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      Dietary supplementation with n-3-fatty acids in patients with pancreatic cancer and cachexia: marine phospholipids versus fish oil - a randomized controlled double-blind trial

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          Abstract

          Background

          Like many other cancer patients, most pancreatic carcinoma patients suffer from severe weight loss. As shown in numerous studies with fish oil (FO) supplementation, a minimum daily intake of 1.5 g n-3-fatty acids (n-3-FA) contributes to weight stabilization and improvement of quality of life (QoL) of cancer patients. Given n-3-FA not as triglycerides (FO), but mainly bound to marine phospholipids (MPL), weight stabilization and improvement of QoL has already been seen at much lower doses of n-3-FA (0,3 g), and MPL were much better tolerated. The objective of this double-blind randomized controlled trial was to compare low dose MPL and FO formulations, which had the same n-3-FA amount and composition, on weight and appetite stabilization, global health enhancement (QoL), and plasma FA-profiles in patients suffering from pancreatic cancer.

          Methods

          Sixty pancreatic cancer patients were included into the study and randomized to take either FO- or MPL supplementation. Patients were treated with 0.3 g of n-3-fatty acids per day over six weeks. Since the n-3-FA content of FO is usually higher than that of MPL, FO was diluted with 40% of medium chain triglycerides (MCT) to achieve the same capsule size in both intervention groups and therefore assure blinding. Routine blood parameters, lipid profiles, body weight, and appetite were measured before and after intervention. Patient compliance was assessed through a patient diary. Quality of life and nutritional habits were assessed with validated questionnaires (EORTC-QLQ-C30, PAN26). Thirty one patients finalized the study protocol and were analyzed (per-protocol-analysis).

          Results

          Intervention with low dose n-3-FAs, either as FO or MPL supplementation, resulted in similar and promising weight and appetite stabilization in pancreatic cancer patients. MPL capsules were slightly better tolerated and showed fewer side effects, when compared to FO supplementation.

          Conclusion

          The similar effects between both interventions were unexpected but reliable, since the MPL and FO formulations caused identical increases of n-3-FAs in plasma lipids of included patients after supplementation. The effects of FO with very low n-3-FA content might be explained by the addition of MCT. The results of this study suggest the need for further investigations of marine phospholipids for the improvement of QoL of cancer patients, optionally in combination with MCT.

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          Most cited references35

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          Cachexia in cancer patients.

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            Prostaglandins and cancer.

            Chemoprevention has been considered as a possible approach for cancer prevention. A significant effort has been made in the development of novel drugs for both cancer prevention and treatment over the past decade. Recent epidemiological studies and clinical trials indicate that long term use of aspirin and similar agents, also called non-steroidal anti-inflammatory drugs (NSAIDs), can decrease the incidence of certain malignancies, including colorectal, oesophageal, breast, lung, and bladder cancers. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. COX-2 derived prostaglandin E(2)(PGE(2)) can promote tumour growth by binding its receptors and activating signalling pathways which control cell proliferation, migration, apoptosis, and/or angiogenesis. However, the prolonged use of high dosages of COX-2 selective inhibitors (COXIBs) is associated with unacceptable cardiovascular side effects. Thus it is crucial to develop more effective chemopreventive agents with minimal toxicity. Recent efforts to identify the molecular mechanisms by which PGE(2) promotes tumour growth and metastasis may provide opportunities for the development of safer strategies for cancer prevention and treatment.
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              Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not?

              Because inflammation is appreciated as a unifying basis of many widely occurring diseases, the mechanisms involved in its natural resolution are of considerable interest. Using contained, self-limited inflammatory exudates and a systems approach, novel lipid-derived mediators and pathways were uncovered in the resolution of inflammatory exudates. These new families of local mediators control both the duration and magnitude of acute inflammation as well as the return of the site to homeostasis in the process of catabasis. This new genus of specialized proresolving mediators (SPM) includes essential fatty acid-derived lipoxins, resolvins, protectins, and, most recently, maresins. These families were named based on their unique structures and potent stereoselective actions. The temporally initiated biosynthesis of SPM and their direct impact on leukocyte trafficking and macrophage-directed clearance mechanisms provide clear evidence that resolution is an active, programmed response at the tissue level. Moreover, SPM that possess anti-inflammatory (ie, limiting PMN infiltration) and proresolving (enhance macrophage uptake and clearance of apoptotic PMN and microbial particles) actions as well as stimulating mucosal antimicrobial responses demonstrate that anti-inflammation and proresolution are different responses of the host and novel defining properties of these molecules. The mapping of new resolution circuits has opened the possibility for understanding mechanisms that lead from acute to chronic inflammation, or to the resolution thereof, as well as to potential, resolution-based immunopharmacological therapies.
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                Author and article information

                Contributors
                kristin.werner@uniklinik-freiburg.de
                kuellenberg@cochrane.de
                lenka.taylor@med.uni-heidelberg.de
                tobias.keck@uksh.de
                unger@zentrum-krebsmedizin.de
                ulrich.hopt@uniklinik-freiburg.de
                ulrich.massing@pharmazie.uni-freiburg.de
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                2 June 2017
                2 June 2017
                2017
                : 16
                : 104
                Affiliations
                [1 ]ISNI 0000 0000 9428 7911, GRID grid.7708.8, , Institute of Surgical Pathology, Medical Center-University of Freiburg, ; Freiburg, Germany
                [2 ]ISNI 0000 0000 9428 7911, GRID grid.7708.8, German Cochrane Center Freiburg, , Medical Center-University of Freiburg, ; Freiburg, Germany
                [3 ]ISNI 0000 0000 9428 7911, GRID grid.7708.8, Department of Surgery, , Medical Center-University of Freiburg, ; Freiburg, Germany
                [4 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Pharmacy, , Ruprecht-Karls-University Heidelberg, ; Heidelberg, Germany
                [5 ]ISNI 0000 0001 0057 2672, GRID grid.4562.5, Clinic for Surgery, , Medical Center University of Lübeck, ; Lübeck, Germany
                [6 ]Cancer Center Freiburg, Freiburg, Germany
                [7 ]GRID grid.5963.9, Institute of Pharmaceutical Science, , University of Freiburg, ; Freiburg, Germany
                [8 ]Tumor Biology Center Freiburg, Freiburg, Germany
                Author information
                http://orcid.org/0000-0002-5979-5982
                Article
                495
                10.1186/s12944-017-0495-5
                5455128
                28578704
                91172450-e4fb-4bee-a17b-485e9553be3c
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 March 2017
                : 23 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: 0315477B
                Award Recipient :
                Funded by: Verein zur Förderung der Krebsmedizin - Kirstins Weg e.V.
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Biochemistry
                pancreatic cancer,cancer cachexia,marine phospholipids,fish oil,medium chain triglycerides,n-3-fatty acids,weight stabilization,randomized controlled trial

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