gain and the FA content in emale guinea pigs. The treatments resulted from supplementing with pectin and plant sterol a guinea pig diet (rich in saturated FA), following a 3×3 factorial design, with three levels of pectin (0,3.67 and 6.93%) and three levels of phytosterols (0, 1.37, and 2.45%). Seventy-two female Dunkin Hartley guinea pigs were randomly assigned to the treatment groups (8 animals/group), the duration of the treatment being 4 wk. Pectin dietary intake led to a significant increase in body weight (P<0.001), food consumption (P=0.025), and feed efficiency (P<0.001), but no influence of phytosterols on weight gain or food consumption was detected. We found a significant negative effect of the addition of phytosterols on lauric, myristic, and palmitic acid concents in feces, and a positive effect on their concentration in plasma and liver, but no significant effect on stearic acid content. Apparent FA absorption was assessed by calculating the ratio of FA in feces and diets that the absorption of the different FA could be compared, and the negative effect of phytosterol supplementation on these ratios, especially for lauric and myristic acids, was established.     

Effect of Dehulling Treatment on the Oxidative Stability of Cold-Pressed Low Erucic Acid Rapeseed Oil

This study compared the oxidative stability of cold-pressed rapeseed oil (CPRO) and dehulled cold-pressed rapeseed oil (DCPRO) in the dark at 60 °C and monitored the evolution of minor constituents (tocopherols, phytosterols, phenolics). The results showed that dehulling significantly influenced the oxidative stability of the oils, the DCPRO was more easily oxidized. During the autoxidation, the peroxide value (PV) and anisidine value (p-AV) of the DCPRO ranged from 2.38 to 95.97 mequiv O₂ kg⁻¹ and from 1.20 to 30.75, whereas those of the CPRO ranged from 3.80 to 46.17 mequiv O₂ kg⁻¹and from 2.69 to 14.87, respectively. Dehulling affected the contents and the rates of decrease of tocopherols and phytosterols of the cold-pressed oils, and the rates of decrease of tocopherols and phytosterols of the CPRO were lower than those of the DCPRO (10% less, on average). The rancimat induction periods (IPs) were positively correlated with the concentrations of the total tocopherols (For DCPRO, R ² = 0.9622, For CPRO, R ² = 0.8334). The total phenolics contents as determined by spectrophotometry first increased and then decreased. Tocopherols and phytosterols had a greater effect on oxidative stability of the rapeseed oils during the first 30 days, and phenolics had a greater effect in the 30–40 day period.     

Omega-3 Index Correlates with Healthier Food Consumption in Adolescents and with Reduced Cardiovascular Disease Risk Factors in Adolescent Boys

The Omega-3 Index, a measure of long-chain omega-3 fats in red blood cell membranes, predicts heart disease mortality in adults, but its association with cardiovascular risk factors in younger populations is unknown. We determined the Omega-3 Index in adolescents participating in the Western Australian Pregnancy (Raine) Cohort, assessed associations with diet, lifestyle and socioeconomic factors, and investigated independent associations with cardiovascular and metabolic risk factors. Red blood cell fatty acid analysis was determined for 1,301 adolescents aged 13–15 years. Risk factors examined were blood pressure, fasting blood insulin and glucose concentrations, and fasting blood lipids including ratios. The mean Omega-3 Index was 4.90 ± 1.04% (range 1.41–8.42%). When compared with categories identified in adults, 15.6% of adolescents were in the high risk category (Index < 4%). Age (P < 0.01), maternal education (P < 0.01) and BMI (P = 0.05) were positively associated with the Omega-3 Index. The Index was positively associated with dietary intakes of eicosapentaenoic and docosahexaenoic acid (P < 0.01), protein (P < 0.01), omega-3 fats (P < 0.04), and food groups of fish and wholegrains (both P < 0.01), and negatively associated with intakes of soft drinks and crisps (both P < 0.01). In boys, the Omega-3 Index was independently associated with total (β = 0.06, P = 0.01) and HDL-cholesterol (β = 0.03, P = 0.01), and diastolic blood pressure (β = −0.68, P = 0.04). The predictability of the Index for the risk of cardiovascular disease later in life warrants further investigation in the adolescent population.     

The Spectrum of Plant and Animal Sterols in Different Oil-Derived Intravenous Emulsions

Intravenous lipid constituents have different effects on various biological processes. Some of these effects are protective, while others are potentially adverse. Phytosterols, in particular, seem to be implicated with parenteral nutrition-associated cholestasis. The aim of this study is to determine the amount of plant and animal sterols present in lipid formulations derived from different oil sources. To this end, animal (cholesterol) and plant (β-sitosterol, campesterol, and stigmasterol) sterols in seven different commercially available intravenous lipid emulsions (ILEs) were quantified by capillary gas chromatography after performing a lipid extraction procedure. The two major constituents of the lipid emulsions were cholesterol (range 14–57% of total lipids) and β-sitosterol (range 24–55%), followed by campesterol (range 8–18%) and stigmasterol (range 5–16%). The fish oil-derived formulation was an exception, as it contained only cholesterol. The mean values of the different sterols were statistically different across ILEs (P = 0.0000). A large percentage of pairwise comparisons were also statistically significant (P = 0.000), most notably for cholesterol and stigmasterol (14 out of 21 for both), followed by campesterol (12 out 21) and β-sitosterol (11 out 21). In conclusion, most ILEs combined significant amounts of phytosterols and cholesterol. However, their phytosterols:cholesterol ratios were reversed compared to the normal human diet.