Maternal fish oil and/or probiotics intervention: Allergic diseases in children up to two years old.

BACKGROUND: As n-3 long-chain polyunsaturated fatty acids and probiotics possess immunomodulatory properties, theoretically they could lower the risk of allergic diseases. But their effects remain controversial. We aimed to study the effects of fish oil and probiotics separately or in combination from early pregnancy onwards to lower the risk of allergic diseases in the infants. METHODS: In this double-blind trial, women (n = 439) in early pregnancies were randomized into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic (Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) supplements were provided for daily consumption from randomization up to 6 months postpartum. All analyses were adjusted with pet ownership. RESULTS: No difference between the infants in the four intervention groups were found regarding physician-diagnosed food allergy, atopic eczema, or atopy at the age of 12 or 24 months (all p > .05). The probiotic intervention was associated with lower odds of recurrent wheezing at 24 months (OR 0.39, 95% CI 0.18-0.84, p = .017), but not at 12 months. CONCLUSIONS: The use of fish oil and/or probiotics from early pregnancy onwards did not lower the odds of childhood allergic diseases or atopy, with the exception of the probiotic intervention which decreased the risk of recurrent wheezing when the infants were two years old. This suggests that the incidence of asthma could also decrease later in childhood and thus these outcomes need to be clarified in further investigations.

Cardiovascular Diseases and Marine Oils: A Focus on Omega-3 Polyunsaturated Fatty Acids and Polar Lipids.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFAs regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFAs. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

Properties of Degradable Polyhydroxyalkanoates Synthesized from New Waste Fish Oils (WFOs).

The synthesis of PHA was first investigated using WFOs obtained from smoked-sprat heads, substandard fresh sprats, and fresh mackerel heads and backbones. All the WFOs ensured the growth of the wild-type strain Cupriavidus necator B-10646 and the synthesis of PHA, regardless of the degree of lipid saturation (from 0.52 to 0.65) and the set and ratio of fatty acids (FA), which was represented by acids with chain lengths from C14 to C24. The bacterial biomass concentration and PHA synthesis were comparable (4.1-4.6 g/L and about 70%) when using WFO obtained from smoked-sprat heads and fresh mackerel, and it was twice as high as the bacterial biomass concentration from the fresh sprat waste. This depended on the type of WFO, the bacteria synthesized P(3HB) homopolymer or P(3HB-co-3HV-co-3HHx) copolymer, which had a lower degree of crystallinity (Cx 71%) and a lower molecular weight (Mn 134 kDa) compared to the P(3HB) (Mn 175-209 kDa and Cx 74-78%) at comparable temperatures (Tmelt and Tdegr of 158-168 °C and 261-284 °C, respectively). The new types of WFO, studied for the first time, are suitable as a carbon substrates for PHA synthesis. The WFOs obtained in the production of canned Baltic sprat and Baltic mackerel can be considered a promising and renewable substrate for PHA biosynthesis.

Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation.

BACKGROUND: The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF). METHODS: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9 years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression. RESULTS: Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile. CONCLUSIONS: A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.

Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis.

PURPOSE OF REVIEW: We discuss current controversies in the clinical use of omega-3 fatty acids (FA), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and examine discrepancies between recent trials. Furthermore, we discuss potential side effects reported in these studies and the role of mixed omega-3 FA dietary supplements and concerns about their use. RECENT FINDINGS: REDUCE-IT showed that addition of icosapent ethyl, a highly purified form of EPA, can reduce risk of cardiovascular events among statin-treated individuals with high triglycerides. Additional supportive evidence for EPA has come from other trials and meta-analyses of omega-3 FA therapy. In contrast, trials of mixed EPA/DHA products have consistently failed to improve cardiovascular outcomes. Discrepancies in results reported in RCTs could be explained by differences in omega-3 FA products, dosing, study populations, and study designs including the placebo control formulation. Evidence obtained from highly purified forms should not be extrapolated to other mixed formulations, including "over-the-counter" omega-3 supplements. Targeting TG-rich lipoproteins represents a new frontier for mitigating ASCVD risk. Clinical and basic research evidence suggests that the use of omega-3 FA, specifically EPA, appears to slow atherosclerosis by reducing triglyceride-rich lipoproteins and/or inflammation, therefore addressing residual risk of clinical ASCVD.

A dose-response meta-analysis of the association between the maternal omega-3 long-chain polyunsaturated fatty acids supplement and risk of asthma/wheeze in offspring.

BACKGROUND: Prenatal exposure to omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in oily fish may prevent asthma or wheeze in childhood. OBJECTIVE: By limiting n-3 LC-PUFA capsules interventions commenced in pregnancy, this systematic review aimed to find more clear evidence on the relationship between the supplement with n-3 LC-PUFA during pregnancy and the risk of asthma/wheeze in offspring and to improve the life satisfaction of children with asthma. METHODS: The Cochrane library, Embase, Medline, Web of Science, and PubMed were searched from origin to March 2021 in the above-mentioned databases. Studies selection, data of characteristics extraction, and risk of bias assessment were conducted by two authors, independently. A total of 3037 mother-infant pairs from eight randomized controlled trials were ultimately analyzed. The primary outcome was the risk of "asthma and/or wheeze", and the secondary outcome was "Allergic asthma" in this dose-response meta-analysis. Sensitivity analysis and subgroup analysis were conducted. The robust-error meta-regression model was used for dose-response analysis. RESULTS: This meta-analysis showed that n-3 LC-PUFA during pregnancy did not obviously reduce the risk of asthma/wheeze (RR 0.93; 95% CI 0.82 to 1.04, p = 0.21) and allergic asthma (RR 0.66, 95% CI 0.24 to 1.86, p = 0.44). The risk of asthma/wheeze in offspring was significantly decreased in the subgroup analysis when:: (1) studies conducted in Europe (RR 0.69; 95% CI 0.53 to 0.89); (2) daily supplementary dose of n-3 LC-PUFA was at least 1200 mg (RR 0.69; 95% CI 0.55 to 0.88); (3) supplementation lasts from pregnancy to lactation period (RR 0.69; 95% CI 0.51 to 0.95). Furthermore, the risk of asthma/wheeze reduce 2% when daily supplemental dose of n-3 LC-PUFA was increased by 100 mg in the linear dose-response analysis model. CONCLUSIONS: Perinatal supplementation with n-3 LC-PUFA can reduce the incidence of asthma/wheeze and allergic asthma in children under certain conditions, and higher doses indicate better protective effects. Further studies are required to confirm the hypothesis of an association between n-3 LC-PUFA intake and childhood asthma/wheeze prevention.

Valorization of Side Stream Products from Sea Cage Fattened Bluefin Tuna (Thunnus thynnus): Production and In Vitro Bioactivity Evaluation of Enriched ω-3 Polyunsaturated Fatty Acids.

The valorization of side streams from fishery and aquaculture value-chains is a valuable solution to address one of the challenges of the circular economy: turning wastes into profit. Side streams produced after filleting of sea cage fattened bluefin tuna (Thunnus thynnus) were analyzed for proximate composition and fatty acid profile to evaluate the possibility of producing tuna oil (TO) as a valuable source of ω-3 polyunsaturated fatty acids (PUFA) and testing its bioactivity in vitro. Ethyl esters of total fatty acids (TFA), obtained from TO, were pre-enriched by urea complexation (PUFA-Ue) and then enriched by short path distillation (SPD) up to almost 85% of the PUFA fraction (PUFA-SPe). The bioactivity of TFA, PUFA-SPe, and ethyl esters of depleted PUFA (PUFA-SPd) were tested in vitro, through analysis of lipid metabolism genes, in gilthead sea bream (Sparus aurata) fibroblast cell line (SAF-1) exposed to oils. TFA and PUFA-SPd upregulated transcription factors (pparß and pparγ) and lipid metabolism-related genes (D6D, fas, fabp, fatp1, and cd36), indicating the promotion of adipogenesis. PUFA-SPe treated cells were similar to control. PUFA-SPe extracted from farmed bluefin tuna side streams could be utilized in fish feed formulations to prevent excessive fat deposition, contributing to improving both the sustainability of aquaculture and the quality of its products.

The Truth About Fish (Oil) in the Treatment of Dyslipidemia.

PURPOSE OF REVIEW: To discuss the effect of fish oils on dyslipidemias and associated disorders. RECENT FINDINGS: The most important lipid effect of fish oils is reducing plasma triglycerides and the main potential protection against cardiovascular events is very probably mediated also through other mechanisms including anti-inflammatory ones. The best results are available for omega-3 fatty acids, namely, eicosapentaenoic acid. Less evidence is available for the impact of ω-3 fatty acids on liver steatosis/steatohepatitis and acute pancreatitis. In addition, particular fish oils have variable content of saturated and unsaturated fatty acids with different anti- or pro-oxidative potential, and the suboptimal ratio of these compounds could attenuate or abolish their beneficial properties. Fish products with optimal proportion of fatty acids, particularly high content of eicosapentaenoic acid, could be recommended to patients with dyslipidemias, especially to those at high risk for cardiovascular disease; less evidence is available for liver disease and acute pancreatitis.

Farmed Gilthead Sea Bream (Sparus aurata) by-Products Valorization: Viscera Oil ω-3 Enrichment by Short-Path Distillation and In Vitro Bioactivity Evaluation.

This study shows a pilot scale protocol aimed to obtain an omega 3-enriched oil after the processing of farmed gilthead sea bream viscera (SBV); this was oil was tested in vitro for bioactivity, attesting to the possibility to turn waste into profit The quality of the oil, in terms of requirements for animal and human consumption, was assessed by determining some chemical parameters, such as peroxide value (PV), thiobarbituric acid reactive substances (TBARS), ρ-anisidine (ρ-AV) content, total oxidation value (TOTOX), and phospholipids and free fatty acid (%), both in crude viscera oil (CVO) and refined viscera oil (RVO). Among the extraction conditions, the higher CVO yields were obtained at 60 °C for 10 min (57.89%) and at 80 °C for 10 min (67.5%), and the resulting oxidation levels were low when utilizing both extraction conditions. RVO, obtained from CVO extracted at 60 °C, showed the highest quality on the basis of the assessed parameters. The ethyl esters of the total fatty acid (TFA) contents extracted from RVO were enriched in the ω-3 polyunsaturated fatty acid fraction (PUFAE) up to almost 56% via short path distillation (SPD). Antioxidant activities and adipogenic properties were tested in vitro. PUFAE protected 3T3 L1 cells from oxidative stress and exerted an anti-adipogenic effect in Dicentrarchus labrax pre-adipocytes, attesting to the beneficial properties for both farmed fish and human health. These results could stimulate the adoption of solutions aimed to recover and utilize aquaculture by-products at a higher scale, turning "waste into profit" and indicating a strategy to reach more sustainable business models in aquaculture resource utilization according to the principles of the circular economy.

[Primary prevention of coronary heart disease : Evidence-based drug treatment]. / Primärprävention der koronaren Herzkrankheit : Evidenzbasierte medikamentöse Therapie.

Coronary artery disease (CAD) is the most frequent cause of morbidity and mortality worldwide. Lifestyle modifications and drug treatment of cardiovascular risk factors are able to effectively prevent CAD. The basis of prevention is the assessment of the individual cardiovascular risk, e.g. by using a validated risk score. Documented evidence for prevention of CAD is available for the control of hypertension using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium antagonists, for the treatment of hypercholesterolemia using statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors and for the treatment of type 2 diabetes mellitus with metformin, sodium-glucose transporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. There is no positive benefit-risk ratio for people with a low risk in the use of acetylsalicylic acid in primary prevention, in contrast to the positive recommendations for secondary prevention. There is no evidence for the efficacy of primary prevention with beta blockers, dipeptidyl peptidase 4 (DPP-4) inhibitors, glitazones, sulfonylureas or insulin. Similarly, there is no evidence for drug treatment of obesity, any supplementation with vitamins or hormone preparations or omega­3 fatty acids.

Increases in Colonic Bacterial Diversity after ω-3 Fatty Acid Supplementation Predict Decreased Colonic Prostaglandin E2 Concentrations in Healthy Adults.

BACKGROUND: The intestinal microbiome is an important determinant of inflammatory balance in the colon that may affect response to dietary agents. OBJECTIVE: This is a secondary analysis of a clinical trial, the Fish Oil Study, to determine whether interindividual differences in colonic bacteria are associated with variability in the reduction of colonic prostaglandin E2 (PGE2) concentrations after personalized supplementation with ω-3 (n-3) fatty acids. METHODS: Forty-seven healthy adults (17 men, 30 women, ages 26-75 y) provided biopsy samples of colonic mucosa and luminal stool brushings before and after personalized ω-3 fatty acid supplementation that was based on blood fatty acid responses. Samples were analyzed using 16S ribosomal RNA sequencing. The data analyses focused on changes in bacterial community diversity. Linear regression was used to evaluate factors that predict a reduction in colonic PGE2. RESULTS: At baseline, increased bacterial diversity, as measured by the Shannon and Inverse Simpson indexes in both biopsy and luminal brushing samples, was positively correlated with dietary fiber intakes and negatively correlated with fat intakes. Dietary supplementation with ω-3 fatty acids increased the Yue and Clayton community dis-similarity index between the microbiome in luminal brushings and colon biopsy samples post-supplementation (P = 0.015). In addition, there was a small group of individuals with relatively high Prevotella abundance who were resistant to the anti-inflammatory effects of ω-3 fatty acid supplementation. In linear regression analyses, increases in diversity of the bacteria in the luminal brushing samples, but not in the biopsy samples, were significant predictors of lower colonic PGE2 concentrations post-supplementation in models that included baseline PGE2, baseline body mass index, and changes in colonic eicosapentaenoic acid-to-arachidonic acid ratios. The changes in bacterial diversity contributed to 6-8% of the interindividual variance in change in colonic PGE2 (P = 0.001). CONCLUSIONS: Dietary supplementation with ω-3 fatty acids had little effect on intestinal bacteria in healthy humans; however, an increase in diversity in the luminal brushings significantly predicted reductions in colonic PGE2. This trial was registered at www.clinicaltrials.gov as NCT01860352.

Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial).

BACKGROUND: N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD). MATERIALS AND METHODS: The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD. RESULTS: Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 ± 1.2%, P < 0.001; placebo: -0.4 ± 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and mono-hydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A5 (fish oil: 0.57 ± 0.70 pg/mL, P = 0.05; placebo: 0.01 ± 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 ± 171 pg/mL, P = 0.04; placebo: 32 ± 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity C-reactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group. CONCLUSIONS: Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD.

Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet.

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases andtype 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damagebiomolecules, especially proteins. The present study was designed to investigate the effect of marineomega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid(DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins fromplasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS)diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of proteincarbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification byMS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combinationof both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in bothplasma and liver. The analysis of carbonylated protein targets, also referred to as the 'carbonylome',revealed an individual response of liver proteins to supplements and a modulatory effect on specificmetabolic pathways and processes due to, at least in part, the control exerted by the supplements on theliver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grapeseed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption ofHFHS diets.

[Confusion about the effects of omega-3 fatty acids : Contemplation of study data taking the omega-3 index into consideration]. / Verwirrung um die Wirkung von Omega-3-Fettsäuren : Betrachtung von Studiendaten unter Berücksichtigung des Omega-3-Index.

BACKGROUND: Confusion reigns about omega­3 fatty acids and their effects. Scientific investigations did not appear to clarify the issue. Guidelines and regulatory authorities contradict each other. OBJECTIVE: This article provides clarity by considering not intake but levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes as a percentage of all fatty acids measured (omega­3 index). CURRENT DATA: The largest database of all methods of fatty acid analyses has been generated with the standardized HS-Omega­3 Index® (Omegametrix, Martinsried, Deutschland). The omega­3 index assesses the in EPA+DHA status of a person, has a minimum of 2%, a maximum of 20%, and is optimal between 8% and 11%. In many western countries but not in Japan or South Korea, mean levels are suboptimal. Suboptimal levels correlate with increased total mortality, sudden cardiac death, fatal and non-fatal myocardial infarction, other cardiovascular diseases, cognitive impairment, major depression, premature birth and other health issues. Interventional studies on surrogate and intermediary parameters demonstrated many positive effects, correlating with the omega­3 index when measured. Due to issues in methodology that became apparent from the perspective of the omega­3 index many, even large interventional trials with clinical endpoints were not positive, which is reflected in pertinent meta-analyses. In contrast, interventional trials without issues in methodology the clinical endpoints mentioned were reduced. CONCLUSION: All humans have levels of EPA+DHA that if methodologically correctly assessed in erythrocytes, are optimal between 8% and 11%. Deficits can cause serious health issues that can be prevented by optimal levels.

Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation.

All n-3 PUFA are not the same: MD simulations reveal differences in membrane organization for EPA, DHA and DPA.

Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers. They were run in the absence and presence of 20mol% cholesterol. Multiple double bonds confer high disorder on all three n-3 PUFA. The different number of double bonds and chain length for each n-3 PUFA moderates the reduction in membrane order exerted (compared to OA-PC, S¯CD=0.152). EPA-PC (S¯CD=0.131) is most disordered, while DPA-PC (S¯CD=0.140) is least disordered. DHA-PC (S¯CD=0.139) is, within uncertainty, the same as DPA-PC. Following the addition of cholesterol, order in EPA-PC (S¯CD=0.169), DHA-PC (S¯CD=0.178) and DPA-PC (S¯CD=0.182) is increased less than in OA-PC (S¯CD=0.214). The high disorder of n-3 PUFA is responsible, preventing the n-3 PUFA-containing phospholipids from packing as close to the rigid sterol as the monounsaturated control. Our findings establish that EPA, DHA and DPA are not equivalent in their interactions within membranes, which possibly contributes to differences in clinical efficacy.

Targeting Hepatic Protein Carbonylation and Oxidative Stress Occurring on Diet-Induced Metabolic Diseases through the Supplementation with Fish Oils.

The present study addressed the ability of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFA), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to ameliorate liver protein damage derived from oxidative stress and induced by consumption of high-caloric diets, typical of Westernized countries. The experimental design included an animal model of Sprague-Dawley rats fed high-fat high-sucrose (HFHS) diet supplemented with ω-3 EPA and DHA for a complete hepatic proteome analysis to map carbonylated proteins involved in specific metabolic pathways. Results showed that the intake of marine ω-3 PUFA through diet significantly decreased liver protein carbonylation caused by long-term HFHS consumption and increased antioxidant system. Fish oil modulated the carbonylation level of more than twenty liver proteins involved in critical metabolic pathways, including lipid metabolism (e.g., albumin), carbohydrate metabolism (e.g., pyruvate carboxylase), detoxification process (e.g., aldehyde dehydrogenase 2), urea cycle (e.g., carbamoyl-phosphate synthase), cytoskeleton dynamics (e.g., actin), or response to oxidative stress (e.g., catalase) among others, which might be under the control of diet marine ω-3 PUFA. In parallel, fish oil significantly changed the liver fatty acid profile given by the HFHS diet, resulting in a more anti-inflammatory phenotype. In conclusion, the present study highlights the significance of marine ω-3 PUFA intake for the health of rats fed a Westernized diet by describing several key metabolic pathways which are protected in liver.

Omega-3 fatty acid fish oil dietary supplements contain saturated fats and oxidized lipids that may interfere with their intended biological benefits.

Widely available fish oil dietary supplements (DS) may contain fats and oxidized lipids in addition to the beneficial omega-3 fatty acids (OM3FAs) for which they are purchased. Little is known about the potential biological effects of these oxidized lipids. The objective of this study was to assess the fatty acid content, oxidation products, and biological effects of leading fish oil DS available in the United States. Three top-selling fish oil DS in the US were included in this analysis. Fatty acid composition was measured using gas chromatography. Lipid oxidation (primary and secondary products) was measured by spectroscopy in both DS and a prescription OM3FA product. OM3FAs were also isolated and concentrated from DS and were tested for the ability to inhibit copper-induced oxidation of human small dense low-density lipoprotein particles (sdLDL) in vitro. Fish oil DS were found to contain more than 30 different fatty acids, including 10 to 14 different saturated species comprising up to 36% of the total fatty acid content. Levels of OM3FAs also varied widely among DS (33%-79%). Primary (peroxide), secondary (anisidine), and total oxidation products exceeded maximum levels established by international standards of quality in the DS but not the prescription OM3FA product. Oxidation of sdLDL was inhibited by >95% (P < 0.001) with non-oxidized forms of OM3FA but not with OM3FAs isolated from DS, which were a mixture of oxidized and non-oxidized OM3FAs. These data indicate that levels of saturated fat and oxidized OM3FAs found in common DS may interfere with their intended/potential biological benefits.

The compositional and metabolic responses of gilthead seabream (Sparus aurata) to a gradient of dietary fish oil and associated n-3 long-chain PUFA content.

The replacement of fish oil (FO) with vegetable oil (VO) in feed formulations reduces the availability of n-3 long-chain PUFA (LC-PUFA) to marine fish such as gilthead seabream. The aim of this study was to examine compositional and physiological responses to a dietary gradient of n-3 LC-PUFA. Six iso-energetic and iso-nitrogenous diets (D1-D6) were fed to seabream, with the added oil being a blend of FO and VO to achieve a dietary gradient of n-3 LC-PUFA. Fish were sampled after 4 months feeding, to determine biochemical composition, tissue fatty acid concentrations and lipid metabolic gene expression. The results indicated a disturbance to lipid metabolism, with fat in the liver increased and fat deposits in the viscera reduced. Tissue fatty acid profiles were altered towards the fatty acid compositions of the diets. There was evidence of endogenous modification of dietary PUFA in the liver which correlated with the expression of fatty acid desaturase 2 (fads2). Expression of sterol regulatory element binding protein 1 (srebp1), fads2 and fatty acid synthase increased in the liver, whereas PPARα1 pathways appeared to be supressed by dietary VO in a concentration-dependent manner. The effects in lipogenic genes appear to become measurable in D1-D3, which agrees with the weight gain data suggesting that disturbances to energy metabolism and lipogenesis may be related to performance differences. These findings suggested that suppression of ß-oxidation and stimulation of srebp1-mediated lipogenesis may play a role in contributing toward steatosis in fish fed n-3 LC-PUFA deficient diets.