Influence of enhanced bioavailable curcumin on obesity-associated cardiovascular disease risk factors and arterial function: A double-blinded, randomized, controlled trial.

OBJECTIVES: This study aimed to determine whether an enhanced bioavailable curcumin formulation, CurQfen®, would improve circulating cardiovascular disease-related blood biomarkers and arterial function in young (age 18-35 y), obese (body mass index ≥ 30.0 kg/m2) men. METHODS: This double-blinded, placebo-controlled trial evaluated 22 men. The participants were matched based on body mass index and randomized to the intervention (curcumin formulated with fenugreek soluble fiber, for enhanced absorption) or control (fenugreek soluble fiber) group for 12 wk at 500mg/d without dietary modification or exercise. Blood samples and endothelial function measures were acquired at 0 and 12 wk, and blood samples were analyzed for cardiovascular disease-related blood biomarkers. Furthermore, central (aortic) blood pressure and augmentation index were monitored at 0, 4, 8, and 12 wk. RESULTS: After 12 wk of intervention, homocysteine levels were lower (curcumin before: 12.22 ± 2.29 µg/mL, after: 8.62 ± 1.02 µg/mL versus placebo before: 9.45 ± 0.84 µg/mL, after: 11.84 ± 1.63 µg/mL; P = 0.04) and high-density lipoprotein levels were higher (curcumin before: 40.77 ± 5.37 mg/dL, after: 54.56 ± 11.72 mg/dL versus placebo before: 61.20 ± 5.76 mg/dL, after: 48.82 ± 5.49 mg/dL; P = 0.04) in the curcumin group relative to the placebo group. However, there was no significant difference in changes between the circulating concentrations of glucose, insulin, leptin, adiponectin, or oxidative stress biomarkers in the curcumin group compared with the placebo group (P > 0.05). No changes were found with endothelial function, augmentation index, or central blood pressure in the curcumin group compared with the placebo group (P > 0.05). CONCLUSIONS: Our data provide evidence for an enhanced bioavailable curcumin to improve homocysteine and high-density lipoprotein concentrations, which may promote favorable cardiovascular health in young, obese men. Improvements in endothelial function or blood pressure were not observed with curcumin supplementation, thus further investigation is warranted.

Impacto da suplementação com ácidos graxos ômega-3 nas subfrações da lipoproteína de alta densidade de indivíduos tabagistas / Impact of omega-3 fatty acid supplementation on high density lipoprotein subfractions of smokers

RESUMO Objetivo Avaliar o efeito da suplementação com ômega-3 nas subfrações das lipoproteínas de alta densidade em indivíduos tabagistas. Métodos Ensaio clínico, randomizado, duplo-cego. Foi selecionada uma amostra com 33 tabagistas, de ambos os sexos, com idade entre 30 e 60 anos, suplementados com ômega-3 (n=17) ou placebo (ácidos graxos ômega-6, n=16) por dois meses. As subfrações das lipoproteínas de alta densidade foram analisadas pelo sistema Lipoprint. Os testes estatísticos foram realizados com o auxílio do programa Statistical Package for the Social Sciences, versão 20.0. Resultados A média de idade foi 49 anos, com predominância da raça branca. Após a intervenção, o grupo ômega-3 modificou positivamente o perfil lipídico e as subfrações das lipoproteínas de alta densidade dos tabagistas. Nos modelos de regressão linear testados, o percentual de ácido docosahexaenoico plasmático apresentou associações negativas com o percentual das lipoproteínas de alta densidade-pequena. Conclusão A suplementação com ômega-3 está associada a uma alteração favorável na distribuição das subfrações das lipoproteínas de alta densidade, aumentando as lipoproteínas de alta densidade-grande e diminuindo as lipoproteínas de alta densidade-pequena. Isso reforça a importância do ômega-3 na saúde cardiovascular de indivíduos tabagistas.

ABSTRACT Objective To assess the effect of omega-3 supplementation on smokers' high density lipoprotein subfractions. Methods This randomized, double-blind clinical trial included 33 male and female smokers aged 30 to 60 years. The sample took omega-3 fatty acids (n=17) or placebo (omega-6 fatty acids, n=16) for two months. The Lipoprint system analyzed the high density lipoprotein subfractions. The statistical tests were performed by the software Statistical Package for the Social Sciences, version 20.0. Results The mean age of the sample was 49 years, and most individuals were white. After the intervention, the lipid profile and high density lipoprotein subfractions of the omega-3 group improved. In the tested linear regression models, the percentage of plasma docosahexaenoic acid was negatively associated with the percentage of small high density lipoprotein. Conclusion Omega-3 supplementation is associated with a favorable change in the distribution of high density lipoprotein subfractions, increasing the large and reducing the small high density lipoproteins. This finding reinforces the importance of omega-3 fatty acids for smokers' cardiovascular health.

Effects of Ginger on Serum Lipids and Lipoproteins in Peritoneal Dialysis Patients: A Randomized Controlled Trial.

UNLABELLED: ♦ BACKGROUND: In peritoneal dialysis (PD) patients, one of the major risk factors for cardiovascular disease is lipid abnormalities. This study was designed to investigate the effects of ginger supplementation on serum lipids and lipoproteins in PD patients. ♦ METHODS: In this randomized, double-blind, placebo-controlled trial, 36 PD patients were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1,000 mg ginger daily for 10 weeks, while the placebo group received corresponding placebos. At baseline and at the end of week 10, 7 mL of blood were obtained from each patient after a 12- to 14-hour fast, and serum concentrations of triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and lipoprotein (a) [Lp (a)] were measured. ♦ RESULTS: Serum triglyceride concentration decreased significantly up to 15% in the ginger group at the end of week 10 compared with baseline (p < 0.01), and the reduction was significant in comparison with the placebo group (p < 0.05). There were no significant differences between the 2 groups in mean changes of serum total cholesterol, LDL-C, HDL-C, and Lp (a). ♦ CONCLUSION: This study indicates that daily administration of 1,000 mg ginger reduces serum triglyceride concentration, which is a risk factor for cardiovascular disease, in PD patients.

High-dose statin therapy with rosuvastatin reduces small dense LDL and MDA-LDL: The Standard versus high-dose therApy with Rosuvastatin for lipiD lowering (SARD) trial.

BACKGROUND: Cardiovascular events (CV) continue to occur due to residual risks in high-risk patients in spite of substantial reductions in the low-density lipoprotein cholesterol (LDL) with statins. It has been reported that the small-dense LDL (sd-LDL) components of high atherogenic particles are associated with an increased risk of CV, more than large buoyant LDL. However, there are few reports regarding the effects of high-dose statin therapy in improving atherogenic lipoproteins. METHODS AND RESULTS: In this prospective, randomized, open-label, multicenter study, a total of 111 high-risk patients were randomly assigned to two groups. In the high-dose therapy group, 58 patients were administered 5mg of rosuvastatin per day for four weeks, after which the dose was titrated to 10mg for the following eight weeks. In the low-dose therapy group, 53 patients were given 2.5mg for 12 weeks. We evaluated the lipid profiles, including the levels of sd-LDL, malondialdehyde-modified LDL-cholesterol (C) (MDA-LDL) as oxidized-LDL, and remnant-like particle-cholesterol. The LDL-C, non-high-density lipoprotein (HDL), and LDL-C/HDL-C ratio were decreased in the high-dose therapy group (p<0.01). Moreover, the sd-LDL and MDA-LDL levels were significantly reduced in the high-dose therapy group (p<0.05). There were no serious adverse events in either group. CONCLUSIONS: High-dose statin therapy significantly reduced the sd-LDL and MDA-LDL components of atherosclerotic lipoproteins without adverse events in comparison with low-dose statin therapy.

Effects of olanzapine on the elevation of macrophage infiltration and pro-inflammatory cytokine expression in female rats.

The metabolic side-effects of olanzapine have undermined drug compliance and increased concern for this otherwise-effective treatment for schizophrenia. As obesity and type 2 diabetes are associated with low-grade inflammation, and olanzapine-induced weight gain has three typical stages, the current study investigated the inflammatory effects of olanzapine in three treatment stages. Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg three times daily) or vehicle for one week, two weeks, and five weeks. Olanzapine significantly increased body weight and white visceral fat deposition in all three treatment stages compared to control. Olanzapine enhanced average adipocyte size and level of macrophage infiltration in white adipose tissue (WAT) compared to control, with levels of macrophage infiltration increased over time. There was a high correlation between adipocyte size and macrophage infiltration rate. Olanzapine also caused increased macrophage infiltration in brown adipose tissue (BAT), but not liver. Additionally, pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin (IL)-1ß, and IL-6 were upregulated by olanzapine in the hypothalamus, WAT, and BAT compared to control, but not the liver. Finally, plasma triglycerides were elevated by olanzapine compared to control, but not total cholesterol, high density lipoprotein (HDL) or low density lipoprotein (LDL). These findings indicate that olanzapine-induced inflammation and adiposity are closely related, and that peripheral low-grade inflammation develops during olanzapine treatment.

Emerging therapeutic approaches to treat dyslipidemia.

Statins are safe, efficacious and the cornerstone of cardiovascular disease prevention strategies. A number of add-on therapies with complementary actions on the plasma lipid profile have been tested in large scale trials to see if they give incremental benefit. In particular, the 'HDL hypothesis' - that raising this lipoprotein will promote reverse cholesterol transport and reduce cardiovascular risk - has been examined using drugs such as dalcetrapib and niacin. So far, results have been negative, and this has raised questions over the nature of the association of HDL with atherosclerosis, and whether statins reduce cardiovascular risk through multiple mechanisms. There is still an unmet clinical need especially in those patients who cannot tolerate statins and those with severe hyperlipidemia, and so new therapeutic approaches have been developed. These show significant promise in terms of LDL-cholesterol lowering but significant challenges include cost, route of administration (subcutaneous injection) and side effects. Testing in major outcome trials will be required to demonstrate their clinical utility.

Epanova(®) and hypertriglyceridemia: pharmacological mechanisms and clinical efficacy.

While LDL-cholesterol lowering has become the cornerstone of cardiovascular risk reduction strategies, considerable interest in additional targeting of hypertriglyceridemia continues. While ω-3 fatty acids are commonly used in clinical practice for triglyceride lowering, no large-scale clinical trial evaluating their impact on clinical events has been performed. As a result, there remains a lack of consensus with regards to their optimal clinical use. Epanova(®) (Omthera Pharmaceuticals Inc., NJ, USA) is a novel ω-3 free fatty acid formulation, developed to maximize eicosapentenoic acid and docosahexenoic acid bioavailability with low-fat diets, suggesting a potential therapeutic advantage compared with ω-3-acid ethyl esters in the treatment of patients with hypertriglyceridemia. Additional human studies are needed to define more clearly the cellular and molecular basis for the triglyceride-lowering effects of Epanova and this drug's favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.

Effect of green tea extract on body weight, serum glucose and lipid profile in streptozotocin-induced diabetic rats. A dose response study.

OBJECTIVE: To examine the effect of green tea extract on body weight, serum levels of glucose, and lipids in streptozotocin-induced diabetic rats. METHODS: This experimental study was carried out in the Diabetes Research Center, Ahvaz University of Medical Sciences, Ahvaz, Iran from January 2011 to March 2011. Forty-eight male wistar rats (200-250 g) were divided randomly into 6 groups. Diabetes was induced by a single intraperitoneal injection of stereptozotocin (55 mg/kg). The experimental groups received alcohol extract of green tea leaves (100 mg/kg and 200 mg/kg) for 4 weeks and the body weight of animals were measured every day. Finally, blood samples were collected and analyzed for glucose and lipid profile levels. RESULTS: Administration of green tea extract caused a significant decrease in serum glucose and total cholesterol levels and significantly improved the body weight loss in diabetic rats treated with 200 mg/kg green tea in comparison to diabetic control group. No significant changes were observed in triglyceride (p=0.04), low-density-lipoprotein cholesterol (p=0.000), and high-density-lipoprotein cholesterol levels (p=0.01) following intervention. CONCLUSION: It appears that green tea extract had both antihyperglycemic and hypocholesterolmic effects in diabetic rats, although further work is needed to determine their mechanism.

Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability.

BACKGROUND: This study was designed to evaluate the effects of omega-3 fatty acids supplements and simvastatin on lipoproteins and heart rate variability (HRV), a surrogate parameter of cardiac autonomic function, in patients with mixed dyslipidemia. METHODS: This study was a prospective, randomized, open-label study. Among the 171 patients screened, 62 who met the inclusion criteria after 6 weeks on a strict diet therapy were randomized into two treatment groups. The inclusion criteria were mixed dyslipidemia with a high triglyceride level (200-499 mg per 100 ml) and a total cholesterol level >200 mg per 100 ml. After a run-in period of 6 weeks, the patients were randomized into two groups and given a combination treatment with 4 g of omega-3 fatty acids (four 1 g Omacor (eicosapentaenoic acid, 465 mg; docosahexaenoic acid, 375 mg; other omega-3 fatty acids, 60 mg; others 100 mg, Gun-il Pharmacy, Seoul, Korea)) and 20 mg of simvastatin daily or a monotherapy of 20 mg simvastatin for 6 weeks. In the combination therapy group, seven patients dropped out, and in the simvastatin alone therapy group, five patients dropped out during the study period. RESULTS: After 6 weeks of drug treatment, triglyceride levels decreased by 41.0% in the combination treatment group and 13.9% in the simvastatin monotherapy group (from 309.2 ± 95 mg per 100 ml to 177.7 ± 66 versus 294.6 ± 78 mg per 100 ml to 238.3 ± 84 mg per 100 ml, respectively, P = 0.0007). No significant changes in the HRV parameters were observed in either group. CONCLUSION: The combination of omega-3 fatty acids plus simvastatin, which achieved a significantly greater reduction of triglycerides without adverse reactions, should be considered as an optimal treatment option for patients with mixed dyslipidemia.

Effects of trace elements on albumin and lipoprotein glycation in diabetic retinopathy.

OBJECTIVE: To test the effect of some trace elements, on protein and lipoprotein glycosylation and their impact on the severity of diabetic retinopathy. METHODS: A case control study was conducted in 42 diabetic patients (14 without retinopathy [DC]; 14 with non-proliferative diabetic retinopathy [NPDR]; 14 with proliferative diabetic retinopathy [PDR]) at Ebin Al-Haitham Specialized Hospital, Baghdad, Iraq for Ocular Diseases from February to December 2008. In addition to 20 age and gender matched healthy controls (NC). The glycation of albumin, alpha-, pre beta-, and beta-lipoproteins was measured by agarose gel electrophoresis. Serum levels of cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and copper (Cu) were analyzed by flameless atomic absorption spectrophotometer. RESULTS: There was significant elevation in the mean serum glycated beta-lipoprotein in DC (p<0.05) and a near significant increase (p=0.06) in the means of both glycated albumin and pre beta-lipoproteins among the PDR and NPDR groups. Moreover, a significant reductions in serum means of Cd (p<0.05) and Zn/Cu ratios (p<0.001) were recorded in all diabetic retinopaths as compared to DC. The Cd level rises with the increase in duration of diabetes (p<0.001) and hyperglycemia (p<0.025) whereas, the serum Cr values decreases with the progression of diabetes (p<0.025). CONCLUSION: Both glycation and oxidative processes are involved in the development of diabetic retinopathy, and changes in the concentration of Cd, Se, Cr, Zn, and Cu have some impact on the disease progression.

Atheroprotective lipoprotein effects of a niacin-simvastatin combination compared to low- and high-dose simvastatin monotherapy.

BACKGROUND: Niacin has multiple lipoprotein effects that may provide cardiovascular benefit when added to statin monotherapy. METHODS: In this randomized, placebo-controlled trial (n = 75) of magnetic resonance imaging of carotid atherosclerosis, we performed a secondary comparison of combination niacin-statin (simvastatin 20 mg/Niacin-ER 2G [S20/N]) to monotherapy with moderate (20 mg [S20]) and high-dose (80 mg [S80]) simvastatin on lipids, apolipoproteins (apo), low density lipoprotein (LDL) and high density lipoprotein (HDL) particle subclasses, and inflammatory markers. RESULTS: At baseline, average age was 71, 72% were male, 62.5% used statins, and average LDL-cholesterol was 111 mg/dL. At 12 months, S20/N, compared to S80, significantly reduced apoB (-36.6% vs -11.9%; P = .05) and lipoprotein(a) (-18% vs +3.5%; P = .001) and had at least an equivalent effect on LDL-cholesterol (-39.3% vs -24.3%; P = .24). The combination reduced the proportion of subjects with atherogenic LDL pattern-B (50% to 11.5%) compared to S80 (56% to 56%) (P = .01). Despite increases in plasma free fatty acids (+62.4%; F = 5.65, P = .005 vs S20 and S80), plasma triglycerides (-29.4%; F = 6.88, P = .002 vs S20 and S80), and very-low-density lipoprotein (-44.2%; F = 7.94, P < .001 vs S20 and S80), levels were reduced by S20/N. S20/N increased HDL-cholesterol levels (+18.1%) as compared to S20 (0%) and S80 (+5.9%) (P < .001 vs both statin arms), largely due to an increase in HDL particle size (+4.6%; P = .01 vs both statin arms). CONCLUSIONS: We demonstrate that full-dose niacin/moderate-dose simvastatin combination has sustained benefits on atherogenic apoB lipoproteins, at least comparable to high-dose simvastatin, while also raising HDL-cholesterol. Results of large clinical trials will inform whether niacin-statin combinations reduce cardiovascular disease events.

Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia.

Prescription omega-3 acid ethyl esters (P-OM3) are commonly used for treatment of very high triglyceride levels, often in combination with a statin, to lower persistent hypertriglyceridemia. This randomized, crossover trial evaluated 6 weeks of combination therapy with simvastatin 20 mg/day plus P-OM3 4 g/day or placebo in 39 men and women (average age 58 years) with a triglyceride concentration 200 to 600 mg/dl and non-high-density lipoprotein (non-HDL) cholesterol greater than their National Cholesterol Education Program treatment goals after a 5-week diet lead-in. Non-HDL cholesterol decreased from baseline (209 mg/dl) by 40% for P-OM3 + simvastatin compared with 34% for placebo + simvastatin (p <0.001). Favorable changes for P-OM3 + simvastatin versus placebo + simvastatin were also observed for very low-density lipoprotein (VLDL) cholesterol (-42% vs -22%), triglyceride (-44% vs -29%), total cholesterol (-31% vs -26%), HDL cholesterol (+16% vs +11%), apolipoprotein B (-32% vs -28%), total cholesterol:HDL cholesterol ratio (-39% vs -33%), triglyceride:HDL cholesterol ratio (-51% vs -37%), and systolic (-5.0 vs 0.3 mm Hg) and diastolic (-3.3 vs -1.8 mm Hg) blood pressures (p <0.05 for all). VLDL particle concentration and size decreased and LDL particle size increased significantly more with P-OM3 + simvastatin than with placebo + simvastatin (all p <0.05). Changes in LDL cholesterol, LDL particle concentration, HDL particle size and concentration, and apolipoprotein A-I did not differ significantly between treatments. In conclusion, P-OM3 + simvastatin appears to be a useful therapeutic option for the management of mixed dyslipidemia.

The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation.

BACKGROUND: Lutein and docosahexaenoic acid (DHA) may protect against age-related macular degeneration (AMD). Lutein is a component of macular pigment. DHA is in the retina. OBJECTIVE: The objective of this 4-mo study was to determine the effects of lutein (12 mg/d) and DHA (800 mg/d) on their serum concentrations and macular pigment optical density (MPOD). DESIGN: Forty-nine women (60-80 y) were randomly assigned to placebo, DHA, lutein, or lutein + DHA supplement. Serum was analyzed for lutein and DHA (0, 2, and 4 mo). MPOD was determined (0 and 4 mo) at 0.4, 1.5, 3, and 5 degrees temporal retinal eccentricities. Serum was analyzed for lipoproteins (4 mo). RESULTS: There was no interaction between lutein and DHA supplementations for serum lutein and MPOD. The lutein supplementation x DHA supplementation x month interaction was significant for serum DHA response (P < 0.05). In the lutein group, serum lutein increased from baseline at 2 and 4 mo (P < 0.001), and MPOD increased at 3.0 degrees (P < 0.01). In the DHA group, serum DHA increased at 2 and 4 mo (P < 0.0001), and MPOD increased at 0.4 degrees (P < 0.05). In the lutein + DHA group, serum lutein and DHA increased at 2 and 4 mo (P < 0.01), and MPOD increased at 0.4, 1.5, and 3 degrees (P = 0.06, 0.08, and 0.09, respectively). Differences from placebo in lipoprotein subfractions were greatest for the lutein + DHA group (4 mo). CONCLUSIONS: Lutein supplementation increased MPOD eccentrically. DHA resulted in central increases. These results may be due to changes in lipoproteins. Lutein and DHA may aid in prevention of age-related macular degeneration.

Fish oil in the treatment of dyslipidemia.

PURPOSE OF REVIEW: The recent availability of a concentrated prescription omega-3 fatty acid preparation provides physicians with an additional anti-dyslipidemic agent at a time when limitations of statin therapy in dyslipidemic high-risk patients are recognized. This review examines the evidence supporting the use of omega-3 fatty acid treatment in dyslipidemic states. RECENT FINDINGS: There is now considerable evidence that omega-3 fatty acid treatment at the prescription strength of 4 g/day effectively and safely lowers triglyceride levels and increases low-density lipoprotein size, as well as affecting high-density lipoprotein metabolism. Similar effects have been noted in patients treated with statins, and add-on prescription omega-3 fatty acid therapy significantly increases the proportion of statin-treated dyslipidemic patients reaching their non-high-density lipoprotein cholesterol goals. In addition to past studies showing a cardioprotective effect of low-dose omega-3 fatty acid treatment against sudden death, a recent controlled clinical trial showed that 1.8 g of omega-3 fatty acid in statin-treated patients reduced major coronary events by 19% compared with statin plus placebo treatment. SUMMARY: Omega-3 fatty acid treatment should be considered in patients with severe hypertriglyceridemia as well as in high-risk patients with an atherogenic lipoprotein phenotype.

Downregulation of hepatic lipoprotein assembly in rats by fermented products of Monascus pilosus.

OBJECTIVE: Hypercholesterolemia is a major risk factor for atherosclerosis. The fermented products of Monascus sp. have been known for their antihypercholesterolemic effect; however, the studies mostly have focused on the inhibition of cholesterol biosynthesis in liver. In this study, we examined whether fermented products of Monascus pilosus have regulatory effects on the hepatic lipoprotein assembly. METHODS: Male Wistar rats were fed 1% cholesterol diet for 2 wk. After hypercholesterolemia was induced, the animals were maintained on this cholesterol diet supplemented with M. pilosus-fermented products grown in regular medium/garlic-containing medium or garlic powder for another 6 wk. The concentration of blood lipids and the expression of proteins involved in lipoprotein assembly and hepatic antioxidation were assayed. RESULTS: Maintenance on a 1% cholesterol diet for 2 wk significantly (P < 0.05) raised animals' blood lipid levels and increased the expression of intestinal microsomal triacylglycerol transfer protein, hepatic apolipoprotein B-100, and acyl-coenzyme A:cholesterol acyltransferase. Supplementation of M. pilosus-fermented products or garlic powder significantly (P < 0.05) lowered animals' blood lipid levels and inhibited the expression of intestinal microsomal triacylglycerol transfer protein and hepatic apolipoprotein B-100. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase was downregulated by the M. pilosus-fermented product grown in regular medium but not in garlic-containing medium. The expression of antioxidant enzymes was significantly upregulated by the M. pilosus-fermented product grown in garlic-containing medium. CONCLUSION: Monascus sp.-fermented products exert the hypocholesterolemic effect by mechanisms other than the inhibition of cholesterol biosynthesis.

Effects of marine n-3 fatty acid supplementation on lipoprotein subclasses measured by nuclear magnetic resonance in subjects with type II diabetes.

OBJECTIVE: To measure effects of fish oil supplements on lipoprotein subclasses by nuclear magnetic resonance (NMR) in subjects with type II diabetes and relate them to insulin sensitivity. DESIGN: Two-armed, parallel, placebo-controlled, randomized. SUBJECTS: Normotriglyceridemic subjects with type II diabetes without insulin treatment were given either fish oil (n=12, median intake 5.9 g/day total n-3 fatty acids (FA) (1.8 g 20:5n-3, 3.0 g 22:6n-3)) or corn oil (n=14, 8.5 g/day 18:2n-6 FA). METHODS: Size and concentration of lipoproteins subclasses were measured by NMR, insulin sensitivity by hyperinsulinemic, isoglycemic clamps. RESULTS: After 9 weeks, there were differences between those treated with fish and corn oil with respect to very low-density lipoprotein (VLDL) size (median -15 vs +0.6%, P=0.001), particle concentrations of large VLDL (-99 vs -4.1%, P=0.041) and small high-density lipoprotein (HDL) (-12 vs +10%, P=0.051). Compared with corn oil fish oil tended to increase HDL size and small low-density lipoprotein (LDL) concentration (P=0.063 and 0.068, respectively, for differences between groups). There was no effect on oxidized LDL. Insulin sensitivity (glucose utilization) decreased in the fish oil group compared with the corn oil group (P=0.049). The decrease in insulin sensitivity did not correlate with the effects on lipoprotein subclasses. CONCLUSIONS: A high intake of n-3 FA exerts effects on several lipoprotein subclasses without obvious influence from changes in insulin sensitivity.

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

BACKGROUND: The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. METHODS: Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. RESULTS: Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). CONCLUSION: High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Combined effects of curcumin and vitamin C to protect endothelial dysfunction in the iris tissue of STZ-induced diabetic rats.

This study was aimed to evaluate the combined effect of curcumin with vitamin C supplementation on hyperglycemic and dyslipidemia conditions and endothelial cell dysfunction induced in diabetic rats. Wistar Furth rats were used and divided into four groups: control (single injection of 0.9% sterile saline), STZ (streptozotocin, Sigma, 55 mg/kg.BW, i.v.), STZ-vitC (1 g/l ascorbic acid mixed in drinking water), STZ-cur (daily oral treatment of 300 mg/kg.BW curcumin; Cayman Chemical Co., USA), and STZ-cur+vitC (1 g/l ascorbic acid mixed in drinking water and oral treatment of 300 mg/kg.BW curcumin). On 8th week after STZ-injection, the microcirculation in the iris tissue was observed using intravital fluorescence videomicroscopy, and also leukocyte adhesion in the venule was examined for each group. Blood glucose (BG), lipid profiles, glycosylated hemoglobin (HbA1c) were measured in blood samples collected at the end of each experiment. The contents of liver malondialdehyde (MDA) were also quantified for each group. Feeding curcumin (STZ-cur) could decrease BG, HbA1c, dyslipidemia, and MDA significantly, compared to STZ. In cases of feedings curcumin with vitamin C, these results were more effective in all aspects, including leukocyte adhesion. In conclusion, curcumin might increase the effect of vitamin C in protecting the function of endothelial cells through its anti-oxidant with hypoglycemic and hypolipidemic actions.

Dietary fats, fatty acids, and their effects on lipoproteins.

All saturated fatty acids, with the notable exception of stearic acid (C18:0), raise low-density lipoprotein (LDL) cholesterol levels. A few less ubiquitous fatty acids also have LDL cholesterol effects. Trans-monounsaturated fatty acids, at equivalent doses of saturated fatty acids, raise LDL cholesterol. Polyunsaturated fatty acids, at three times the dose of saturated fatty acids, lower LDL cholesterol. Higher intakes of most fatty acids raise high-density lipoprotein (HDL) cholesterol, with the notable exception of trans-monounsaturated fatty acids, which lower HDL cholesterol to the same extent as carbohydrate when either is substituted for other dietary fatty acids. Conjugated linoleic acids containing both cis and trans bonds and cis-monounsaturated fatty acids neither raise nor lower cholesterol concentrations of lipoproteins. The omega-3 fatty acids from fish lower triglyceride levels. Although dietary composition remains an important, modifiable predictor of dyslipidemia, overconsumption of any form of dietary energy may replace overconsumption of saturated fat as the primary factor that increases lipid and lipoprotein levels.

A randomized factorial study of the effects of long-term garlic and micronutrient supplementation and of 2-wk antibiotic treatment for Helicobacter pylori infection on serum cholesterol and lipoproteins.

BACKGROUND: Little is known about the long-term effects of garlic or micronutrient supplementation on total, HDL, and LDL cholesterol in disease-free persons. OBJECTIVE: We aimed to assess the effects of long-term supplementation with garlic and micronutrients and of short-term amoxicillin and omeprazole treatment on serum total, HDL, and LDL cholesterol in a rural Chinese population. DESIGN: We conducted a randomized, double-blind, placebo-controlled, 2 x 2 x 2 and 2 x 2 factorial study of precancerous gastric lesions in 3411 subjects in Linqu County, Shandong Province, China. Thirty-four subjects were randomly selected from each of 12 treatment strata. Sera were analyzed at 3.3 and 7.3 y to measure effects on total, HDL, and LDL cholesterol after 2-wk twice-daily treatment with 1 g amoxicillin and 20 mg omeprazole and supplementation throughout the study with 1) 2 capsules twice daily, each containing 200 mg aged garlic extract and 1 mg steam-distilled garlic oil, or 2) twice-daily micronutrient capsules containing 250 mg vitamin C, 100 IU vitamin E, and 37.5 mg selenium. RESULTS: Regressions adjusted for covariates indicated increases of 0.22 mmol total cholesterol/L (P = 0.01) and 0.19 mmol LDL/L (P = 0.02) after 7.3 y of micronutrient supplementation, but no effect of garlic supplementation or short-term amoxicillin and omeprazole treatment. CONCLUSIONS: In this rural Chinese population with low meat intake and moderate cholesterol concentrations, long-term garlic supplementation had no effect on lipid profiles, whereas micronutrient supplementation was associated with small but significant increases in total and LDL-cholesterol concentrations at 7.3 y.