Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Patients undergoing elective coronary artery bypass grafting exhibit poor pre-operative intakes of fruit, vegetables, dietary fibre, fish and vtiman D
    Ruiz-Nunez, B. ; Hurk, Y.A.C. van den; Vries, J.H.M. de - \ 2015
    The British journal of nutrition 113 (2015). - ISSN 0007-1145 - p. 1466 - 1476.
    cardiovascular-disease risk - low-grade inflammation - heart-disease - fatty-acids - eicosapentaenoic acid - gut microbiota - brain-function - life-style - metaanalysis - consumption
    CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80 % men) undergoing elective CABG. Of these, fifty-five were finally included (84 % men, median age 69 years; range 46–84 years). The median BMI was 27 (range 18–36) kg/m2. The dietary intake items were fruits (median 181 g/d; range 0–433 g/d), vegetables (median 115 g/d; range 0–303 g/d), dietary fibre (median 22 g/d; range 9–45 g/d), EPA+DHA (median 0·14 g/d; range 0·01–1·06 g/d), vitamin D (median 4·9 µg/d; range 1·9–11·2 µg/d), saturated fat (median 13·1 % of energy (E%); range 9–23 E%) and linoleic acid (LA; median 6·3 E%; range 1·9–11·3 E%). The percentages of patients with dietary intakes below recommendations were 62 % (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150–200 g/d), 73 % (dietary fibre; recommendation 30–45 g/d), 91 % (EPA+DHA; recommendation 0·45 g/d), 98 % (vitamin D; recommendation 10–20 µg/d) and 13 % (LA; recommendation 5–10 E%). The percentages of patients with dietary intakes above recommendations were 95 % (saturated fat; recommendation <10 E%) and 7 % (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks.
    Functional ingredients from microalgae
    Buono, S. ; Langellotti, A.L. ; Martello, A. ; Rinna, F. ; Fogliano, V. - \ 2014
    Food & Function 5 (2014)8. - ISSN 2042-6496 - p. 1669 - 1685.
    polyunsaturated fatty-acids - induced oxidative stress - chlorella-vulgaris - dunaliella-salina - spirulina-fusiformis - beta-carotene - eicosapentaenoic acid - in-vivo - haematococcus-pluvialis - antioxidant activity
    A wide variety of natural sources are under investigation to evaluate their possible use for new functional ingredient formulation. Some records attested the traditional and ancient use of wild harvested microalgae as human food but their cultivation for different purposes started about 40 years ago. The most popular species are Arthrospira (traditional name, Spirulina), Chlorella spp., Dunaliella spp. and Haematococcus spp. Microalgae provide a bewildering array of opportunities to develop healthier food products using innovative approaches and a number of different strategies. Compared to other natural sources of bioactive ingredients, microalgae have many advantages such as their huge biodiversity, the possibility to grow in arid land and with limited fresh water consumption and the flexibility of their metabolism, which could be adapted to produce specific molecules. All these factors led to very sustainable production making microalgae eligible as one of the most promising foods for the future, particularly as source of proteins, lipids and phytochemicals. In this work, a revision of the knowledge about the use of microalgae as food and as a source of functional ingredients has been performed. The most interesting results in the field are presented and commented upon, focusing on the different species of microalgae and the activity of the nutritionally relevant compounds. A summary of the health effects obtained together with pros and cons in the adoption of this natural source as functional food ingredients is also proposed.
    Effects of oxygen concentration on the growth of Nannochloropsis sp.
    Raso, S. - \ 2013
    Wageningen University. Promotor(en): Rene Wijffels, co-promotor(en): Marian Vermue. - S.l. : s.n. - ISBN 9789461737472 - 157
    algen - voer - aquacultuur - visvoeding - fotobioreactoren - eicosapentaeenzuur - zuurstof - algae - feeds - aquaculture - fish feeding - photobioreactors - eicosapentaenoic acid - oxygen

    ANannochloropsissp. is a promising microalgal resource for production of food, feed and bio-based commodities, as it can grow relatively fast and combines high lipid content with high content of poly-unsaturated fatty acids. High productivity with constant product quality can be achieved in fully controlled closed photobioreactors. In these closed photobioreactors, however, oxygen accumulation occurs and causes inhibition of the growth by photorespiration combined with photoinhibition.

    The inhibitory effects of photorespiration and photoinhibition can be partly dealt with via the carbon concentration mechanism of the cells and by activation of the water-water cycle. At constant high oxygen concentration and high light intensity, however, the growth of the cells ceases. To our surprise, the accumulating oxygen did not affect the growth rate of the algae if the oxygen was removed regularly. In large scale production in closed photobioreactors, it is thus crucial apply degassing to achieve high algal productivity.

    Gezonde vis alternatieven literatuurstudie binnen het beleidsondersteunende project "Nieuwe marktgerichte duurzame eiwitconcepten"
    Sluis, A.A. van der; Vereijken, J.M. - \ 2013
    Wageningen : Wageningen UR - Food & Biobased Research (Rapport / Wageningen UR Food & Biobased Research nr 1383) - 39
    vis - visconsumptie - docosahexaeenzuur - eicosapentaeenzuur - omega-3 vetzuren - voedingsstoffenbronnen - algen - aanbevolen dagelijkse hoeveelheden - voedingsmiddelenwetgeving - voedselverrijking - voeding en gezondheid - Nederland - fish - fish consumption - docosahexaenoic acid - eicosapentaenoic acid - omega-3 fatty acids - nutrient sources - algae - recommended dietary allowances - food legislation - food enrichment - nutrition and health - Netherlands
    Within the policy supporting project "New market-oriented sustainable protein concepts" (BO-08-018.03-002), a literature study is performed to healthy fish alternatives. The research question was: "What is the nutritional importance of fish consumption, what are alternatives to fish, are there technological and legal barriers, and what are the limits for enrichment with nutritional components?"
    Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues
    Balvers, M.G.J. ; Verhoeckx, K.C.M. ; Bijlsma, S. ; Rubingh, C.M. ; Meijerink, J. ; Wortelboer, H.M. ; Witkamp, R.F. - \ 2012
    Metabolomics 8 (2012)6. - ISSN 1573-3882 - p. 1130 - 1147.
    polyunsaturated fatty-acids - n-acylethanolamines - eicosapentaenoic acid - lipid mediators - endogenous cannabinoids - docosahexaenoic acid - amide hydrolase - anandamide - liver - docosatrienes
    It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC–MS/MS. FO generally increased ‘n-3’ NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status.
    Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum and adipose tissue in C57BL/6 mice fed a fish-oil diet
    Balvers, M.G.J. ; Verhoeckx, K.C.M. ; Meijerink, J. ; Bijlsma, S. ; Rubingh, C.M. ; Wortelboer, H.M. ; Witkamp, R.F. - \ 2012
    International Immunopharmacology 13 (2012)2. - ISSN 1567-5769 - p. 204 - 214.
    polyunsaturated fatty-acids - tandem mass-spectrometry - eicosapentaenoic acid - lipidomic analysis - amide hydrolase - human-platelets - expression - mediators - n-3 - dysregulation
    Eicosanoids and endocannabinoids/N-acylethanolamines (NAEs) are fatty acid derived compounds with a regulatory role in inflammation. Considering their complex metabolism, it is likely that inflammation affects multiple compounds at the same time, but how lipid profiles change in plasma and other tissues after an inflammatory stimulus has not been described in detail. In addition, dietary fish oil increases levels of several n-3 fatty acid derived eicosanoids and endocannabinoids, and this may lead to a broader change in the profiles of bioactive lipids. In the present study mice were fed a diet containing 3% w/w fish oil for 6 weeks before receiving i.p. saline or 3 mg/kg lipopolysaccharide (LPS) to induce an inflammatory response. Eicosanoid and endocannabinoid/NAE levels (in total 61 metabolites) in plasma, liver, ileum, and adipose tissue were quantified using targeted lipidomics after 2, 4, 8, and 24 h, respectively. Tissue- and time-dependent effects of LPS on bioactive lipid profiles were observed. For example, levels of CYP derived eicosanoids in the ileum were markedly affected by LPS, whereas this was less pronounced in the plasma and adipose tissue. For some compounds, such as 9,10-DiHOME, opposing effects of LPS were seen in the plasma compared to the other tissues, suggesting differential regulation of bioactive lipid levels after an inflammatory stimulus. Taken together, our results show that plasma levels do not always correlate with the effects found in the tissues, which underlines the need to measure profiles and pathways of mediators involved in inflammation, including endocannabinoid-like structures, in both plasma and tissues
    Metabolic Effects of n-3 PUFA as Phospholipids Are Superior to Triglycerides in Mice Fed a High-Fat Diet: Possible Role of Endocannabinoids
    Rossmeisl, M. ; Jilkova, Z.M. ; Kuda, O. ; Jelenik, T. ; Medrikova, D. ; Stankova, B. ; Kristinsson, B. ; Haraldsson, G.G. ; Svensen, H. ; Stoknes, I. ; Sjövall, P. ; Magnusson, Y. ; Balvers, M.G.J. ; Verhoeckx, K.C.M. ; Tvrzicka, E. ; Bryhn, M. ; Kopecky, J. - \ 2012
    PLoS ONE 7 (2012)6. - ISSN 1932-6203
    krill oil supplementation - tof-sims analysis - seal blubber oil - adipose-tissue - fish-oil - eicosapentaenoic acid - insulin sensitivity - induced obesity - cb1 antagonism - serum-lipids
    Background n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. Methodology/Principal Findings In a ‘prevention study’, C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids ~35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. Conclusions/Significance Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the endocannabinoid system activity in WAT
    Omega-3 fatty acids and coronary heart disease. The final verdict?
    Kromhout, D. - \ 2012
    Current Opinion in Lipidology 23 (2012)6. - ISSN 0957-9672 - p. 554 - 559.
    n-3 fatty-acids - randomized controlled-trials - postmyocardial infarction patients - fatal myocardial-infarction - fish consumption - cardiovascular-disease - eicosapentaenoic acid - risk - metaanalysis - mortality
    Purpose of review: The fish fatty acids eicosapentenoic acid (EPA) and docosahexenoic acid (DHA) may be protective against fatal coronary heart disease (CHD) and sudden cardiac death. This review summarizes the recent findings of prospective cohort studies and randomized controlled trials. Recent findings: A recently published meta-analysis of 17 prospective cohort studies showed that eating fish once a week compared to eating less fish was associated with a 16% lower risk of fatal CHD. Epidemiologic studies with cardiac arrest or sudden cardiac death as endpoint observed also an inverse relation with fish consumption. In contrast, a recently published meta-analysis of 14 randomized, double-blind, placebo-controlled trials in cardiovascular patients did not show a protective effect of an additional amount of EPA-DHA on fatal CHD and sudden cardiac death. Subgroup analyses suggested that this could be because of a low absolute risk as a consequence of the state-of-the-art drug treatment. Summary: Eating fatty fish once or lean fish twice a week is recommended for both primary and secondary prevention of CHD. A definite statement cannot be made about the dosage of EPA-DHA required for secondary prevention of CHD
    Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice
    Horakova, O. ; Medrikova, D. ; Schothorst, E.M. van; Bunschoten, A. ; Keijer, J. - \ 2012
    PLoS ONE 7 (2012)8. - ISSN 1932-6203
    polyunsaturated fatty-acids - impaired glucose-tolerance - induced insulin-resistance - type-2 diabetes-mellitus - activated-receptor-alpha - fish-oil - weight-loss - marine origin - eicosapentaenoic acid - ceramidase activity
    Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.
    Effect of oxygen concentration on the growth of Nannochloropsis sp. at low light intensity
    Raso, S. ; Genugten, B. van; Vermuë, M.H. ; Wijffels, R.H. - \ 2012
    Journal of Applied Phycology 24 (2012)4. - ISSN 0921-8971 - p. 863 - 871.
    eicosapentaenoic acid - inorganic carbon - reactors - mass - photobioreactors - optimization - temperature - metabolism - microalgae - outdoors
    In large-scale microalgal production in tubular photobioreactors, the build-up of O2 along the tubes is one of the major bottlenecks to obtain high productivities. Oxygen inhibits the growth, since it competes with carbon dioxide for the Rubisco enzyme involved in the CO2 fixation to generate biomass. The effect of oxygen on growth of Nannochloropsis sp. was experimentally determined in a fully controlled flat-panel photobioreactor operated in turbidostat mode using an incident photon flux density of 100 µmol photons m-2 s-1 and with only the oxygen concentration as variable parameter. The dissolved oxygen concentration was varied from 20 to 250% air saturation. Results showed that there was no clear effect of oxygen concentration on specific growth rate (mean of 0.48¿±¿0.40 day-1) upon increasing the oxygen concentration from 20% to 75% air saturation. Upon further increasing the oxygen concentration, however, a linear decrease in specific growth rate was observed, ranging from 0.48¿±¿0.40 day-1 at a dissolved oxygen concentration of 75% air saturation to 0.18¿±¿0.01 day-1 at 250% air saturation. In vitro data on isolated Rubisco were used to predict the quantum yield at different oxygen concentrations in the medium. The predicted decrease in quantum yield matches well with the observed decrease that was measured in vivo. These results indicate that the effect of oxygen on growth of Nannochloropsis sp. at low light intensity is only due to competitive inhibition of the Rubisco enzyme. At these sub-saturating light conditions, the presence of high concentrations of oxygen in the medium induced slightly higher carotenoid content, but the increased levels of this protective antioxidant did not diminish the growth-inhibiting effects of oxygen on the Rubisco.
    Fish oil and omega-3 fatty acids in cardiovascular disease: do they really work?
    Kromhout, D. ; Yasuda, S. ; Geleijnse, J.M. ; Shimokawa, H. - \ 2012
    European Heart Journal 33 (2012)4. - ISSN 0195-668X - p. 436 - 443.
    coronary-heart-disease - polyunsaturated fatty-acids - sudden cardiac death - placebo-controlled trial - endothelium-dependent responses - randomized controlled-trials - nitric-oxide synthase - long-term treatment - cod-liver oil - eicosapentaenoic acid
    Omega-3 fatty acids, which are found abundantly in fish oil, exert pleiotropic cardiometabolic effects with a diverse range of actions. The results of previous studies raised a lot of interest in the role of fish oil and omega-3 fatty acids in primary and secondary prevention of cardiovascular diseases. The present review will focus on the current clinical uses of omega-3 fatty acids and provide an update on their effects. Since recently published trials in patients with coronary artery diseases or post-myocardial infarction did not show an effect of omega-3 fatty acids on major cardiovascular endpoints, this review will examine the limitations of those data and suggest recommendations for the use of omega-3 fatty acids
    Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice
    Lu, Y. ; Boekschoten, M.V. ; Wopereis, S. ; Muller, M.R. ; Kersten, A.H. - \ 2011
    Physiological genomics 43 (2011)23. - ISSN 1094-8341 - p. 1307 - 1318.
    activated-receptor-alpha - polyunsaturated fatty-acids - coronary-heart-disease - ppar-alpha - gene-expression - eicosapentaenoic acid - vitamin-k - lipoprotein metabolism - adiponectin secretion - protein expression
    Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 wk treatment with fenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased by fenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for peroxisome proliferator-activated receptor-a, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent toward modulating plasma free fatty acids, cholesterol, and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention.
    The ethanolamide metabolite of DHA, docosahexaenoylethanolamine, shows immunomodulating effects in mouse peritoneal and RAW264.7 macrophages: evidence for a new link between fish oil and inflammation
    Meijerink, J. ; Plastina, P. ; Vincken, J.P. ; Poland, M.C.R. ; Attya, M. ; Balvers, M.G.J. ; Gruppen, H. ; Gabriele, B. ; Witkamp, R.F. - \ 2011
    The British journal of nutrition 105 (2011)12. - ISSN 0007-1145 - p. 1798 - 1807.
    nitric-oxide synthase - monocyte chemoattractant protein-1 - fatty-acid-composition - docosahexaenoic acid - n-acylethanolamine - insulin-resistance - adipose-tissue - reduces atherosclerosis - eicosapentaenoic acid - dietary-fat
    Several mechanisms have been proposed for the positive health effects associated with dietary consumption of long-chain n-3 PUFA (n-3 LC-PUFA) including DHA (22 : 6n-3) and EPA (20 : 5n-3). After dietary intake, LC-PUFA are incorporated into membranes and can be converted to their corresponding N-acylethanolamines (NAE). However, little is known on the biological role of these metabolites. In the present study, we tested a series of unsaturated NAE on the lipopolysaccharide (LPS)-induced NO production in RAW264.7 macrophages. Among the compounds tested, docosahexaenoylethanolamine (DHEA), the ethanolamide of DHA, was found to be the most potent inhibitor, inducing a dose-dependent inhibition of NO release. Immune-modulating properties of DHEA were further studied in the same cell line, demonstrating that DHEA significantly suppressed the production of monocyte chemotactic protein-1 (MCP-1), a cytokine playing a pivotal role in chronic inflammation. In LPS-stimulated mouse peritoneal macrophages, DHEA also reduced MCP-1 and NO production. Furthermore, inhibition was also found to take place at a transcriptional level, as gene expression of MCP-1 and inducible NO synthase was inhibited by DHEA. To summarise, in the present study, we showed that DHEA, a DHA-derived NAE metabolite, modulates inflammation by reducing MCP-1 and NO production and expression. These results provide new leads in molecular mechanisms by which DHA can modulate inflammatory processes.
    Increasing fish consumption does not affect genotozicity markers in the colon in an intervention study
    Pot, G.K. ; Habermann, N. ; Majsak-Newman, G. ; Harvey, L.J. ; Geelen, A. ; Witteman, B.J.M. ; Meeberg, P.C. van de; Hart, A.R. ; Schaafsma, G. ; Hooiveld, G.J.E.J. ; Glei, M. ; Lund, E.K. ; Pool-Zobel, B.L. ; Kampman, E. - \ 2010
    Carcinogenesis 31 (2010)6. - ISSN 0143-3334 - p. 1087 - 1091.
    polyunsaturated fatty-acids - rectal cell-proliferation - fecal water genotoxicity - colorectal-cancer risk - induced dna-damage - comet assay - oxidative stress - eicosapentaenoic acid - dietary - carcinogenesis
    Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly oil-rich fish, which could increase genotoxicity. Therefore, the objective was to investigate the effects of fish on genotoxicity markers in the colon in a randomized controlled parallel intervention study. For a period of 6 months, subjects were randomly allocated to receive two extra weekly portions of (i) oil-rich fish (salmon), (ii) lean fish (cod) or (iii) just dietary advice (DA). The Comet Assay was used to measure the DNA damage-inducing potential of fecal water (n = 89) and DNA damage in colonocytes (n = 70) collected pre- and post-intervention as markers of genotoxicity. Genotoxicity of fecal water was not markedly changed after fish consumption: 1.0% increase in tail intensity (TI) [95% confidence interval (CI) -5.1; 7.0] in the salmon group and 0.4% increase in TI (95% CI -5.3; 6.1) in the cod group compared with the DA group. DNA damage in colonocytes was also not significantly changed after fish consumption, in either the salmon group (-0.5% TI, 95% CI -6.9; 6.0) or cod group (-3.3% TI, 95% CI -10.8; 4.3) compared with the DA group. Measurements of genotoxicity of fecal water and DNA damage in colonocytes did not correlate (r = 0.06, n = 34). In conclusion, increasing consumption of either oil-rich or lean fish did not affect genotoxicity markers in the colon.
    Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: Design and baseline characteristics of the Alpha Omega Trial
    Geleijnse, J.M. ; Giltay, E.J. ; Schouten, E.G. ; Goede, J. de; Oude Griep, L.M. ; Teitsma-Jansen, A.M. ; Katan, M.B. ; Kromhout, D. - \ 2010
    American Heart Journal 159 (2010). - ISSN 0002-8703 - p. 539 - 546.
    coronary-heart-disease - serum cholesteryl esters - fish consumption - linolenic acid - eicosapentaenoic acid - myocardial-infarction - secondary-prevention - risk - metaanalysis - mortality
    Background Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether alpha-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention. Objectives The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction. Design The multicenter Alpha Omega Trial is a randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD. Results The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrolment. Mean body mass index was 27.7 kg/m(2), and 17% smoked. Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD. Current status Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010. (Am Heart J 2010; 159: 539-546. e2.)
    Fish consumption and markers of colorectal cancer risk: a multicenter randomized controlled trial.
    Pot, G.K. ; Majsak-Newman, G. ; Geelen, A. ; Harvey, L. ; Nagengast, F.M. ; Witteman, B.J.M. ; Meeberg, P.C. van de; Timmer, R. ; Tan, A. ; Wahab, P.J. ; Hart, A.R. ; Williams, M.P. ; Przybylska-Philips, K. ; Dainty, J.R. ; Schaafsma, G. ; Kampman, E. ; Lund, E.K. - \ 2009
    American Journal of Clinical Nutrition 90 (2009)2. - ISSN 0002-9165 - p. 354 - 361.
    inflammatory-bowel-disease - rectal cell-proliferation - whole crypt mounts - n-3 fatty-acids - eicosapentaenoic acid - healthy-subjects - colonic-mucosa - rat colon - apoptosis - oil
    Background: Diet is a major factor in the etiology of colorectal cancer, with high fish consumption possibly decreasing colorectal cancer risk, as was shown in several observational studies. To date, no intervention trials have examined the possible beneficial effects of fish intake on colorectal cancer risk. Objective: The objective was to investigate the effects of a 6-mo intervention with oil-rich or lean fish on apoptosis and mitosis within the colonic crypt. Design: In a multicenter, randomized, controlled intervention trial, patients with colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease were recruited (n = 242) and randomly allocated to receive dietary advice plus either 300 g oil-rich fish (salmon) per week (n = 82), 300 g lean fish (cod) per week (n = 78), or only dietary advice (DA) (n = 82). Apoptosis and mitosis were measured in colonic biopsy samples collected before and after intervention (n = 213). Results: The total number of apoptotic cells per crypt did not increase in the salmon or cod group: –0.10 (95% CI: –0.36, 0.16) and –0.06 (95% CI: –0.32, 0.20), respectively, compared with the DA group. The total number of mitotic cells per crypt decreased nonsignificantly in the salmon group (–0.87; 95% CI: –2.41, 0.68) and in the cod group (–1.04; 95% CI: –2.62, 0.53) compared with the DA group. Furthermore, the distribution of mitosis within the crypt did not significantly change in either group. Conclusion: An increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6 mo does not markedly change apoptotic and mitotic rates in the colonic mucosa. This trial was registered at as NCT00145015
    No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-aged individuals
    Pot, G.K. ; Brouwer, I.A. ; Enneman, A. ; Rijkers, G.T. ; Kampman, E. ; Geelen, A. - \ 2009
    European Journal of Clinical Nutrition 63 (2009)11. - ISSN 0954-3007 - p. 1353 - 1359.
    polyunsaturated fatty-acids - long-chain n-3 - physical-activity scale - adhesion molecules - dietary supplementation - eicosapentaenoic acid - cytokine production - human monocytes - elderly pase - plasma
    Background: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. Methods: Individuals (n=77) aged 50–70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. Results: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. Conclusion: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent
    Identification of potential serum biomarkers of inflammation and lipid modulation that are altered by fish oil supplementation in healthy volunteers
    Roos, B. de; Geelen, A. ; Ross, K. ; Rucklidge, G. ; Reid, M. ; Duncan, G. ; Caslake, M.J. ; Horgan, G. ; Brouwer, I.A. - \ 2008
    Proteomics 8 (2008)10. - ISSN 1615-9853 - p. 1965 - 1974.
    tumor-necrosis-factor - n-3 fatty-acids - high-density-lipoprotein - human endothelial-cells - acute-phase response - eicosapentaenoic acid - dietary supplementation - plasma triglycerides - mobilizing factor - factor-alpha
    Long chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) lower risk of coronary heart disease (CHD), but mechanisms are not well understood. We used proteomics to identify human serum proteins that are altered by n-3 LCPUFA. Such proteins could identify pathways whereby they affect CHD. Eighty-one healthy volunteers entered a double blind randomised trial to receive 3.5 g of fish oil or 3.5 g of high oleic sunflower oil daily. Serum was collected before and after 6 wk of intervention. Serum was analysed by proteomics using 2-DE. Proteins that were differentially regulated were identified by MS. We also analysed serum apolipoprotein A1 (apo A1), high-density lipoprotein (HDL) particle size and haptoglobin. Serum levels of apo A1, apo L1, zinc--2-glycoprotein, haptoglobin precursor, -1-antitrypsin precursor, antithrombin III-like protein, serum amyloid P component and haemopexin were significantly downregulated (all p
    A comparative study on the effect of algal and fish oil on viability and cell proliferation of Caco-2 cells
    Beelen, V.A. van; Roeleveld, J. ; Mooibroek, H. ; Sijtsma, L. ; Bino, R.J. ; Bosch, H.J. ; Rietjens, I.M.C.M. ; Alink, G.M. - \ 2007
    Food and Chemical Toxicology 45 (2007)5. - ISSN 0278-6915 - p. 716 - 724.
    marine fatty-acids - eicosapentaenoic acid - docosahexaenoic acid - lipid-peroxidation - cancer prevention - health-benefits - rapid method - rat colon - n-3 - apoptosis
    Polyunsaturated fatty acid (PUFA) rich micro-algal oil was tested in vitro and compared with fish oil for antiproliferative properties on cancer cells in vitro. Oils derived from Crypthecodinium cohnii, Schizochytrium sp. and Nitzschia laevis, three commercial algal oil capsules, and menhaden fish oil were used in cell viability and proliferation tests with human colon adenocarcinoma Caco-2 cells. With these tests no difference was found between algal oil and fish oil. The nonhydrolysed algal oils and fish oil showed a much lower toxic effect on cell viability, and cell proliferation in Caco-2 cells than the hydrolysed oils and the free fatty acids (FFAs). Eicosapentaenoic acid (EPA; C20:5n ¿ 3) and docosahexaenoic acid (DHA; C22:6n ¿ 3) were used as samples for comparison with the tested hydrolysed and nonhydrolysed oils. The hydrolysed samples showed comparative toxicity as the free fatty acids and no difference between algal and fish oil. Oxidative stress was shown to play a role in the antiproliferative properties of EPA and DHA, as ¿-tocopherol could partially reverse the EPA/DHA-induced effects. The results of the present study support a similar mode of action of algal oil and fish oil on cancer cells in vitro, in spite of their different PUFA content
    N-3 fatty acids, cardiac arrhythmia and fatal coronary heart disease
    Brouwer, I.A. ; Geelen, A. ; Katan, M.B. - \ 2006
    Progress in Lipid Research 45 (2006)4. - ISSN 0163-7827 - p. 357 - 67.
    dietary fish-oil - acute myocardial-infarction - rat ventricular myocytes - reinfarction trial dart - atrial-fibrillation - sudden-death - eicosapentaenoic acid - cardiovascular health - risk stratification - clinical-trial
    n-3 Polyunsaturated fatty acids (n-3 PUFA) are suggested to prevent cardiac death via inhibition of cardiac arrhythmia. In this review we discuss the results of human studies on intake of n-3 PUFAs and heart disease and, more specifically, on cardiac arrhythmia. Observational studies indicate that intake of fish is associated with a lower incidence of fatal coronary heart disease in several populations. These studies are fairly consistent, but people that have a high intake of fatty fish might have a healthier lifestyle in general, and such confounding is difficult to remove completely with statistical adjustments and corrections. Evidence from trials is less clear. In two open label trials in patients with a previous myocardial infarction intake of fish or fish oil prevented fatal coronary heart disease. In contrast, a trial in patients with angina suggested a higher risk of sudden cardiac death in patients taking fish oil. Furthermore, results of trials in patients with an implantable cardioverter defibrillator (ICD) that investigated effects of fish oil on arrhythmia in patients already suffering from ventricular tachycardia are not consistent. Also, studies on relationships between intake of n-3 PUFA from fish and less life-threatening forms of arrhythmia, such as atrial fibrillation and premature ventricular complexes (PVCs) are equivocal. Thus, after 35 years of research the question whether fish prevents heart disease remains unanswered, and an anti-arrhythmic effect of fish oil remains unproven although the idea is still viable and is being actively tested in further trials.
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