Ultraviolet radiation (UVR) is a complete carcinogen, inducing skin cancer via DNA photodamage that can lead to mutagenesis, and promoting its growth via photoimmunosuppression (PI). The omega-3 polyunsaturated fatty acid (n-3 PUFA) eicosapentaenoic acid was shown in murine studies to protect against PI and UV-induced skin cancer although the mechanism is uncertain. The principal objectives of this thesis were to (i) examine whether n-3 PUFA can protect against a clinical model of PI in healthy humans and (ii) explore whether the underlying mechanism could be abrogation of UV-induced depletion of antigen-presenting Langerhans cells (LC) from the epidermis, and/or impact on immunomodulatory cytokines. Nickel (Ni) allergic females (n=79) were randomized to 3 months of daily supplementation with 5g n-3 PUFA (70% eicosapentaenoic acid, EPA; 10% docosahexaenoic acid, DHA) or the placebo medium chain triglyceride, GTCC. Local PI was clinically assessed post supplementation using the nickel contact hypersensitivity (Ni CHS) model. In each volunteer, Ni patches were applied to 3 skin sites that were irradiated for 3 consecutive days with UV-doses of 1.89, 3.82 & 7.59J/cm2 respectively. CHS responses were measured and compared to responses of control patches applied on unirradiated skin using a reflectance erythema meter. In the same subjects, assessments of cellular and biochemical mediators of PI were made pre and post supplementation. At 24hr post irradiation with an erythemal UV-dose (4 minimal erythemal doses) to upper buttock skin, half the subjects (n=39) had skin punch biopsies taken and the other half (n=40) had suction blisters raised on this irradiated skin and on unirradiated skin of the contralateral buttock. Epidermal sheets were prepared from the punch biopsies and immunohistochemically stained to assess UV-induced LC numbers. Levels of immunomodulatory cytokines were analysed in the suction blister fluid using Luminex multiplex assay kits. To evaluate compliance and bioavailability, blood samples were taken from all volunteers, pre and post supplementation and EPA% weight in red blood cell membranes was examined using gas chromatography. Post supplementation, EPA %wt was significantly higher in the active group compared to control: mean 3.61% ± 0.22% (SEM) vs. 0.93% ± 0.06% (p<0.001). 3 volunteers showed evidence of non-compliance and were excluded from further analysis. Compared to placebo, evidence for protection against local PI of Ni CHS was apparent post n-3 PUFA at all UV doses, reaching statistical significance at the UV-dose of 3.8J/cm2 (p<0.05). No significant difference in post-UV epidermal LC numbers after supplementation was seen between active and placebo groups, with a % fall following UV of 76.61 ± 3.39% (SEM) in the active group and 73.52 ± 5.24% (SEM) in the control group. When intragroup comparisons were made pre vs. post supplementation, a similar increase in UV-induced LC depletion from the epidermis was seen in both groups, reaching statistical significance following n-3 PUFA (p=0.018). Levels of interleukins IL-10 and IL-8, and of TNF-α, increased post-UVR in both active and control groups pre-supplementation, with no changes occurring following supplementation. In conclusion, supplemental EPA was bioavailable and evidence of protection against clinical PI of Ni CHS was seen in the actively treated group. However, no evidence was found that this abrogation of PI was mediated through a reduced effect of UV on migration of epidermal LC or the immunomodulatory cytokines examined. This original study gives the first evidence that dietary n-3 PUFA may protect against clinical PI, and potentially skin cancer promotion, in humans. Further research is needed to confirm this finding, and to examine the underlying mechanisms, which could involve other immunoregulatory cells of the skin, such as dermal dendritic cells and T regulatory cells and other mediators of UV-immunosuppression including the prostanoids, which may be modified by n-3 PUFA.

PUFAs have been shown to modulate ALD by several mechanisms, including free radical generation from hepatic lipid peroxidation. However, how they modulate lipid peroxidation and generation of bioactive metabolites in ALD is poorly understood and it is still not clear which PUFAs (ω-3 or ω-6) are beneficial or detrimental in ALD. Thus, our objective was to study the effect of ω-3/ω-6 PUFAs on lipid peroxidation and ethanol mediated steatosis and inflammation. Using standard liquid diet (LDC), LDC with fish oil (rich in ω-3) and safflower oil (rich in ω-6), we studied the generation of bioactive metabolites, such as eicosanoids and free radicals generated via lipid peroxidation. In addition, we determined the effect of PUFAs on several inflammatory and fibrotic factors, e.g. gene as well as protein expression, using western blot and RT-PCR, respectively. We also investigated the effect of PUFA diets on novel targets, such as hepatic membrane transporters with potential role in liver inflammation. Our results suggest that ω-3 diet prevented while ω-6 based diets promoted the development of fatty liver and inflammation. ω-3 PUFA reduced AA-peroxidation by lowering hepatic AA concentration and expression of peroxidation enzymes, COX-2 and 5-LOX, resulting in lower generation of pro-inflammatory AA-derived PGs (Series-2), HETEs and free radicals, along with increase in anti-inflammatory EPA and DHA-derived PGs (Series-3). ω-3 diet might also reduce liver inflammation by preventing activation of NF-кB and induction of TNF-α. Rats fed with ω-3 diet showed high protein expression of efflux transporters, MRP-2 and ABCA1, indicating elimination of peroxidation metabolites and triglycerides from the liver and decreased inflammation. In contrast, ω-6 diets led to increase in AA-peroxidation and generation of AA-derived pro-inflammatory metabolites. ω-6 based diets also promoted fatty liver and inflammation by activating NF-кB, inducing TNF-α and downregulation of efflux transporters, MRP-2 and ABCA1. This study not only provides new insights into the effects and possible mechanisms by which ω-3 and ω-6 PUFAs may alter hepatic steatosis and inflammation, but also put forward new targets of research, such as hepatic membrane transporters in relation to liver pathology in ALD.

Yes / As pre-clinical and clinical research interest in ω-3 polyunsaturated fatty acids (PUFA) increases, so does the need for a fast, accurate and reproducible analytical method to measure fatty acids (FA) in biological samples in order to validate potential prognostic and predictive biomarkers, as well as establishing compliance in ω-3 PUFA intervention trials. We developed a LC-ESI-MS/MS method suitable for high throughput development to measure FAs and validated it in the context of treatment with the ω-3 PUFA eicosapentaenoic acid (EPA). Uniquely we directly compared the LC-ESI-MS/MS method to a GC-MS protocol. We demonstrated the LC-ESI-MS/MS method is accurate and reproducible, with coefficients of variation consistently below 15% for each PUFA analysed. The relative FA content values correlated well with those obtained by GC-MS (r2 = 0.94, p<0.001 for EPA) in vitro. The data obtained following analysis of FA content of liver tissues from mice fed an eicosapentaenoic acid enriched diet showed similar results to that of published studies in which GC-MS was used. The LC-ESI-MS/MS method allows concomitant analysis of unesterified (free, unbound) and esterified (bound) FAs in biological samples, allowing investigation of different PUFA pools in cells and tissues. / Yorkshire Cancer Research, MRC/NIHR

No description available.

University of Macau / Institute of Chinese Medical Sciences

Doctor of Philosophy / Department of Human Nutrition / Mark D. Haub / Mark D. Haub / Psychological problems and human error are leading causes of death and disability among military service members. Strategies to improve the psychological health and cognitive performance of those in the military are much needed. Recent advances in neuroscience suggest that omega-3 fatty acids may play an important role in the psychological well-being of those in the military. The purpose of this research was to explore the relationship between omega-3 status and psychological outcome variables among soldiers deploying to combat. Data collection was preceded by the development and reliability testing of a novel food frequency questionnaire (FFQ) designed to capture intake from contemporary sources of omega-3 fatty acids including functional foods and supplements. Based on the instrument assessment study (Chapter 2) conducted among university students (n = 165), this FFQ appears to be a comprehensive and reliable (n = 54, ρ = 0.86, p < 0.001) instrument for measuring docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intakes in young adults. As described in Chapter 3, intake of EPA + DHA as estimated by the FFQ was positively correlated (r = 0.39, p < 0.001) with biomarker measurements of omega-3 status. Primary data were obtained from a volunteer sample of soldiers (n = 272) scheduled for deployment to Iraq. Preliminarily analyses revealed relationships between attention deficit hyperactivity disorder (ADHD) screening scores and psychological outcome variables (Chapter 4). Primary analyses (Chapter 5) indicated intake of EPA + DHA was not significantly correlated with mood, nor were omega-3 exposure variables correlated with cognitive performance based on the required p value (< 0.001) calculated using the Bonferroni correction for multiple tests. Among participants with EPA + DHA intakes at or below the median, omega-3 HUFA was related (p < 0.002) to happiness (β = -0.46), depression (β = 0.44), and fatigue (β = 0.43). Although exploratory in nature, the results of this study suggest a relationship between omega-3 fatty acids and mood. Given the current concerns regarding the psychological health of those in the military, additional research is warranted.

Master of Science / Grain Science and Industry / Greg Aldrich / Processing pet food can be beneficial, but can also have adverse effects on shelf-life and nutrient survival. Most affected are supplemental vitamins and essential fatty acids (EFA). Pet food complicates this relative to human foods by combining all elements into the product before processing and requiring an extensive shelf-life (up to 2 years). The objective of this research was to determine the effects of processing, diet, and storage conditions on vitamin (vitamin A, vitamin D₃, vitamin E, folic acid and thiamine) and omega-3 fatty acid (with an emphasis on eicosapentaenoic acid; EPA 20:5n3, and docosahexaenoic acid; DHA; 22:6n3) retention. The research was conducted in two separate experiments. Each experimental diet was produced on a single-screw extruder and triple-pass dryer. Target nutrients were evaluated in premixes in tandem to extruded diets. The vitamin study was conducted as a 3 X 2 X 2 factorial arrangement of treatments with 3 levels of dietary crude protein (CP), 2 screw speeds in the extruder, and 2 levels of time X temperature combinations in the dryer. Vitamins were added at 10 times normal levels to aid in analysis. The EFA study was conducted as a 3 X 3 factorial arrangement of treatments with 3 levels of dietary protein and 3 different omega-3 sources: fish oil, fish meal, or purpose-grown algae rich in DHA. In the vitamin premix study, the quantity of vitamins declined by approximately 50% over 6 months storage in ambient conditions (AMB; 20C, 50%RH), and all except folic acid were lost to some degree in stressed shelf life testing (SSLT; 50C, 70% RH) over 6 weeks. In all cases, the concentration of vitamins in food exiting the extruder and dryer were lower than target levels. As CP increased, the retention was higher (P ≤ 0.05) for vitamins A, E, and folic acid off the extruder (e.g. 225,352 vs. 219,184 and 206,249 IU/kg of vitamin A for high vs. medium and low CP, respectively), and vitamin D₃, E, and folic acid off the dryer (e.g. 9,047 vs. 7,473 and 6,945 IU/kg of vitamin D₃ for high vs. medium and low CP, respectively). During storage of finished pet food in AMB, vitamins A and D₃ were lost (P < 0.05) to the greatest degree (49 and 22%, respectively). The total retention following both processing and AMB storage was 27, 68, 78% for vitamins A, D₃, and E, respectively, while folic acid and thiamine were relatively stable. In SSLT storage, all vitamins except vitamin E were depleted more than 60% (P < 0.05) by 24 weeks, whereas total retention following both processing and SSLT storage was 3, 59, 43, 33, and 7% for vitamins A, D₃, and E, folic acid, and thiamine, respectively. This would suggest that beyond processing losses, the vitamins are relatively stable in premixes and foods if stored in AMB conditions. In the study to evaluate fatty acid stability within a vitamin premix, EPA, DHA, and total omega-3 fatty acids were relatively stable during storage over 6 weeks with losses no greater than 12% in stressed shelf life testing (SSLT; 40C, 70% RH). While in ambient conditions (23C, 50% RH) over 3 months, there was a total loss of EPA, DHA and total fatty acids by 17, 9, and 11%, respectively. Exiting the extruder and dryer, EPA and DHA were not affected by CP level or Omega-3 source. As SSLT storage of finished pet food increased through 24 weeks, EPA, DHA, and total fatty acids declined slightly (P < 0.05; 125, 82 mg/kg for EPA and 77, 60 mg/kg for DHA, and 418, 476 mg/kg for total fatty acids at 0 vs. 24 wk. As time in ambient storage reached 24 months, EPA, DHA, and total fatty acids declined slightly (P < 0.05; 125 vs. 78 mg/kg for EPA and 77 vs. 50 mg/kg for DHA, and 387 vs. 373 for total fatty acids at 0 vs. 24 mo.) Algal-DHA appears to be a stable source of DHA when compared to fish oil and fishmeal. During processing retention of fat soluble vitamins was less than water soluble vitamins, and the omega-3 fatty acids were relatively unaffected. Whereas, vitamins appeared to be more sensitive to temperature during storage and the omega 3 fatty acids more affected by time.

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: Américo Garcia da Silva Sobrinho / Banca: Mateus José Rodrigues Paranhos da Costa / Banca: Mauro Sartori Bueno / Banca: Márcia Helena Machado da Rocha Fernandes / Banca: Fabiana Alves de Almeida / Banca: Juliana Duarte Messana / Resumo: Objetivou-se avaliar o desempenho, a digestibilidade dos nutrientes, os parâmetros quantitativos da carcaça e os qualitativos e sensoriais da carne de cordeiros Ile de France terminados em confinamento, recebendo dietas com crescentes inclusões de farinha de algas marinhas. Foram utilizados 32 cordeiros não castrados com aproximadamente 60 dias de idade e 20 ± 0,2 kg de peso corporal, alojados em baias individuais e abatidos aos 35,0 ± 0,2 kg. Os tratamentos foram compostos por quatro dietas: D0- silagem de milho + concentrado sem farinha de algas; D2- silagem de milho + concentrado + 2% de farinha de algas; D4- silagem de milho + concentrado + 4% de farinha de algas e D6- silagem de milho + concentrado + 6% de farinha de algas. A relação volumoso:concentrado foi 40:60, compondo dietas com semelhantes teores proteicos (15%) e energéticos (3,3 Mcal de energia digestível/kg de matéria seca). Os dados foram avaliados num delineamento experimental inteiramente casualizado, com quatro tratamentos e oito repetições. Os resultados foram submetidos à análise de variância e regressão, com os graus de liberdade desdobrados em efeitos linear, quadrático e cúbico. As inclusões de farinha de algas marinhas influenciaram (P<0,05) o consumo de nutrientes, com efeito linear decrescente para matéria seca (MS), matéria orgânica (MO), proteína bruta (PB), fibra insolúvel em detergente neutro (FDN), fibra insolúvel em detergente ácido (FDA) e energia bruta (EB), e crescente para a fração EE (ext... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study was undertaken to evaluate the performance, nutrient digestibility, quantitative parameters of carcass, and qualitative and sensory parameters of meat in feedlot-finished lambs fed diets with increasing levels of marine algae meal inclusion. Thirty-two newly weaned 60-day-old uncastrated Ile de France lambs weighing 20.0 ± 0.2 kg body weight were used. The animals were housed in invidual pens and slaughtered at 35.0 ± 0.2 kg. The treatments were composed of four diets: D0- corn silage + concentrate without algae meal; D2- corn silage + concentrate + 2% algae meal; D4- corn silage + concentrate + 4% algae meal; and D6- corn silage + concentrate + 6% algae meal. The roughage:concentrate ratio was 40:60, and diets were formulated with similar protein (15%) and energy (3.3 Mcal digestible energy/kg DM) contents. The data were evaluated in a completely randomized experimental design, with four treatments and eight replications. The results were submitted to analysis of variance and regression. The algae meal contente were broken down into linear, quadratic and cubic effects. Marine algae meal levels influenced (P<0.05) nutrient intake, with a linear decrease seen in DM, OM, CP, NDF, ADF and GE; the opposite effect was found on EE, which increased linearly. Likewise, nutrient digestibility was influenced (P<0.05) by the algae meal levels, which linearly reduced the digestibilities of DM, OM, NDF, ADF, TC, and NFC. The digestibility of the EE fraction rose linearly (P<0.0... (Complete abstract click electronic access below) / Doutor

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. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1283720 / Thesis (PhD) -- School of Molecular and Biomedical Science, 2007