Pretreatment with n-6 PUFA protects against subsequent high fat diet induced atherosclerosis--potential role of oxidative stress-induced antioxidant defense

ObjectivesRecent evidence suggests that oxidative stress can promote antioxidant defense and thus be athero-protective. n-6 polyunsaturated fatty acids (n-6 PUFA) are more prone to oxidation, compared to monounsaturated fatty acids (MUFA) and yet have proven anti-atherosclerotic effects. In this study, we tested whether early exposure to a diet rich in n-6 PUFA, compared to a MUFA rich diet would reduce lesion burden, even with subsequent exposure to a high fat, high cholesterol diet (HF). Further, we tested to determine whether oxidative mechanisms are involved in such protection.Methods and resultsTwenty four, 4 week old, male, LDL receptor knockout (LDL-R^?/?) mice were divided into two groups and fed either a n-6 PUFA rich or a MUFA rich diet for a period of 12 weeks. At this point, 4 mice from each group were euthanized and the remaining 8 mice from each group were fed a HF diet for four weeks. Atherosclerotic lesions, plasma lipids, autoantibodies to lipid peroxide modified proteins, isoprostanes and aortic catalase levels were measured. The n-6 PUFA diet reduced aortic lesions and plasma lipids compared to the MUFA diet and this reduction in lesions continued even after the mice were switched over to the HF diet, despite the fact that the plasma lipids were similar in both groups after the HF diet. n-6 PUFA fed mice had highest plasma isoprostane levels, indicating oxidative stress, but also had higher levels of aortic catalase. On the other hand, MUFA fed mice had comparatively lower levels of isoprostanes and their aortic catalase levels remained low. Finally, aortic lesions were negatively correlated with isoprostanes and catalase.ConclusionAn initial exposure to a n-6 PUFA rich diet compared to a MUFA rich diet reduces atherosclerotic lesions and this protection probably involves oxidative stress induced by PUFA.     

Steatosis and Collagen Content in Experimental Liver Cirrhosis Are Affected by Dietary Monounsaturated and Polyunsaturated Fatty Acids

Background and Methods: We used thioacetamide administered orally to induce cirrhosis in rats, and after these had recovered for 1 and 2 weeks we examined the effects of dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids, or with a combination of n-3 and n-6 polyunsaturated fatty acids, on the extent of steatosis and collagen content in the liver. Results: Nodular cirrhosis, increased collagen content, and lipid accumulation were established after 4 months of treatment with thioacetamide. When the animals were fed a diet rich in oleic acid for 2 weeks, the steatosis and fibrosis decreased. Supplementation with n-3 polyunsaturated fatty acids favored reductions in collagen content but did not reduce the fat accumulation. With a diet supplemented with a mixture of n-3 and n-6 fatty acids we found no reduction in either lipid accumulation or collagen content. Conclusions: Fibrosis and steatosis may be influenced by dietary fat, and monounsaturated fat appears to influence favorably the histologic recovery of the damaged liver.     

Influence of administration of long-chain polyunsaturated fatty acids on process of histological recovery in liver cirrhosis produced by oral intake of thioacetamide

Patients with liver cirrhosis frequently show some degree of protein-energy malnutrition and obviously require nutritional support. In this study, the treatment of rats consisted of thead libitum oral intake of a 300 mg/liter thioacetamide solution, used as drinking water for four months. Thioacetamide treatment produced a severe alteration in the plasma fatty acid profile with significant decreases of these, which mimicked changes described in human cirrhosis. This hepatotoxic agent causes nodular cirrhosis, with loss of the normal architecture of the liver and disruption of the vascular pattern. The goal of the study was to evaluate the influence of n-3 and n-6 series long-chain polyunsaturated fatty acid dietary supplementation in experimental animals and to assess the effects of those dietary components on structural recovery in the liver. Significant increases of saturated and monounsaturated fatty acids as well as n-6 polyunsaturated fatty acids were seen only in the animals given the n-6 polyunsaturated fatty acid supplemented diet. However, only rats given the standard diet exhibited some degree of histological regeneration.     

Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles

Background and AimsDietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated.MethodsIn a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA.ResultsThe diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (− 8%, p = 0.013) and LDL cholesterol (LDL-C) level (− 8%, p = 0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency.ConclusionImprovement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles.     

Effects of Dietary Supplementation with n-6 and n-3 Long-chain Polyunsaturated Fatty Acids on Serum Lipoproteins and Platelet Function in Hypertriglyceridaemic Patients

ABSTRACT Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid (GLA, 18: 3 n-6) (n=13) or a marine oil concentrate containing n-3 fatty acids (n=14) in a double-blind cross-over design during 8+8 weeks with olive oil as placebo. During GLA supplementation, increases in GLA and dihomogammalinolenic acid (20: 3 n-6) were found in plasma lipid esters and platelet phospholipids, whereas platelet function and serum lipoproteins were unaffected. During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol. A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets, mainly at the expense of the n-6 fatty acids. No pronounced effects on platelet reactivity could be demonstrated. Our results confirm a triglyceride-lowering effect of n-3 fatty acids, whereas no such effect of GLA could be demonstrated.     

Dietary lipids and NAFLD: suggestions for improved nutrition

Non-alcoholic fatty liver disease (NAFLD) ranges from steatosis and hepatic insulin resistance to non-alcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. NAFLD is now considered as the hepatic manifestation of the metabolic syndrome, and both are triggered by mechanisms including inflammation, lipid overload and oxidative stress in adipose tissue and liver. Despite accumulation of numerous data on NAFLD physiopathology, therapeutic modulation of the pathways involved appear insufficiently efficient or associated with serious adverse effects. The increased prevalence of NAFLD and metabolic syndrome during the last decades was associated with deep modifications of dietary habits, especially increased fat intakes. Recent literature provides clues of increased saturated (SFA) and n-6 polyunsaturated fatty acids (PUFA) as well as reduced n-3 PUFA in the diet of NAFLD and NASH patients. Indeed, strong data support the detrimental role of high SFA and n-6/n-3 ratio as well as low monounsaturated fatty acids (MUFA) and n-3 PUFA on metabolic parameters, which are ameliorated by administration of n-3 PUFA and MUFA. Despite governments and health associations having revised their recommendations for n-3 PUFA intakes upward during the last decade, those are still inferior to levels proved of therapeutic efficiency and are still not reached in the general population. This short review discusses these issues and provides consequent pragmatic suggestions for enhanced dietary measures for prevention of NAFLD and metabolic syndrome in the general population.     

The Effect of Cod Liver Oil in Two Populations with Low and High Intake of Dietary Fish

ABSTRACT Two subgroups of healthy males from an inland and a coastal community in Norway with a traditionally low and high consumption of dietary fish were given a dietary supplement of 20 ml cod liver oil rich in n-3 polyunsaturated fatty acids for 3 weeks. Cod liver oil induced an increase in serum high density lipoprotein (HDL) cholesterol in men from the inland. Both groups showed a prolonged primary bleeding time, whereas platelet aggregation and thromboxane A₂ production induced by collagen were mainly unaffected. Platelet phospholipid fatty acids showed similar changes in both groups with a decrease in n-6 and an increase in n-3 polyunsaturated fatty acids. No changes were observed in total cholesterol or platelet phospholipid content. This study shows that dietary supplement with cod liver oil induces changes in serum lipids and platelets that may reduce the tendency to thrombosis both in subjects with a low and in those with a high intake of dietary fish. The effects were more pronounced in the subjects with a traditionally low fish consumption.     

Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines

Cytokines such as tumor necrosis factor alpha (TNF-alpha) are key factors in liver inflammation. Supplementation with essential omega-3 polyunsaturated fatty acids (n-3 PUFA) has been demonstrated to lower TNF-alpha and IL-1 production in mononuclear cells. An inflammation-dampening effect has been observed with increased omega-3 fatty acid supplementation in several inflammatory diseases. In this study, we used the transgenic fat-1 mouse, expressing a Caenorhabditis elegans desaturase endogenously forming n-3 PUFA from n-6 PUFA, to analyze the effect of an increased n-3 PUFA tissue status in the macrophage-dependent acute D-galactosamine/lipopolysaccaride (D-GalN/LPS) hepatitis model. We show less severe inflammatory liver injury in fat-1 mice with a balanced n-6/n-3 PUFA ratio as evidenced by reduced serum alanine aminotransferase levels and less severe histological liver damage. This decreased inflammatory response was associated with decreased plasma TNF-alpha levels and with reduced hepatic gene expression of TNF-alpha, IL-1beta, IFN-gamma and IL-6 in fat-1 mice, leading to a decreased rate of apoptosis in livers from fat-1 animals, as measured by DAPI-staining. CONCLUSION: The results of this study offer evidence for an inflammation dampening effect of omega-3 polyunsaturated fatty acids in the context of liver inflammation.     

Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study

BACKGROUND/AIMS: Low hepatic n-6 and n-3 polyunsaturated fatty acid (PUFA) may contribute to steatosis and steatohepatitis and can be affected by diet and oxidative stress. METHODS: Seventy-three patients referred for elevated liver enzymes and suspected NAFLD were assessed. Nutritional assessment, hepatic FA composition and oxidative stress were compared between these groups: simple steatosis (SS, n=18), steatohepatitis (NASH, n=38) and minimal findings on liver biopsy (MF, n=17). RESULTS: Patients with NASH had higher: BMI, central obesity, body fat, insulin resistance, dyslipidemia and lower physical activity compared to the other groups. They also had relatively lower hepatic n-3 and n-6 PUFA, a decrease in the ratio of metabolites to essential FA precursors for both n-6 and n-3 FA (eicosapentaenoic+docosahexaenoic/linolenic and arachidonic/linoleic acid ratios) and higher liver lipid peroxides with lower antioxidant power, when compared to MF. Overall, there was no significant difference between SS and NASH in FA composition. Self-reported dietary intake and red blood cell FA composition were similar among the three groups. CONCLUSIONS: NASH patients have more metabolic abnormalities. This is associated with higher oxidative stress and lower n-3 and n-6 PUFA in the liver in the absence of any differences in dietary FA composition.     

N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials

PURPOSE: Observational studies have shown an inconsistent association between n-3 polyunsaturated fatty acids and the risk of coronary heart disease. We investigated the effects of dietary and non-dietary (supplemental) intake of n-3 polyunsaturated fatty acids on coronary heart disease. SUBJECTS AND METHODS: We searched the literature to identify randomized controlled trials that compared dietary or non-dietary intake of n-3 polyunsaturated fatty acids with a control diet or placebo in patients with coronary heart disease. Studies had to have at least 6 months of follow-up data, and to have reported clinical endpoint data. We identified 11 trials, published between 1966 and 1999, which included 7951 patients in the intervention and 7855 patients in the control groups. RESULTS: The risk ratio of nonfatal myocardial infarction in patients who were on n-3 polyunsaturated fatty acid-enriched diets compared with control diets or placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.2, P = 0.16; Breslow-Day test for heterogeneity, P = 0.01), and the risk ratio of fatal myocardial infarction was 0.7 (95% CI: 0.6 to 0.8, P <0.001; heterogeneity P >0.20). In 5 trials, sudden death was associated with a risk ratio of 0.7 (95% CI: 0.6 to 0.9, P <0.01; heterogeneity P >0.20), whereas the risk ratio of overall mortality was 0.8 (95% CI: 0.7 to 0.9, P <0.001; heterogeneity P >0.20). There was no difference in summary estimates between dietary and non-dietary interventions of n-3 polyunsaturated fatty acids for all endpoints. CONCLUSION: This meta-analysis suggests that dietary and non-dietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease.     

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A₂ generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A₂ production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A₂ production.     

The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

Background and objectives

Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants.

Design, setting, participants, & measurements

In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation.

Results

There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality.

Conclusions

Higher plasma phospholipid marine n-3 polyunsaturated fatty acid levels were independently associated with better patient survival.     

Plasma phospholipid fatty acid pattern in severe liver disease

BACKGROUND/AIMS: In acute liver failure the liver has to regenerate, which may increase the consumption of essential fatty acids. Nutritional support consists mainly of infusion of glucose. It is therefore possible that essential fatty acid deficiency may develop in such patients. METHODS: Plasma phospholipid composition was studied in healthy controls (n=11), in patients with acute liver failure, (n=10), in patients with stable cirrhosis (n=7), and in patients with acute on chronic liver disease with hepatic encephalopathy (n=6). The influence of 2 days of fat-free diet followed by infusion of glucose was studied in five healthy controls. RESULTS: The ratio between the sums of nonessential/ essential fatty acids, (n-7+n-9)/(n-3+n-6), was higher in patients with acute liver failure (0.73+/-0.17) compared to healthy controls (0.35+/-0.06, p<0.001). The ratio was also higher in patients with acute on chronic liver disease (1.11+/-0.39) compared to patients with cirrhosis (0.61+/-0.18, p<0.01). These differences were mainly due to low levels of linoleic acid and high levels of oleic acid in the patients with acute liver failure and acute on chronic liver disease. Two days of fat-free diet followed by infusion of glucose did not change this ratio (0.40+/-0.04 vs. 0.47+/-0.05, NS) in healthy controls. The essential fatty acid deficiency indicator eicosatrienoic acid was detectable in 2 out of 11 controls, in 5/10 with acute liver failure, in 7/7 with cirrhosis, and in 6/7 with acute on chronic liver disease. CONCLUSION: Acute severe deterioration of liver function was associated with changes in the fatty acid composition of plasma phospholipids suggestive of essential fatty acid deficiency.     

Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis

Recent studies have demonstrated that n-3 polyunsaturated fatty acids ameliorate nonalcoholic fatty liver disease. Although eicosapentaenoic acid (EPA), one of the major components of n-3 polyunsaturated fatty acids, is widely used as an antilipidemic agent, its single efficacy for nonalcoholic steatohepatitis (NASH) remains unclear. As such, we aimed to evaluate the efficacy and safety of EPA on 23 biopsy-proven NASH patients in a pilot trial. Highly purified EPA (2700 mg/d) was administered for 12 months and efficacy was assessed by biochemical parameters and liver histology. All patients completed the treatment with no adverse events, indicating acceptable tolerance to the treatment. After 12 months, serum alanine aminotransferase levels were significantly improved (from 79+/-36 to 50+/-20 U/L), and serum free fatty acids, plasma soluble tumor necrosis factor receptor 1 and 2 levels, and serum ferritin and thioredoxin levels, which may reflect hepatic oxidative stress, were significantly decreased. Body weight, blood glucose, insulin, and adiponectin concentrations remained unchanged. Seven of the 23 patients consented to undergo posttreatment liver biopsy, which showed improvement of hepatic steatosis and fibrosis, hepatocyte ballooning, and lobular inflammation in 6 patients. In conclusion, EPA treatment seems to be safe and efficacious for patients with NASH, largely due to its anti-inflammatory and antioxidative properties. To confirm these results, appropriately powered, controlled trials are needed.     

Lipid composition, fluidity and enzymatic activities of rat liver plasma and mitochondrial membranes in dietary obese rats

Total lipids and fatty acid composition were determined in liver plasma and mitochondrial membranes from control and dietary obese rats after 4 weeks of the experimental period. The lipid composition of liver plasma and mitochondrial membranes showed an increase of triacylglycerols in obese rats. The liver plasma membranes showed a decrease of saturated/unsaturated fatty acid ratio and an increase of (n-6) polyunsaturated fatty acids, whereas the (n-3) polyunsaturated acids were decreased. Contrary to what occurs with plasma membranes, few modifications were observed in mitochondrial membranes. Changes of the fatty acid composition of the phospholipid bilayer are of potentially great importance in structural and functional parameters of membrane. Fluidity of liver plasma membranes of dietary obese rats was highly increased, while the mitochondrial ones remained unchanged. These results can be well explained by the decreased saturated/unsaturated fatty acid ratio. A significant decrease of (Na+-K+) ATPase activity (a membrane bound enzyme) was found in plasma membranes of dietary obese rats. Mitochondrial enzymatic activities and oxidative phosphorylation showed few changes except a small, but significant decrease of state 3 respiratory rate. In this study we also determined the fatty acid composition of all the foods offered to animals and their daily intakes in order to discuss their possible influence on changes in structural and functional membrane parameters.     

Can we consider the right hepatic lobe size/albumin ratio a noninvasive predictor of oesophageal varices in hepatitis C virus-related liver cirrhotic Egyptian patients?

BackgroundThe current guidelines recommend the screening of all cirrhotic patients by endoscopy, but repeated endoscopic examinations are unpleasant for patients and have a high cost impact and burden on endoscopic units. The aim of this study is to evaluate the optimal liver lobe size/albumin ratio and to compare this ratio with spleen size, platelet count and platelet count/spleen diameter ratio as potential noninvasive predictors of oesophageal varices in hepatitis C virus (HCV)-related liver cirrhosis in Egyptian patients.MethodsThis prospective study included one hundred patients with HCV-related liver cirrhosis. All studied subjects underwent a detailed clinical examination, biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound. The platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio for all patients were calculated.ResultsThe 4 predictors demonstrated a high statistically significant correlation with the presence and grade of oesophageal varices (P values < 0.001). The platelet count/spleen diameter ratio had the highest accuracy, followed by the right liver lobe/albumin concentration ratio, spleen size and then platelet count.ConclusionThe use of the studied noninvasive predictors, especially the platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio, can help physicians by restricting the use of endoscopic screening only to patients presenting a high probability of oesophageal varices. This is especially useful in clinical settings where resources are limited and endoscopic facilities are not present in all areas. Such is the case in Egypt, where there is a large number of patients who require oesophageal screening for oesophageal varices.     

The effect of a menhaden oil-containing diet on hemostatic and lipid parameters of nonhuman primates with atherosclerosis

Three species of nonhuman primates were fed an atherogenic diet for 6 months (baseline period) and a menhaden oil (EPA)-containing diet for 8 weeks (test period) during which various hemostatic and lipid parameters were compared. The EPA-rich diet prolonged bleeding times, inhibited platelet aggregation response to ADP and collagen, and increased mean platelet lifespan. This diet elicited an increase in the polyunsaturated fatty acids C20:5 (EPA) and C22:6 (docosahexaenoic acid) at the expense of C18:2 (linoleic acid) and C20:4 (arachidonic acid) in pooled samples of platelet membranes, creating an increase in the ratio of n-3/n-6 polyunsaturated fatty acids. The serum lipid response to a menhaden oil diet comprised a nonsignificant decrease in total serum cholesterol and a significant decrease in HDL cholesterol.     

MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations

Background and AimDietary n-3 polyunsaturated fatty acids (PUFAs) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. The S-adenosylmethionine synthetase type-1 (MAT1A), an essential enzyme in the conversion of methionine to S-adenosylmethionine, plays a key role in homocysteine metabolism. This study investigated the interaction between dietary fatty acids and MAT1A genotypes on plasma Hcy concentrations among Boston Puerto Ricans.Methods and ResultsPlasma Hcy and MAT1A genotypes were determined in 994 subjects of the Boston Puerto Rican Health Study. Dietary fatty acid intakes were assessed by interviews using a questionnaire adapted from the NCI/Block food frequency form.ResultIn the cross-sectional analysis, genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n-3:n-6 PUFA ratio in determining plasma Hcy (p-value for interaction = 0.025). 3U1510G homozygotes had significantly lower plasma Hcy concentration than major allele homozygotes and heterozygotes (AA + AG) (p-value for trend = 0.019) when the n-3:n-6 ratio was >0.09. Two other MAT1A variants, d18777 and i15752, also showed significant interactions with different constituents of dietary fat influencing Hcy concentrations. Furthermore, haplotypes consisting of three variants displayed a strong interaction with n3:n6 ratio influencing Hcy concentrations.ConclusionsOur results suggest that MAT1A genotypes appear to modulate effects of dietary fat on plasma Hcy.     

Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.     

The role of neutrophil to lymphocyte ratio for the assessment of liver fibrosis and cirrhosis: a systematic review

Introduction: Neutrophil to lymphocyte ratio (NLR) is widely used to assess inflammatory diseases. We performed a systematic review to explore the prognostic role of NLR for the assessment of liver fibrosis and cirrhosis.

Areas covered: We searched the PubMed and EMBASE databases for the eligible papers which explored the association between NLR and liver fibrosis/cirrhosis or investigated the prognostic value of NLR in cirrhotic patients.

Expert commentary: In accordance with assessment of liver fibrosis stage, we classified papers into four subgroups by etiology. For the patients with nonalcoholic fatty liver disease (NAFLD) there was a significant association between NLR and fibrosis stage and nonalcoholic fatty liver disease activity score (NAS), while NLR had a negative correlation with fibrosis stage for the patients with chronic hepatitis B (CHB). As for the patients with and chronic hepatitis C (CHC), NLR might not be significantly associated with fibrosis stage. Moreover, NLR seemed to be significantly useful for predicting outcomes in cirrhotic patients. Hence, NLR might be associated with liver fibrosis stage, especially in patients with NAFLD. Furthermore, NLR might be a useful biomarker for evaluating the prognosis in cirrhotic patients.