Omega-3 Polyunsaturated Fatty Acid Supplementation Research Articles

Statin Use Mitigate the Benefit of Omega-3 Fatty Acids Supplementation-A Meta-Regression of Randomized Trials.

During last 2 decades, multiple studies have evaluated omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation for cardiovascular prevention. The benefit found in previous studies was not demonstrated in more contemporary trials. We aimed to investigate effect of study characteristics, particularly concomitant statin therapy on results of randomized controlled trials. We systematically searched electronic databases for randomized controlled trials evaluating ω-3 PUFA supplementation and reporting clinical outcomes. A meta-analysis was performed using a random effect model, followed by a meta-regression of dose, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio, and duration of treatment and use of lipid-lowering/statin therapy in control group. Twenty-three studies with 77,776 patients (38,910 PUFA; 38,866 controls) were included. PUFA had no effect on total mortality [risk ratio (RR) = 0.96; 95% confidence interval (CI), 0.92-1.01] and myocardial infarction (RR = 0.87; 95% CI, 0.73-1.02), but marginally reduced cardiovascular mortality (RR = 0.93; 95% CI, 0.87-0.98). Lower control group statin use (b = 0.222, P = 0.027) and higher DHA/EPA (b = -0.105, P = 0.033) ratio was associated with higher reduction in total mortality. Duration and dose had no effect. None of the variables except duration had significant effect on reduction in cardiovascular mortality by PUFA supplementation. There was evidence of publication bias. Statin use may mitigate, and higher DHA/EPA ratio is associated with the beneficial effect of PUFA supplementation.

Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation.

Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use can cause neurobiological side-effects associated with depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), the essential fatty acids found in fish oil, possess neuroprotecitve and antidepressant activities. Thus, the aim of this study was to explore the potential protective effects of ω-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. ω-3 PUFAs were given daily by gavage (1.5 g/kg) over three weeks starting seven days before DOX administration (2.5 mg/kg). Open-field test (OFT) and forced swimming test (FST) were conducted to assess exploratory activity and despair behavior, respectively. Our data showed that ω-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. ω-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, ω-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the protein levels of NF-κB and iNOS were significantly increased in brain tissues of DOX-treated group, whereas ω-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, ω-3 PUFAs can effectively protect against DOX-induced depressive-like behaviors, and the mechanisms underlying the neuroprotective effect are potentially associated with its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Changes in plasma metabolites and glucose homeostasis during omega-3 polyunsaturated fatty acid supplementation in women with polycystic ovary syndrome

BackgroundBoth fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA. Methods and findingsIn this six-week, randomized, 3-parallel arm, double-blinded study, 54 women received 3.5g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end.As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, l-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and l-cysteine degradation. ConclusionEffects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary.

Omega-3 fatty acids for the treatment of dementia.

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish and plant sources are commonly considered as a promising non-medical alternative to improve brain functions and slow down the progression of dementia. This assumption is mostly based on findings of preclinical studies and epidemiological research. Resulting explanatory models aim at the role omega-3 PUFAs play in the development and integrity of the brain's neurons, their protective antioxidative effect on cell membranes and potential neurochemical mechanisms directly related to Alzheimer-specific pathology. Epidemiological research also found evidence of malnutrition in people with dementia. Considering this and the fact that omega-3 PUFA cannot be synthesised by humans, omega-3 PUFAs might be a promising treatment option for dementia. To assess the efficacy and safety of omega-3 polyunsaturated fatty acid (PUFA) supplementation for the treatment of people with dementia. We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) portal/ICTRP on 10 December 2015. We contacted manufacturers of omega-3 supplements and scanned reference lists of landmark papers and included articles. We included randomised controlled trials (RCTs) in which omega-3 PUFA in the form of supplements or enriched diets were administered to people with Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) or frontotemporal dementia (FTD). The primary outcome measures of interest were changes in global and specific cognitive functions, functional performance, dementia severity and adverse effects. Two review authors independently selected studies, extracted data and assessed the quality of trials according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We received unpublished data from the trial authors and collected adverse effects information from the published articles. We conducted meta-analyses for available outcome measures at six months. We included three comparable randomised, placebo-controlled trials investigating omega-3 PUFA supplements in 632 participants with mild to moderate AD over six, 12 and 18 months. We found no studies investigating other types of dementia. All trials were of high methodological quality. The overall quality of evidence for most of the outcomes was high.There was no evidence of a benefit from omega-3 PUFAs on cognitive function when measured at six months with the Alzheimer's Disease Assessment Scale - Cognitive subscale (standardised mean difference (SMD) -0.02, 95% confidence interval (CI) -0.19 to 0.15; 566 participants; 3 studies; high quality evidence) or Mini-Mental State Examination (mean difference (MD) 0.18, 95% CI -1.05 to 1.41; 202 participants; 2 studies; high quality evidence) or on activities of daily living (SMD -0.02, 95% CI -0.19 to 0.16; 544 participants; 2 studies; high quality evidence). There was also no effect at six months of treatment on severity of dementia measured with the Clinical Dementia Rating - Sum of Boxes (MD -0.00, 95% CI -0.58 to 0.57; 542 participants; 2 studies; high quality evidence) or on quality of life measured with the Quality of Life Alzheimer's Disease scale (MD -0.10, 95% CI -1.28 to 1.08; 322 participants; 1 study; high quality evidence). There was no difference at six months on mental health measured with the Montgomery-Åsberg Depression Rating Scale (MD -0.10, 95% CI -0.74 to 0.54; 178 participants: 1 study; high quality of evidence) or the Neuropsychiatric Inventory (SMD 0.10, 95% CI -0.07 to 0.27; 543 participants; 2 studies; high quality of evidence). One very small study showed a benefit for omega-3 PUFAs in instrumental activities of daily living after 12 months of treatment (MD -3.50, 95% CI -4.30 to -2.70; 22 participants; moderate quality evidence). The included studies did not measure specific cognitive function. The studies did not report adverse events well. Two studies stated that all adverse events were mild and that they did not differ in overall frequency between omega-3 PUFA and placebo groups. Data from one study showed no difference between groups in frequency of any adverse event (risk ratio (RR) 1.02, 95% CI 0.95 to 1.10; 402 participants; 1 study; moderate quality evidence) or any serious adverse event (RR 1.05, 95% CI 0.78 to 1.41; 402 participants; 1 study; high quality evidence) at 18 months of treatment. We found no convincing evidence for the efficacy of omega-3 PUFA supplements in the treatment of mild to moderate AD. This result was consistent for all outcomes relevant for people with dementia. Adverse effects of omega-3 PUFAs seemed to be low, but based on the evidence synthesised in this review, we cannot make a final statement on tolerability. The effects on other populations remain unclear.

Omega-3 polyunsaturated fatty acid supplementation in the prevention of cardiovascular disease.

Omega-3 polyunsaturated fatty acids (PUFAs) have purported protective cardiovascular (CV) effects. We sought to assess the evidence available for the use of omega-3 PUFAs for the prevention of cardiovascular disease (CVD). A systematic literature search was conducted using MEDLINE and EMBASE from 1999 to 2015. Placebo-controlled, randomized controlled trials (RCTs) that enrolled over 1000 patients with follow-up greater than 1 year and meta-analyses of RCTs were included. Eight RCTs and 2 meta-analyses were included. In patients with preexisting CVD, only 1 of 5 included RCTs demonstrated a reduction in CV events with omega-3 PUFAs; however, the effect size was minimal, and the study was limited by an open-label design and lack of placebo control. Two meta-analyses concluded omega-3 PUFAs do not reduce CV events in addition to standard, evidence-based therapy in patients after myocardial infarction. Of the 3 predominantly primary prevention RCTs, only 1 demonstrated a minor reduction in major coronary events; however, it was also an open-label study. Furthermore, the safety of omega-3 PUFAs should be considered. While data from RCTs have not demonstrated serious safety concerns, omega-3 PUFAs can increase the risk of bleeding and may interact with other medications that affect hemostasis, such as antiplatelet agents and warfarin. There is currently a lack of evidence to support the routine use of omega-3 PUFAs in the primary and secondary prevention of CVD. Pharmacists are ideally situated to engage patients in the discussion of the lack of benefit and possible risk of omega-3 PUFA supplements.

Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.

Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114–0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I2=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009–0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017–0.01144), P=0.044) and earlier publication year (β=−0.0735 (−0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.

P.3.011 Attenuated cortisol response to blockade of the mineralocorticoid receptor in depressed patients

The current study examined the psychological effects of acute and low-dose long-chain omega-3 polyunsaturated fatty acids (LCPUFAs) supplementation on young adults with depressive symptoms. Participants (N=23, M age (SD)=20.2 (1.25), 78% female), with a Beck Depression Inventory (BDI) score of greater than 10, were randomly assigned to a placebo (corn oil) or LCPUFAs group (1.4 g of eicosapentaenoic and docosahexaeonic acids) and were instructed to consume the assigned capsules daily for 21-days. BDI was completed prior to supplementation and at day 21. Group differences in depression status on day 21 were analyzed using chi-square tests. After 21-days of supplementation, there was a significant difference in depression status between groups. 67% of the LCPUFAs no longer met criteria for being depressed, while only 20% in the placebo group were no longer depressed. A mixed ANOVA revealed a significant group x time interaction for BDI scores. Post-hoc analyses revealed the LCPFUAs group had a significant reduction in BDI scores over time, while the placebo group's scores did not significantly change. These findings suggest that LCPUFAs may alter depression and depressive symptomology in young adults in a relatively short amount of time.

Omega-3 fatty acids do not alter P-wave parameters in electrocardiogram or expression of atrial connexins in patients undergoing coronary artery bypass surgery.

We previously reported omega-3 polyunsaturated fatty acids (n-3PUFAs) supplementation does not reduce atrial fibrillation (AF) following coronary artery bypass graft (CABG) surgery. The aim of the present study is to evaluate the impact of n-3 PUFAs on electrocardiogram (ECG) atrial arrhythmic markers and compare with expression of gap-junction proteins, Connexins. Subset of clinical trial subjects with right atrial sampling during CABG surgery included. Twelve-lead ECG performed at recruitment and at surgery [after supplementation with n-3 PUFA (∼1.8 g/day) or matched placebo] for ∼14 days. Electrocardiograms analysed for maximum P-wave duration (P-max) and difference between P-max and minimum P-wave duration, P-wave dispersion (PWD). Right atrial specimens analysed for expression of Connexins 40 and 43 using real-time quantitative polymerase chain reaction (qPCR) and western blot. Serum levels of n-3 PUFA at baseline, at surgery, and atrial tissue levels at surgery collated from file. Postoperative AF was quantified by analysing data from stored continuous electrograms. A total of 61 patients (n-3 PUFA 34, Placebo 27) had ECG analysis and AF burden, of which 52 patients (26 in each group) had qPCR and 16 (8 in each group) had western blot analyses for Connexins 40 and 43. No difference between the two groups in ECG parameters or expression of Connexin 40 or 43. P-wave dispersion in the preoperative ECG independently predicted occurrence of AF following CABG surgery. Omega-3 polyunsaturated fatty acids supplementation does not alter pro-arrhythmic P-wave parameters in ECG or connexin expression in human atrium with no effect on the incidence of AF following CABG surgery.

Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial

IntroductionOmega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied. Methods205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I–III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6months after. Plasma BNP and serum creatinine levels were also measured. ResultsAs compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p=0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p=0.047) and 3.7% (p=0.01), maximum diameter of left atrium was decreased by 8.4% (p=0.004), left atrium ejection fraction was ameliorated by 6.03% (p=0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p=0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients. ConclusionOmega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure.

Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression

White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = −1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.

Omega-3 fatty acids for cystic fibrosis

Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review. To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted.Date of last search: 13 August 2013. Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The searches identified 15 studies; four studies with 91 participants (children and adults) were included; duration of studies ranged from six weeks to six months. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another study (43 participants) demonstrated a significant increase in serum phospholipid essential fatty acid content and a significant drop in the n-6/n-3 fatty acid ratio following omega-3 fatty acid supplementation compared to control. The longer-term study (17 participants) demonstrated a significant increase in essential fatty acid content in neutrophil membranes and a significant decrease in the leukotriene B4 to leukotriene B5 ratio in participants taking omega-3 supplements compared to placebo. This review found that regular omega-3 supplements may provide some benefits for people with cystic fibrosis with relatively few adverse effects, although evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. This review has highlighted the lack of data for many outcomes meaningful to people with or making treatment decisions about cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes.

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer's Disease: A Randomised Controlled Trial.

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer’s disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer’s disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.

Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders.

Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention against major depression, bipolar disorders, interferon-α-induced depression patients with chronic hepatitis C viral infection, and posttraumatic stress disorder. The biological mechanisms underlying omega-3 PUFAs’ psychotropic effects are proposed and reviewed. Nutrition is a modifiable environmental factor that might be important in prevention medicine, which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs. This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more researches on prospective clinical studies to justify the preventive application of omega-3 PUFAs in daily practice.

Fish Oil Enhances T Cell Function and Tumor Infiltration and Is Correlated With a Cancer Prevention Effect in HER-2/neu But Not PyMT Transgenic Mice

Few studies have explored the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on immune modulation in murine models of mammary carcinogenesis. HER-2/neu and PyMT mice were randomized to 2 dietary interventions: AIN-93G-based diet with 1) 11% of diet (per gram weight) as corn oil (CO) or 2) 10% of diet as menhaden fish oil plus 1% of diet as corn oil (FO). FO significantly reduced the incidence and multiplicity of tumors (P < 0.001) in HER-2/neu, but not PyMT mice. FO-fed mice had significantly larger splenocyte counts than CO-fed mice in both the HER-2/neu and PyMT models; and in both models this was comprised of an increase in most cell types, including Gr-1+/CD11b+ cells. T cells from FO-fed HER-2/neu mice produced significantly more interleukin-2 (P = 0.004) and interferon-γ (P = 0.012) in response to in vitro stimulation with anti-CD3 (0.5 µg/ml). Lastly, FO-fed HER-2/neu mice had significantly more tumor immune infiltrates than CO-fed mice, including NK1.1+, F4/80+, and Gr-1+/CD11b+ cells (P ≤ 0.05). Greater Th1 cytokine production and significantly more tumor immune infiltrates in FO-fed Her2/neu mice may account for the cancer prevention effect of fish oil in this model.

Short-term supplementation of acute long-chain omega-3 polyunsaturated fatty acids may alter depression status and decrease symptomology among young adults with depression: A preliminary randomized and placebo controlled trial

The current study examined the psychological effects of acute and low-dose long-chain omega-3 polyunsaturated fatty acids (LCPUFAs) supplementation on young adults with depressive symptoms. Participants (N=23, M age (SD)=20.2 (1.25), 78% female), with a Beck Depression Inventory (BDI) score of greater than 10, were randomly assigned to a placebo (corn oil) or LCPUFAs group (1.4g of eicosapentaenoic and docosahexaeonic acids) and were instructed to consume the assigned capsules daily for 21-days. BDI was completed prior to supplementation and at day 21. Group differences in depression status on day 21 were analyzed using chi-square tests. After 21-days of supplementation, there was a significant difference in depression status between groups. 67% of the LCPUFAs no longer met criteria for being depressed, while only 20% in the placebo group were no longer depressed. A mixed ANOVA revealed a significant group x time interaction for BDI scores. Post-hoc analyses revealed the LCPFUAs group had a significant reduction in BDI scores over time, while the placebo group's scores did not significantly change. These findings suggest that LCPUFAs may alter depression and depressive symptomology in young adults in a relatively short amount of time.

Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are promoted as cognitive enhancers with consumption recommended in the general population and those with neurocognitive deficits such as attention deficit hyperactivity disorder (ADHD). However, evidence from randomised placebo-controlled trials is inconclusive. This study aimed to conduct a systematic review and meta-analysis examining the effect of n-3 PUFA supplementation on cognition in healthy populations and those with ADHD and related disorders (RDs). Databases were searched for randomised controlled trials (RCTs) in adults and school-aged children (who were healthy and typically developing (TD) or had ADHD or a related-neurodevelopmental disorder (ADHD+RD) which assessed the effects of n-3 PUFA on cognition. In the 24 included studies n-3 PUFA supplementation, in the whole sample and the TD and ADHD+RD subgroup, did not show improvements in any of the cognitive performance measures. In those with low n-3 PUFA status, supplementation improved short-term memory. There is marginal evidence that n-3 PUFA supplementation effects cognition in those who are n-3 PUFA deficient. However, there is no evidence of an effect in the general population or those with neurodevelopmental disorders. This has important implications given the widespread advertisement and consumption of n-3 PUFA; claims of cognitive benefit should be narrowed.

Effect of omega-3 polyunsaturated fatty acid supplementation on central arterial stiffness and arterial wave reflections in young and older healthy adults.

Increased central arterial stiffness and enhanced arterial wave reflections may contribute to increased risk of cardiovascular disease development with advancing age. Omega-3 polyunsaturated fatty acid (n-3) ingestion may reduce cardiovascular risk via favorable effects exerted on arterial structure and function. We determined the effects of n-3 supplementation (4 g/day for 12 weeks) on important measures of central arterial stiffness (carotid-femoral pulse wave velocity; PWV) and arterial wave reflection (central augmentation index) in young (n = 12; 25 ± 1-year-old, mean ± SE) and older (n = 12; 66 ± 2) healthy adults. We hypothesized that n-3 supplementation would decrease carotid-femoral PWV and central augmentation index in older adults. Our results indicate that carotid-femoral PWV and central augmentation index were greater in older (988 ± 65 cm/sec and 33 ± 2%) than in young adults (656 ± 16 cm/sec and 3 ± 4%: both P < 0.05 compared to older) before the intervention (Pre). N-3 supplementation decreased carotid-femoral PWV in older (Δ-9 ± 2% Precompared to Post; P < 0.05), but not young adults (Δ2 ± 3%). Central augmentation index was unchanged by n-3 supplementation in young (3 ± 4 vs. 0 ± 4% for Pre and Post, respectively) and older adults (33 ± 2 vs. 35 ± 3%). Arterial blood pressure at rest, although increased with age, was not altered by n-3 supplementation in young or older adults. Collectively, these data indicate that 12 weeks of daily n-3 supplementation decreases an important measure of central arterial stiffness (carotid-femoral PWV) in older, but not young healthy adults. The mechanism underlying decreased central arterial stiffness with n-3 supplementation is unknown, but appears to be independent of effects on arterial blood pressure or arterial wave reflections.

Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial

& aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. Patients received three capsules daily, each containing 0.315g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n=27) or mineral oil (placebo group, n=23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. At baseline, NAS was comparable between the groups (p=0.98). After intervention with omega-3 PUFAs, plasma ALA and EPA levels increased (p≤0.05). However in the placebo group, we also observed increased EPA and DHA (p≤0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p=0.02) and with increased EPA (p=0.04) and DHA (p=0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p=0.01). In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology. (ID 01992809).

78 Influence of omega-3 polyunsaturated fatty acid supplementation on plasma prostaglandin E2 production in young exercising horses

78 Influence of omega-3 polyunsaturated fatty acid supplementation on plasma prostaglandin E2 production in young exercising horses

Effect of omega-3 polyunsaturated fatty acids supplementation on traumatic brain injury in a rat model

Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation on brain edema, autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats and the related mechanisms. Methods TBI rat models were established using Feeney's method. Seventy-two SD rats were divided into 4 groups using random number table: sham operation group, TBI group, ω-3 PUFA supplementation group (TBI+ ω-3 group) and autophagy inhibitor 3-methyladenine group (TBI+ 3-MA group) (all n=18), each group was further divided into 3 sub-groups (n=6) corresponding to 3 time points (days 1, 3, and 7 after TBI). On each of the 3 time points, we measured rat behavioral outcomes with modified neurologic severity score (mNSS) tests; brain water content was measured with wet-dry weight method. The mRNA and protein expressions of autophagy-related factors (LC3-Ⅱ and Beclin-1) in TBI cerebral cortex were determined by immunohistochemistry staining, reverse transcription-polymerase chain reaction and Western blot on day 3 after TBI. Results Compared with the sham group, on days 1, 3, and 7 after injuary, the TBI group, the TBI+ ω-3 group, and the TBI+ 3-MA group had significantly higher mNSS scores (TBI group: 12.42±0.27 vs.1.34±0.32, 12.07±0.27 vs. 1.16±0.29, 10.22±0.39 vs. 1.22±0.30; TBI+ ω-3 group: 12.05±0.23 vs. 1.34±0.32, 11.38±0.21 vs. 1.16±0.29, 8.20±0.21 vs. 1.22±0.30; TBI+ 3-MA group: 11.93±0.20 vs. 1.34±0.32, 11.09±0.19 vs. 1.16±0.29, 7.93±0.17 vs. 1.22±0.30; all P=0.00) and brain water content [TBI group: (79.82±0.61)% vs. (71.87±0.43)%, (83.04±0.42)% vs. (72.13±0.53)%, (75.12±0.72)% vs. (71.78±0.38)%; TBI+ ω-3 group: (76.81±0.63)% vs. (71.87±0.43)%, (79.39±0.59)% vs. (72.13±0.53)%, (73.86±0.38)% vs. (71.78±0.38)%; TBI+ 3-MA group: (75.98±0.49)% vs. (71.87±0.43)%, (77.14±0.46)% vs. (72.13±0.53)%, (72.24±0.37)% vs. (71.78±0.38)%; all P=0.00]. The mRNA and protein expressions of LC3-Ⅱ and Beclin-1 in the brain were also significantly higher on day 3 in the TBI group, the TBI+ ω-3 group, and the TBI+ 3-MA group (all P=0.00). Compared with the TBl group, on day 3 and day 7 after injury, the TBI+ ω-3 group and the TBI+ 3-MA group had significantly lower mNSS scores (TBI+ ω-3 group: 11.38±0.21 vs. 12.07±0.27, P=0.04, 8.20±0.21 vs. 10.22±0.39, P=0.01; TBI+ 3-MA group: 11.09±0.19 vs. 12.07±0.27, P=0.01, 7.93±0.17 vs. 10.22±0.39, P=0.00). On days 1, 3, and 7, compared with the TBI group, the TBI+ ω-3 group and the TBI+ 3-MA group had significantly lower brain water content [TBI+ ω-3 group: (76.81±0.63)% vs. (79.82±0.61)%, P=0.04, (79.39±0.59)% vs. (83.04±0.42)%, P=0.01, (73.86±0.38)% vs. (75.12±0.72)%, P=0.03; TBI+ 3-MA group: (75.98±0.49)% vs. (79.82±0.61)%, P=0.01, (77.14±0.46)% vs. (83.04±0.42)%, P=0.00, (72.24±0.37)% vs. (75.12±0.72)%, P=0.02]. On day 3, the TBI+ ω-3 group and the TBI+ 3-MA group had significantly reduced LC3-Ⅱ and Beclin-1 mRNA expression compared with the TBI group (TBI+ ω-3 group: P=0.04, P=0.01; TBI+ 3-MA group: P=0.01, P=0.00) and protein expression (TBI+ ω-3 group: P=0.01, P=0.03; TBI+ 3-MA group: both P=0.00). Conclusion ω-3 PUFA supplementation could markedly reduce brain edema and improve neurological functions after TBI, showing a neuroprotective effect, possibly through inhibiting TBI-induced autophagy responses. Key words: Traumatic brain injury; Omega-3 polyunsaturated fatty acids; Autophagy; Neuroprotection