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Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME* trial.
Manousopoulou, A, Scorletti, E, Smith, DE, Teng, J, Fotopoulos, M, Roumeliotis, TI, Clough, GF, Calder, PC, Byrne, CD, Garbis, SD
Clinical nutrition (Edinburgh, Scotland). 2019;(4):1952-1955
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterised by liver fat accumulation and often considered to be the liver manifestation of metabolic syndrome. The aim of this study was to examine in patients with NAFLD the system-wide effects of treatment with docosahexaenoic acid + eicosapentaenoic acid (DHA + EPA) versus placebo on the plasma proteome. METHODS Plasma from patients that participated in a 15-18 months randomised, double-blind placebo-controlled trial testing the effects of 4 g DHA + EPA daily was analysed using depletion-free quantitative proteomics. RESULTS Bioinformatics interpretation of the proteomic analysis showed that DHA + EPA treatment affected pathways involving blood coagulation, immune/inflammatory response and cholesterol metabolism (p < 0.05). Two key proteins of cardiovascular risk, prothrombin and apolipoprotein B-100, were shown to decrease as a result of DHA + EPA supplementation [Prothrombin: Males DHA + EPA Mean iTRAQ log2ratio (SD) = -0.13 (0.20) p = 0.05, Females DHA + EPA Mean iTRAQ log2ratio (SD) = -0.48 (0.35) p = 0.03; Apo B-100: Males DHA + EPA Mean iTRAQ log2ratio (SD) = -0.24 (0.16) p = 0.01, Females DHA + EPA Mean iTRAQ log2ratio (SD) = -0.15 (0.05) p = 0.02]. CONCLUSIONS Plasma proteomics applied in a randomised, placebo-controlled trial showed that high dose DHA + EPA treatment in patients with NAFLD affects multiple pathways involved in chronic non-communicable diseases.
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Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study.
Vors, C, Allaire, J, Marin, J, Lépine, MC, Charest, A, Tchernof, A, Couture, P, Lamarche, B
Atherosclerosis. 2017;:116-122
Abstract
BACKGROUND AND AIMS Whether EPA and DHA exert similar anti-inflammatory effects through modulation of gene expression in immune cells remains unclear. The aim of the study was to compare the impact of EPA and DHA supplementation on inflammatory gene expression in subjects at risk for cardiometabolic diseases. METHODS In this randomized double-blind crossover trial, 154 men and women with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1) EPA (2.7 g/d); 2) DHA (2.7 g/d); 3) corn oil (3 g/d), separated by a 9-wk washout. Pro- and anti-inflammatory gene expression was assessed in whole blood cells by RT-qPCR after each treatment in a representative sample of 44 participants. RESULTS No significant difference was observed between EPA and DHA in the expression of any of the genes investigated. Compared with control, EPA enhanced TRAF3 and PPARA expression and lowered CD14 expression (p < 0.01) whereas DHA increased expression of PPARA and TNFA and decreased CD14 expression (p < 0.05). Variations in gene expression after EPA and after DHA were strongly correlated for PPARA (r = 0.73, p < 0.0001) and TRAF3 (r = 0.66, p < 0.0001) and less for TNFA (r = 0.46, p < 0.005) and CD14 (r = 0.16, p = 0.30). CONCLUSIONS High-dose supplementation with either EPA or DHA has similar effects on the expression of many inflammation-related genes in immune cells of men and women at risk for cardiometabolic diseases. The effects of EPA and of DHA on anti-inflammatory gene expression may be more consistent than their effects on expression of pro-inflammatory genes in whole blood cells.
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Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial.
Healy, LA, Ryan, A, Doyle, SL, Ní Bhuachalla, ÉB, Cushen, S, Segurado, R, Murphy, T, Ravi, N, Donohoe, CL, Reynolds, JV
Annals of surgery. 2017;(5):720-728
Abstract
OBJECTIVE This randomized controlled trial (RCT) hypothesized that prolonged enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3 fatty acid with immune and anabolic properties, may impact on clinical and nutritional outcomes. BACKGROUND Esophagectomy is associated with significant weight loss and catabolism, and negatively impacts quality of life (QL). Strategies to counter sustained catabolism have therapeutic rationale. METHODS This multicenter, double-blind, placebo-controlled RCT was powered on a 5% difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and at 1, 3, and 6 months included weight, body mass index (BMI), body composition, muscle strength, cytokines, complications, and QL. RESULTS The median (range) nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For the entire cohort, a significant (P < 0.005) decrease in weight (-7.4 ± 6.6 kg), BMI (-2.6 ± 2.2 kg/m), LBM (-2.5 ± 8.7 kg), and fat mass (-3.4 ± 5.8 kg) was evident from preoperatively to 6 months. The mean (±SD) loss of LBM (kg) at 1 month was -3.7 ± 8.7 in the EN-S group, compared with -5.6 ± 12.1 in the EN-EPA group (P = 0.355). Per-protocol analysis revealed no difference between the EN-EPA and EN-S in any clinical, nutritional, functional, QL or immune parameter at any time point. CONCLUSIONS The thesis that EPA impacts on anabolism, immune function, and clinical outcomes post-esophagectomy was not supported. Compliance with home EN was excellent, but weight, muscle, and fat loss was significant in 30% of patients, highlighting the complexity of postoperative weight loss.
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Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer.
Ida, S, Hiki, N, Cho, H, Sakamaki, K, Ito, S, Fujitani, K, Takiguchi, N, Kawashima, Y, Nishikawa, K, Sasako, M, et al
The British journal of surgery. 2017;(4):377-383
Abstract
BACKGROUND Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).
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Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review.
de Aguiar Pastore Silva, J, Emilia de Souza Fabre, M, Waitzberg, DL
Clinical nutrition (Edinburgh, Scotland). 2015;(3):359-66
Abstract
BACKGROUND & AIMS Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in vitro and in vivo, used along with anticancer drugs, have improved cancer treatment outcome. Clinical studies have reported positive results with omega-3 supplements in oncologic patients. We summarized only randomized controlled clinical trials involving the administration of DHA and/or EPA during chemotherapy and/or radiotherapy to assess the effects on treatment outcomes. METHODS We conducted a systematic literature search using specific terms. Of 157 publications, 10 were selected on the basis of their methodological quality, according to the Oxford Quality Scale and the Cochrane Concealment Assessment. Outcome included body weight and composition, peripheral neuropathy, immune, inflammatory and oxidative status, quality of life, and membrane omega-3 fatty acids incorporation. RESULTS Treatment regimens included radiotherapy (1), chemotherapy (8), and chemoradiotherapy (1). The number of patients ranged from 11 to 92 and the daily dose of EPA and/or DHA from 600 mg to 3.6 g. For high quality methodology studies only, the combination of omega-3 fatty acids supplements with conventional chemotherapy was beneficial. None of the studies reported a worse outcome for the supplement patients. CONCLUSIONS There are beneficial effects of omega-3 fatty acids supplements in patients undergoing chemotherapy and/or radiotherapy on different outcomes, being the preservation of body composition the most evident. Some important outcome like decrease tumor size and prolonging patient survival, are not observed.
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Preemptive enteral nutrition enriched with eicosapentaenoic acid, gamma-linolenic acid and antioxidants in severe multiple trauma: a prospective, randomized, double-blind study.
Kagan, I, Cohen, J, Stein, M, Bendavid, I, Pinsker, D, Silva, V, Theilla, M, Anbar, R, Lev, S, Grinev, M, et al
Intensive care medicine. 2015;(3):460-9
Abstract
BACKGROUND Severe injury triggers a complex systemic immune response which may result in significant respiratory compromise, including the development of acute respiratory distress syndrome (ARDS). No randomized clinical trial has assessed the role of nutritional interventions to limit respiratory complications. METHODS This was a single-center, prospective, randomized, comparative, double-blind, controlled study of patients with severe trauma requiring mechanical ventilation. Patients were randomly assigned to receive either a control formula (n = 58) or a formula enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA) and antioxidants (n = 62) at time of admission to the intensive care unit (ICU). Primary outcome measures included the level of oxygenation (PaO2/FiO2 ratio, PF ratio) on days 4 and 8, incidence of acute lung injury (ALI) and/or ARDS and length of ventilation. The development of infectious complications and fatty acid red blood cell membrane composition were also assessed. RESULTS In this intention-to-treat population, no significant differences between the control and study groups were found for the PF ratio at day 4 (213.7 ± 85.6 vs. 227.2 ± 67.7, respectively; P = 0.24) and day 8 (187.8 ± 65.2 vs. 188.9 ± 56.0, respectively; P = 0.82), the incidence of ARDS/ALI (24.1 vs. 29.0 %, respectively; P = 0.68), length of ventilation time (13.6 ± 10.7 vs. 17.0 ± 15.1 days, respectively; P = 0.15), duration of ICU stay (16.4 ± 11.3 vs. 19.5 ± 15.3 days, respectively; P = 0.21) and 28-day mortality (8.6 vs. 12.9 %, respectively P = 0.56). While the study group showed a significant increase in EPA and GLA concentrations at day 4 (P = 0.05) and day 8 (P < 0.001), the Omega-3 Index (O-3I) failed to reach those suggested as being optimal to obtain clinical efficacy. The significantly higher incidence of bacteremia noted in the study group (P = 0.03) was associated with a higher number of patients with multiple trauma and a higher red blood cell transfusion requirement (P = 0.008). CONCLUSION This study failed to show a significant benefit for the preemptive use of the study formula in patients with severe trauma. Additional studies need to be performed in which the amount of supplementation is targeted to a potentially measurable endpoint, e.g. the O-3I.
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Acute respiratory distress syndrome: use of specialized nutrients in pediatric patients and infants.
Hamilton, LA, Trobaugh, KA
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2011;(1):26-30
Abstract
With a high rate of mortality, acute respiratory distress syndrome (ARDS) has limited treatments options. Immune-enhanced formulas, containing eicosapentaenoic acid, borage oil, and antioxidants, have shown to be beneficial in adults patients with ARDS, decreasing mortality, length of mechanical ventilation, and new organ dysfunction. There is promising research in pediatric patients with improvement in oxygenation status found, but further trials are needed to realize these benefits in pediatric and infant populations.
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Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation.
Chapkin, RS, Kim, W, Lupton, JR, McMurray, DN
Prostaglandins, leukotrienes, and essential fatty acids. 2009;(2-3):187-91
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Abstract
The inflammatory response is designed to help fight and clear infection, remove harmful chemicals, and repair damaged tissue and organ systems. Although this process, in general, is protective, the failure to resolve the inflammation and return the target tissue to homeostasis can result in disease, including the promotion of cancer. A plethora of published literature supports the contention that dietary n-3 polyunsaturated fatty acids (PUFA), and eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in particular, are important modulators of a host's inflammatory/immune responses. The following review describes a mechanistic model that may explain, in part, the pleiotropic anti-inflammatory and immunosuppressive properties of EPA and DHA. In this review, we focus on salient studies that address three overarching mechanisms of n-3 PUFA action: (i) modulation of nuclear receptor activation, i.e., nuclear factor-kappaB (NF-kappaB) suppression; (ii) suppression of arachidonic acid-cyclooxygenase-derived eicosanoids, primarily prostaglandin E(2)-dependent signaling; and (iii) alteration of the plasma membrane micro-organization (lipid rafts), particularly as it relates to the function of Toll-like receptors (TLRs), and T-lymphocyte signaling molecule recruitment to the immunological synapse (IS). We propose that lipid rafts may be targets for the development of n-3 PUFA-containing dietary bioactive agents to down-modulate inflammatory and immune responses and for the treatment of autoimmune and chronic inflammatory diseases.
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Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial.
Ryan, AM, Reynolds, JV, Healy, L, Byrne, M, Moore, J, Brannelly, N, McHugh, A, McCormack, D, Flood, P
Annals of surgery. 2009;(3):355-63
Abstract
BACKGROUND Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear. OBJECTIVES To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications. METHODS In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines. RESULTS Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFalpha, IL-10, and IL-8 compared with the standard group. CONCLUSIONS EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.