Serum Low-density Lipoprotein Cholesterol Concentrations Research Articles

Dohaekseunggi-tang extract inhibits obesity, hyperlipidemia, and hypertension in high-fat diet-induced obese mice.

BackgroundDohaekseunggi-tang (DHSGT) is a traditional plant-based medicine prescribed to promote blood circulation and to treat obesity and hypertension. The present study aimed to identify potential anti-obesity activities of DHSGT extract.MethodsAnti-obesity, anti-hyperlipidemic, and anti-hypertensive effects of orally-administered DHSGT extract were evaluated in high-fat diet- (HFD)-induced obese mice. Serum biochemistry profiles and expression of diverse metabolic regulatory gene mRNAs in mouse visceral fat were assessed by RT-PCR. The effects of DHSGT on angiotensin-1 converting enzyme (ACE) and pancreatic lipase activities were determined using in vitro inhibition assays.ResultsOral DHSGT treatment reduced obese HFD C57BL/6 J mouse body weight, liver and adipose tissue mass, adipocyte size, and blood pressure versus untreated HFD mice. DHSGT also decreased serum total cholesterol, LDL-cholesterol, triglyceride, glucose, and leptin concentrations, and increased HDL-cholesterol and adiponectin levels in HFD mice. Furthermore, DHSGT markedly increased mRNA expression of peroxisome proliferator activated receptor-gamma, uncoupling protein-2, and adiponectin in visceral adipose tissue of HFD mice. In vitro tests revealed that DHSGT effectively inhibited porcine pancreatic lipase and ACE activities, with IC50 values of 7.58 mg/ml and 0.56 mg/ml, respectively.ConclusionsThese results validate traditional knowledge and suggest that DHSGT may be potentially useful for managing hyperlipidemia, hyperglycemia, hypertension, and obesity.

Effect of cold stress on expression of AMPKalpha-PPARalpha pathway and inflammation genes.

Animals are exposed to various environmental stresses every day, including the stress associated with living in cold temperatures. The aim of this study was to investigate the possible mechanisms of interaction between lipid metabolism and inflammation induced by cold stress in the livers of chickens. Fifteen-day-old male chicks were randomly allocated into 12 groups (10 chickens per group). After exposure of the chickens to the cold stress, cholesterol fractionation was used to examine high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations. Aminotransferase activities were examined with the use of the aspartate transaminase (AST) and alanine transaminase (ALT) assay. The AMP-activated protein kinase alpha-proliferator-activated receptor alpha (AMPKalpha-PPARalpha) pathway genes (AMPKalpha1, AMPKalpha2, PPARalpha, carnitine palmitoyltransferaseI [CPTI], acetyl-CoA carboxylase [ACC]) and inflammatory cytokines (prostaglandin E synthase [PGEs], inducible nitric oxide synthase [iNOS], heme oxygenase-1 [HO-1], nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kappaB], cyclooxygenase-2 [COX-2], and TNF-alpha-like factor [LITAF]) were also measured. The results showed that during the response to cold stress, serum LDL and HDL cholesterol concentrations increased. Histopathologic analyses provided evidence that liver tissues were seriously injured in the chickens exposed to the cold stress. Serum aminotransferase activities were also increased in the group of animals exposed to the cold stress. Additionally, the expressions of AMPKalpha-PPARalpha pathway genes and inflammatory cytokine genes were significantly increased in the animals exposed to cold temperatures. These results suggested that increased inflammation was a feature associated with a lipid-metabolism disorder in the livers of chickens exposed to cold stress.

Factors associated with sustained virological response in 24‐week telaprevir‐based triple therapy for chronic hepatitis C genotype 1b patients with the IL28B minor genotype

Single nucleotide polymorphisms (SNP) near the interleukin-28B (IL28B) gene affect the outcome of 24-week telaprevir-based triple therapy with telaprevir, pegylated interferon-α and ribavirin for chronic hepatitis C virus (HCV) genotype 1b patients. We aimed to identify factors associated with treatment outcomes in patients with the unfavorable minor IL28B SNP genotype, who have poor response to combination therapy. Pretreatment and on-treatment factors associated with sustained virological response (SVR) for 24-week telaprevir-based triple therapy were analyzed using multiple logistic regression analysis in 106 HCV genotype 1b patients with the minor IL28B SNP rs8099917 genotype (non-TT). Of the 106 non-TT patients, 62 (58.5%) achieved SVR. Of the 44 remaining patients, 22 experienced relapse, 13 experienced viral breakthrough and nine were non-responders. Pretreatment factors such as treatment-naïve/prior treatment response (P = 0.0041), high fasting serum low-density lipoprotein cholesterol (LDL-C) concentration (P = 0.0068) and low serum HCV RNA levels (P = 0.0088) were significantly and independently associated with SVR. On-treatment factors such as achievement of rapid virological response (RVR) were significantly and independently associated with SVR (P = 0.0001). For both pre- and on-treatment factors, treatment-naïve/prior treatment response (P = 0.0018), low pretreatment serum fasting LDL-C (P = 0.0062) and achieving RVR (P = 0.0021) were significantly and independently associated with SVR. In HCV genotype 1b patients with the minor IL28B SNP rs8099917 genotype, evaluating prior treatment response and achieving RVR and pretreatment serum fasting LDL-C concentrations were useful for predicting SVR achievement after 24-week telaprevir-based triple therapy.

The protective effects of Ziziphus vulgaris L. fruits on biochemical and histological abnormalities induced by diabetes in rats.

Diabetes mellitus arises from a deficient production and action of insulin. Ziziphus vulgaris L. (jujube) is a medicinal plant that is known to have anti-diabetic actions. The aim of the present study was to investigate the protective effects of jujube fruit powder and extract against biochemical imbalances in streptozotocin (STZ)-induced diabetes. Diabetes was induced in rats using intraperitoneal injection of STZ at a dose of 60 mg/kg body weight (bw). Jujube powder (1 g/kg bw) and extract (1 g/kg bw) were administered daily via gavage, from two weeks prior to three weeks after STZ injection. Serum concentrations of glucose, insulin, and lipids and histological changes of the pancreas tissue were assessed at the end of study. The kaempferol content of jujube extract was found to be 0.013 ± 0.0005% (w/w). Two weeks of supplementation with jujube powder resulted in a significant reduction of serum glucose levels compared with the non-diabetic control group prior to STZ treatment. Both jujube preparations prevented serum insulin decrease following STZ treatment, increased antioxidant capacity, and reduced total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde levels. Jujube powder reduced serum low-density lipoprotein cholesterol and C-reactive protein concentrations while jujube extract had no effect on these parameters. Histopathological examination revealed a significant attenuation of pancreatic inflammation in the jujube-treated animals. The present findings suggest a protective role of jujube supplementation, in particular in the powdered form, against diabetes-induced biochemical and histopathological abnormalities.

Black tea consumption and serum cholesterol concentration: Systematic review and meta-analysis of randomized controlled trials

The results of randomized controlled trials in relation to the effect of regular black tea consumption on serum cholesterol concentration were inconsistent. We aimed to investigate and quantify the effect of black tea consumption on serum concentrations of total, LDL and HDL cholesterol. We systematically searched and identified relevant literatures in PubMed, Scopus and the Cochrane Library. Inclusion and exclusion of studies, data extraction, quality assessment and meta-analysis were conducted according to the PRISMA statement. Ten eligible studies with 411 participants were identified in the present meta-analysis. No significant heterogeneity was found between studies. Consumption of black tea significantly reduced LDL cholesterol concentration (-4.64 mg/dL; 95% CI: -8.99, -0.30 mg/dL; P = 0.036). No remarkable change was detected in total cholesterol (-2.04 mg/dL; 95% CI: -6.43, 2.35 mg/dL; P = 0.363) or HDL cholesterol (-1.15 mg/dL; 95% CI: -3.04, 0.75 mg/dL; P = 0.236). Subgroup analysis showed that the lowering effect on LDL cholesterol was more effective in subjects with higher cardiovascular risk. Black tea consumption significantly lowered serum concentration of LDL cholesterol, especially in subjects with higher cardiovascular risk. Black tea intake did not impose obvious effect on serum concentrations of total and HDL cholesterol.

Effects of feeding various levels of full fat soybean extruded at high temperature on performance, serum components and intestinal morphology of broiler chickens

This study was conducted to evaluate the effect of dietary levels of extruded full fat soybean (EFFSB) on growth performance, physiological enzymes and intestinal morphology of broiler chickens at market age. A batch of FFSB was wet-extruded at 170°C for 15 s to provide the EFFSB. Ross 308 male broiler chicks (144 one-day old) were divided into 12 groups of 12 birds each and allocated to one of the starter, grower and finisher diets containing 0%, 7.5% and 15% of EFFSB. Feed intake and weight gain of chicks fed the diet containing 15% of EFFSB were significantly (P < 0.05) reduced compared with those fed the control diet during 0–10 days of age, but were not influenced during grower and finisher stages and the whole period (P > 0.05). The triglyceride and low-density lipoprotein (LDL) concentrations in blood serum were significantly (P < 0.05) decreased with an increase in dietary levels of EFFSB at 42 days of age. Length of villi and villus absorptive surface area in duodenum section were linearly decreased (P < 0.05) with an increase in dietary level of EFFSB (P < 0.05), although crypt depth and villus length : crypt depth ratio were not affected (P > 0.05). These morphological criteria were not affected by the dietary level of EFFSB measured in jejunum and ileum sections (P > 0.05). It is concluded that the use of EFFSB in feed may reduce the duodenal surface area and serum triglyceride and LDL cholesterol concentrations, but has no effect on performance of broiler chickens at market age.

Inhibition of hepatic microsomal triglyceride transfer protein – a novel therapeutic option for treatment of homozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density lipoprotein (LDL)-receptor gene (LDLR). Patients with homozygous FH (hoFH) have inherited a mutated LDLR gene from both parents, and therefore all their LDL-receptors are incapable of functioning normally. In hoFH, serum LDL levels often exceed 13 mmol/L and tendon and cutaneous xanthomata appear early (under 10 years of age). If untreated, this extremely severe form of hypercholesterolemia may cause death in childhood or in early adulthood. Based on recent data, it can be estimated that the prevalence of hoFH is about 1:500,000 or even 1:400,000. Until now, the treatment of hoFH has been based on high-dose statin treatment combined with LDL apheresis. Since the LDL cholesterol-lowering effect of statins is weak in this disease, and apheresis is a cumbersome treatment and not available at all centers, alternative novel pharmaceutical therapies are needed. Lomitapide is a newly introduced drug, capable of effectively decreasing serum LDL cholesterol concentration in hoFH. It inhibits the microsomal triglyceride transfer protein (MTTP). By inhibiting in hepatocytes the transfer of triglycerides into very low density lipoprotein particles, the drug blocks their assembly and secretion into the circulating blood. Since the very low density lipoprotein particles are precursors of LDL particles in the circulation, the reduced secretion of the former results in lower plasma concentration of the latter. The greatest concern in lomitapide treatment has been the increase in liver fat, which can be, however, counteracted by strictly adhering to a low-fat diet. Lomitapide is a welcome addition to the meager selection of drugs currently available for the treatment of refractory hypercholesterolemia in hoFH patients.

The Cholesterol-Lowering Potential of Whole Grains

Diet is a contributing factor in the risk, development, and progression of cardiovascular disease. Emphasizing whole grain intake in a heart healthy diet is sometimes overlooked. Whole grains confer cardioprotective benefits and those whole grains higher in soluble, or viscous, fiber aid in the reduction of serum total cholesterol and low-density lipoprotein cholesterol concentrations. Whole grains contain all 3 parts of the grain kernel, and the unique combination of nutrients and phytochemicals inherent in all 3 parts of the kernel account for the many health benefits of whole grains. Health care providers have the opportunity to influence whole grain intake. By highlighting the health benefits associated with whole grain consumption and offering practical tips to help identify and add more whole grains to the diet, patients will be better equipped and more apt to increase their whole grain intake.

Association Between Serum Soluble Low‐Density Lipoprotein Receptor Levels and Metabolic Factors in Healthy Japanese Individuals

Soluble low-density lipoprotein receptor (sLDL-R) is formed by cleavage of the extracellular domain of low-density lipoprotein receptor (LDL-R). It is unclear whether serum sLDL-R is a marker of diseases associated with triglyceride (TG) metabolism. We investigated the association between serum sLDL-R concentrations and other biochemical parameters in healthy Japanese individuals. Study subjects consisted of 102 healthy adult Japanese volunteers (42 men, 60 women) with body mass index (BMI) < 30 kg/m(2) and serum TGs, LDL cholesterol (LDL-C), aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, and glucose concentrations within normal ranges. Serum sLDL-R concentrations were determined by enzyme-linked immunosorbent assay and their correlations with biochemical parameters were analyzed. Mean serum sLDL-R concentration was 120.9 ± 39.9 ng/ml. Serum sLDL-R levels were significantly and positively correlated with BMI (rs = 0.252) and TG (rs = 0.408) and LDL-C (rs = 0.325) concentrations. Multiple regression analysis adjusted for age, gender, and smoking showed that BMI (β = 0.274), TG (β = 0.328), and LDL-C (β = 0.224) were factors independently correlated with sLDL-R levels. Serum sLDL-R concentration may be a marker of diseases associated with TG metabolism. This is the first report to date describing the clinical relevance of sLDL-R.

Serum total cholesterol concentration and 10-year mortality in an 85-year-old population

Little is known about the association between total cholesterol (TC) and all-cause mortality in the elderly (especially the very elderly). Here we examined the association between TC and all-cause mortality in 207 very elderly (85-year-old) participants. In 2003, we performed a baseline laboratory blood examination, and blood pressure (BP) and body mass index (BMI) measurements, and lifestyle questionnaires were completed by the participants. The participants were followed for the subsequent 10 years. As of 2013, of the 207 participants in 2003, 70 participants had survived, 120 individuals had died, and 17 were lost to follow up. The TC values were divided into high-TC (≥209 mg/dL), intermediate-TC (176–208 mg/dL), and low-TC (≤175 mg/dL) categories. With the Kaplan–Meier method, we found that both the high-TC and intermediate-TC participants survived longer than the low-TC participants. The men with high TC survived longer than those with low TC, but no corresponding difference was found for the women. A multivariate Cox proportional hazards regression model, with adjustment for gender, smoking, alcohol intake, history of stroke or heart disease, serum albumin concentration, BMI, and systolic BP, revealed that the total mortality in the low-TC group was 1.7-fold higher than that in the high-TC group. Mortality, adjusted for the same factors, decreased 0.9% with each 1 mg/dL increase in the serum TC concentration and decreased 0.8% with each 1 mg/dL increase in the serum (low-density lipoprotein) LDL-cholesterol (LDL-C) concentration. Our results indicate an association between lower serum TC concentrations and increased all-cause mortality in a community-dwelling, very elderly population. Mortality decreased with the increases in both TC and LDL-C concentrations, after adjustment for various confounding factors. These findings suggest that low TC and low LDL-C may be independent predictors of high mortality in the very elderly.

Negative Associations Between Arterial Stiffness Parameter Evaluated by Cardio-Ankle Vascular Index and Serum Low-Density Lipoprotein Cholesterol Concentration in Early-Stage Atherosclerosis

The cardio-ankle vascular index (CAVI), calculated values from cardio-ankle pulse wave velocity and blood pressure, corresponds predominantly to the stiffness of the aorta and peripheral arteries of the lower limbs. However, the reported associations between CAVI and serum low-density lipoprotein cholesterol (LDL-C) levels remain inconsistent. A cross-sectional study of 1878 consecutive patients (mean age: 59.2 years) who underwent general health checkup showed a negative association between CAVI and serum LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) concentrations with age-adjusted correlation and multiple regression analysis. Using the similar analyses divided by the status of risk factors and degree of maximum carotid intima-media thickness (maxIMT), negative correlations between CAVI and LDL-C or non-HDL-C levels were observed only in nonrisk groups including nondiabetics patients or patients with maxIMT <1.0 mm, in those with expected low extent of advanced atherosclerotic lesions. In contrast, such a correlation was not found in each comparable risk-loaded group.

Effect of aqueous root bark extract of Tetrapleura tetraptera (Taub) on blood glucose and lipid profile of streptozotocin diabetic rats

Background: Tetrapleura tetraptera (Schum. and Thonn) Taub is used in Africa as a spice and in folk medicine. Its documented biological activities include molluscicidal, hypotensive, anti-convulsant, anti-inflammatory, hypoglycaemic and anti-microbial effects.Objective: This study evaluated the potential role of the aqueous root-bark extract of T. tetraptera in the treatment of diabetes and its antihyperlipidemic effect in streptozotozin-induced diabetic rats.Methods: T. tetraptera extract was orally administered to streptozotocin (STZ) diabetic rats at 150 and 300mg/kg body weight (Groups 3 and 4). The effect of the extract on body weight, fasting blood sugar (FBS) and serum lipid profile of the treated diabetic rats were compared with untreated control rats (Group 1) and untreated diabetic control rats (Group 2) after 35 days of treatment.Results: T. tetraptera treatment caused a non-significant improvement of STZ-induced weight loss and significantly (p<0.05) reduced FBS in treated diabetic rats. Serum triacylglycerol, total cholesterol and LDL-cholesterol concentration significantly (p<0.05) reduced in treated diabetic rats while the HDL- cholesterol concentration of the 150mg/kg body weight treated group increased.Conclusion: The antidiabetic effect of the aqueous root bark extract of T. tetraptera validates the folkloric use of this part of the plant as an antidiabetic remedy. The associated anti-hyperlipidaemic effect may be useful in the treatment of chronic diabetic complications.Keywords: Tetrapleura tetraptera, diabetes, Antidiabetic, Antihyperlipidemic, Rats

패 추출물의 항산화 활성 및 난소절제 흰쥐의 혈중 지질 함량 변화에 미치는 영향

This study investigated antioxidant activity and the lipid content of serum for the possible outcome of improving the activity of Ishige okamurae extracts in ovariectomized rats. The antioxidant effects of an Ishige okamurae water extract and an Ishige okamurae ethanol extract were measured by evaluating DPPH free radical scavenging activity and SOD-like activity. Fifty, seven-week old female Sprague Dawley rats were randomly assigned to five groups as follows: sham-operated rats (SHAM), ovariectomized rats (OVX-CON), ovariectomized rats that were treated with 17-beta-estradiol (200 μg/kg/day), and ovariectomized rats that were treated with Ishige okamurae extracts (50 mg/kg/day and 200 mg/kg/day, respectively). The diets were fed to the rats for seven weeks after ovariectomy. The antioxidant activities of the water and ethanol extracts of Ishige okamurae increased in a dose-dependent manner, and the ethanol extract was found to be higher than the water extract. Therefore, we examined the effect of an Ishige okamurae ethanol extract on total serum cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol levels, and anti-platelet aggregation. The total-cholesterol and triglyceride content of the serum increased in the OVX-CON group compared to the SHAM group, but supplementation with the Ishige okamurae ethanol extract caused these factors to decrease. Notably, the serum LDL-cholesterol concentration in the supplemented 200 mg/kg/day Ishige okamurae ethanol extract group was significantly more reduced than it was in the OVX-CON group. In addition, the platelet aggregation ability was lower in the groups treated with Ishige okamurae than it was in the OVX-CON group. According to these results, the effects of Ishige okamurae extract on serum lipid content in ovariectomized rats were illuminated.

Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomized, single-blind, placebo-controlled, phase 1 trial

Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomized, single-blind, placebo-controlled, phase 1 trial

Effects of dietary olive oil on egg quality, serum cholesterol characteristics, and yolk fatty acid concentrations in laying hens

A total of 252 Hy-Line laying hens were used to evaluate the effects of dietary olive oil on egg production, egg quality, serum cholesterol characteristics, and yolk fatty acid (FA) concentrations. Layers were randomly allocated into three treatments with seven replications for 4 weeks. Dietary treatments were: CON (control diet, 5% tallow), OLO2 (3% tallow + 2% olive oil), and OLO5 (5% olive oil). Throughout the experimental period, yolk color was greater in OLO5 group than CON group (P < 0.05). The OLO2 and OLO5 groups showed greater egg shell breaking strength than CON group (P < 0.05). Egg shell thickness was increased in OLO2 and OLO5 groups compared with CON group (P < 0.05). The total serum cholesterol concentrations in OLO2 and OLO5 groups were lower than CON group (P < 0.05). Serum high-density lipoprotein cholesterol was elevated in OLO2 and OLO5 treatments compared with CON group (P < 0.05). Layers fed OLO2 diet had greater serum low-density lipoprotein cholesterol concentration than those fed CON and OLO5 diets (P < 0.05). Total yolk unsaturated fatty acids (UFA) were greater in OLO2 treatment compared with CON group (P < 0.05). In conclusion, 2% or 5% olive oil could improve yolk color, increase total yolk UFA, and decrease serum cholesterol concentration in laying hens.

The relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients as evidenced by measurement of carotid intima-media thickness and soluble CD146 levels: a cross sectional study

BackgroundDetection of early vascular changes prior to clinical manifestations of atherosclerosis, such as increased arterial carotid intima-media thickness (CIMT) and impaired endothelial function is of paramount importance for early identification of subjects at increased risk of accelerated atherosclerosis. The present study was designed to evaluate the relationship between early atherosclerosis and endothelial dysfunction in type 1 diabetic patients based on measurements of CIMT and soluble CD146 (sCD146) levels.MethodsThirty-seven patients with type 1 diabetes, 14 males (37.8%) and 23 females (62.2%), of mean (SD) age 26.2 (4.1) years admitted to the outpatient diabetes clinic at Okmeydani Training and Research Hospital, Istanbul, between January 2008 and December 2012, and 37 healthy controls, 16 males (43.2%) and 21 females (56.8%), of mean (SD) age 25.8 (3.1) years, selected from relatives of patients, were included. Anthropometric measures; fasting plasma glucose; and serum HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and creatinine concentrations were compared, as were CIMT and serum sCD146.ResultsMean (SD) sCD146 levels were significantly higher in patients than in controls (314.6 (141.9) ng/ml vs. 207.8 (34.5) ng/ml, p = 0.001), but mean (SD) CIMT did not differ (0.5 (0.1) mm vs. 0.4 (0.1) mm). ROC curves for sCD146 significantly differed in differentiating type 1 diabetics from healthy controls (p = 0.0047) with a significantly higher percentage of patients than controls having sCD146 levels >260 ng/ml (21/37 (56.8%) vs. 2/37 (5.4%), p = 0.00011).ConclusionOur findings emphasize that sCD146 levels may be a more sensitive marker than CIMT for earlier identification of type 1 diabetic patients at high risk for atherosclerosis.

Lipidemic Responses of Male Broiler Chickens to Enzyme-supplemented Wheat-soybean Meal-based Diets with Various Levels of Metabolizable Energy

Effects of 2 various levels of AME (according to the manual recommendation and 100 kcal kg(-1) less than it), 2 levels of endo-beta-D-mannanase enzyme (0, 1 g kg(-1)) and 2 levels of xylanase enzyme (0 and 1 g kg(-1)) on serum lipid parameters as a 2(3) factorial arrangement were tested in 120 male broiler chicks fed wheat-soybean meal-based diet. These birds were randomly assigned to 8 experimental groups with 3 pen per group and 5 birds per pen. The serum HDL-cholesterol (HDL), LDL-cholesterol (LDL), Total-cholesterol (TC) and Triglycerides (TG) concentrations were measured at 31 and 41 day of age. The concentrations of serum TG, TC and LDL of 41-day-old birds demonstrated to be lower than those of 31-d-old (p < 0.001). Some hypolipidemic responses were observed in the broiler chicks fed on (1) Diet supplemented with only beta-mannanase, (2) Normal-AME diets supplemented with p-mannanase, (3) Normal-AME diets supplemented with Xylanse and (4) Normal-AME diets supplemented with both beta-mannanase and Xylanase (p < 0.01). In the other hand, some hyperlipidemic responses were detected in the broiler chicks fed on low-AME diets supplemented with xylanse or beta-mannanase enzymes, alone or in combination (p < 0.01). Regardless of AME, adding both xylanse and beta-mannanase to the wheat-soybean meal-based diets have both hyperlipidemic and hypolipidemic effects together (p < 0.01).

Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation. Genetics studies have shown that loss-of-function mutations in PCSK9 result in reduced plasma LDL cholesterol and decreased risk of coronary heart disease. We aimed to investigate the safety and efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in healthy volunteers with raised cholesterol who were not on lipid-lowering treatment. We did a randomised, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of 3·00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging from 0·015 to 0·400 mg/kg) or placebo. The primary endpoint was safety and tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL cholesterol. Study participants were masked to treatment assignment. Analysis was per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This trial is registered with ClinicalTrials.gov, number NCT01437059. Of 32 participants, 24 were randomly allocated to receive a single dose of ALN-PCS (0·015 mg/kg [n=3], 0·045 mg/kg [n=3], 0·090 mg/kg [n=3], 0·150 mg/kg [n=3], 0·250 mg/kg [n=6], or 0·400 mg/kg [n=6]) and eight to placebo. The proportions of patients affected by treatment-emergent adverse events were similar in the ALN-PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly distributed, with peak concentration and area under the curve (0 to last measurement) increasing in a roughly dose-proportional way across the dose range tested. In the group given 0·400 mg/kg of ALN-PCS, treatment resulted in a mean 70% reduction in circulating PCSK9 plasma protein (p<0·0001) and a mean 40% reduction in LDL cholesterol from baseline relative to placebo (p<0·0001). Our results suggest that inhibition of PCSK9 synthesis by RNA interference (RNAi) provides a potentially safe mechanism to reduce LDL cholesterol concentration in healthy individuals with raised cholesterol. These results support the further assessment of ALN-PCS in patients with hypercholesterolaemia, including those being treated with statins. This study is the first to show an RNAi drug being used to affect a clinically validated endpoint (ie, LDL cholesterol) in human beings. Alnylam Pharmaceuticals.

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

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

Very High Fructose Intake Increases Serum LDL-Cholesterol and Total Cholesterol: A Meta-Analysis of Controlled Feeding Trials

Fructose is widely used as a sweetener in the production of many foods, yet the relation between fructose intake and cholesterol remains uncertain. In this study, we performed a systematic review and meta-analysis of human, controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serum total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in adult humans. Weighted mean differences were calculated to determine changes from baseline cholesterol concentrations by means of generic, inverse variance, random-effect models. The Heyland Methodological Quality was used to assess the quality of the study. Subgroup analyses and meta-regression were conducted to explore the possible influences of study characteristics. Twenty-four trials (with a total of 474 participants) were included in the meta-analysis. In an overall pooled estimate, it was shown that fructose exerted no effect on HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C. Subgroup analyses showed that isocaloric fructose exchange for carbohydrates increased TC by 13.0 mg/dL [(95% CI: 4.7, 21.3); P = 0.002] and LDL-C by 11.6 mg/dL [(95% CI: 4.4, 18.9); P = 0.002] at >100 g fructose/d. However, no effect was shown on TC or LDL-C when the fructose intake was ≤100 g/d. In conclusion, it was shown that very high fructose intake (>100 g/d) increases serum LDL-C and TC concentrations. Larger, longer, and higher-quality human, controlled, feeding trials are needed to confirm these results.