Dissertations / Theses on the topic 'Periodontitis; omega-3; fish oil'

Mestrado em Engenharia Alimentar - Instituto Superior de Agronomia
ω-3 polyunsaturated fatty acids (PUFAs) ingredients, especially eicosapentaenoic acid (EPA, 20:5ω3) and docosahexaenoic acid (DHA, 22:6ω3) are known for its vital and unique role in human health and well-being by an extensive scientific research. These facts are widely spread by media. At present, the major source of ω-3 PUFAs is fish oil from oily fish like sardine (Sardina pilchardus). This work proposes the use of heterotrophic microalgae such as Crypthecodinium cohnii as an alternative source of interest for the commercial production of ω-3 EPA and DHA. It is also suggested the use of a common process suitable for both feedstock. EPA and/or DHA production are accomplished through oil saponification and PUFAs concentration winterization and urea concentration. PUFAs purification by chromatography is only necessary when oil is extracted from fish since fractions obtained from C. cohnii have high proportions in DHA and they do not require further purification steps for food applications. The combination of traditional (seasonal) and alternative sources (year-round) using a common production process shows an economic advange with increasing earnings for market development.

A diet rich in omega-3 fats has been shown to reduce the risk of cardiovascular disease. Long chain omega-3 fats found in fatty fish are especially important to cardiovascular health. Consumption of these fats is low, in part because there are few natural sources. This has led to the development of omega-3 fortified foods. Currently available fortified foods demonstrate conflicting nutritional information. Addition of omega-3 fats to an otherwise unhealthy food is perceived by consumers as an advertising gimmick. Mistrust of food companies and confusing ingredient labels negatively impact sales. Careful nutritional guidance, combined with proper sensory analysis, is critical to developing omega-3 fortified food products that are consistent with medical recommendations. Results from this study indicate that a therapeutic dose of fish oil (1000 mg per serving) can be added to two heart-healthy foods without adversely affecting sensory qualities.

Two of the major dietary food sources of omega-3 fatty acids are flaxseed oil and fish oil; the former being a rich source of PUFA (e.g. α-linolenic acid (α-LA)), while the latter is a source of HUFA (e.g. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). In this study, palm oil, a commonly used vegetable oil that is widely available in Asian and African countries, was blended with flaxseed (omega 3-PUFA) and fish oil (menhaden oil) (omega-3 HUFA); respectively, to obtain blended oils that both contained a 1: 4 ratio of omega-3 :omega 6 fatty acids. Rosemary extract (0.02% w/w) was added to the oil blends to stabilize the oil during use for deep-fat frying. Eight hours of heating at 180 °C was used to determine the stability of omega-3 fatty acids and uptake from the omega-3 enriched palm oil into fried potatoes. Lipid oxidation and thermal degradation of the palm oil blends, along with retention of α-LA , EPA, and DHA were measure of oil blends stability. Linoleic acid content in flax-palm oil blend did not change during frying when in the presence of different antioxidant treatments. The α-LA content of heated flax-palm oil blend was significantly reduced (P<0.05) after 8 hours of frying. Meanwhile, linoleic acid and EPA content in the fish-palm oil blend revealed significant (P<0.05) decreases in concentration after 8 hours of frying regardless of the presence of antioxidant. The DHA concentration was significantly lower when present in the absence of antioxidant (P<0.05). Totox significantly increased (P<0.05) in the blended oils after 8 hours of frying; albeit the extent of oxidation and thermal degradation was reduced when rosemary extract was added. A significant uptake of omega-3 fatty acids in both the omega-3 PUFA (e.g. α-LA) and HUFA (e.g. EPA and DHA), respectively, occurred in potatoes fried in the respective blended oils. Although omega-3 fatty acid uptake was prevalent in potatoes fried in both blended oils, the effect of heating reduced the optimal 1:4 ratio of omega-3 :omega-6 to a 1:6-l :7 ratio. This loss in omega-3, relative to omega- 6, was attributed to thermal oxidation; a reaction not totally preventable by adding antioxidants to the frying oils. These functional omega-3 enhanced oils when used to process potatoes gave forth products that represented 1/10th suggested intake for EPA+DHA and l/50th the daily requirement for α-LA .
Land and Food Systems, Faculty of
Graduate

Omega-3 polyunsaturated fatty acids (Ï 3 PUFAs) provide important health benefits, but dietary consumption is low. Supplementing foods with Ï 3 PUFAs is of interest, but intervention strategies are necessary to preserve the integrity of these unstable compounds. Microencapsulation of Ï 3 PUFA sources is one means of improving their stability. In this work, Ï 3 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 Ï 3 PUFA microcapsule properties, (2) to evaluate the effect of blending chitosan with high-amylose starch and pullulan on Ï 3 PUFA microcapsule properties, and (3) to evaluate the oxidative stability of Ï 3 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 3μm to 11μm. Moisture contents were all below 7% and water activities (aw) 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 Ï 3-PUFA source during 5 weeks of storage. Chitosan, high-amylose starch, and pullulan are effective materials for microencapsulation of Ï 3 PUFA sources.
Ph. D.

Introducción. La hipertrigliceridemia es común en los pacientes con infección por VIH. Los ácidos grasos omega 3 reducen los niveles de triglicéridos (TG) en pacientes con infección por VIH. Se desconoce si la suplementación con ácido docosahexanóico (DHA) puede reducir los niveles de TG y/o modificar la distribución corporal de grasa en pacientes con infección por VIH- Métodos. Se trata de un estudio randomizado, doble ciego, controlado con placebo con 84 pacientes tratados con antirretrovirales que tenían niveles de TG en ayunas entre 2.26 y 5.65 mmol/l y fueron ranzomizados a recibir DHA o placebo durante 48 semanas. Se midieron los niveles de TG basalmente, a las 4, 12, 24, 36 y 48 semanas. Se realizó una densitometría (DXA) basalmente y a las 48 semanas para estudiar la distribución de grasa corporal. En un subgrupo de 39 pacientes se midieron marcadores de inflamación y moleculares en tejido adiposo subcutáneo basalmente y a las 48 semanas. Este estudio está registrado con Clinical Trials.gov, NCT02005900. Resultados. Los pacientes que recibieron DHA tuvieron un descenso del nivel de TG del 43.9% de media en la semana 4 (IQR: -31% a 56%) comparado con un -2.9% (-18.6% a 16.5%) en el grupo de placebo (p < 0.0001). Se observó una correlación significativa entre los niveles de DHA y el descenso de los niveles de TG en la semana 4 en la rama de DHA ( r = 0.7110, p < 0.0001). En la semana 12 la media de descenso de los niveles de TG en la rama de DHA fue de -43,7% (-32.4% a -57.5%) y en la placebo fue 2.9% (-21.3% a 30.1%). La diferencia entre ambos brazos siguió siendo estadísticamente significativa a la semana 48 ( p = 0.0253). Los niveles de colesterol de baja densidad (LDL) aumentaron significativamente en la rama de DHA a la semana 4, 7.1% (IQR: -4.8% a 35.3%) pero no en el brazo de placebo. No se observaron diferencias significativas en los niveles de colesterol de alta densidad (HDL), insulina, HOMA, ni FGF 19 y FGF21. La grasa en las ectremidades aumentó significativamente en ambos grupos sin diferencias significativas ( p = 0.3889). La proteína C reactiva de alta sensibilidad (hsPCR) y los niveles de ácido araquidónico disminuyeron en el grupo de DHA. Los genes relacionados con la adipogénesis (PPAR-γ, adiponectina) y la expresión de genes relacionados con la mitocondria no tuvieron cambios significativos en ambos grupos. El DNA mitocondrial disminuyó en el grupo placebo significativamente. La expresión de genes relacionados con la inflamación en tejido adiposo subcutáneo (TNF-α, MCP-1) disminuyó significativamente en el grupo de DHA permaneciendo estables en el placebo. DHA fue muy bien tolerado, solo 3 pacientes experimentaron toxicidad limitante del tratamiento. Conclusiones. La suplementación con DHA reduce los niveles de TG en ayunas en pacientes con infección por VIH en tratamiento con antirretrovirales. DHA fue muy bien tolerado con síntomas gastrointestinales leves. La grasa periférica aumentó significativamente en el grupo de DHA pero no comparándolo con el grupo de placebo. La suplementación con DHA disminuye la expresión genética de inflamación en el tejido adiposo subcutáneo pero no modifica la expresión genética de la adipogénesis. DHA disminuye significativamente los niveles de hsPCR y ácido araquidónico
Background. Hypertriglyceridemia is common in HIV-infected patients. Omega-3 fatty acids reduce fasting serum triglyceride (TG) levels in HIV-infected patients. It is not known whether docosahexanoic acid (DHA) supplementation can reduce hypertriglyceridemia and modify fat distribution in HIV-infected patients. Methods. We conducted a randomized, double-blind, placebo-controlled trial with 84 antiretroviral-treated patients who had fasting TG levels from 2.26-5.65 mmol/l and were randomized to receive DHA or placebo for 48 weeks. TG levels were assessed at baseline, week 4 and every 12 weeks. Body composition was assessed at baseline and at week 48. And systemic inflammatory and molecular SAT markers were assessed at baseline and at week 48 in a subgroup of 39 patients. This study is registered with ClinicalTrials.gov, NCT02005900. Results. Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to 16.5%) in the placebo group (P < 0.0001). There was a significant correlation between DHA levels and decrease in TG at week 4 in the DHA arm (r = 0.7110, P < 0.0001). By week 12, the median reduction in TG levels in the DHA arm was -43.7% (-32.4% to -57.5%), and in the placebo arm +2.9% (-21.3% to +30.1%). The difference between study arms remained statistically significant at week 48 (P = 0.0253). Low-density lipoprotein cholesterol levels had significantly increased at week 4 by 7.1% (IQR: -4.8% to +35.3%) in the DHA arm but not in the placebo group. No significant changes were observed in HDL cholesterol, insulin, and HOMA-IR during the study. Limb fat significantly increased in both arms, without statistically significant differences between groups (P = 0.3889). High sensitivity C reactive protein (hsCRP) and arachidonic acid levels significantly decreased in the DHA group. Adipogenesis-related genes (PPAR-γ, adiponectin) and mitochondrial-related gene expression did not experience significant changes in either group. Mitochondrial DNA (mtDNA) significantly decreased in the placebo group. SAT inflammation-related gene expression (TNF-α, MCP-1) significantly decreased in the DHA but remained unaltered in the placebo group. DHA was well tolerated; only 3 patients experienced treatment-limiting toxicity. Conclusions Supplementation with DHA reduced fasting TG levels in antiretroviral-treated HIV-infected patients with mild hypertriglyceridemia. DHA was well tolerated with minor GI symptoms. Peripheral fat significantly increased in the DHA group but did not increase significantly compared with placebo. DHA supplementation down-regulated inflammatory gene expression in SAT, but did not modify adipogenesis-related gene expression. DHA impact on markers of systemic inflammation was restricted to a significant decrease in hsCRP and arachidonic acid.

In food and pharma industry, fish oils are highly demanded due to the many associated health benefits of omega-3 fatty acids. However, the delivery of fish oil through food is a major challenge as this oil is susceptible to oxidation and to produce off-flavors. To prevent these undesired effects, microencapsulation techniques are used. Typically oil encapsulation is carried out by two steps (i) emulsion preparation (ii) drying. The main objective is to study the effect of the emulsification method, emulsion formulation, membrane type and microcapsule formulation on relevant physic-chemical parameters of fish oil microcapsules.The approach of the project is to combine, for the first time, the advantages of using a low energy emulsification technique (membrane emulsification) and spray drying to obtain food-grade fish oil microcapsules. The results show a clear improvement in the oil encapsulation efficiency (OEE) when decreasing the droplet size of the emulsion and increasing the amount of wall material. The combination of a polysaccharide with a protein has been found to improve protection against oxidation during storage of the microcapsules, while the addition of denatured proteins as a part of the microcapsule wall material enhances OEE but does not improve the mechanical strength of the microcapsules.
El aceite de pescado es altamente valorado en la industria alimentaria por su demostrada actividad en la prevención y tratamiento de numerosas patologías, asociada a su contenido en ácidos grasos omega-3. La incorporación de aceite de pescado en alimentos presenta algunas dificultades relacionadas con su rápida oxidación y su característico aroma y sabor. La encapsulación del aceite de pescado retrasa la oxidación y permite enmascarar sus propiedades sensoriales. Tradicionalmente, la encapsulación se lleva a cabo combinando una etapa de emulsificación seguida de secado por atomización. El objetivo principal del trabajo es estudiar el efecto del método de emulsificación y la formulación de la emulsión y las microcápsulas en los parámetros físico-químicos más relevantes de las microcápsulas. En este proyecto se combina por primera vez la emulsificación por membranas con el secado por atomización para obtener microcápsulas de aceite de pescado aplicables a la industria alimentaria. Los resultados muestran una clara mejora en la eficiencia de encapsulación del aceite cuando se reduce el tamaño de gota de la emulsión y se incrementa la cantidad de material de pared de las microcápsulas. La combinación de un polisacárido con una proteína para la formación de la pared mejora la estabilidad oxidativa de las microcápsulas durante el almacenamiento. Por otra parte la adición de proteínas desnaturalizadas para reforzar las paredes de las microcápsulas ha resultado en una mejora de la eficiencia de encapsulación de aceite pero no ha mejora su resistencia mecánica

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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.

Introduction Advanced Pancreatic Cancer (APC) has an appalling prognosis characterised by rapidly declining quality of life mediated by circulating pro-inflammatory cytokines and growth factors (CAF). Omega-3 fatty acids (n-3FAs) are proven to have antineoplastic and anti-inflammatory effects. Oral trials of n-3FAs in patients with advanced cancer have shown mixed results due in part to poor bioavailability and compliance with these preparations. Methods A phase II single arm trial was carried out using gemcitabine and intravenous n-3Fas in patients with APC. Primary outcome measure was overall radiological response rate (ORR) with secondary outcome measures of Overall (OS) and Progression-Free Survival (PFS), quality of life using validated questionnaires, Clinical Benefit Response (CBR) rates, adverse events, changes in CAF, complement, uptake of n-3FAs into cell membranes and plasma. Results Twenty nine patients were recruited: 21 were evaluable for ORR which was 3/21 (14.3%). Median OS=4.8 months, median PFS=3.5 months. Improvements and percentage of patients experiencing it in QOL outcomes of at least 10% over baseline was seen in the following domains: Global health- 57%, Summated QOL- 43%, Pain scores- 57%. CBR rates were 38%. PDGF, TRAIL and FGF concentrations reduced significantly with treatment over time. Low baseline IL-6 and IL-8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS. Restoration of hypoactive Mannose Binding Lectin complement activity was associated with improved time to progression. Proportions of n-3FA fractions in cell membranes increased significantly with time. Conclusions Intravenous n-3FAs plus gemcitabine may improve quality of life and provide clinical benefit response in patients with APC. These changes may be mediated by manipulation of CAFs and complement pathways. The independent effect of n-3Fas over gemcitabine warrants further investigation in randomised trials.

Orientador: Lireny Aparecida Guaraldo Gonçalves
Texto em português e inglês
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: Óleos e gorduras são importantes na alimentação humana como fonte de energia,além de alguns serem considerados essenciais ao funcionamento dos organismos, tais como determinados ácidos graxos polinsaturados ômega-3. O ácido eicosapentaenóico (EPA) e o ácido docosahexaenóico (DHA), provenientes de fontes marinhas, são as principais formas de ingestão direta de ômega-3,porém estes são muito sensíveis à oxidação e apresentam flavors característicos que levam à rejeição por alguns consumidores. Uma alternativa para contornar estes problemas é a microencapsulação. Uma técnica muito difundida para este tipo de produto sensível é a coacervação, no entanto algumas novas técnicas vêm surgindo na busca de solução destas deficiências. A gelificação enzimática pode ser citada como uma nova tecnologia que objetiva reduzir algumas etapas do processo e tempo de produção, se comparado ao processo de coacervação.Neste trabalho buscou-se compreender o comportamento do material de recheio (éster etílico de óleo de peixe), visto que são encontrados poucos estudos referentes às análises da integridade dos materiais de recheio de natureza lipídica quando encapsulados, e dos materiais de parede (principalmente isolado protéico de soja e isolado protéico de soro) quando utilizados para a produção de microcápsulas por gelificação enzimática e por coacervação complexa, avaliando tanto as cargas eletrostáticas do meio pelo seu potencial zeta para a coacervação, quanto na caracterização completa das cápsulas produzidas por gelificação enzimática e coacervação. Entre os materiais de parede estudados, foram utilizados isolado protéico de soro e isolado protéico de soja, sendo que este último na concentração de 10% apresentou formação de microcápsulas com características superiores pela técnica de gelificação enzimática. Quando estudadas mais a fundo as características das microcápsulas produzidas por gelificação enzimática, a ánalise do material encapsulado constatou-se que ocorreu a encapsulação de óleo de milho da segunda emulsão, reduzindo assim a eficiência real de encapsulação, mostrando-se assim uma técnica não eficaz,mesmo se obtendo cápsulas com elevada resistência mecânica. Comparando-se os métodos de degradação destas cápsulas, foi observada a total degradação da parede para a metodologia de degradação ácida, e parcial para a metodologia de degradação enzimática alcalina. Entretanto a melhor metodologia de degradação para se determinar a composição do material encapsulado foi a degradação ácida com determinação direta da composição em ácidos graxos. No estudo estatístico de microcápsulas contendo éster etílico de óleo de peixe produzidas por coacervação complexa utilizando isolado protéico de soja e goma arábica como material de parede obteve-se cápsulas contendo mais de 20 g de EPA + DHA / 100 g microcápsulas, sendo necessária a adição de menos de 0,5 g de microcápsulas em porções de 100 g ou 100 mL de alimentos para este poder ser considerado funcional. Contudo, uma grande variação no processo foi observadalevando a um estudo mais aprofundado do processo de coacervação através do potencial zeta dos materiais de parede e de recheio separadamente e em diferentes misturas, onde foi constatado que o isolado protéico de soja, por possuir variação na sua constituição e baixa solubilidade, dificulta a determinação exata do potencial zeta zero das misturas, sendo a máxima eficiência de encapsulação encontrada quando as misturas de 1,5:1,0 (massa:massa) isolado protéico de soja:Goma arábica e 2,0:1,0 (massa:massa) material de parede:material de recheio em pH 4,0 foram testados
Abstract: Fats and oils are important energy sources in human feeding, and some, such as the omega-3 polyunsaturated fatty acids, are considered essential to the functioning of the organisms. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from marine sources are the principal forms used for the direct ingestion of omega-3, but are highly sensitive to oxidation and present characteristic flavors leading to their rejection by some consumers. One alternative to overcome these problems is microencapsulation, and one well known technique for this type of sensitive product is coacervation, although some new techniques are currently appearing which also attempt to overcome these deficiencies.Enzymatic gelation could be cited as a new technology which aims to reduce some of the processing steps and production time when compared to coacervation. This work aimed to understand the behavior of the core material (fish oil ethyl ester),since few studies can be found referring to analyses of the integrity of the core materials of a lipid nature when encapsulated, and of the wall materials (principally soy protein isolate and whey protein isolate), when used in the production of microcapsules by enzymatic gelation and by complex coacervation, evaluating both the electrostatic charges in the medium from their zeta potential for coacervation, and a complete characterization of the resulting capsules produced by both enzymatic gelation and coacervation. Of the wall materials studied, whey protein isolate and soy protein isolate were used, the latter, at a concentration of 10%, producing microcapsules with the best characteristics by the enzymatic gelation technique. However, when the characteristics of the microcapsules produced by enzymatic gelation were studied at greater depth, the analysis of the core material showed that lipid material from another source had been coencapsulated due to the processing conditions, thus reducing the true efficiency of the encapsulation, showing that this technique was not efficient, despite the elevated mechanical resistance of the microcapsules. A comparison of the methods used to degrade the capsules showed total degradation of the wall by the acid degradation methodology, and only partial degradation for the enzymatic alkaline degradation methodology. Thus the best degradation methodology to determine the composition of the encapsulated material was acid degradation with the direct determination of the fatty acid composition. In the statistical study of the production of microcapsules containing fish oil ethyl ester by complex coacervation using soy protein isolate and gum Arabic as the wall materials, capsules were obtained containing more than 20 g EPA + DHA / 100 g of microcapsules, requiring the addition of less than 0.5 g of microcapsules to 100 g or 100 mL portions of foods for the food to be considered functional. However considerable process variation was observed, leading to a study in greater depth of the coacervation process as from the zeta potential of the wall and core materials separately, and in different mixtures. Thus it was shown that the soy protein isolate presented variation in its constitution and low solubility, which made it difficult to determine the exact zero zeta potential of the mixtures, the maximum encapsulation efficiency being found with mixtures of 1.5:1.0 (w:w) soy protein isolate: gum Arabic as the wall material and a ratio of 2.0:1.0 (w:w) for the wall material: core material at pH 4.0
Doutorado
Tecnologia de Alimentos
Doutora em Tecnologia de Alimentos

Foram utilizadas 288 galinhas poedeiras Babcock, durante o periodo de 9 semanas, com o objetivo de se verificar o efeito de teores crescentes de linhaça, associados ou não ao óleo de peixe na ração, sobre o perfil de ácidos graxos do ovo. Paralelamente, avaliou-se o desempenho das aves, qualidade externa e interna, características sensoriais e teor de colesterol dos ovos. Foi empregado esquema fatorial 2X6 em blocos casualizados, sendo as aves alimentadas com dieta controle (isenta de produtos de origem animal) contendo linhaça moída (0%, 7%, 14%,21%, 28% e 35%), adicionada ou não de óleo de peixe (2%). O peso dos ovos sofreu redução significativa (p<0,05) a partir do uso de 21% de linhaça na ração, e de 14% quando da associação com o óleo de peixe. A postura das aves foi reduzida com a utilização de 28% e 35% de linhaça na ração, independentemente do uso de óleo de peixe na dieta. A qualidade dos ovos não foi alterada com o uso de ambos ingredientes e o teor de colesterol, expresso em mg/g, foi significativamente aumentado com 35% de linhaça. O teor de ácido linolênico na gema sofreu aumento crescente com a elevação da concentração dietética de linhaça, sendo sua deposição acentuada com a adição concomitante de óleo de peixe. A porcentagem de EPA (ácido eicosapentaenóico) na gema foi significativamente elevada com a utilização de 35% de linhaça na ração, sendo que o uso combinado de óleo de peixe determinou incremento do EPA a partir de 7% de linhaça na dieta. A concentração de DHA (ácido docosahexaenóico) na gema foi significativamente aumentada a partir de 7% de linhaça dietética, sendo este incremento mais marcante com a associação do óleo de peixe. O óleo de peixe e a linhaça na ração determinaram relação ômega-6/ômega-3 (n-6/n-3) estreita na gema, de acordo com recomendações nutricionais vigentes. As equações de regressão permitem estimar os teores de ácido Iinolênico, EPA, DHA, ácido araquidônico, total de ácidos graxos poliinsaturados (PUFAs) n-3 e relação n-6/n-3 na gema a partir de concentrações de linhaça e de ácido linolênico na ração. O sabor de peixe foi detectado nos ovos provenientes dos grupos alimentados com óleo de peixe combinado com 28 e 35% de linhaça. Para se maximizar os teores de PUFAs n-3, especialmente os de cadeia longa, sem resultar em prejuízo do desempenho produtivo e do sabor dos ovos, a combinação de 2% de óleo de peixe com 7% de linhaça na ração mostrou ser a mais adequada.
To investigate the effect of increasing levels of dietary flaxseed, combined or not with fish oil, upon fatty acid composition of eggs, 288 Babcock laying hens were used for a 9 week experimental period. Reproductive performance of hens, internal and external egg quality, egg flavor, and yolk cholesterol levels were evaluated. The experiment had a 2X6 factorial design, hens were fed a basal diet (without animal products) supplemented with ground flaxseed (0%, 7%, 14%,21%,28% and 35%), combined or not with fish oil (2%). Egg weight was significantly decreased (p<0,05) frem 21% dietary flaxseed, and from 14% when fish oil was added to the diet. In birds fed either 28% or 35% flaxseed, egg production was depressed, regardless of the addition of fish oil. Feeding diets containing both fat sources did not affect egg quality, and yolk cholesterol content (mg/g) was significantly increased in eggs laid by hens fed 35% flaxseed. Yolk concentrations of linolenic acid were enhanced as a result of feeding hens increasing levels of dietary flaxseed, and its deposition was markedly increased when fish oil was included in the diet. Yolk contents of EPA (eicosapentaenoic acid) were significantly increased when diets included 35% flaxseed, and the combination with fish oil produced enhanced levels of EPA from 7% dietary flaxseed. Egg contents of DHA (docosahexaenoic acid) were significantly increased from 7% dietary flaxseed, and the deposition of such n-3 fatty acid was greater when in combination with fish oil. Dietary fish oil and flaxseed caused a narrow ratio of n-6 to n-3 fatty acids, meeting the current dietary allowances. Regression equations allow to predict contents of linolenic acid, EPA, DHA, arachidonic acid, total of n-3 fatty acids and ratio of n-6 to n-3 in the yolk from levels of dietary flaxseed or linolenic acid. Fishy flavor was detected in eggs from hens fed 2% fish oil combined with flaxseed at 28 or 35%. In order to maximize the content of n-3, mainly the longer chain n-3 fatty acids, without impairing performance parameters and egg flavor, the combination of 2% fish oil and 7% flaxseed in the hen\'s diet is the most appropriate.

Orientador: Fernando Antonio Cabral
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: Os ácidos graxos polinsaturados ômega-3 (EPA, DHA) são compostos com propriedades terapêuticas no tratamento e prevenção de doenças coronárias, hipertensão, arteriosclerose e artrite, além de serem essenciais para o desenvolvimento e manutenção das funções do sistema nervoso central. Os óleos de peixes de origem marinha são as fontes mais ricas em ômega-3 e por isso têm sido usados com freqüência para a obtenção de concentrados destes ácidos graxos. A deficiência de ômega-3 na dieta da população causada pela baixa ingestão destes ácidos graxos, através do consumo de peixes, toma interessante o enriquecimento de alimentos mais populares como a margarina, pães e produtos lácteos com esses ácidos graxos. A extração com fluido supercrítico é um processo de separação relativamente novo que traz vantagens em relação às técnicas convencionais. Para alimentos, o dióxido de carbono tem sido o solvente mais empregado, por ser inerte, relativamente barato e não inflamável e por possuir pressão e temperatura crítica moderadas (304,15 K, 7,38 MPa), evitando problemas de degradação térmica. Neste trabalho, estudou se o fracionamento com dióxido de carbono supercrítico do óleo de peixe em diferentes condições de temperatura e pressão. Os experimentos foram realizados de 14,7 a 29,4 Mpa e de 301,15 a 323,15 K. O procedimento experimental consistiu em promover o contato entre o óleo de peixe aderido à esferas de vidro e o CO2 supercrítico, em um processo dinâmico, de forma a promover o equilíbrio de fases. O corpo do sistema permanecia imerso dentro de um banho termostatizado. O extrato do óleo de peixe (amostra da fase leve) foi coletado no final do extrator em condições de equilíbrio com a fa_e pesada e a sua composição em ácidos graxos foi determinada através de cromatografia em fase gasosa. A altas pressões (14,7 a 29,4 MPa), o extrato apresentou pouca diferença na sua composição em ácidos graxos em relação a fase pesada. A 7,8 MPa e 301,15 K um pequeno fracionamento foi obtido para o ácido docosahexaenóico (DHA). O ácido eicosapentaenóico (EPA) foi o ácido graxo que mostrou maior resistência ao fracionamento em todas as condições estudadas. Logo, neste estudo o dióxido de carbono supercrítico não se mostrou efetivo para o fracionamento do óleo de peixe rico em ácidos graxos polinsaturados. Estas dificuldades podem ser atribuídas à complexidade da composição do óleo de peixe em triacilgliceróis, os quais apresentam-se distribuídos em muitas frações com baixa porcentagem mássica no óleo e por serem formados por ácidos graxos de diferentes tamanhos de moléculas
Abstract: The omega-3 (EPA and DHA) polyunsaturated fatty acids are compounds with therapeutic properties, that may play an important role in the prevention and treatment of cardiovascular disease, hypertension, atherosclerosi, and arthriti. Furthermore, they are essencial for development and maintaince of central nervous system. Because there is a gap between intake of n-3 fatty acids by fish consumption and the recommended amount, it would be useful to enrich ordinary foods as margarine, bread and dairy foods with this fatty acids. The marine fish oils are the richest source of n-3 and it has been used as raw material for preparation of this fatty acid concentrate. Supercritical fluid extraction is a relatively new separation process that may circumvent some of the problems associated with the use of conventional separation techniques. In foods processes, carbon dioxide is the most used solvent, because it is inert, inexpensive and non-flamable and it has moderate critical temperature and pressure (304,15 K, 7,38 MPa), which avoid problems of thermo degradation. In the present work, the fractionation of fish oil with supercritical carbon dioxide at different conditions of temperature and pressure: pressure ranged from from 14,7 to 29,4 MPa and temperature ranged from 301,15 to 323,15 K. A known amount of fish oil was mixed with glass spheres and put inside the column extraction. The supercritical carbon dioxide was contacted with the fish oil in a dynamic system and the oil present in the light phase was collected in the end columm, which was in equilibrium conditions with the heavy phase. All the experimental body system was immersed in water bath to ensure isothermal conditions. The oil present in the light phase was trapped in a flask and its fatty acids composition was determined by gas phase chromatography. At higher pressures the extract obtained (Iight phase) showed similar composition in poliunsatured fatty acids when compared with heavy phase, so no fractionation effect was observed at this conditions. At 7,8 MPa and 301,15 K a modest fractionation was obtained for docosahexaenoic acid (DHA). The eicosapentaenoic acid (EPA) was the most difficult one to fraction at the studied conditions. So, in the present work, the supercritical carbon dioxide didn't show effective in the fractionation of fish oil rich in polyunsaturated fatty acids. This difficult can be explained by the complex composition of fish oil in triacylglicerols with different chain length fatty acids ligants and by similar molecular mass
Mestrado
Mestre em Engenharia de Alimentos

Un procédé enzymatique sans solvant a été développé permettant la synthèse d'un ester phénolique de DHA. L'optimisation des paramètres réactionnels a permis d'atteindre des rendements élevés (440 g/L) d'ester de DHA et d'alcool vanillique (DHA-VE), dont les activités biologiques et le potentiel applicatif ont été évalués. L'activité inhibitrice du DHA-VE vis-à-vis des radicaux ABTS, DPPH et hydroxyle a été démontrée. Un effet neuroprotecteur de l'ester a également été mis en évidence sur des neurones primaires de rat, exposés aux oligomères du peptide [bêta]-amyloïde. Une étude in vivo a permis de montrer que le greffage d'alcool vanillique conduit à une augmentation du taux de DHA au niveau des globules rouges et des neurones, indiquant une biodisponibilité accrue du DHA lorsque celui-ci est couplé au composé phénolique. Aucune toxicité visible de l'ester n'a été constatée. Par ailleurs, l'incorporation de DHA-VE dans divers systèmes émulsionnés a permis d'accroître leur stabilité à l'oxydation, quelles que soient les conditions de stockage. Ceci montre le potentiel de cet ester pour enrichir diverses matrices alimentaires en DHA, tout en améliorant leur stabilité à l'oxydation. Le procédé enzymatique développé a été appliqué à de l'huile de saumon, utilisée comme source d'acides gras polyinsaturés de la série oméga-3. L'incorporation totale de l’alcool vanillique (50 g/L) a été obtenue après 24 h de réaction, conduisant à la production d'une grande variété d'esters, représentatifs de la composition initiale de l'huile en acides gras. Le milieu réactionnel brut issu de l'alcoolyse de l'huile présente une grande stabilité et des propriétés antioxydantes importantes par rapport à l'huile de saumon native. En conclusion, l'approche consistant à assembler des composés phénoliques et des lipides polyinsaturés au sein d'une même structure semble prometteuse pour renforcer le potentiel applicatif de ces deux familles de biomolécules et produire de nouveaux ingrédients bioactifs stables
An efficient solvent-free bioprocess was developed for the synthesis of DHA phenolic ester, using the lipase B from Candida antarctica. The protocol developed here led to high-level production (440 g/L) of DHA vanillyl ester (DHA-VE) that exhibits interesting application potential as food ingredient. DHA-VE was characterized by a high stability and a high radical scavenging activity towards DPPH, ABTS and hydroxyl radicals. Neuroprotective properties of DHA-VE were also demonstrated in rat primary neurons exposed to amyloid-[beta] oligomers. Enzymatic esterification of DHA with vanillyl alcohol (VA) led to increased DHA levels in erythrocytes and brain tissues of mice fed DHA-VE-supplemented diet comparing with DHA. No visible toxicity of the ester was found. Enrichment of emulsions with DHA-VE improved significantly their oxidative stability whatever the conditions of storage, showing the potential of DHA-VE to enrich various food matrices with DHA while protecting them against oxidation. The enzymatic process was applied to salmon oil as a source of omega-3 polyunsaturated fatty acids (PUFA). The total conversion of VA (50 g/L) was achieved after 24 h of reaction, leading to the production of a wide variety of esters that mirror the initial composition of the oil. The crude reaction medium recovered from salmon oil alcoholysis exhibited a high stability together with high antioxidant properties in comparison with native salmon oil. In conclusion, the approach that consists in bringing phenolic compounds and PUFA-rich lipids together within a single structure is expected to provide stable bioactive ingredients that should broaden the scope of application of omega-3 PUFAs whose health benefits are increasingly sought

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The keratoconjunctivitis sicca ( CCS ) , or dry eye, is a common chronic inflammatory eye disease in dogs and humans , which occurs due to deficiency of production of the aqueous portion of the tear film ( quantitative deficiency ) and / or excessive tear evaporation (disability qualitative ) , mainly affecting the cornea and conjunctiva may result in blindness . Treatment consists mainly in the use of tear substitutes as the use of immunosuppressive drugs (cyclosporine , tacrolimus and pimecrolimus ) (Stevenson et al , 2012) . Some studies in medicine and veterinary showed good results in controlling the CCS with the use of essential fatty acids (AGE ) , ω -3 and ω -6 , due to its ability to produce anti -inflammatory mediators ( BARABINO et al. 2003 , . NEVES et al , 2013 ) How fish oil and flaxseed oil are sources of AGE , but with differences in composition and concentration , and to the present time there is a comparative study of the efficacy of these compounds in the treatment of CCS . The objective of this study is to compare these two important sources of ω - 3 and ω - 6 , orally , in the treatment of experimentally induced in rabbits CCS .In order to compare the efficacy in the treatment of keratoconjunctivitis sicca ( CCS ) induced experimentally in rabbits , between two sources of omega 3 and 6 orally , fish oil ( FO) and linseed oil ( OL ) . We used 28 female rabbits of New Zealand breed , divided into 4 groups of 7 animals each : Group C (control ) , Group OP ( fish oil) , OL Group ( flaxseed oil ) and Group OPL ( Oil fish oil and flaxseed ) . The animals were evaluated by Schirmer Tear Test ( TLS ) , Rose Bengal Test ( TRB ) , Fluorescein test ( TF ) , Time Tear Film Break ( TRFL ) , ocular cytology and histopathology . The results showed a significant increase in the values of TLS and TRFL in all treatment groups , but this increase was earlier in the OP group . TRB in the performance of the groups was similar. With respect to the parameter TF , negative marking was delayed in group OPL . There was a significant decrease in the number of goblet cells in the OPL group in relation to other grupos.Os results showed that OL and OP orally improve the clinical signs of CCS , however this improvement was more rapid with the OP . The combined use of oils brought no additional benefit . These results can help in the future with new oral formulations useful in the adjuvant treatment of CCS .
A ceratoconjuntivite seca (CCS), ou olho seco, é uma doença ocular inflamatória crônica frequente em cães e humanos, que ocorre devido a deficiência de produção da porção aquosa do filme lacrimal (deficiência quantitativa) e/ou pela evaporação excessiva da lágrima (deficiência qualitativa), afetando principalmente a córnea e a conjuntiva podendo evoluir para cegueira. O tratamento consiste principalmente no uso como substitutos da lágrima e o uso de imunossupressores (ciclosporina, tacrolimus e pimecrolimus) (STEVENSON et al, 2012). Alguns estudos na Medicina e na Veterinária mostraram bons resultados no controle da CCS com a utilização de ácidos graxos essenciais (AGE), ω-3 e ω-6, devido à sua capacidade de produzir mediadores anti-inflamatórios (BARABINO et al., 2003; NEVES et al., 2013) Como o óleo de peixe e o óleo de linhaça são fontes de AGE, porém com diferenças na sua composição e concentração, e até o presente momento não há um estudo comparativo da eficácia destes compostos no tratamento da CCS. O objetivo deste estudo foi comparar a eficácia no tratamento de ceratoconjuntivite seca (CCS) induzida experimentalmente em coelhos, entre duas fontes de ômega 3 e 6 por via oral, o óleo de peixe (OP) e o óleo de linhaça (OL). Foram utilizados 28 coelhos, fêmeas, da raça Nova Zelândia, divididos em 4 grupos com 7 animais cada: Grupo C (controle), Grupo OP (óleo de peixe), Grupo OL (óleo de linhaça) e Grupo OPL (óleo de peixe e óleo de linhaça). Os animais foram avaliados pelo Teste Lacrimal de Schirmer (TLS), Teste de Rosa Bengala (TRB), Teste de Fluoresceína (TF), Tempo de Ruptura do Filme Lacrimal (TRFL), citologia ocular e análise histopatológica. Os resultados demonstraram que houve aumento significativo nos valores de TLS e TRFL em todos os grupos de tratamento, porém esse aumento foi mais precoce no grupo OP. No TRB o desempenho dos grupos foi similar. Com relação ao parâmetro TF, a marcação negativa foi mais tardia no grupo OPL. Houve uma diminuição significativa no número de células caliciformes no grupo OPL em relação aos demais grupos.Os resultados demonstraram que o OP e OL por via oral melhoram os sinais clínicos da CCS, porém essa melhora foi mais rápida com o OP. O uso combinado dos óleos não trouxe benefício adicional. Esses resultados podem contribuir no futuro com novas formulações orais úteis no tratamento adjuvante da CCS.

Colon cancer is one of the most commonly diagnosed cancers in the US, yet small intestine cancer is a rare event. While there are many similarities between these two tissues, inherent differences such as redox status, may contribute to the variation in cancer occurrence. We examined the difference in reactive oxygen species (ROS) generation, antioxidant enzyme activity and oxidative DNA damage in the small and large intestine of rats under normal conditions and following exposure to exogenous oxidative stress. Basal ROS and antioxidant enzyme activities were greater in the colon than the small intestine, and the balance of ROS to antioxidant enzymes in the colon was more pro-oxidant than in the small intestine. During oxidative stress, ROS and oxidative DNA damage were greater in the colon than the small intestine. Thus the colon responds to oxidative stress less effectively than the small intestine, possibly contributing to increased cancer incidence at this site. We next wanted to understand how diets containing a combination of fish or corn oil and pectin or cellulose may alter the redox environment of the colon. ROS, oxidative DNA damage, antioxidant enzyme activity and apoptosis were measured in colonocytes of rats fed one of four diets containing either corn oil or fish oil and cellulose or pectin. Measurements were madein rats untreated with carcinogen and rats exposed to a chemical carcinogen and radiation. In rats not treated with a carcinogen, fish oil enhanced ROS, and fish oil/pectin suppressed antioxidant enzymes as compared to corn oil/cellulose. Oxidative DNA damage was inversely related to ROS in the fish oil/pectin diet and apoptosis was enhanced relative to other diets. In carcinogen treated and irradiated rats, a similar protective effect was seen with fish oil/pectin as evidenced by a reduction in oxidative DNA damage and enhancement of apoptosis. This suggests that a diet containing fish oil/pectin may protect against colon carcinogenesis by modulation of the redox environment to promote apoptosis and minimize oxidative DNA damage.

Background and Aim: Animal studies and early clinical trials suggest a role for long chain omega-3 fatty acids (LCn3PUFAs) in the treatment of periodontal disease due to their anti-inflammatory and pro-resolution actions. The aim of this study was to evaluate the clinical efficacy of fish oil supplementation as an adjunct to non-surgical periodontal therapy in the treatment of advanced chronic periodontitis. Specific objectives were to establish the relative benefit of docosahexaenoic acid (DHA) versus eicosapentaenoic acid (EPA) compared with a placebo. Materials and Methods: Thirty-four subjects (10 male, 24 female; mean age 50.1) with advanced chronic periodontitis were recruited for this parallel group double-blind placebo-controlled randomised trial. All participants received non-surgical periodontal therapy and were randomly allocated to receive either adjunctive dietary fish oil supplements (equivalent of 2g LCn3PUFA per day) or placebo. Clinical parameters were recorded at baseline, 4, 7, 10 and 13 months. Additionally, erythrocytes were isolated from fasting blood samples to allow assessment of fatty acid biomarkers including EPA, DHA, Omega-3 Index and total LCn3PUFAs. Data for the 4 month follow-up is presented in this initial report. Results: One participant was lost to follow-up (placebo group), reporting poor compliance with their allocated capsules. Both treatment groups were effective at improving clinical outcomes, demonstrating significant reduction of full-mouth bleeding scores, probing pocket depth reduction and clinical attachment gain. At the 4 month follow-up, no significant difference was seen between groups for the percentage of sites that had ≥2 mm gain of clinical attachment (P = 0.229) or reduction in probing pocket depth (P = 0.264). The mean number of sites with residual pocket depth ≥5 mm at follow-up were not significantly different for the test group (6.6%) or placebo group (5.3%) (P = 0.264). Additionally, there were no statistically significant differences in clinical parameters for subjects that received supplements containing EPA, DHA or placebo. Conclusion: Within its limitations, the findings of this study do not support an additional benefit of adjunctive LCn3PUFA supplementation for the treatment of advanced chronic periodontitis. Additionally, no correlation was found between clinical periodontal parameters and fatty acid profiles, and there was no significant difference between EPA and DHA subgroups. There is a need for further research to establish the clinical efficacy of LCn3PUFA as a host modulatory therapy for the treatment of periodontitis, particularly larger multi-centre randomised controlled trials.
Thesis (D.Clin.Dent.) -- University of Adelaide, School of Dentistry, 2015

abstract: Objective: The purpose of this randomized parallel arm trial was to demonstrate the effects of daily fish oil supplementation (600mg per day for eight weeks) on body composition and body mass in young healthy women, aged 18-38, at a large southwestern university. Design: 26 non-obese (mean BMI 23.7±0.6 kg/m2), healthy women (18-38y; mean, 23.5±1.1 y) from a southwestern Arizona university campus community completed the study. Subjects were healthy, non-smokers, consuming less than 3.5 oz of fish per week according to self-report. Participants were randomized to one of two groups: FISH (600 mg omega-3 fatty acids provided in one gel capsule per day), or CON (1000 mg coconut oil placebo provided in one gel capsule per day). Body weight, BMI, and percent body fat were measured using a stadiometer and bioelectrical impedance scale at the screening visit and intervention weeks 1, 4, and 8. 24-hour dietary recalls were also performed at weeks 1 and 8. Results: 8 weeks of omega-3 fatty acid supplementation did not significantly alter body weight (p=0.830), BMI (p=1.00), or body fat percentage (p=0.600) as compared to placebo. Although not statistically significant, 24-hour dietary recalls performed at the beginning and end of the intervention revealed a trend towards increased caloric intake in the FISH group and decreased caloric intake in the CON group throughout the course of the study (p=0.069). If maintained, this difference in caloric intake could have physiological relevance. Conclusions: Omega-3 fatty acids do not significantly alter body weight or body composition in healthy young females. These findings do not refute the current recommendations for Americans to consume at least 8 oz of omega-3-rich seafood per week, supplying 250 mg EPA and DHA per day. More research is needed to investigate the potential for omega-3 fatty acids to modulate daily caloric intake.
Dissertation/Thesis
M.S. Nutrition 2013

Omega-3 fatty acids, particularly docosahexaenoic (DHA) and eicospentaenoic acid (EPA), are important mediators for cardiovascular disease, fetal/infant development, neurological disorders and inflammatory diseases. Supplementation and washout studies are important for future research on the physiological effects of omega-3 fatty acids and for determination of the proper washout period for future cross-over studies. In this study, omega-3 fatty acid blood biomarker comparisons are made for the n-3 HUFA score (% of n-3 HUFAs in total HUFAs) and omega-3 index (sum of EPA + DHA) in plasma, erythrocytes, whole blood and a novel finger-tip prick blood method (FTPB) of analysis. This FTPB method of fatty acid analysis is further tested to determine the potential for its use in fatty acid analysis. In addition, gender differences in response to omega-3 fish oil supplementation are analyzed in all four blood fractions. Nine males and seven females were supplemented with 8 fish-oil capsules per day (providing 3.2 g/day EPA and 1.6 g/day DHA) for four weeks, followed by an eight-week omega-3 washout period. Venous plasma, erythrocyte and whole blood samples were collected during weeks 0, 4, 8 and 12 and FTPB samples were collected weekly during supplementation and washout fatty acid analysis was performed. EPA and DHA incorporation is lowest in magnitude in erythrocytes relative to all other blood fractions. Omega-3 blood biomarker comparisons demonstrate that the n-3 HUFA score is a more reliable measure across all blood fractions compared to the omega-3 index. In addition, the n-3 HUFA score demonstrates no differences (p > 0.05) between FTPB and whole blood analysis, providing evidence to support its usefulness as a tool for fatty acid analysis. However, differences (p < 0.05) do exist between these methods for saturated fatty acid, monounsaturated fatty acids, omega-6 polyunsaturated fatty acids (PUFAs) and omega-3 PUFAs. Baseline fatty acid levels for DHA, and the DHA:EPA and DHA:DPA ratios tend to be higher (p < 0.05) in females, and docosapentaenoic acid n-3 (DPAn-3) is higher (p > 0.05) in males across all blood fractions. Furthermore, a gender effect (p < 0.05) is seen for the DHA:EPA ratio across all blood fractions. At baseline, female DHA:EPA is higher (p < 0.05) than males with supplementation lowering both male and female values and removing any differences (p > 0.05) between genders. Washout results in a return of levels towards baseline, however, baseline levels are not fully reached. Furthermore, while gender differences do begin to reform during washout, these differences are not significant (p > 0.05). In conclusion, omega-3 fatty acid responses, particularly DHA:EPA ratio, demonstrate significant gender differences that may be related to differences in long-chain PUFA synthesis pathways between males and females. In addition, the n-3 HUFA score may be a more valuable omega-3 blood biomarker than the omega-3 index, as the n-3 HUFA score displays more consistent levels across all blood fractions. Finally, the FTPB method of analysis may be a useful tool in the measurement of fatty acid composition, however, some microwave methylation problems do exist, specifically in the phospholipid class of lipids.

Förlust av muskelmassa med åldrande försämrar den fysiska funktionen, vilket även minskarlivskvaliteten och kan leda till svaghet och för tidig död. Omega-3-fettsyror stimulerar protein-anabolism och kan därför vara användbart för att förebygga och behandla sarkopeni. Syfte:Syftet med denna studie var att utvärdera effekten av omega-3-fettsyra-tillskott på graden avmuskelproteinsyntes hos vuxna. Metod: Studien är utförd som en litteraturstudie där relevantavetenskapliga och publicerade studier utvärderats och dess resultat har analyserats för attbesvara studiens syfte. Studiernas relevans bedömdes utifrån artiklarnas titel och abstrakt. 234studier i Onesearch, 5 studier i PubMed gicks igenom till en början. 30 abstrakt lästes, 21studier lästes i fulltext, 7 studier baserat på in- och exklusionskriterierna valdes ut till studienefter läst fulltext. Resultat: De flesta studier har utvärderat effekten av omega-3-tillskott hosyngre vuxna 18-30 år och äldre vuxna 65 år och äldre. Även om det finns en relativ brist påstudier som utvärderar effekten av omega-3-tillskott på muskelproteinsyntes (MPS) hos vuxna30-70 år, verkar det som om omega-3 kan främja anabola ökningar vid styrketräning hos äldreindivider. Slutsats: Ytterligare forskning behövs inom detta område för att dra relevantaslutsatser. Denna litteraturstudie drar slutsatsen att omega-3-fettsyror stimulerar syntesen avmuskelprotein hos vuxna och kan vara användbart för att förebygga och behandla sarkopeni.
Loss of muscle mass with aging impairs physical functions, but also reduces quality of life andcan lead to weakness and premature death. Omega-3 fatty acids stimulate protein anabolism andmay therefore be usefull to treat sarcopenia. Purpose: The aim of this study was to evaluate theeffect of omega-3 fatty acid supplements on the degree of muscle protein synthesis in adults.Metod: The study is conducted as a literature study where relevant scientific and publishedstudies, evaluations and its results have been analyzed to answer the purpose of the study. Therelevance of the studies were assessed on the basis of the title and abstract of the articles. 234studies in Onesearch, 5 studies in PubMed were initially reviewed. 30 abstracts were read, 21studies were read in full text, based on the inclusion and exclusion criteria 7 studies wereselected for the study after reading in full text. Results: Most studies have evaluated the effect ofomega-3 supplements in younger adults (18-30 years) and older adults (65 years and older).Although there is a relative lack of studies evaluating the development of omega-3 supplementson MPS in adults 30-70 years, it seems that omega-3 can promote anabolic increases in olderindividuals. Couclusion: Further research is needed in this area to draw relevant conclusions.This literature review concludes that omega-3 fatty acids stimulate the synthesis of muscleprotein in adults and may be useful to prevent and treat sarcopenia.

abstract: The omega-3 fatty acids in fatty fish and fish oil, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), have been associated with a reduction in risk for cardiovascular disease. Blood type is a known contributor to risk for cardiovascular events. This study evaluated the effect of fish oil supplements on cardiovascular risk markers in adults with blood types A or O. An 8-week parallel-arm, randomized, double-blind trial was conducted in healthy adult men and women with either blood type A (BTA) or blood type O (BTO). Participants were randomized to receive fish oil supplements (n=10 [3 BTA/7 BTO]; 2 g [containing 1.2 g EPA+DHA]/d) or a coconut oil supplement (n=7 [3 BTA/4 BTO]; 2 g/d). Markers that were examined included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), high-sensitivity C-reactive protein (hsCRP), and hemoglobin A1C (HbA1C). Results indicated that the percent change in LDL cholesterol was significantly greater in the coconut oil group vs the fish oil group (-14.8±12.2% vs +2.8±18.9% respectively, p=0.048). There were no other significant differences between treatment groups, or between blood types A and O, for the other cardiovascular risk markers. Further research with a larger and more diverse sample may yield a more conclusive result.
Dissertation/Thesis
M.S. Nutrition 2014

Indiana University-Purdue University Indianapolis (IUPUI)
Asthma, a chronic inflammatory disease of the airways, affects nearly 25 million Americans. The vast majority of these patients suffer from exercise-induced bronchoconstriction (EIB), a complication of asthma. Although traditionally treated pharmacologically, nutritional strategies provide a promising alternative for managing EIB as the prevalence of asthma may be due in part to changes in diet. Our objective was to determine the effects of novel nutritional strategies on hyperpnea-induced bronchoconstriction (HIB) in asthmatic individuals. HIB uses rapid breathing to identify EIB in a research or clinical setting. Fish oil, a combination of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docsahexaenoic acid (DHA), has been shown to be effective in suppressing EIB. However, its use in combination with other nutritional supplements, the optimal fish oil formula, and its effect on smooth muscle contractility have not been fully explored. An in vivo study (study 1) was conducted in individuals with both asthma and HIB to determine whether a combination of fish oil and vitamin C was more effective than either one alone in alleviating HIB. Pulmonary function was significantly improved with both fish oil and the combination treatment but not with vitamin C alone. In study 2, individuals with both asthma and HIB were supplemented with DHA alone since the optimal formula for fish oil has yet to be ascertained; previous in vitro studies have suggested DHA may be the more potent omega-3 fatty acid in fish oil. However, no significant changes in pulmonary function or airway inflammation were seen with DHA supplementation. For study 3, canine airway smooth muscle tissue was treated with fish oil to determine the in vitro effect of fish oil on smooth muscle contractility. Acute treatment with fish oil relaxed smooth muscle strips that had been contracted with 5-hydroxytryptamine. These minor relaxations in smooth muscle tension with fish oil may represent significant changes at the level of the smaller airways. These studies have confirmed that fish oil represents a viable treatment modality for asthmatic individuals with EIB and suggest that fish oil may influence airway smooth muscle contractility.

ABSTRACT Worldwide harvest of wild marine fisheries for fish oil cannot increase. However, the demand for fish oil is increasing due to a rapidly expanding aquaculture industry and is further increased by nutraceutical/biomedical and agricultural companies. Aquaculture uses fish oil as a source for essential fatty acids in particular omega-3 long chainpolyunsaturated fatty acids (ω3 LC-PUFA) and for energy. Other novel sources of renewable, environmentally sustainable oil that provide these nutritional requirements for Atlantic salmon (Salmo salar L.) are needed. This research looked at alternate sources of oil containing the ω3 LC-PUFA that are associated with the many health benefits of eating Atlantic salmon. This thesis also contributed to the development of three techniques for use in aquaculture lipid nutrition research: 1) advanced chromatography and mass spectroscopy to examine intact molecular membrane lipids; 2) nuclear magnetic resonance (13C NMR) to assess the regiospecific distribution of ω3 LC-PUFA in oil, and 3) molecular RT-PCR to investigate endogenous ω3 LC-PUFA production.

The current obesity epidemic has intensified research on lifestyle interventions aimed at combating obesity and associated cardiovascular (CV) and metabolic risk. This clustering of risk factors with obesity is known as the “Metabolic Syndrome” (MS). There is now a large body of evidence detailing the ability of omega-3 fatty acids (n-3 FA) and regular moderate exercise to independently ameliorate several CV risk factors; however the combination of these interventions may be a more effective strategy in reducing CV risk than either treatment alone. This thesis describes the independent and combined effects of supplementation with docosahexaenoic acid (DHA) rich fish oil, and regular moderate exercise, on CV, metabolic and inflammatory biomarkers. Sedentary, overweight volunteers (BMI > 25kg/m2) with mild hypertension (140/90 – 160/100mmHg), elevated plasma triglycerides (TAG) (>1.6mmol/L) or elevated total cholesterol (TC) (>5.5mmol/L) were recruited in three cohorts for a 12-week intervention trial. Subjects were randomised to one of the following interventions: fish oil, fish oil and exercise, sunflower oil (placebo), sunflower oil and exercise. Subjects consumed 6 g/day of DHA-rich fish oil (26% DHA, 6% EPA; ~1.9g n-3 FA) or sunflower oil. The exercise groups walked 3 days/wk for 45 min, at 75% age-predicted maximal heart rate (HR). Outcome measures were assessed and compared across each intervention group at Weeks 0, 6 and 12, with the exception of body composition, heart rate variability (HRV) and immune functions, which were assessed at Weeks 0 and 12 only. Apart from the consumption of allocated capsules, all subjects were instructed to maintain their normal diet during the study. If not asked to exercise as part of the intervention subjects were also instructed to maintain their normal level of physical activity. Supplementation with DHA rich fish oil resulted in substantial increases in total long chain n-3 FA and DHA levels in erythrocyte membranes, accompanied by reduction of TAG, increase of high-density lipoprotein (HDL) cholesterol and reduction of superoxide production by stimulated neutrophils. Both the increase in HDL and the decrease in superoxide production were correlated with the change in erythrocyte DHA. Endothelium dependent arterial vasodilation (assessed by flow-mediated dilatation, FMD), HRV and HR response to exercise were also improved in subjects supplemented with the DHA-rich fish oil. Regular moderate intensity exercise, either alone or in addition to the DHA-rich fish oil supplementation, had no effect on these parameters, although it improved the compliance of small resistance arteries. Interestingly, however, both DHA-rich fish oil and regular exercise reduced body fat and these effects were additive when the interventions were combined. The change in fat mass was accompanied by an increase in fat oxidation during exercise, as measured by the respiratory exchange ratio. For the population as a whole, reductions in total and abdominal fat mass were associated with reductions in blood pressure. In summary, this study is the first to evaluate the metabolic and CV benefits that can be achieved by combining n-3 FA supplementation from fish oil and regular aerobic exercise in overweight/obese adults. While this combination did not produce any synergistic effects, several independent benefits were attained. The high compliance rate (>85%) within this study indicates that this intervention is well tolerated and may therefore be sustainable in the longer term. Future research should evaluate the mechanisms underlying the n-3 FA - mediated improvements in body composition.
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Thesis (PhD) -- School of Molecular and Biomedical Science, 2007

The current obesity epidemic has intensified research on lifestyle interventions aimed at combating obesity and associated cardiovascular (CV) and metabolic risk. This clustering of risk factors with obesity is known as the “Metabolic Syndrome” (MS). There is now a large body of evidence detailing the ability of omega-3 fatty acids (n-3 FA) and regular moderate exercise to independently ameliorate several CV risk factors; however the combination of these interventions may be a more effective strategy in reducing CV risk than either treatment alone. This thesis describes the independent and combined effects of supplementation with docosahexaenoic acid (DHA) rich fish oil, and regular moderate exercise, on CV, metabolic and inflammatory biomarkers. Sedentary, overweight volunteers (BMI > 25kg/m2) with mild hypertension (140/90 – 160/100mmHg), elevated plasma triglycerides (TAG) (>1.6mmol/L) or elevated total cholesterol (TC) (>5.5mmol/L) were recruited in three cohorts for a 12-week intervention trial. Subjects were randomised to one of the following interventions: fish oil, fish oil and exercise, sunflower oil (placebo), sunflower oil and exercise. Subjects consumed 6 g/day of DHA-rich fish oil (26% DHA, 6% EPA; ~1.9g n-3 FA) or sunflower oil. The exercise groups walked 3 days/wk for 45 min, at 75% age-predicted maximal heart rate (HR). Outcome measures were assessed and compared across each intervention group at Weeks 0, 6 and 12, with the exception of body composition, heart rate variability (HRV) and immune functions, which were assessed at Weeks 0 and 12 only. Apart from the consumption of allocated capsules, all subjects were instructed to maintain their normal diet during the study. If not asked to exercise as part of the intervention subjects were also instructed to maintain their normal level of physical activity. Supplementation with DHA rich fish oil resulted in substantial increases in total long chain n-3 FA and DHA levels in erythrocyte membranes, accompanied by reduction of TAG, increase of high-density lipoprotein (HDL) cholesterol and reduction of superoxide production by stimulated neutrophils. Both the increase in HDL and the decrease in superoxide production were correlated with the change in erythrocyte DHA. Endothelium dependent arterial vasodilation (assessed by flow-mediated dilatation, FMD), HRV and HR response to exercise were also improved in subjects supplemented with the DHA-rich fish oil. Regular moderate intensity exercise, either alone or in addition to the DHA-rich fish oil supplementation, had no effect on these parameters, although it improved the compliance of small resistance arteries. Interestingly, however, both DHA-rich fish oil and regular exercise reduced body fat and these effects were additive when the interventions were combined. The change in fat mass was accompanied by an increase in fat oxidation during exercise, as measured by the respiratory exchange ratio. For the population as a whole, reductions in total and abdominal fat mass were associated with reductions in blood pressure. In summary, this study is the first to evaluate the metabolic and CV benefits that can be achieved by combining n-3 FA supplementation from fish oil and regular aerobic exercise in overweight/obese adults. While this combination did not produce any synergistic effects, several independent benefits were attained. The high compliance rate (>85%) within this study indicates that this intervention is well tolerated and may therefore be sustainable in the longer term. Future research should evaluate the mechanisms underlying the n-3 FA - mediated improvements in body composition.
Thesis (PhD) -- School of Molecular and Biomedical Science, 2007

There is no more important period in human development than conception through early childhood in maximizing developmental potential. It is during the last trimester of pregnancy when brain development accelerates (1, 2) and where accumulation of docosahexaenoic acid (DHA) in neural tissues occurs most rapidly (1, 3). Dietary intake and maternal stores of DHA during pregnancy and lactation have important implications for the developing brain. Uncertainty surrounding the ability of Westernised diets to fulfill requirements of DHA during pregnancy has raised concern for the developmental outcome of children raised in this dietary context (4). Some children in Australia have very limited language ability, impacting both the individual and society. Intervention for language development during the early years should be a primary focus for research. The role that DHA might play presents as a compelling area of investigation undertaken in this thesis. This thesis contains a literature review, including a systematic review and meta-analysis, and also proposes a theoretical framework from which to understand the potential variation in language development as a function not only of DHA but also of interacting biological and social variables (Chapter 1). The methods used in the current study are detailed (Chapter 2). Within a randomised controlled trial design (Chapter 3) the current study investigates whether DHA supplementation during the prenatal period has an effect on language development at 4 years of age. Interactions between DHA and other individually contributing factors posed by the bio-ecological model (Chapter 4) and relationships between markers of DHA and language development (Chapter 5) are examined. A model proposed to provide a broader or more comprehensive conceptualization of the role of DHA within the larger system of influences on language development was tested (Chapter 6). The current study found no significant effect of DHA supplementation during pregnancy on children‟s language development at 4 years of age as measured by the primary outcome of the current study: mean Core Language Scores, assessed using the second edition of the Clinical Evaluation of Language Fundamentals Preschool. There were no significant interactions between treatment group and child sex, maternal age, in utero exposure to maternal cigarette smoking or alcohol consumption, or maternal depression. There was, however, a significant interaction for maternal education. There was also no significant relationship between markers of DHA status and language development for the whole group, and no significant difference in language development between those with cord blood DHA in the 25th and 75th percentile. There were, however, both significant positive and negative relationships between the number of fish meals and DHA foods (respectively) the child consumed in the month prior to the 4-year assessment and language development at 4 years of age. Findings from structural equation modelling analyses provided no support for understanding the relationship between DHA and children‟s language development through focusing on the relationships proposed by the bio-ecological model. Overall, findings suggest that prenatal DHA supplementation does not benefit children‟s language development. Longer-term follow-up of early DHA supplementation is required to determine whether delayed effects emerge.
Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2016.

Research Doctorate - Doctor of Philosophy (PhD)
Thrombosis is a critical event that accounts for considerable morbidity and mortality in the Western world. Thrombosis is associated with arterial diseases including, myocardial infarction, stroke, and peripheral occlusive disease as well as with venous thromboembolic disorders. Consequently, the primary goal for the prevention of arterial and venous thrombosis to combat disease progression is to limit thrombus extension. Platelet activation and aggregation is considered to be central to thrombus production; thus anti-thrombotic treatments to inhibit platelet activity have been a major drug target to retard the thrombotic and atherosclerotic processes. Despite extensive resource investment in cardiovascular research and treatment, the current pharmacological strategies for the inhibition of platelet aggregation, although effective, may present limitations and adverse health effects have been reported. Given the toll taken by thrombotic complications, a safe and efficacious non-pharmacological approach may be paramount for the prevention and management of thrombotic disease. While a wealth of evidence supports that fish oil provides preventative or ameliorative effects against thrombotic disease, the mechanisms responsible for this association are not understood and are further complicated by contrasting reports. Fish oils are a rich source long chain omega-3 polyunsaturated fatty acids including eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), however it is not clear whether the anti-thrombotic effects are due to EPA or DHA or whether both are equally effective. In the available literature relating fish oil and platelet aggregation, wide variability in terms of dosage, concentration ratios, study design, subject characteristics and gender inequality are apparent, hence there is discrepancy regarding the effect of fish oils on platelet activity. Consequently, the anti-thrombotic potential of fish oil supplementation is controversial and largely disregarded by the medical community. This dissertation investigated the independent effects of EPA and DHA on platelet and coagulant activity. A series of three controlled studies were undertaken to elucidate the mechanisms by which EPA and DHA influence hemostatic parameters with the hope to resolve the existing controversy. The ultimate and unifying theme of these studies was to provide a safe and efficacious approach to optimise cardio-protection via anti-thrombotic potential of EPA versus DHA. Firstly, an in vitro investigation was carried out that compared the effects of EPA with DHA on platelet aggregation in healthy male and female subjects. The inhibition of platelet aggregation by EPA/DPA/DHA was equally effective and correlated with lag time; however most strikingly the results were influenced in a gender-specific manner. These observations suggest that interactions between sex hormones and fish oils exist to influence platelet response differentially. With a new perspective of gender bias effects, an acute supplementation study monitored the platelet responses up to 24 hours after consumption of a single dose of an EPA versus DHA-rich oil capsule in thirty male and female subjects. The kinetics of the EPA and DHA supplement on platelet activity was examined according to gender stratified treatment. Subgroup gender analysis showed that the anti-aggregatory effects of EPA were predominately evident in males while female platelets were more responsive to DHA. The marked decrease in platelet aggregation with EPA supplementation was paralleled with a reduction in platelet microparticle activity in the male subjects only, and an inverse relationship between testosterone levels and platelet responses were observed. Findings from this study reflected the in vitro observations and suggest that EPA and DHA inhibit platelet aggregation via independent pathways compounded by sex hormonal influences. Confirmation of gender-specific platelet responses with omega-3 fatty acid supplementation was achieved in a chronic supplementation study involving ninety-four healthy male and female subjects. Subsequently, this four week dietary intervention trial demonstrated that the anti-thrombotic potential is apparent with longer term exposure to EPA/DHA and explored the mechanistic pathways. Significant interactions between gender and treatment were observed; the effects of EPA were specific in reducing platelet aggregation and specific coagulation factors in males, whereas no effects were observed in the female cohort. Conversely, the effects of DHA were unique to females with a similar decrease in platelet aggregability. Interactions between sex hormones with coagulation factors and retention of EPA and DHA in plasma were also observed.In conclusion, the study findings presented in this thesis provide evidence that the effects of EPA and DHA on platelet aggregation are apparent; the effects are neither shared nor complementary, rather they are gender-specific. Furthermore, the results herein may explain the existing controversy between fish oils, platelets and thrombosis that have intrigued clinical investigators for several decades. With respect to thrombotic disease risk, males would likely benefit more from supplementation with EPA while females are more responsive to DHA. The significance of these findings allows optimal cardio-protection tailored for both gender groups offering a safe and efficacious non-pharmacological approach.

Circulating lipids play an important role in human physiology and pathophysiology. Lipids, as the major components in various cellular membranes, are involved in homeostatic regulation, particularly in relation to immune function and inflammatory mechanisms. With the growing global prevalence of lifestyle-related diseases, including obesity, diabetes, cardiovascular disorders and cancers, dietary lipids have received a great attention. Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) have been associated with a broad range of health benefits. The three main LC n-3 PUFA are eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3) and docosapentaenoic acids (DPA, 22:5n-3). Fish oil and krill oil are currently the most available sources of EPA and DHA as over-the-counter supplements, although other marine sources such as algae oil are also rich in EPA and DHA. Krill oil, derived from Antarctic krill (Euphausia Superba), is rich in EPA and DHA found in phospholipids (predominantly phosphatidylcholine) rather than triacylglycerol (TAG), in which EPA and DHA in fish oil are found. Krill oil also contains astaxanthin, a carotenoid contributing to its red colour which may also have beneficial health effects (Barros et al. 2014a, Pashkow et al. 2008). Despite a number of studies examining the effects of krill oil compared with fish oil on the incorporation of LC n-3 PUFA into different tissues, the outcomes have been conflicting, which might be associated with the different study designs using different chemical forms of fish oil and/or different doses of LC n-3 PUFA, and focusing at different target tissues. The research presented in this thesis consists of nine chapters covering a literature review (Chapter two) and two intervention studies in humans (Chapters four, five, six and seven) which have examined the effect of krill oil compared with fish oil on the incorporation of LC n-3 PUFA into plasma lipid fractions. There were a postprandial and a longer-term (30 days) intervention studies, and both clinical studies were randomised crossover designs involved healthy women (n = 10 and n = 11, respectively). All participants were instructed to maintain the habitual dietary intake and habitual physical activity throughout the interventions. The aim of the postprandial study was to compare the incorporation of LC n-3 PUFA into the plasma and circulating lipids in plasma and chylomicron fractions from five capsules (1 g each) of krill oil compared with five capsules (1g each) of fish oil and 5 g of the olive oil (control) over a 5-hour postprandial period. The second study aimed to investigate the longer-term effect of krill oil supplementation (containing 1,269 mg/d of LC n-3 PUFA including EPA, DHA and DPA) on the plasma LC n-3 PUFA, plasma circulating TAG and inflammatory biomarkers compared with fish oil supplementation (containing the closest possible match to these fatty acids from the capsules, 1,441 mg/d) over a 30-day intervention period. In both studies, lipidomics, was applied to identify the differences in plasma lipid molecular responses between krill oil and fish oil supplementation. Using this technique, a number of plasma lipid classes, and lipid molecular species containing EPA and DHA were identified and quantified. In the 5-hour postprandial study (Chapters four and five), there were no significant differences in the levels of TAG or cholesterol in plasma or chylomicron between the three study oil interventions, although the expected increases in chylomicron TAG were observed in all groups. In comparison to the olive oil, both krill oil (containing 907 mg of LC n-3 PUFA) and fish oil (containing 1,441 mg of LC n-3 PUFA) supplementation significantly increased the level of plasma EPA, which plateaued after three hours; there were no significant differences in the plasma EPA levels between krill oil and fish oil supplementation groups. There were no significant changes in either DHA or DPA between the three groups. Krill oil, with a lower dose of EPA in this study, showed a similar incorporation outcome of EPA into plasma lipids as fish oil. Given that there were 31% less EPA from krill oil, these results indicate a differential extent of incorporation of EPA between krill oil and fish oil, suggesting that EPA from krill oil may be more efficiently incorporated into the plasma than fish oil. The advanced technique for lipidomics was performed by high-performance liquid chromatography-mass spectrometer analysis (HPLC MS/MS), which was able to identify and quantify changes in various lipid molecular species containing LC n-3 PUFA in both the postprandial and the longer-term studies. Therefore, the HPLC MS/MS facilitated a comparison between differences in the individual lipid molecular species between krill oil and fish oil supplementation. A more sensitive setting of HPLC MS/MS was applied to the postprandial data than the longer-term data, based on the settings applied by the research laboratory at Baker Heart and Diabetes Institute where these analyses were conducted. In Chapter five, the postprandial plasma lipidomic changes are reported at hours zero (baseline), 3 and 5. A total of 29 lipid classes (≥ 500 pmol/mL) (for example: TAG, diacylglycerol (DAG), phosphatidylcholine (PC), cholesterol esther (CE)) were identified; six of these including O-linked phosphatidylethanolamine classes had significantly greater the incremental area under the curve from baseline (net iAUC 0-5 h) after krill oil supplementation compared with fish oil supplementation. Over the postprandial period, 56 EPA-containing and 76 DHA-containing molecular species (for example 16:0-20:5-PC, 16:0-18:1-20:5-TAG, 16:0-22:6-PC, 16:0-18:1-22:6-TAG) were significantly increased after both krill oil and fish oil supplementation. There were 33 phospholipid molecular species containing EPA, and 16 of these molecular species, including six ether-phospholipid molecular species had significantly greater increased net iAUC 0-5 h after krill oil than fish oil supplementation. In contrast, for TAG and DAG molecular species containing EPA, seven out of a total of 21 showed significantly increased net iAUC 0-5 h for fish oil compared with krill oil. Put simply, the EPA from krill oil was associated with increases in phospholipid EPA-molecular species, while the EPA from fish oil was associated with increased TAG and DAG EPA-molecular species. There were 49 phospholipid molecular species containing DHA, and 11 of these including six ether-phospholipid molecular species, had significantly greater increased net iAUC 0-5 h after krill oil supplementatin than fish oil supplementation. In a total of 61 AA-containing molecular species (for example 16:0-20:4-PC, 16:1-20:4-DAG) identified, there were 51 phospholipid molecular species containing AA, and seven of these including six ether-phospholipid molecular species, had significantly greater increased net iAUC 0-5 h after krill oil supplementation than fish oil. A novel finding from this postprandial study was that there was a consistent trend that ether-phospholipid classes (O-linked (containing an alkyl bond) or P-linked (containing an alkenyl bond) phosphatidylcholine and phosphatidylethanolamine) were significantly increased after krill oil supplementation, but decreased after fish oil supplementation. Consistently, it was found that EPA- and DHA-containing ether-phosphatidylethanolamines were significantly increased after the krill oil supplementation, but decreased after the fish oil supplementation. While the significance of this finding is not clear, it is worth noting that plasma levels of O- and P-linked phosphatidylethanolamine have been reported to be decreased in a number of disease states including Alzheimer’s disease. Little is known about the origin of these ether-phospholipids in plasma, but the fact that krill oil increased their post-prandial levels and fish oil decreased them is a clear differentiation between these two omega-3 oils. In the longer-term study (Chapters six and seven), EPA, DHA and DPA were significantly increased after both krill oil and fish oil supplementation over the 30-day period (p < 0.001). The main response to the 30-day krill oil supplementation was that the increase of plasma EPA level was significantly greater in the net iAUC 0-30 d than that of fish oil supplementation (p < 0.05). Both krill oil and fish oil significantly reduced plasma TAG over the intervention period (p < 0.05 and p < 0.01, respectively), but no significant differences were observed between the two groups. Over the 30-day intervention period, some plasma pro-inflammatory cytokines including IL-1β, IL-10, IL-4 and IL-5 (p ≤ 0.05) were significantly reduced after krill oil supplementation, while no such changes were found after fish oil supplementation. In Chapter seven, the long-term lipidomic changes (≥ 500 pmol/mL), at days zero (baseline), 15 and 30, are reported. Twenty three EPA-containing and 46 DHA-containing molecular species were significantly increased after both krill oil and fish oil supplementation over the 30-day supplementation period. Among EPA-, DHA-, and DPA-containing molecular species, there were 20 cases of net iAUC 0-30 d significant differences between the two supplementation. Fourteen of these molecular species in phospholipid species, including 12 ether-phospholipid species, had significantly greater increased net iAUC 0-30 d after krill oil than fish oil (p ≤ 0.05) supplementation. Consistently, it was found that EPA- and DHA-containing ether-phospholipid species, including six ether-phosphatidylethanolamines, were significantly increased after the krill oil supplementation, and decreased after the fish oil supplementation. The changes in the ether-phospholipids in the long-term trial were consistent with the changes described in the postprandial trial (Chapter five). These results support strongly the differentiation between krill oil and fish oil although there are still many unanswered questions flowing from this novel finding. What is known about plasmalogens is that they play a role in anti-inflammatory response, which might be linked to the significant decrease in pro-inflammatory cytokines observed in the present study. Overall, both postprandial and longer-term studies demonstrated that EPA from krill oil is efficiently incorporated into plasma, has a similar effect on the plasma TAG-lowering and a greater efficacy on the plasma inflammatory biomarkers when compared with fish oil. No previous studies have investigated plasma lipidomic responses to krill oil and fish oil supplementation in humans. There were significant increases in molecular species containing EPA and DHA following supplementation with krill oil and fish oil over both the postprandial and the longer-term periods. The plasma lipidomic changes of net iAUC over both intervention periods were significantly different between krill oil and fish oil supplementation, particularly for phospholipids (krill oil resulted in a greater increase than fish oil) and TAG (fish oil resulted in a greater increase than krill oil, as described in Chapter five). A novel aspect identified in this study was that krill oil increased ether-phospholipids, particularly ether-linked phosphatidylethanolamine, whereas fish oil decreased ether-phospholipids. The biological relevance of this novel lipidomic finding has yet to be fully explored.

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

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Os ácidos gordos polinsaturados incluem classes como os ácidos gordos ómega-3 (AG ω-3) e os ácidos gordos ómega-6 (AG ω-6) essenciais na dieta humana, cuja estrutura dita o seu papel biológico. Enquanto os AG ω-6 estão associados a comportamentos pro-inflamatórios, os ácidos gordos ómega-3 têm vindo a conquistar uma elevada importância devido aos seus efeitos pro-resolutivos e anti-inflamatórios. Os AG ω-3, tal como o ácido eicosapentaenóico (EPA) e o ácido docosahexaenóico (DHA), presentes em grandes quantidades em peixes gordos e óleos de peixe, possibilitam a produção de eicosanóides (tais como prostaglandinas e leucotrienos) biologicamente menos potentes do que os produzidos através da metabolização do ácido araquidónico (ARA), um AG ω-6, e a produção de mediadores especializados na pró-resolução, como é o caso das resolvinas e das protectinas. Igualmente, reduzem a quimiotaxia de leucócitos, a expressão da molécula de adesão, a própria interação leucócito-endotélio, a produção de citocinas inflamatórias e da reatividade das células T. A obtenção destes efeitos anti-inflamatórios ainda não se encontra totalmente esclarecida, porém, mostra-se estar relacionada com a alteração da composição dos ácidos gordos na membrana fosfolipídica (permitindo uma maior metabolização de EPA e/ou DHA ao invés doARA), com a redução da expressão de genes inflamatórios através da inibição da ativação do Fator Nuclear Kappa B (NF-B) e através da ativação do fator de transcrição anti-inflamatório, denominado recetor ativado por proliferadores de peroxissoma tipo gama (PPAR-γ), e do recetor acoplado à proteína G (GPR120). Esta diminuição de eventos inflamatórios e posterior sintomatologia pode, então, ser atenuada pelos AG ω-3, motivo pelo qual apresenta benefícios em patologias inflamatórias crónicas como a asma e a artrite reumatoide, ou até mesmo nodesenvolvimento cerebral, obesidade, diabetes e doenças cardiovasculares.
Polyunsaturated fatty acids include classes such as omega 3 fatty acids (ω-3 FA) and omega-6 fatty acids (ω-6 FA) essential in the human diet, whose structure dictates their biological role. While ω-6 FA are associated with pro-inflammatory effects, ω-3 FA have managed to gain significant importance due to their pro-resolving and anti inflammatory effects. The ω-3 FA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present in large amounts in oily fish and fish oils, enable the production of eicosanoids (such as prostaglandins and leukotrienes), biologically less potent than those produced by the metabolism of arachidonic acid (ARA), an ω-6 FA, and the production of specialized pro-resolving mediators,such as resolvins and protectins. It also decreases leukocyte chemotaxis, adhesion molecule, the own leukocyte-endothelium interaction expression, production of inflammatory cytokines and T-cell reactivity. The achievement of these anti inflammatory effects is not yet fully understood, but it has been shown to be related to an altered fatty acid composition in membrane phospholipids (allowing metabolism of EPA and/or DHA instead of ARA), decreasing inflammatory gene expression by inhibiting transcription factor nuclear factor kappa B (NF-B) activation, and by activating the anti-inflammatory transcription factor named peroxisome gamma proliferator activated receptor (PPAR-γ) and G protein coupled receptor (GPR120). This decrease in inflammatory events and subsequent symptoms can be attenuatedby FA ω-3, which is why it has benefits in chronic inflammatory pathologies such as asthma and rheumatoid arthritis, or even in brain development, obesity, diabetes and in cardiovascular diseases.

Sammanfattning  Bakgrund Vitamin- och mineralbrister hos gravida kvinnor kan leda till missfall och allvarliga störningar i barnets utveckling. Moderns tarmflora överförs med stor sannolikhet till barnet under förlossningen och kan därför innebära ett viktigt steg i utvecklingen av barnets tarmflora. En tänkbar lösning för att säkra ett adekvat intag kan vara konsumtion av kosttillskott och probiotika. I dagsläget finns osäkra uppgifter om hur många gravida kvinnor som intar tillskott.  Syfte Att undersöka hur många gravida kvinnor i Västerbottens län som valde att inta kosttillskott, främst järn och probiotika, samt om det fanns en skillnad mellan olika faktorer och intag.  Metod En kvantitativ tvärsnittsstudie där gravida kvinnor (n=1473) från Northpop-studien i Västerbottens län svarade på ett frågeformulär gällande intag av kosttillskott och faktorer som ålder, utbildning, kostregim etc. De statistiska tester som användes var Chi-2-test, oberoende t-test och Mann Whitney U-test. Materialet analyserades i SPSS. Signifikansnivån sattes till p<0,05.  Resultat Majoriteten av deltagarna svarade att de intog kosttillskott. Faktorer som ökade intaget av kosttillskott hos gravida kvinnor var högre ålder (p=0,030) jämfört med lägre ålder, högre utbildningsnivå (p=0,006) jämfört med lägre utbildningsnivå och vegetarisk/vegansk kost (p=0,021) jämfört med blandkost. Femtiofem procent uppgav att de intog järntillskott. De faktorer som ökade intaget av järntillskott hos gravida kvinnor var vegetarisk/vegansk kost (p=0,001) jämfört med blandkost. Probiotika intogs av 2 procent. Ett högre intag av probiotika sågs hos personer boende i stadsområde (p=0,024) jämfört med övriga boenderegioner samt de som åt vegetarisk/vegansk kost (p=0,001) jämfört med blandkost.  Slutsats Majoriteten av deltagarna intog någon typ av kosttillskott, hälften intog järntillskott och en liten andel intog probiotika. Lågutbildade, yngre, de som äter blandkost och bor utanför stadsområde verkar vara i riskgruppen för att inte inta kosttillskott.
Abstract  Background Vitamin and mineral deficiencies in pregnant women can lead to miscarriage and serious disturbances in children’s development. The intestinal flora of the mother is most likely transmitted to the child during childbirth and may lay the foundation for the child's health. One possible solution to ensure an adequate intake may be the consumption of dietary supplements and probiotics. At present, there is insufficient data on supplement consumption among pregnant women.  Objective The purpose of the study was to examine how many pregnant women in Västerbotten County chose to consume dietary supplements, mainly iron and probiotics, and whether there was a difference between different factors and intake.  Method A quantitative cross-sectional study where pregnant women (n=1473) from the Northpop-study in Västerbotten County responded to a questionnaire regarding consumption of dietary supplements and factors such as age, education, diet etc. The material was analyzed in SPSS with Chi-2-test, independent T-Test and Mann-Whitney U-Test. Using significance level <0.05.  Results The majority of participants, 90 percent, responded that they consumed dietary supplements. The factors that increased the intake of dietary supplements in pregnant women were higher age (p=0.030), higher education (p=0.006) and vegetarian/vegan diet (p=0.021). Iron was reported to be consumed by 804 people, 55 percent. The factors that increased the intake of iron supplement in pregnant women were vegetarian/vegan diet (p=0.001). Probiotics were consumed by 25 people, 2 percent. Living in urban areas (p=0.024) and eating vegetarian/vegan diet (p=0.002) increased consumption of probiotics.  Conclusion The majority of participants chose to consume some type of dietary supplement, half of the participants consumed iron supplements and a small part consumed probiotics. It appears that pregnant women who are low educated, younger, eating an omnivorous diet and living outside urban areas are in the risk zone for not consuming dietary supplements.
Northpop