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Bioactive products formed in humans from fish oils.
Skarke C, Alamuddin N, Lawson JA, Li X, Ferguson JF, Reilly MP, FitzGerald GA
(2015) J Lipid Res 56: 1808-20
MeSH Terms: Adult, Anti-Inflammatory Agents, CD59 Antigens, Dietary Supplements, Fatty Acids, Omega-3, Female, Fish Oils, Healthy Volunteers, Humans, Inflammation, Inflammation Mediators, Lipid Metabolism, Lipopolysaccharides, Male
Show Abstract · Added March 28, 2016
Resolvins, maresins, and protectins can be formed from fish oils. These specialized pro-resolving mediators (SPMs) have been implicated in the resolution of inflammation. Synthetic versions of such SPMs exert anti-inflammatory effects in vitro and when administered to animal models. However, their importance as endogenous products formed in sufficient amounts to exert anti-inflammatory actions in vivo remains speculative. We biased our ability to detect SPMs formed in healthy volunteers by supplementing fish oil in doses shown previously to influence blood pressure and platelet aggregation under placebo-controlled conditions. Additionally, we sought to determine the relative formation of SPMs during an acute inflammatory response and its resolution, evoked in healthy volunteers by bacterial lipopolysaccharide (LPS). Bioactive lipids, enzymatic epoxyeicosatrienoic acids (EETs), and free radical-catalyzed prostanoids [isoprostanes (iPs)] formed from arachidonic acid and the fish oils, served as comparators. Despite the clear shift from ω-6 to ω-3 EETs and iPs, we failed to detect a consistent signal, in most cases, of SPM formation in urine or plasma in response to fish oil, and in all cases in response to LPS on a background of fish oil. Our results question the relevance of these SPMs to the putative anti-inflammatory effects of fish oils in humans.
Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
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14 MeSH Terms
Update to A.S.P.E.N. position paper: clinical role for alternative intravenous fat emulsions.
Vanek VW, Seidner DL, Allen P, Bistrian B, Collier S, Gura K, Miles JM, Valentine CJ, Novel Nutrient Task Force, American Society for Parenteral and Enteral Nutrition
(2014) Nutr Clin Pract 29: 841
MeSH Terms: Dietetics, Fat Emulsions, Intravenous, Fish Oils, Humans, Phytosterols, Plant Oils, Societies, Scientific, Triglycerides, United States
Added September 30, 2015
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9 MeSH Terms
Omega-3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers.
Ferguson JF, Mulvey CK, Patel PN, Shah RY, Doveikis J, Zhang W, Tabita-Martinez J, Terembula K, Eiden M, Koulman A, Griffin JL, Mehta NN, Shah R, Propert KJ, Song WL, Reilly MP
(2014) Mol Nutr Food Res 58: 601-13
MeSH Terms: Adolescent, Adult, Dietary Supplements, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Drug Combinations, Eicosapentaenoic Acid, Endotoxemia, Fatty Acids, Omega-3, Female, Fish Oils, Healthy Volunteers, Humans, Inflammation, Isoprostanes, Lipopolysaccharides, Lipoproteins, Male, Middle Aged, Young Adult
Show Abstract · Added January 20, 2015
SCOPE - Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity. However, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans.
METHODS AND RESULTS - The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-wk randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465 mg eicosapentaenoic acid (EPA) + 375 mg docosahexaenoic acid (DHA)) at "low" (1/day, 900 mg) or "high" (4/day, 3600 mg) dose in healthy individuals (N = 60; age 18-45; BMI 18-30; 43% female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6 ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (p = 0.03) but not low-dose EPA + DHA compared to placebo. Although there was no statistically significant impact of EPA + DHA on individual inflammatory responses (tumor necrosis factor-α (TNF-α), IL-6, monocyte chemotactic protein (MCP-1), IL-1 receptor agonist (IL-1RA), IL-10, C-reactive protein (CRP), serum amyloid A (SAA)), there was a pattern of lower responses across all biomarkers with high-dose (nine of nine observed), but not low-dose EPA + DHA.
CONCLUSION - EPA + DHA at 3600 mg/day, but not 900 mg/day, reduced fever and had a pattern of attenuated LPS induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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20 MeSH Terms
Plasma phospholipid omega-3 fatty acids and incidence of postoperative atrial fibrillation in the OPERA trial.
Wu JH, Marchioli R, Silletta MG, Macchia A, Song X, Siscovick DS, Harris WS, Masson S, Latini R, Albert C, Brown NJ, Lamarra M, Favaloro RR, Mozaffarian D
(2013) J Am Heart Assoc 2: e000397
MeSH Terms: Aged, Atrial Fibrillation, Cardiac Surgical Procedures, Dietary Supplements, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Unsaturated, Female, Fish Oils, Humans, Incidence, Male, Middle Aged, Postoperative Complications, Prospective Studies
Show Abstract · Added March 7, 2014
BACKGROUND - Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFA) demonstrated antiarrhythmic potential in experimental studies. In a large multinational randomized trial (OPERA), perioperative fish oil supplementation did not reduce the risk of postoperative atrial fibrillation (PoAF) in cardiac surgery patients. However, whether presupplementation habitual plasma phospholipid n-3 PUFA, or achieved or change in n-3 PUFA level postsupplementation are associated with lower risk of PoAF is unknown.
METHODS AND RESULTS - In 564 subjects undergoing cardiac surgery between August 2010 and June 2012 in 28 centers across 3 countries, plasma phospholipid levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were measured at enrollment and again on the morning of cardiac surgery following fish oil or placebo supplementation (10 g over 3 to 5 days, or 8 g over 2 days). The primary endpoint was incident PoAF lasting ≥ 30 seconds, centrally adjudicated, and confirmed by rhythm strip or ECG. Secondary endpoints included sustained (≥ 1 hour), symptomatic, or treated PoAF; the time to first PoAF; and the number of PoAF episodes per patient. PoAF outcomes were assessed until hospital discharge or postoperative day 10, whichever occurred first. Relative to the baseline, fish oil supplementation increased phospholipid concentrations of EPA (+142%), DPA (+13%), and DHA (+22%) (P < 0.001 each). Substantial interindividual variability was observed for change in total n-3 PUFA (range = -0.7% to 7.5% after 5 days of supplementation). Neither individual nor total circulating n-3 PUFA levels at enrollment, morning of surgery, or change between these time points were associated with risk of PoAF. The multivariable-adjusted OR (95% CI) across increasing quartiles of total n-3 PUFA at enrollment were 1.0, 1.06 (0.60 to 1.90), 1.35 (0.76 to 2.38), and 1.19 (0.64 to 2.20); and for changes in n-3 PUFA between enrollment and the morning of surgery were 1.0, 0.78 (0.44 to 1.39), 0.89 (0.51 to 1.55), and 1.01 (0.58 to 1.75). In stratified analysis, demographic, medication, and cardiac parameters did not significantly modify these associations. Findings were similar for secondary PoAF endpoints.
CONCLUSIONS - Among patients undergoing cardiac surgery, neither higher habitual circulating n-3 PUFA levels, nor achieved levels or changes following short-term fish oil supplementation are associated with risk of PoAF.
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15 MeSH Terms
Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.
Mozaffarian D, Marchioli R, Macchia A, Silletta MG, Ferrazzi P, Gardner TJ, Latini R, Libby P, Lombardi F, O'Gara PT, Page RL, Tavazzi L, Tognoni G, OPERA Investigators
(2012) JAMA 308: 2001-11
MeSH Terms: Aged, Atrial Fibrillation, Cardiovascular Surgical Procedures, Dietary Supplements, Double-Blind Method, Fatty Acids, Omega-3, Female, Fish Oils, Humans, Male, Middle Aged, Odds Ratio, Risk, Treatment Outcome
Show Abstract · Added March 26, 2014
CONTEXT - Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results.
OBJECTIVE - To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF.
DESIGN, SETTING, AND PATIENTS - The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment.
INTERVENTION - Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.
MAIN OUTCOME MEASURE - Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events.
RESULTS - At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.
CONCLUSION - In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.
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14 MeSH Terms
Dietary fish oil supplementation inhibits formation of endometriosis-associated adhesions in a chimeric mouse model.
Herington JL, Glore DR, Lucas JA, Osteen KG, Bruner-Tran KL
(2013) Fertil Steril 99: 543-50
MeSH Terms: Administration, Oral, Adult, Animals, Dietary Fats, Unsaturated, Dietary Supplements, Disease Models, Animal, Endometriosis, Female, Fish Oils, Humans, Mice, Mice, Nude, Middle Aged
Show Abstract · Added May 29, 2014
OBJECTIVE - To examine whether dietary fish oil supplementation reduces development of spontaneous endometriosis-associated adhesions using an established model.
DESIGN - Laboratory-based study.
SETTING - Medical center research laboratory. PATIENT(S)/ANIMAL(S): Disease-free women of reproductive age and nude mice.
INTERVENTION(S) - Women were not provided any intervention. Mice were randomized to receive fish oil supplementation or control diet.
MAIN OUTCOME MEASURE(S) - Experimental endometriosis was established in mice via injection of human endometrial tissue within 16 hours of ovariectomy. Mice were provided standard or menhaden fish oil-supplemented diets for ≥ 2 weeks before initiation of experimental endometriosis and until killing them 1 week later. At necropsy, mice were examined for the presence and extent of adhesions and endometriotic-like lesions. Tissues were excised and morphologically characterized.
RESULT(S) - Adhesions/lesions were reduced in mice provided with dietary fish oil compared with control animals. Leukocytes were more numerous within the adhesions/lesions of the mice maintained on the standard diet compared with animals provided with fish oil. As indicated by staining intensity, collagen deposition was greater at adhesion sites within control mice compared with fish oil-supplemented animals.
CONCLUSION(S) - Wound-healing associated with surgery created an inflammatory peritoneal microenvironment that promoted the development of both experimental endometriosis and adhesions in a murine model. Targeting excessive inflammation with fish oil may be an effective adjuvant therapy to reduce the development of postsurgical adhesions related to endometriosis.
Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR(-/-) mice.
Murali G, Milne GL, Webb CD, Stewart AB, McMillan RP, Lyle BC, Hulver MW, Saraswathi V
(2012) J Lipid Res 53: 2186-97
MeSH Terms: Animals, Anti-Inflammatory Agents, Cytochrome P-450 Enzyme System, Dyslipidemias, Fatty Liver, Female, Fish Oils, Hypolipidemic Agents, Indomethacin, Liver, Mice, Pregnane X Receptor, RNA, Messenger, Receptors, LDL, Receptors, Steroid
Show Abstract · Added March 26, 2014
Fish oil (FO) is a potent anti-inflammatory and lipid-lowering agent. Because inflammation can modulate lipid metabolism and vice versa, we hypothesized that combining FO with cyclooxygenase inhibitors (COXIBs), well-known anti-inflammatory drugs, can enhance the anti-inflammatory and lipid-lowering effect of FO. LDLR(-/-) mice were fed a high-fat diet supplemented with 6% olive oil or FO for 12 wk in the presence or absence of indomethacin (Indo, 6 mg/l drinking water). FO reduced plasma total cholesterol by 30% but, in combination with Indo, exerted a greater decrease (44%). The reduction of liver cholesterol ester (CE) and triglycerides (TG) by FO (63% and 41%, respectively) was enhanced by Indo (80% in CE and 64% in TG). FO + Indo greatly increased the expression of genes modulating lipid metabolism and reduced the expression of inflammatory genes compared with control. The mRNA and/or protein expression of pregnane X receptor (PXR) and cytochrome P450 isoforms that alter inflammation and/or lipid metabolism are increased to a greater extent in mice that received FO + Indo. Moroever, the nuclear level of PXR is significantly increased in FO + Indo group. Combining FO with COXIBs may exert their beneficial effects on inflammation and lipid metabolism via PXR and cytochrome P450.
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15 MeSH Terms
Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice.
Depner CM, Torres-Gonzalez M, Tripathy S, Milne G, Jump DB
(2012) J Nutr 142: 1495-503
MeSH Terms: Animal Feed, Animals, Biomarkers, Cytokines, Dietary Fats, Fatty Liver, Fish Oils, Gene Expression Regulation, Inflammation, Lipid Metabolism, Liver Cirrhosis, Mice, Mice, Knockout, Mice, Obese, Oxidative Stress, Receptors, LDL, Transcription Factors
Show Abstract · Added March 26, 2014
The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20-22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20-22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet-induced fatty liver disease in mice. Wild-type (WT) and Ldlr(-/-) C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF-high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1α1), and oxidative stress (heme oxygenase-1) (P ≤ 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr(-/-) mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr(-/-) mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20-22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet-induced markers of fatty liver disease in mice.
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17 MeSH Terms
A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions.
Vanek VW, Seidner DL, Allen P, Bistrian B, Collier S, Gura K, Miles JM, Valentine CJ, Kochevar M, Novel Nutrient Task Force, Intravenous Fat Emulsions Workgroup, American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors
(2012) Nutr Clin Pract 27: 150-92
MeSH Terms: Europe, Fat Emulsions, Intravenous, Fish Oils, Humans, Immunity, Inflammation, Linoleic Acid, Lipids, Olive Oil, Parenteral Nutrition, Plant Oils, Societies, Medical, Soybean Oil, Triglycerides, United States
Show Abstract · Added September 30, 2015
The currently available, standard soybean oil (SO)-based intravenous fat emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients. There are alternative oil-based fat emulsions, such as medium-chain triglycerides (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in Europe, have an equivalent safety profile to SO. These alternative IVFEs are metabolized via different pathways, which may lead to less proinflammatory effects and less immune suppression. These alternative oil-based IVFEs are not currently available in the United States. Many patients who require IVFEs are already in a compromised state. Such patients could potentially have better clinical outcomes when receiving one of the alternative IVFEs to diminish the intake of the potentially proinflammatory ω-6 fatty acid-linoleic acid-which comprises more than 50% of the fatty acid profile in SO. Further research is needed on these alternative oil-based IVFEs to identify which IVFE oils or which combination of oils may be most clinically useful for specific patient populations.
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15 MeSH Terms
The effects of an oral supplement enriched with fish oil, prebiotics, and antioxidants on nutrition status in Crohn's disease patients.
Wiese DM, Lashner BA, Lerner E, DeMichele SJ, Seidner DL
(2011) Nutr Clin Pract 26: 463-73
MeSH Terms: Adipose Tissue, Administration, Oral, Adult, Aged, Antioxidants, Arachidonic Acid, Body Fluid Compartments, Crohn Disease, Dietary Fiber, Dietary Supplements, Docosahexaenoic Acids, Drug Combinations, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Female, Fish Oils, Humans, Male, Middle Aged, Nutritional Status, Phospholipids, Pilot Projects, Prebiotics, Severity of Illness Index, Surveys and Questionnaires, Vitamin D, Young Adult
Show Abstract · Added September 30, 2015
BACKGROUND - Research in the treatment of Crohn's disease (CD) supports anti-inflammatory benefits of n-3 fatty acids from fish oil, prebiotics, and antioxidants. A nutritionally balanced inflammatory bowel disease nutrition formula (IBDNF) enriched with these compounds has the potential to improve nutrition status and disease activity in CD.
METHODS - This is an open-label pilot study investigating the effects of IBDNF on nutrition status in CD patients. Twenty-eight patients with active CD on stable medication were asked to consume 16 oz of IBDNF/d for 4 months. Nutrition status was assessed with dual-energy X-ray absorptiometry scans and serum micronutrient levels. Disease activity and quality of life were measured using the Crohn's Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ).
RESULTS - Twenty patients completed the final visit. After 4 months, there was a significant decrease in plasma phospholipid levels of arachidonic acid with increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid. Ten patients had a final EPA concentration of >2%. There was improvement in fat-free and fat mass in patients with final EPA >2% (P = .014 and P = .05). Vitamin D (25-OH) levels improved in all patients (18.5-25.9 ng/mL, P < .001). Those with EPA >2% had significantly lower CDAI (116 ± 94.5 vs 261.8 ± 86.5; P = .005) and higher IBDQ (179.1 ± 26.6 vs 114.6 ± 35.9, P < .001) compared to those with EPA <2%.
CONCLUSIONS - IBDNF has the potential to deposit fat-free and fat mass, improve vitamin D status, and improve quality of life in CD patients.
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28 MeSH Terms