Changes In Serum Lipids Research Articles

The Effect of Soybean Lunasin on Cardiometabolic Risk Factors: A Randomized Clinical Trial

Lunasin, a peptide isolated from soybeans, has been shown to exert antioxidant, anticarcinogenic, and hypocholesterolemic effects in animal and in vitro models. In a triple-blind, placebo-controlled crossover study, 31 participants (female: 19, male: 12, mean age 61 ± 9.9 years) were randomized to an 8-week treatment of lunasin-enriched soy extract (335mg/d) or placebo. A 3-week washout period was utilized between treatments. Serum lipids, glucose, and insulin, as well as blood pressure and anthropometrics, were measured at baseline, week 7, and week 8 of each treatment period. There were nonsignificant reductions in cardiometabolic risk factors with treatment: total cholesterol −0.1mmol/L, 95% CI [−0.28, 0.03]; LDL cholesterol −0.07mmol/L, 95% CI [−0.2, 0.06]; triglyceride 0% mmol/L, 95% CI (−10%, 11%]; fasting serum glucose −2% mmol/L, 95% CI [−4%, 1%]; BMI −0.05 kg/m2, 95% CI [−0.17, 0.07] and waist circumference −0.63cm, 95% CI [−1.8, 0.53]. Supplementation with lunasin-enriched soy extract for 8 weeks did not result in significant changes in serum lipids, glucose, insulin resistance, blood pressure, BMI, or waist circumference. Future studies should focus on a higher dosage, larger sample size, and/or longer treatment to determine the independent role of lunasin, if any, in the effect of soy on cardiometabolic risk factors.

High Levels of Serum Uric Acid, Cystain C and Lipids Concentration and their Clinical Significance in Primary Gouty Arthritis Patients.

To investigate the changes of serum Uric Acid (sUA), lipids and Cystatin C (CysC) in primary gout patients, and to explore the clinical significance in gout patients. sUA, CysC, high-sensitivity C-reactive Protein (hsCRP) and other biochemical parameters were measured in 326 gout patient and 210 healthy control subjects, blood cell counts were also detected. Clinical data were collected from gout patients. sUA, CysC, hsCRP, Body Mass Index (BMI), White Blood Cell (WBC) counts, neutrophil Granulocyte (GR), Monocyte (Mo), Triglycerides (TG), plasma Total Cholesterol (TC), Very Low Density Lipoprotein (VLDL), apolipoprotein B100 (apoB100), Blood Glucose (GLU), serum Creatinine (sCr) and Urea Nitrogen (BUN) were significantly increased in gout patients compared with HC subjects (P<0.01, respectively), while lymphocyte counts and High Density Lipoprotein- Cholesterol (HDL-C) were significantly decreased in gout patients compared with HC subjects (P<0.01, respectively). Positive correlations were observed between concentration of sUA and age, TG, VLDL, sCr and CysC (P<0.05, respectively). While negative correlations were observed between the concentration of sUA and HDL-C(P<0.01). Besides, Positive correlations were observed between concentration of CysC and WBC, GR, Mo, apoA1, GLU, sCr, BUN, sUA, hsCRP (P<0.05, respectively). While negative correlations were observed between the concentration of CysC and TC, LDL-C(P<0.01, respectively). Blood lipid profile changes in gout patients. Gout patients who suffer from lipid metabolism disorder and vascular diseases might be associated with hyperuricemia, which leads to endothelial cell damage and vascular smooth muscle cell proliferation. CysC might be a marker for renal function damage and inflammation. Hyperuricemia is the risk factor of renal disorder in gout patients.

Relação cintura/estatura e índice de conicidade estão associados a fatores de risco cardiometabólico em idosos

The purpose of this study was to determine and compare a magnitude of the association between anthropometric indicators with risk of cardiometabolic risk in the elderly. This is a cross-sectional study with 402 elderly people attended by the Family Health Strategy in the city of Viçosa-MG. Risk factors for excess body fat, hypertension, blood glucose and serum lipid changes. An association between conicity index (CI) and waist-to-height ratio (WtHR) with cardiometabolic risk factors was assessed by multiple linear regression analysis. Sample was composed of 60.4% of women and 36.3% of overweight elderly. The connectivity index and a waist-to-height ratio were higher in 57.2% and 88.1% in the elderly, respectively. The results showed that the increase in body fat, diastolic blood pressure, triglycerides, glycemia and reduction of HDL-cholesterol are related to higher values of anthropometric indices evaluated. However, the waist-to-height ratio presented a greater magnitude of association with the cardiometabolic risk factors than the connectivity index.

Breastfeeding and long-term maternal metabolic health in the HUNT Study: a longitudinal population-based cohort study.

Breastfeeding (BF) has been reported to improve long-term maternal metabolic health in observational studies, but not in the randomised controlled PROBIT study. Research also suggests that maternal pre-pregnant metabolic health may affect BF. We aimed to disentangle effects of BF on long-term maternal metabolic health from effects of pre-pregnant metabolic health on BF duration and long-term metabolic health. Longitudinal population-based cohort study. Nord-Trøndelag county, Norway. Women with a first live-born baby (1987-2008) participating in the Nord-Trøndelag Health Study (HUNT). Odds ratios (ORs) for short BF duration (<3months) by pre-pregnant body mass index (BMI), waist circumference (WCF), blood pressures (BPs), and heart rate (HR) were adjusted for age and smoking using logistic regression. Mixed linear models were used to estimate effects of BF duration (<3, 3-6, >6months) on mean values of metabolic health parameters from baseline to follow-up. Mean change in BMI, WCF, BPs, HR, serum-glucose, and serum-lipids from baseline to follow-up by BF duration categories. We analysed 1403 women with a median follow-up of 12years (interquartile range 11-22). Pre-pregnant WCF and HR correlated inversely with BF duration. Pre-pregnant BMI had a u-shaped correlation-pattern with BF duration. We observed similar between-group differences in metabolic health parameters at baseline and at follow-up, which implies that mean change in metabolic health parameters was similar across BF groups. Those women who started out with the best health had the longest BF duration and ended up with the best health, and those women who started out with the poorest health had shortest BF duration and ended up with the poorest health. Our results do not support a causal relationship between long BF duration and improved metabolic health. It is more likely that pre-pregnant metabolic health affects both BF duration and long-term metabolic health. Reverse causality can explain previously observed improved long-term metabolic health after BF. Breastfeeding seems not to affect long-term maternal metabolic health, but good pre-pregnant metabolic health does.

2248. Changes in Lipid Profiles for Patients to Tenofovir Alafenamide (TAF)-Containing Regimens: Perspectives from a Military HIV-Positive Cohort

BackgroundTenofovir alafenamide (TAF) was approved in 2015 for use in HIV-1. TAF decreases risk of renal and bone toxicity compared with tenofovir disproxil fumarate (TDF). Early clinical trials reported median increases in low-density lipoprotein (LDL) of 20–29 and 9–13 mg/dL for total cholesterol (TC) following switch therapy from TDF-containing regimens at 48 weeks, raising concern for increased cardiovascular (CVD) risk over time. We assessed real-world changes in serum lipid concentrations following transition to TAF-containing regimens.MethodsEligible subjects in the U.S. Military Natural History Study, a longitudinal cohort of HIV-infected military beneficiaries, had been switched from TDF to TAF-based regimens, and had pre- and post-switch lipid profiles available. Antiretroviral therapy history, serum lipids, CD4 count and viral load were collected from the study database. Wilcoxon rank-sum test was used to compare lipid profile changes.ResultsAs of January 1, 2018, 408 subjects on TDF switched to TAF; 238 had pre and post lipid profiles. Subjects were primarily male (95%), 45.4% African American, 70% were ≥40 years old at TAF start; 8% had CVD and 10% had diabetes. Changes in lipid profiles and CD4 count are presented in Table 1. No difference was seen when categorized by gender, race, or age. Lipid changes were not seen in subjects switched from an efavirenz (EFV) regimen. Increases in TC, HDL, and LDL were observed in those switched from rilpivirine (RPV) (P = 0.002, P = 0.0404, and P = 0.0296) or elvitegravir (EVG) (P < 0.0001, P = 0.0003, P = 0.0040) regimens.ConclusionWe found significant changes in serum lipids, albeit lower than median changes observed in licensing trials. Changes were not observed in those switching from EFV, contrasting with those switching from RPV or EVG.Table 1:Serum Lipid ProfilesOn TDFAfter TAF-Switch (>6 Weeks)% Change P-ValueTC*174.0 [154.0–197.0]184.0 [161.0–212.0]6.6 [−5.4–18.6]<0.0001HDL47.0 [39.0–57.0]48.0 [41.0–57.0]2.8 [−7.7–17.3]0.007LDL107.0 [86.0–124.0]112.5 [91.0–135.0]6.5 [−10.3–22.0]0.0007TC:HDL3.7 [2.9–4.4]3.7 [3.0–4.5]3.6 [−9.9–17.9]0.03CD4 (cells/µL)676.0 [533.0–880.0]704.0 [562.0–917.0]6.6 [−8.0–20.1]<0.0001*Concentrations in mg/dL. Values are median [Q1–Q3].Disclosures All authors: No reported disclosures.

Koumiss consumption modulates gut microbiota, increases plasma high density cholesterol, decreases immunoglobulin G and albumin

Hyperlipidemia is a risk factor for cardiovascular disease and has become a significant public health problem. In this study, PacBio single-molecule real-time sequencing technology combined with a metabolomics study of koumiss revealed a series of changes in serum lipids, gut microbiota and viscera indices in hyperlipidemia patients 0, 30 and 60 days following daily koumiss treatment. High density lipoprotein cholesterol concentrations significantly increased, while levels of immunoglobulin G and albumin significantly decreased after koumiss treatment. Moreover, the abundance of some Bacteroides, Dorea and Catenibacterium species increased, whereas the abundance of Clostridium and Citrobacter species decreased. Our results indicate that koumiss consumption alleviates the symptoms of hyperlipidemia. This is associated with both the bacterial composition of the koumiss, particularly Lactobacillus and Streptococcus species, and the metabolites present in koumiss, such as s-adenosyl-l-methionine, carnosine, lysophosphatidylinositol and dipeptides. This study provides insight into the mechanisms underpinning the effects of koumiss on hypolipidemic symptoms.

Study of Lipid Profile in Different grades of Non- Alcoholic Fatty Liver Disease

Background: The prevalence of NAFLD (non- alcoholic fatty liver disease) is increasing as it exceed (31.79%) in Middle East and the metabolic syndrome prevalence in patients with NAFLD ranges from 18% to 67%, according to the body weight. Imaging or histology is very important tools in diagnosis of NAFLD. Early detection of NAFLD is very important especially if there is a non-invasive method. The clinicians in the primary, secondary and tertiary care are in need for specific and sensitive diagnostic tool that can be used easily. Aim: To study and analyze serum lipid changes in non-alcoholic fatty liver disease of different grades. Patients and methods: 100 patients diagnosed by ultrasonography as NAFLD, whose age was more than 18 years, were included in the study. History taking, full clinical examination and anthropometric measurement of weight, height and body mass index (BMI) were done for all patients. Serum lipid profiles including total cholesterol, HDL, LDL, triglycerides, ALT, AST. CBC, fasting and 2hpp blood glucose and TSH were measured. Results: The largest group of patients (38%) was in the fifth decade of life. followed by 30% in the sixth decade of life. As the grade of NAFLD increased, there was associated significant increase in levels of serum total cholesterol (P-value 0.005), TG (P-value 0.002) LDL (P-value 0.001) and VLDL (P-value 0.003) and associated significant decrease in HDL (P-value 0.001). Conclusions: abdominal ultrasonography and increased lipid profile values can be used to detect NAFLD early

Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.

The manipulation of gut microbiota via administration of probiotics has been proposed as a potential strategy for the treatment of non-alcoholic fatty liver disease (NAFLD). Hence, we performed a double-blind single center randomized placebo-controlled trial (RCT) to evaluate the efficacy of coadministration of probiotics with omega-3 vs. placebo in type-2 diabetic patients with NAFLD. A total of 48 patients met the criteria for inclusion. They were randomly assigned to receive "Symbiter Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in transaminases level, serum lipids and cytokines levels. In probiotic-omega group, FLI significantly decreased from 83.53±2.60 to 76.26±2.96 (P<0.001) while no significant changes were observed in the placebo group (82.86±2.45 to 81.09±2.84; P=0.156). Changes of LS in both groups were insignificant. Analysis of secondary outcomes showed that the coadministration of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl transpeptidase, triglycerides, and total cholesterol. Chronic systemic inflammatory markers after intervention decrease significantly only in Symbiter Omega group: IL-1β (P=0.029), TNF-α (P<0.001), IL-8 (P=0.029), IL-6 (P=0.003), and INF-γ (P=0.016). Coadministration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can reduce liver fat, improve serum lipids, metabolic profile, and reduce chronic systemic inflammatory state.

Red Meat Consumption and Serum Lipids and Fatty Acids in Toddlers: Secondary Outcomes of a Randomized Controlled Trial.

The aim of the study was to examine the effects of promoting increased lean red meat consumption on serum concentrations of total and high-density lipoprotein (HDL) cholesterol, and serum fatty acid composition, among toddlers. In a 20-week randomized controlled trial healthy 12 to 20-month-old children were assigned to: red meat (n = 90; parents were encouraged to add 56 g/day of lean red meat to their toddler's usual diet), or control (n = 90) groups. Food and nutrient intakes were assessed with 3-day weighed food records (baseline, week 4, and week 20). Serum was analyzed for total and HDL cholesterol concentrations, and fatty acid composition (baseline and week 20). At week 20, relative to control, the red meat group had higher intakes of red meat, all meat, and carbohydrate; and lower intakes of milk, energy, cholesterol, and total, saturated, and monounsaturated fat (P = 0.043 for energy, all others P ≤ 0.002). No effects associated with the intervention were found for total cholesterol, HDL cholesterol, total to HDL cholesterol ratio, or serum fatty acid composition (all P ≥ 0.059) aside from pentadecanoic acid (P = 0.047). An ∼3-fold increase in lean red meat intake, from ∼10 to ∼30 g/day, resulted in no consistent changes in serum lipids or fatty acid composition, suggesting that the addition of ∼2 tablespoons/day of lean red meat to toddlers' diets will likely not adversely affect serum lipids or serum fatty acids.

Untargeted lipidomics based on UPLC-QTOF-MS/MS and structural characterization reveals dramatic compositional changes in serum and renal lipids in mice with glyoxylate-induced nephrolithiasis

Nephrolithiasis is a systemic metabolic disease with a worldwide incidence that is increasing yearly, as well as a high recurrence rate; however, this disease's pathogenesis has not been thoroughly elucidated to date. Several epidemiological studies have shown that the risk for developing kidney stones increases in people with dyslipidemia. To explore the mechanism of lipid-induced kidney stones, we established a mouse model for renal urolithiasis based on intraperitoneal injections of glyoxylate (120 mg/kg/d). Lipidomics based on ultra high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS/MS) was performed to determine the changes in lipid metabolism in serum and kidneys. We screened 179 and 196 different lipid metabolites in the kidneys and serum, respectively, including fatty acyls, glycerophospholipids, sphingolipids, glycerolipids and prenol lipids. We found that polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid, and docosahexoenoic acid, and ceramides and lysophosphocholines mediated inflammatory responses and that the oxidative stress induced by oleylethanolamine and glycerophosphoethanolamine plasmalogens is closely related to the development of kidney stones. These results provide strong evidence for the relationship between lipid metabolism and the development of kidney stones and suggest a clear direction for future research.

A Novel Therapeutic Approach to Intensive Statin Therapy–Resistant Vulnerable Plaque of Coronary Artery in Diabetic Patients by Use of Anti-PCSK9 Antibody and Coronary CT Angiography (CCTA)

Purpose: Coronary plaque progression despite very low levels of LDL-C has been reported in the patients with coronary artery disease (CAD) who received intensive statin therapy (IST). CCTA has been applied to detect vulnerable coronary plaques having low attenuation of CT value. The best characterized function of PCSK9 is the binding to hepatic LDL receptors, leading to their degradation. PCSK9 is produced also in vascular smooth muscle cells constituting the atheriosclerotic lesion in addition to hepatocytes. PCSK9 promotes foam cell formation by suppressing the excretion of cholesterol from macrophages. Recently, statin is demonstrated to promote PCSK9 production. PCSK9 has been proposed to play a crucial role in the pathogenesis of IST resistance. The present study was performed to establish a novel therapeutic approach to IST resistant vulnerable plaque of coronary artery in diabetic patients. Methods: The present study included 1T2DM patients with non-FHC asymptomatic CAD who developed vulnerable plaques in coronary artery despite IST over 1 year. CCTA by use of 320-slice CT was applied to evaluate vulnerable plaques in coronary artery. During the administration of anti-PCSK9 antibody, changes in serum lipids and CT value of vulnerable coronary plaques were determined. Results: After the administration of anti-PCSK9 antibody, 72% decrease in serum LDL-C was observed. Also, improvement of vulnerable coronary plaque e.g., rise in the CT value of plaque (from 45.2 ± 12.0 HU to 107.5 ± 42.3 HU, p&amp;lt;0.0001) was observed in 6 months after administration of the drug. Conclusion: A significant improvement in vulnerable coronary plaques was observed in the patients with asymptomatic CAD who are resistant to IST after 6 months administration of anti-PCSK9 antibody. An analysis of the plaque quality by CCTA is useful method for the evaluation of the effect of the drug on vulnerable coronary plaques. Disclosure A. Hirai: None. K. Fujimura: None. S. Kondo: None. T. Sakai: None. S. Ikejima: None. H. Taniai: None. K. Hirai: None. K. Murata: None. A. Shirakami: None. K. Okuzaki: None. T. Kageyama: None.

Hypoxis hemerocallidea alters metabolic parameters and hepatic histomorphology in streptozotocin-nicotinamide-induced diabetic male rats under antiretroviral therapy.

IntroductionHighly active antiretroviral therapy (HAART) and HIV/AIDS have been demonstrated to induce endocrine/metabolic dysfunction with a consequential increase in morbidity/mortality due to organ toxicities. This study aimed at investigating the possible protective effect of Hypoxis hemerocallidea (HH) against metabolic and hepatic histomorphology of diabetic rats under HAART.Material and methodsSixty-two adult male Sprague-Dawley rats were divided into a normoglycemic group A (n = 6) and 7 diabetic (110 mg/kg nicotinamide + 45 mg/kg streptozotocin) groups (B–H) (n = 8) and treated according to protocols. Concomitant treatment with adjuvant HH and HAART resulted in the least %body weight gain as the liver weight decreased in all treated animals.ResultsSignificant changes in serum lipids were aggravated by treatment with HH and HAART, triglycerides and total cholesterol levels were elevated (p < 0.001/0.05), but changes in high-density lipoprotein (HDL) and total protein levels were insignificant. While artherosclerotic and cardiopulmonary indexes remained insignificant, concomitant use of HH with HAART in diabetes resulted in reduction of low-density lipoprotein (LDL) (p < 0.001), and increased triglyceride (p < 0.05) and total cholesterol (p < 0.001). The parameters of liver injury showed a significant (p < 0.05) increase in ALT of animals treated with HH alone, HAART + HH and melatonin; however, an insignificant decline in AST level was recorded. Treatment with adjuvant HAART, HH and melatonin resulted in significant (p < 0.005/0.0001) up-regulation of ALP and total bilirubin levels. Histopathology derangement ranged from severe hepatocellular distortions, necrosis with reduced glycogen expression following co-treatment of HAART+melatonin, HH and HAART alone in diabetes.ConclusionsPresumptive hypoglycemic use of HH with HAART by people living with HIV/AIDS requires caution as implications for hepatocellular injuries are suspected with further uncontrolled metabolic disorder.

Serum lipid changes during pregnancy and after delivery in women with previous gestational diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Frizzled-related proteins 4 (SFRP4) rs1802073G allele predicts the elevated serum lipid levels during acitretin treatment in psoriatic patients from Hunan, China.

BackgroundAcitretin is a second-generation synthetic retinoid, and is widely used for treating the severe psoriasis vulgaris. However, it should be chosen with caution for its cardiovascular risk, and it is reported that acitretin may increase the serum lipids. The purpose of this study is to investigate the relationship between the Frizzled-related proteins 4 (SFRP4) rs1802073 polymorphism and the changes of serum lipids in Chinese psoriatic patients during the treatment with acitretin.MethodsIn our study, 100 psoriatic patients were recruited systematically treated with acitretin (30 mg/day) for at least eight weeks. Data of the patients’ demographic and clinical characteristics and the results of serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were collected pre- and post-treatment.ResultsA total of 84 psoriatic patients were enrolled and divided into three groups by SFRP4 rs1802073 genotypes. The patients who carried with TT genotype had maintained levels of TG and LDL-C after acitretin treatment, while patients with GG/GT genotypes had significantly elevated levels of serum TG and LDL-C compared to the TT genotype (ΔTG%: 27.53 ± 59.13 vs −1.47 ± 37.79, p = 0.026, ΔLDL-C%: 10.62 ± 26.57 vs −1.29 ± 17.07, p = 0.042). The association of rs1802073 with TG and LDL-C profiles remained significant after adjusting for age, gender, and body mass index. Although without significance, the pre-post change in serum level of TC across rs1802073 GG/GT genotypes demonstrated a trend similar to TG and LDL, and the serum level of HDL-C demonstrated a trend opposite to TG, TC and LDL.ConclusionsOur results demonstrated that SFRP4 rs1802073 polymorphism was found to be associated with elevated serum lipid levels after acitretin treatment, and it may serve as a genetic marker of safe and precise treatment for individual psoriatic patients.

The effects of seed from Linum usitatissimum cultivar with increased phenylpropanoid compounds and hydrolysable tannin in a high cholesterol-fed rabbit

BackgroundDietary fat is considered one of the most important factors associated with blood lipid metabolism and plays a significant role in the cause and prevention of atherosclerosis that has been widely accepted as an inflammatory disease of the vascular system. The aim of the present study was to evaluate the effect of genetically modified flaxseed (W86) rich in phenylpropanoid compounds and hydrolysable tannin in high cholesterol-induced atherosclerosis rabbit models compared to parental cultivar Linola.MethodsTwenty-Eight White New Zealand white rabbits aged 6 months were randomly divided into four groups, control group, high cholesterol group (10 g/kg), Linola flaxseed group (100 g/kg) and W86 flaxseed group (100 g/kg). The rabbits were fed a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, hematological values, total antioxidative status and superoxide dismutase activity in serum were determined. Moreover, body weight and feed intake were measured after sixth and tenth weeks. After each stage of the experiment atherogenic indexes (non-HDL-C/HDL-C, LDL-C/HDL-C, and atherogenic index of plasma) was calculated.ResultsThe intake of a dyslipidaemic diet negatively influenced lipid profile in rabbits at the 10 weeks of feeding. W86 flaxseed significantly decreased total cholesterol, LDL-C, VLDL-C and TG serum levels in cholesterolemic rabbits compared with parental Linola after 10 weeks. Atherogenic indexes decreased over time with a significant difference between the diets and they were the best for W86 flaxseed. Similarly, the experimental addition of W86 significantly decreased atherogenic predictors such as heterophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the mean platelet volume-to-lymphocyte ratio. In rabbits, W86 flaxseed increased the activity of superoxide dismutase and total antioxidative status compared to Linola.ConclusionsResults of the presented study suggest that the addition of W86 flaxseed alleviate serum lipid changes in high cholesterolemic diet-administered rabbits. W86 flaxseed significantly reduced atherogenic indexes, as compared with the Linola and indicate that W86 flaxseed more effectively red CVD risk factors during hypercholesterolemia. Moreover, the presented result suggested that W86 flaxseed can be a part of a heart-healthy and antiatherogenic diet for the human.

A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial

Probiotics have a beneficial effect on nonalcoholic fatty liver disease (NAFLD) in animal models. Randomized placebo-controlled trials (RCTs) in NAFLD are still lacking in humans despite a large number of data from animal research. We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD. A total of 58 patients met the criteria for inclusion. They were randomly assigned to receive the multi-probiotic "Symbiter" (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. The primary main outcomes were the changes in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in aminotransferase activity, serum lipids and cytokines (TNF-α, IL-1β, IL-6, IL-8, and IFN-γ) levels. Analysis of covariance was used to assess the difference between groups. In the probiotic group, FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 (p<0.001) but it did not change in the placebo group (82.57+/-2.45 to 81.6 +/-2.36; p=0.367). In both groups a slight but not significant reduction of LS measured by SWE was detected. Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT. Among the markers of chronic systemic inflammatory state, only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic. The probiotic "Symbiter" reduces liver fat, aminotransferase activity, and the TNF-α and IL-6 levels in NAFLD patients. Modulation of the gut microbiota might represent a new therapy for NAFLD, which should be tested in larger studies.

Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia: a randomized controlled trial

Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia.A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15–30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined.A reduction of endogenous DNA damage by 18.9%±51.3% (P=.002) and 23.1%±47.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%±38.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol.A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients.The trial was registered at ISRCTN.com, ID no. ISRCTN12261900.

Resolution of fatty liver and weight loss: Independent associations with changes in serum lipids and apolipoproteins

Background and aimsIt is uncertain whether resolution of fatty liver can improve cardiovascular disease risk factors, independently of changes in body mass index (BMI). Our aim was to test whether resolution of fatty liver is associated with improvements in components of the lipid profile, independently of changes in BMI, and to quantify and compare the magnitude of benefit of resolution of liver fat, and decreases in BMI on the lipid profile. Methods36,195 subjects with fatty liver were studied. Persistence/resolution of fatty liver was determined by ultrasound at follow up (mean = 4.93 years). Total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoproteins were measured at baseline and follow up. Regression modelling was undertaken to test the independence of associations between change in fatty liver status or change in BMI, with any change in lipid profile concentrations between baseline and follow up. ResultsMean (SD) age was 36.3 ± 6.6 and 39.8 ± 8.7 years (men and women, respectively). Resolution of fatty liver occurred in 7,086, and persisted in 29,109 subjects. Mean ± SD weight change was −3.2 ± 4.3 (∼1 kg/m2 decrease in BMI) with resolution of, and +0.5 ± 3.5 kg with persistence of fatty liver, respectively. Both resolution of fatty liver and decrease in BMI were independently associated with improvements in all components of the lipid profile and there was a similar magnitude of benefit associated with resolution of fatty liver, or 1 kg/m2 decrease in BMI. ConclusionsResolution of fatty liver improves the lipid profile, independently of weight loss.

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats.

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.

Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs

PurposeTo evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. Subjects and methodsWe conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. Key findingsIn total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; −5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (<6 mg/dL) and ESL 1200 mg QD (<10 mg/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. SignificanceThese results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations.