Los ácidos grasos poliinsaturados omega-3 han adquirido especial importancia debido a sus efectos benéficos para la salud humana y animal. La carne de pollo enriquecida está considerada una buena alternativa para el consumo de ácidos grasos poliinsaturados omega-3. La utilización de algunas materias primas vegetales en la dieta, tales como semilla y aceite de lino o de colza, pueden incrementar el contenido de ácidos grasos poliinsaturados omega-3 en forma de ácido linolénico en la carne. Uno de los principales problemas de la carne de pollo enriquecida con ácidos grasos omega-3 es la facilidad de oxidación de los ácidos grasos poliinsaturados de los tejidos, como resultado de sus dobles enlaces, produciendo peróxidos y aldehídos, responsables de un deficiente flavor, oxidación de los tejidos y reducción de la calidad de almacenamiento. La suplementación con vitamina E en la dieta de los pollos parrilleros alimentados con semillas o aceite de origen vegetal favorece la estabilidad a la oxidación de los ácidos grasos insaturados. El objetivo de este trabajo de tesis fue estudiar el efecto de la semilla de lino adicionada a la dieta sobre la calidad y el contenido de los ácidos grasos poliinsaturados en la carne de pollo fresco, refrigerado, congelado y cocido, y evaluar la estabilidad oxidativa de la carne de pollo con las dietas ricas en lino por la adición de diferentes cantidades de vitamina E. Los ensayos de crianza se llevaron a cabo durante tres años. La dieta se elaboró con materias primas de origen vegetal: maíz y harina de soja, complementada con harina de carne, ceniza de hueso y núcleo vitamínico. En los primeros dos ensayos se alimentó a los pollos con esta dieta base y el agregado de 4 u 8 % de semilla de lino y 8 % de semilla de lino más 200 mg de vitamina E / kg, respectivamente. De acuerdo a los resultados obtenidos en los dos años anteriores, a la dieta experimental del último ensayo se le agregó 8 % de semilla de lino y se suplementó con 200 y 400 mg de vitamina E / kg. A los 51 días de comenzado el ensayo, se sacrificó una muestra representativa de los animales por dieta, se pesó la carcasa y se sacó el promedio por pollo, comparando este valor con el peso vivo, en cada tratamiento. Con el objeto de evaluar la calidad y composición de los ácidos grasos en el tejido muscular del pollo fresco, cocido, refrigerado por una semana y congelado, se tomó una muestra representativa de cada lote y de cada unidad se prepararon tres muestras de 200 g cada una que una vez envasadas y etiquetadas fueron inmediatamente enfriadas a 5 C ó congeladas a - 2 C. La extracción de los lípidos se realizó por una adaptación del método de Folch y la metilación por el método de Morrison y Smith. La identificación y cuantificación de los ácidos grasos fue realizada por cromatografía gaseosa. Para medir la estabilidad oxidativa de la carne fresca y refrigerada durante cinco días se utilizó el método de TBARS. Para evaluar la calidad organoléptica de la carne cocida se llevaron a cabo pruebas hedónicas, con jueces no entrenados, durante los tres años. Se utilizó el test triangular para encontrar la muestra estadísticamente diferente. Con estas muestras se realizaron pruebas de aceptabilidad, empleando una escala hedónica y el test de Student. La composición de ácidos grasos de las diferentes dietas en la carne de pollo fresca, refrigerada, congelada y cocida y las determinaciones de TBAR, fueron sometidas al análisis de la varianza con un ANOVA doble (4 x 4) y (4 x 2) Para encontrar las diferencias significativas entre las muestras se utilizó el test de Fisher con un nivel de significancia de α < 0,05. Con referencia a los resultados obtenidos, en los ensayos de producción, las dietas con lino, ricas en grasas insaturadas, mostraron mayor eficiencia productiva en algunos ensayos y menor en otros, por los que los resultados no son concluyentes. El rendimiento de la carcasa fue similar para las diferentes dietas, resultado independiente del agregado de semilla de lino y vitamina E, aunque en los pollos alimentados con las dietas suplementadas se encontró menor proporción de grasa abdominal. El contenido total de grasa del tejido muscular no presentó diferencias significativas entre las dietas. Con relación al contenido de los ácidos grasos poliinsaturados omega-3 (AGPI ω3) en las presas, las diferencias significativas entre carne de pechuga y pata-muslo se encontraron con las dietas suplementadas con lino, resultando mayor en la pechuga. En todos los ensayos no se detectaron ácidos grasos con más de 24 átomos de carbono. Cuando el nivel de insaturación de la dietas aumentó se incrementó el nivel de AGPI ω3 en el tejido muscular del pollo, particularmente el ácido linolénico. En el segundo año de ensayos los valores medios en la carne de pollo fresco aumentaron de 1,94 % en la dieta testigo a 5,52 % en la dieta con 4 % de lino y a 8,19 y 10,8 % en las dietas con 8 % de lino y 8 % de lino + vitamina E, respectivamente. El incremento de los ácidos grasos ω3 fue acompañado por un leve aumento de la familia ω6 y una disminución proporcional de los ácidos grasos saturados y monoinsaturados. La conservación de la carne en frío, ya sea refrigerada o congelada, no afectó la cantidad y composición de los AGPI ω3. No se encontraron diferencias significativas en la misma dieta para cada tratamiento realizado. La cocción sin embargo, disminuyó el nivel de AGPI ω3 en la dieta con lino al 8 %. La mejor relación ω6/ω3 que se obtuvo, teniendo en cuenta las recomendaciones para el consumo en humanos que varía en un rango entre 2:1 a 6:1, fue la proveniente de las dietas con mayor porcentaje de lino. En el tercer año de ensayos, se observó que la contribución porcentual de los AGPI ω3 fue más elevada en las carcasas de los pollos alimentados con las dietas suplementadas con 200 mg de vitamina E / kg, en las que se registró un porcentaje más elevado de AGPI ω3 (9,93 %) versus la dieta suplementada con 400 mg (7,51 %). Con respecto a la estabilidad oxidativa de la carne, la proveniente de pollos alimentados con dietas ricas en AGPI, sin el suplemento de vitamina E, registró los valores más elevados de TBARS. En ambos productos, fresca y refrigerada, la dieta con 400 mg de vitamina E / kg presentó diferencias significativas con el resto de las dietas mostrando un menor deterioro de los AGPI. Con respecto al análisis sensorial, el agregado de hasta 4 % de semilla de lino a la dieta no afectó las características sensoriales, sabor y textura, de la carne de pollo cocida. En algunos casos, la carne proveniente de los pollos alimentados con las dietas enriquecidas con lino resultó la más aceptada con respecto a la de las dietas sin lino por resultar más tierna y con característico sabor a pollo. La suplementación con vitamina E desmejoró las características sensoriales evaluadas, sabor y textura, especialmente a las mayores concentraciones. Del análisis de los resultados obtenidos se puede concluir que es posible mejorar la calidad nutricional y el contenido de los ácidos poliinsaturados omega-3 en la carne de pollo con el agregado de semilla de lino a la dieta y que su incremento, en especial del ácido α-linolénico, es directamente proporcional al incremento de AGPI ω3 en la dieta. Los tratamientos con frío no afectaron significativamente el contenido de los AGPI ω 3 y la suplementación con vitamina E aumentó la estabilidad oxidativa de la carne fresca y refrigerada. Con respecto a la calidad sensorial, la carne proveniente de las dietas con lino resultó superior a la de las dietas con lino suplementadas con vitamina E. / The polyunsaturated omega-3 fatty acids have acquired special importance due to their beneficial effects for human and animal health. Enriched meat of chicken is considered a good alternative for the consumption of polyunsaturated omega-3 fatty acids. The use of some vegetal raw materials in the feed, such as seed and oil of linen or canola, can increase the content of polyunsaturated omega-3 fatty acids in the meat in the α-linolenic acid form. One of the main problems of the chicken meat enriched with fatty acids omega-3 is the facility of oxidation of the polyunsaturated fatty acids in the tissues, as resulting from its double connections, producing peroxides and aldehydes, responsible for a deficient flavor, oxidation of tissues and reduction of the storage quality. The supplementation with vitamin E in the diet of the chicken broilers fed with seeds or oil of vegetal origin favors the stability to the oxidation of unsaturated fatty acids. The objective of this thesis work was to study the effect of the linseed added to the diet on the quality and content of polyunsaturated fatty acids in the meat of chicken fresh, refrigerated, stored and cooked, and to evaluate the oxidative stability of the meat of chicken with the rich linen diets by the addition of different amounts of vitamin E. The raising tests were carried out during three years. The diet was elaborated with raw materials of vegetal origin: corn and flour of soybean, complemented with flour of meat, ash of bone and vitamin nucleus. In the first two tests chicken broilers were fed with this diet and the aggregate of 4 or 8 % of linseed, and 8 % of linseed plus 200 mg of vitamin E / kg, respectively. According to the results obtained in both previous years, the experimental diet of de last test was added with 8 % of linseed and supplemented with 200 and 400 mg of vitamin E / kg. After 51 days of feeding, a representative sample of the animals by diet was sacrificed, the carcass was weighed, and the average value was compared to the live weight, for each treatment. With the intention of evaluating the quality and composition of fatty acids in the muscular tissue of fresh, refrigerated by one week and frozen chicken, a representative sample was taken from each lot. Three 200 g samples were prepared, individually packaged and labeled, and immediately refrigerated to 5 C or stored to - 20 C. The extraction of lipids was made by adaptation of the method of Folch and the methylation by the method of Morrison and Smith. The identification and quantification of fatty acids were made by gaseous chromatography. In order to measure the oxidative stability of the fresh and cooled meat during five days, the thiobarbituric acid reactive substances (TBARS) method was used. In order to evaluate the organoleptic quality of the cooked meat, hedonics tests were carried out the three years, with untrained judges. The triangular test was used to find the statistically different sample. With theses samples acceptability tests were made, using a hedonic scale and the Student test. The fatty acid composition of the different diets in fresh, refrigerated, frozen and cooked chicken meat, and the determinations of TBAR were put under the analysis of the variance with a double ANOVA (4 x 4) and (4 x 2). To find the significant differences between the samples, the test of Fisher with a level of significance of a α < 0, 05 was used. In reference to the obtained results in the production tests, the diets with linen, rich in unsaturated fats, showed a higher productive efficiency in some tests and lower in others, by which the results are not conclusive. The yield of the carcass was similar for the different diets, independently of the aggregate of linen seed and vitamin E, although proportion of abdominal fat was lower in the chickens fed with the supplemented diets. The total fat content of the muscular tissue did not present significant differences between the diets. In relation to the content of polyunsaturated fatty acids omega -3 (PUFA ω3), the significant differences between meat of breast and leg-thigh were found with the diets supplemented with linen, being greater in breast. In all tests fatty acids with more than 22 carbon atoms were not detected. The content level PUFA ω3 in the muscular tissues of the chicken, particularly the linolenic acid, increased with the level of unsaturation of the diets. The average values in the meat of fresh chicken in the second year test increased from 1.94 % with the basic diet to 5.52 % in the diet with 4 % of linen and 8.19 and 10.8 % in the diets with 8 % of linen and 8 % of linen + vitamin E, respectively. The increasing of fatty acid omega-3 was accompanied by a slight increase of the omega-6 family, and a proportional diminution of saturated and monounsaturated fatty acids. The conservation of the meat in refrigerated and/or frozen conditions, did not affect the amount and composition of the PUFA ω3. No significant differences in the same diet for each treatment were observed. Nevertheless, cooking diminished the PUFA ω3 level in the diet with linen to 8 %. The best ω6/ω3 relation, considering the recommendations for the consumption in humans that varies in the rank between 2:1 and 6:1, was obtained in the diets with grater percentage of linen. In the third year test, it was observed that the percentage contribution of the PUFA ω3 was more elevated in the carcass of the chicken fed with the diet supplemented with 200 mg of vitamin E / kg (9.93 %) as compared to that supplemented with 400 mg (7.51 %). The meat of chickens fed with diets rich in PUFA, without vitamin E supplementation, registered the highest values of TBARS, showing a lower oxidative stability. In both fresh and refrigerated products, the diet with 400 mg of vitamin E / kg presented significant differences with the rest of the diets, showing a smaller deterioration of the PUFA. With respect to the sensorial analysis, the aggregate of up to 4 % of flaxseed to the diet did not affect the sensorial characteristics, flavor and texture, of the cooked chicken meat. In some cases, the meat of chickens fed with linen turned out most accepted with respect to the one from the diets without linen, being tenderer and with a characteristic flavor to chicken. The supplementation with vitamin E got worse the evaluated sensorial characteristic flavor and texture, especially to the greater concentrations. From the analysis of the obtained results it can be concluded that it is possible to improve the nutritional quality and the content of polyunsaturated acids omega-3 in the chicken meat by adding linseed to the diet, and that this increase, especially in linolenic acid, is directly proportional to the increase of PUFA ω3 in the diet. The cold treatments did not affect significantly the content of PUFA ω3, and the supplementation with vitamin E increases the oxidative stability of fresh and refrigerated meat. The sensorial quality of chicken meat obtained from the diets with linen was superior to those from the diets supplemented with vitamin E.

Omega-3 polyunsaturated fatty acids (ω3 PUFAs) provide important health benefits, but dietary consumption is low. Supplementing foods with ω3 PUFAs is of interest, but intervention strategies are necessary to preserve the integrity of these unstable compounds. Microencapsulation of ω3 PUFA sources is one means of improving their stability. In this work, ω3 PUFA microcapsules were prepared by spray drying with chitosan and blends of chitosan, high-amylose starch, and pullulan as wall materials. The primary objectives of this research were (1) to evaluate the effect of chitosan type and oil:wall ratio on ω3 PUFA microcapsule properties, (2) to evaluate the effect of blending chitosan with high-amylose starch and pullulan on ω3 PUFA microcapsule properties, and (3) to evaluate the oxidative stability of ω3 PUFA microcapsules by monitoring primary and secondary oxidation products during storage. Microcapsule encapsulation efficiencies (EE) ranged from 63% to 79% with the highest EEs observed for microcapsules prepared from chitosan with higher degree of deacetylation (DD) and lower molecular weight (MW). Median microcapsule size ranged from 3 μm to 11 μm. Moisture contents were all below 7% and water activities (a_w) were below 0.27. Microcapsules prepared from blends of chitosan with starch and/or pullulan had lower aw values than those prepared from chitosan alone. Oxidative stability was evaluated by measuring oxidation induction time (OIT) using pressure differential scanning calorimetry. OIT values ranged from 14 to 20 minutes. Microcapsules prepared from chitosan with lower DD and higher MW had longer OITs than those prepared from chitosan with higher DD and lower MW. Microcapsules prepared from blends of chitosan, starch, and pullulan had longer OITs than those prepared from chitosan alone. Oxidative stability of microcapsules during long term storage was evaluated on one microcapsule formulation by monitoring peroxide value (PV) and secondary oxidation products by HS-SPMEGC/ MS. Volatiles including propanal, 1-penten-3-ol, pentanal, hexanal, and 2,4-heptadienal were detected in the headspace of the microcapsules; however, PVs did not indicate substantial oxidation of the ω3-PUFA source during 5 weeks of storage. Chitosan, high-amylose starch, and pullulan are effective materials for microencapsulation of ω3 PUFA sources. / Ph. D.

Menhaden is the major source of fish oil in the United States. Due to a high amount of polyunsaturated fatty acids which are highly susceptible to autoxidation, menhaden oil deteriorates rapidly, leading to objectionable off-odors and off-flavors. The purpose of this study was to investigate if the enzyme lipoxygenase is present in menhaden gill tissue and if it is a contributing factor in menhaden oil oxidation. Peroxide, TBA and anisidine values of undeodorized and deodorized menhaden oils exhibited two maxima during 20 weeks of storage at 30°C. Peroxide values of the undeodorized oil peaked at week 1 with 6.71 meq/kg and at week 12 with 21.50 meq/kg, while in the deodorized oil it peaked at week 8 (9.28 meq/kg) and week 20 (18.71 meq/kg). TBA maxima were observed at week 2 (1416 μMol/kg) and week 12 (4951 μMol/kg) and at week 8 (1397 μMol/kg) and week 20 (4284 μMo/kg) for undeodorized and deodorized menhaden oil respectively. Anisidine values showed maxima at the same weeks. These results indicate that lipid peroxidation of the deodorized oil lagged a few weeks behind the undeodorized oiL In this study, the conjugated diene and fluorescence analyses were found to be poor indicators for monitoring lipid oxidation in menhaden oil. Enzyme assays indicated that lipoxygenase activity is present in menhaden gill tissue with maximum activity at pH 9-10, resembling that of soybean lipoxygenase-l. A sensory panel judged omega-3 fatty acid ester concentrates treated with the enzyme extract as having a significantly (p < 0.03) stronger smell than the control ester for the first four weeks of an eight week study. However, no significant difference was found between the TBA values of the esters. Of the 60 volatile compounds identified by GC-MS in the undeodorized menhaden oil, 19 were aldehydes, 9 were alcohols and 8 were ketones. Volatiles that are potentially Ii poxygenase derived, namely 2-octenal, 1-octen-3-01, 2-nonenal, 2,6-nonadienal (E,Z), and 2,5-octadien-l-ol were among those identified in the undeodorized menhaden oil. The deooorized oil contained fewer total volatiles, and fewer aldehydes (6), ketones (1) and alcohols (8), but more long chain aliphatic compounds such as hydrocarbons, many of which were not possible to positively identify. No lipoxygenase derived volatiles were identified in the deooorized oil. Most of the volatiles in the omega-3 fatty acid ester concentrates were identified as esterified short chain fatty acids. No difference in the amount of total volatiles was found between four esters that were treated with and without the enzyme extract, a boiled enzyme extract and an enzyme extract that was inocculated with esculetin. However, in a repetition of just the control and the enzyme treated ester, a significantly (p < 0.02) higher amount of total volatiles was found in the enzyme treated ester, supporting the results of the sensory analysis. It was not possible to identify specific volatiles in the enzyme treated ester that were present in larger concentrations than in the other ester treatments. Volatiles identified in EPA and DHA ethyl esters were similar to those volatiles found in the undeodorized and deodorized menhaden oil as well as the omega-3 fatty acid ester concentrates, but no lipoxygenase derived volatiles were found. While lipoxygenase activity was found in the gill extract of menhaden, and sensory analysis was able to distinguish between a control and an enzyme incubated oil, the enzymatic activity was low (apparent Km = 16.7 μMol) and volatile analysis of various oils did not support the hypothesis that lipoxygenase is a major contributor to menhaden oil oxidation. Future research should include isolation and purification of menhaden gill lipoxygenase and the study of model systems to develop a better understanding of the contribution of lipoxygenase activity to oxidation of menhaden oil. / Ph. D.

La innovación juega un rol clave en el desarrollo de nuevos productos y extensiones de línea. La reformulación de productos cárnicos es una estrategia, que aplica la industria actual, basada en el conocimiento de las necesidades y expectativas de los consumidores. Siguiendo estas tendencias se desarrolla un reestructurado de pollo con fibra soluble y omega 3, sin el agregado de grasa y sal. Para proteger los omega 3 de la autoxidación se emplean métodos de cocción a calor moderado y vacío en la precoccion del producto, que luego se va conservar en refrigeración. Además se evaluará la acción del nitrito en la estabilidad oxidativa, aunque se agrega por motivos de seguridad alimentaria. La fibra soluble se incorpora por aspectos tecnológicos como la retención de agua pero además por su reconocido efecto saluble. Y los omega tres vienen a paliar deficit nutricionales considerados críticos para la salud humana, en recientes avances de estudios de desnutrición. / Boari De Greissing, VM. (2014). Reestructurados de pollo saludables, evaluación del efecto de varias estrategias tecnológicas combinadas [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/37192

No / Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. The purpose of this study was to test the hypotheses that boosting plasma levels of eicosapentaenoic and docosahexaenoic acids with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either eicosapentaenoic + docosahexaenoic acid supplementation (Active Group) or placebo. After 28 days the Active Group had significantly higher plasma levels of eicosapentaenoic (p<0.001) and docosahexaenoic acid (p<0.001) than the Placebo Group and significantly lower wound fluid levels of two 15-lipoxygenase products of omega-6 polyunsaturated fatty acids, [9- hydroxyoctadecadienoic (HODE) acid (p = 0.033) and15-hydroxyeicosatrienoic acid (HETrE) (p = 0.006)], at 24 hours post wounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more re-epithelialization on Day 5 post wounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing.

No / Background: Skin cancer is a major public health concern, and the majority of cases are caused by solar ultraviolet radiation (UVR) exposure, which suppresses skin immunity. Omega-3 (n−3) PUFAs protect against photoimmunosuppression and skin cancer in mice, but the impact in humans is unknown. Objectives: We hypothesized that EPA-rich n−3 PUFA would abrogate photoimmunosuppression in humans. Therefore, a nutritional study was performed to assess the effect on UVR suppression of cutaneous cell-mediated immunity (CMI) reflected by nickel contact hypersensitivity (CHS). Design: In a double-blind, randomized controlled study, 79 volunteers (nickel-allergic women, 22–60 y old, with phototype I or II) took 5 g n−3 PUFA–containing lipid (70% EPA plus 10% DHA) or a control lipid daily for 3 mo. After supplementation, nickel was applied to 3 skin sites preexposed on 3 consecutive days to 1.9, 3.8, or 7.6 J/cm2 of solar-simulated radiation (SSR) and to 3 unexposed control sites. Nickel CHS responses were quantified after 72 h and the percentage of immunosuppression by SSR was calculated. Erythrocyte [red blood cell (RBC)] EPA was measured by using gas chromatography. Results: SSR dose-related suppression of the nickel CHS response was observed in both groups. Photoimmunosuppression appeared less in the n−3 PUFA group than in the control group (not statistically significant [mean difference (95% CI): 6.9% (−2.1%, 15.9%)]). The difference was greatest at 3.8 J/cm2 SSR [mean difference: 11% (95% CI: 0.5%, 21.4%)]. Postsupplementation RBC EPA was 4-fold higher in the n−3 PUFA group than in the control group (mean difference: 2.69% (95% CI: 2.23%, 3.14%), which confirmed the EPA bioavailability. Conclusion: Oral n−3 PUFAs appear to abrogate photoimmunosuppression in human skin, providing additional support for their chemopreventive role; verification of study findings is required.

Yes / The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2 × 2 factorial ‘efficacy’ study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55–73 year-old patients, who have been identified as ‘high risk’ (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and ‘advanced’) per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as ‘intermediate risk’ for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients. / Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership

No / Background Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid (FFA), leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases (CRCLM). Design: We performed a Phase II double-blind, randomised, placebo-controlled trial of EPA-FFA 2 g daily in patients undergoing liver resection surgery for CRCLM. The patients took EPA-FFA (n=43) or placebo (n=45) prior to surgery. The primary end-point was the CRCLM Ki67 proliferation index (PI). Secondary end-points included safety and tolerability of EPA-FFA, tumour fatty acid content and CD31-positive vascularity. We also analysed overall survival (OS) and disease-free survival (DFS). Results The median (range) duration of EPA-FFA treatment was 30 (12–65) days. Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy. EPA-FFA treatment was well tolerated with no excess of postoperative complications. Tumour tissue from EPA-FFA-treated patients demonstrated a 40% increase in EPA content (p=0.0008), no difference in Ki67 PI, but reduced vascularity in ‘EPA-naïve’ individuals (p=0.075). EPA-FFA also demonstrated antiangiogenic activity in vitro. In the first 18 months after CRCLM resection, EPA-FFA-treated individuals obtained OS benefit compared with placebo, although early CRC recurrence rates were similar. Conclusions EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted. Trial Identifier: ClinicalTrials.gov NCT01070355. / The Cancer Research UK Clinical Trials Awards and Advisory Committee approved the Trial. PML and ADR were supported by Department of Health/Cancer Research UK Yorkshire Experimental Cancer Medicine Centre funding. The Trial was adopted by the UKCRN Clinical Trials Portfolio (UKCRN ID 8946) allowing West Yorkshire Comprehensive Local Research Network funding of Pharmacy costs. SLA Pharma AG funded some of the experimental work and provided EPA-FFA and placebo. SLA Pharma AG played no role in the design or execution of the Trial. Laboratory costs were also supported by the Leeds Teaching Hospitals Charitable Foundation (Rays of Hope).

Yes / Background: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut. Objectives: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum. Methods: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC–tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing. Results: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05). Conclusions: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy.

Tilapia are freshwater fish that have become important in aquaculture and as a stable global source of seafood due to their ability to thrive in different environments. However, tilapia are sometimes considered nutritionally undesirable due to their high n-6 to n-3 fatty acid ratios. A market study was conducted first to determine fatty acid compositions in tilapia fillets in different US markets. Then a research was conducted to enhance nutritional value of tilapia by improving the n-3 and oleic acid contents in fish fillets without compromising fish growth or feed conversion ratios. Feeds were formulated with combinations of high and low n-6, n-3, and oleic acid levels using soybean oil, fish oil, algae oil, and high-oleic sunflower oil. Then 12 diets, including a commercial diet, were assigned to 24 tanks, each with 25 tilapia per tank. A Recirculating Aquaculture System (RAS) was used to grow the fish for 8 weeks. Fatty acid compositions of tilapia fillets were determined and samples were vacuum packed and stored at -10oC and -20oC to test oxidative degradation and fatty acid compositional changes. The market survey data showed that there were significant differences in fatty acid composition, lipid content, and n-6:n-3 fatty acid ratios depending on the country of origin. Samples from USA had ideal n-6:n-3 ratios (1.3 ±0.85) while samples from Southeast Asia had higher n-6:n-3 fatty acids ratio (6.6 ±0.54). Algae oil incorporation significantly increased DHA level while fish oil incorporation significantly increased both EPA and DPA. High-oleic sunflower oil based diets improved oleic acid levels and reduced linoleic acid compared to the soybean oil based diets. Sensory evaluation indicated that lipid source did not significantly impact preference or overall fillet quality, including texture. Interestingly, a survey showed people were interested in value-added tilapia, and would pay up to 30% more for nutritionally enhanced fish compared to the $5.00/lb fresh fillet price currently available in supermarkets. There was no observable oxidation during long term frozen storage. The oxidation study proved that value-addition would not be compromised during the long term storage conditions, even under temperature abuse. It is possible to improve tilapia nutritional quality through diet to provide consumers with value-added products that maintain quality during frozen storage. / Ph. D. / Tilapia are high quality food with high levels of protein. However, many consumers are skeptical about tilapia due to their undesirable lipid composition containing high levels of omega 6. Therefore initially, the market study was developed to identify the lipid composition of tilapia US consumers were exposed to. Then the experiment was designed to create high omega 3 tilapia by improving the diets using mixture of fish oil, algae oil, high-oleic sunflower oil, and soybean oil. The 8 week tilapia growth trial was conducted with 12 experimental diets. Then the fish fillets were collected and analyzed for their fatty acid composition using GC/MS. Also fillet’s shelf-life study was conducted in 2 frozen storage conditions up to 9 months. The market study proved that the omega 6 to omega 3 ratio was favorable especially in USA sourced tilapia. However it also showed wide variation in omega 6 to omega 3 ratio depending on the country of origin. Tilapia from USA had an ideal omega 6:omega 3 ratio (1.3 ±0.85) while tilapia from Southeast Asia had higher omega 6:omega 3 ratio (6.6 ±0.54). The experimental study showed that the algae oil addition significantly improved DHA level while fish oil addition improved EPA and DPA. Higholeic sunflower oil addition improved omega 9 compared to the soybean oil based diets. Sensory evaluation indicated that different lipid sources had no impact on consumer preference. Interestingly, the survey showed that the people were interested in healthier tilapia, and were willing pay up to 30% more to the $5.00/lb of supermarket fresh fillet price. There was no observable degradation during long term frozen storage. The shelf life study proved that valueaddition would not degrade during the long term storage conditions. Therefore, development of high quality tilapia through diet manipulation is possible that does not degrade over 9 months of frozen storage.