2160 articles - 10.09.10
1: Mol Nutr Food Res. 2010 Sep 7; [Epub ahead of print]
Cho JY, Chi SG, Chun HS.
Korea Food Research Institute, Backhyun-dong, Bundang-gu, Sungnam-si, Kyonggi-do, Korea.
Scope: Dietary supplementation of n-3 PUFAs, containing docosahexaenoic acid (DHA), modulates the symptoms of colitis. Hence, we investigated the effects of oral administration of pure DHA and the therapeutic agent sulfasalazine (SAL) on chemically induced colitis in mice, and analyzed the expression levels of DHA-responsive genes in colonic tissue using cDNA arrays.Methods and results: Colitis in BALB/c mice was induced by feeding 5% dextran sulfate sodium (DSS) in drinking water for 7 days. DHA (30 mg/kg/day, DHA) or SAL (100 mg/kg/day, SAL) was administered orally throughout the treatment along with DSS. The DHA-treated group showed significant reduction of the weight loss and colon shortening compared to the DSS-treated colitis group. In contrast, SAL treatment was effective in reducing colon shortening, stool consistency and bleeding scores. DHA and SAL treatments also significantly reduced the changes in inflammation of the colon, and reversed the increase in myeloperoxidase activity induced by DSS. Among DSS-responsive genes, those for inflammatory cytokines (IL-1beta, CD14 antigen and tumor necrosis factor receptor superfamily, member 1b), membrane remodeling genes (matrix metalloproteinase-3, -10 and -13) and acute phase proteins (S100 calcium-binding protein A8), which were increased by DSS, were downregulated by DHA or SAL treatment.Conclusions: DHA was effective in alleviating DSS-induced colitis in mice, partly by modulating the expression levels of genes involved in colitis.
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PMID: 20824662 [PubMed - as supplied by publisher]2: Mar Pollut Bull. 2010 Sep 3; [Epub ahead of print]
Lloret J.
University of Girona, Faculty of Sciences, Department of Environmental Sciences, 17071 Girona, Catalonia, Spain.
This paper summarizes the overall benefits supplied by Mediterranean marine biodiversity to human health and highlights the anthropogenic and environmental causes that are threatening these benefits. First, the Mediterranean Sea is a valuable source of seafood, which is an important component of the so-called "Mediterranean diet". This type of diet has several health benefits, including cardio and cancer protective effects, which are attributed to the high intake of seafood-derived n-3 (omega-3) fatty acids. Second, the Mediterranean marine organisms, particularly the benthic ones, have furnished a large variety of bioactive metabolites, some of which are being developed into new drugs to threat major human diseases such as cancer. Third, the Mediterranean coastal areas provide environments for practising maritime leisure activities that provide physical and psychological benefits to users. Despite all this, fishing, tourism, contamination and sea warming are deteriorating this rich marine ecosystem, which needs to be protected to assure human welfare. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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PMID: 20822779 [PubMed - as supplied by publisher]3: Prostaglandins Leukot Essent Fatty Acids. 2010 Sep 1; [Epub ahead of print]
McNamara RK, Jandacek R, Rider T, Tso P, Cole-Strauss A, Lipton JW.
Department of Psychiatry, University of Cincinnati College of Medicine, 260 Stetson Street, Suite 3306, Cincinnati, OH 45219-0516, USA.
Omega-3 (n-3) fatty acid deficiency, elevated inflammatory signaling, and central serotonin (5-HT) turnover have separately been implicated in the pathophysiology of major depressive disorder (MDD). In the present study we investigated the interrelationship between n-3 fatty acid status, pro-inflammatory signaling activity, and central 5-HT turnover in vivo. Rats were fed diets with or without the n-3 fatty acid precursor alpha-linolenic acid (ALA) during perinatal development (E0-P100), and a subset of rats fed the ALA- diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). In adulthood (P100), plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), and C-reactive protein (CRP) levels were measured. Additionally, indices of liver n-6 fatty acid biosynthesis, erythrocyte fatty acid composition, and regional brain monoamine turnover were determined. Indices of liver delta-6 desaturase activity were up-regulated in n-3-deficient rats, and were associated with greater erythrocyte membrane arachidonic acid (AA, 20:4 n-6) composition. Plasma IL-6 (p=0.001), TNFalpha (p=0.02), and CRP (p=0.001) concentrations were significantly greater in n-3-deficient rats relative to controls. The 5-HIAA/5-HT ratio was significantly greater in frontal cortex, hypothalamus, and ventral striatum of n-3-deficient rats relative to controls. Changes in membrane n-3 and n-6 fatty acid composition, elevations in plasma IL-6 and TNFalpha, and increased central 5-HT turnover were all prevented by normalization of n-3 fatty acid status. Erythrocyte docosahexaenoic acid (DHA, 22:6 n-3) was inversely correlated, and AA and the AA/DHA and AA/eicosapentaenoic acid ratios were positively correlated, with plasma IL-6, TNFalpha, and CRP levels. Plasma IL-6 levels were positively correlated with 5-HIAA/5-HT ratios in all brain regions. These preclinical data provide evidence for a functional link between n-3 fatty acid deficiency, elevated peripheral inflammatory signaling, and increased central 5-HT turnover. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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PMID: 20817496 [PubMed - as supplied by publisher]4: Oncol Rep. 2010 Oct;24(4):815-28.
Strohle A, Zanker K, Hahn A.
Nutrition Physiology and Human Nutrition Unit, Institute of Food Science, Leibniz University of Hannover, Hannover, Germany. stroehle@nutrition.uni-hannover.de
In the course of cancer disease, many oncological patients develop tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients. The inadequate nutritional status and the cancer anorexia-cachexia syndrome related to it are clinically relevant, as the response to antineoplastic measures, such as radiation and chemotherapy, is diminished, their side effects aggravated and the patient's quality of life and prognosis negatively affected. Therefore, the supportive nutrition care of oncological patients is of central importance. In this context, vitamins, minerals and long-chain omega -3 fatty acids are becoming more and more relevant in oncology although the benefit of such supplements is discussed controversially. Starting from a description of the etiopathogenesis and the pathophysiological consequences of cancer-associated malnutrition, the present study provides an overview of the importance of micronutrients for oncological patients. In the case of reduced food intake and/or inappropriate food choice the use of a multi-vitamin-multimineral supplement administered in physiological doses, i.e. nutrient quantities approximately corresponding to the recommended daily allowances, can be generally recommended. However, to enhance postoperative wound healing, it seems that cancer patients require higher amounts of micronutrients than healthy individuals. Because vitamin D deficiency is highly prevalent in oncological patients, improvement of vitamin D status is of special interest.
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PMID: 20811659 [PubMed - in process]5: Cancer Res. 2010 Aug 26; [Epub ahead of print]
Woodworth HL, McCaskey SJ, Duriancik DM, Clinthorne JF, Langohr IM, Gardner EM, Fenton JI.
Food Science and Human Nutrition, Michigan State University.
Inflammatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components that reduced inflammation are associated with lower cancer risk. The long chain omega-3 fatty acid, docosahexaenoic acid (DHA), is present in fish oil and has potent anti-inflammatory properties. The objective of this study was to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced colitis and colon cancer risk in a mouse model. When SMAD3-/- mice are exposed to Helicobacter hepaticus, mild colitis is observed 4 weeks post infection. Mice were fed isocaloric diets modified to include corn oil, safflower oil, or DFO (doses ranging from 0.75-6.00%) as the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus, DFO feeding continued, and mice were sacrificed 4 weeks after-infection. The colon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected and analyzed for T cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis and adenocarcinoma formation. DFO consumption was associated with decreased CD8+ cell frequency and diminished CD69 expression on CD4+ and CD8+ T cell populations. Mice consuming DFO also exhibited higher FoxP3+ CD25+ CD4+ T regulatory (Treg) cell frequency, FoxP3 expression, and altered L-selectin expression during infection. We concluded DFO-fed mice may be less equipped to mount a successful response to Helicobacter hepaticus infection increasing colon cancer risk. These results support the need to establish a tolerable upper limit for DHA intake particularly in the context of chronic inflammatory conditions like IBD.
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PMID: 20798218 [PubMed - as supplied by publisher]6: J Nutr. 2010 Aug 25; [Epub ahead of print]
van der Meij BS, Langius JA, Smit EF, Spreeuwenberg MD, von Blomberg BM, Heijboer AC, Paul MA, van Leeuwen PA.
Department of Nutrition and Dietetics, Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.
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PMID: 20739445 [PubMed - as supplied by publisher]7: Biochim Biophys Acta. 2010 Aug 21; [Epub ahead of print]
Keijer J, Bekkenkamp-Grovenstein M, Venema D, Dommels YE.
Human and Animal Physiology, Wageningen University, The Netherlands.
Cancer cells are resistant to apoptosis and show a shift in energy production from mitochondrial oxidative phosphorylation to cytosolic glycolysis. Apoptosis resistance and metabolic reprogramming are linked in many cancer cells and both processes center on mitochondria. Clearly, mutated cancer cells escape surveillance and turn into selfish cells. However, many of the mechanisms that operate cellular metabolic control still function in cancer cells. This review describes the metabolic importance of glucose and glutamine, glycolytic enzymes, oxygen, growth cofactors and mitochondria and focuses on the potential role of bioactive food components, including micronutrients. The role of B- and A-vitamin cofactors in (mitochondrial) metabolism is highlighted and the cancer protective potential of omega-3 fatty acids and several polyphenols is discussed in relation to metabolic reprogramming, including the mechanisms that may be involved. Furthermore, it is shown that cancer cell growth reduction by limiting the growth cofactor folic acid seems to be associated with reversal of metabolic reprogramming. Altogether, reversal of metabolic reprogramming may be an attractive strategy to increase susceptibility to apoptotic surveillance. Food bioactive components that affect various aspects of metabolism may be important tools to reverse glycolytic to oxidative metabolism and enhance sensitivity to apoptosis. The success of such a strategy may depend on several actors, acting in concert. Growth cofactors may be one of these, which call for careful (re)evaluation of their function in normal and in cancer metabolism. Copyright (c) 2010. Published by Elsevier B.V.
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PMID: 20732296 [PubMed - as supplied by publisher]8: J Nutr. 2010 Aug 19; [Epub ahead of print]
Hassan A, Ibrahim A, Mbodji K, Coeffier M, Ziegler F, Bounoure F, Chardigny JM, Skiba M, Savoye G, Dechelotte P, Marion-Letellier R.
Appareil Digestif Environnement Nutrition, Medicine University, I.F.R. 23, Institute of biomedical research, 22, 76183 Rouen cedex, France.
We have previously shown that alpha-linolenic acid (ALA), a (n-3) PUFA exerts in vitro antiinflammatory effects in the intestine. In this study, we aimed to evaluate its effect on inflammatory and oxidative stress in a colitis model. Colitis was induced in 2 groups at d 0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas the control group received the vehicle. Rats we fed 450 mgkg(-1)d(-1) of ALA (TNBS+ALA) while the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from d -7 to d 7). RBC fatty acid composition was assessed. Oxidative stress was studied by measuring urinary 8-isoprostanes (8-IP) and colon glutathione (GSH) concentration and inducible nitric oxide synthase (iNOS) expression. Colitis was assessed histologically, by production of proinflammatory mediators, including cytokines, leukotrienes B(4) (LTB(4)), and cyclooxygenase-2 (COX-2) and by nuclear factor-kappaB (NF-kappaB) activation. The ALA-rich diet significantly increased the RBC levels of ALA, eicosapentaenoic acid, and docosapentaenoic acid (n-3) compared with the TNBS group (P < 0.01 for all). The beneficial effect of ALA supplementation on oxidative stress was reflected by lower urinary 8-IP levels (P < 0.05), a normalized colon GSH concentration (P < 0.01), and reduced colon iNOS expression (P < 0.05) compared with the TNBS group. ALA also protected against colon inflammation as assessed by lower tumor necrosis factor-alpha secretion and mRNA level (P < 0.05), reduced NF-kappaB activation (P = 0.01), and lower colon lipid mediator concentrations such as LTB(4) and COX-2 (P < 0.05) compared with the TNBS group. These findings show that an ALA-rich formula is beneficial to TNBS-induced colitic rats via inhibition of oxidative and inflammatory stress.
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PMID: 20724486 [PubMed - as supplied by publisher]9: Lipids. 2010 Sep;45(9):843-54. Epub 2010 Aug 19.
Varma S, Eskin MN, Bird R, Dolenko B, Raju J, Ijare OB, Bezabeh T.
National Research Council Institute for Biodiagnostics, 435 Ellice Ave., Winnipeg, MB, R3B 1Y6, Canada.
People with inflammatory bowel disease (IBD) are at risk for developing colorectal cancer, and this risk increases at a rate of 1% per year after 8-10 years of having the disease. Saturated and omega-6 polyunsaturated fatty acids (PUFAs) have been implicated in its causation. Conversely, omega-3 PUFAs may have the potential to confer therapeutic benefit. Since proton magnetic resonance spectroscopy ((1)H MRS) combined with pattern recognition methods could be a valuable adjunct to histology, the objective of this study was to analyze the potential of (1)H MRS in assessing the effect of dietary fatty acids on colonic inflammation. Forty male Sprague-Dawley rats were administered one of the following dietary regimens for 2 weeks: low-fat corn oil (omega-6), high-fat corn oil (omega-6), high-fat flaxseed oil (omega-3) or high-fat beef tallow (saturated fatty acids). Half of the animals were fed 2% carrageenan to induce colonic inflammation similar to IBD. (1)H MRS and histology were performed on ex vivo colonic samples, and the (1)H MR spectra were analyzed using a statistical classification strategy (SCS). The histological and/or MRS studies revealed that different dietary fatty acids modulate colonic inflammation differently, with high-fat corn oil being the most inflammatory and high-fat flaxseed oil the least inflammatory. (1)H MRS is capable of identifying the biochemical changes in the colonic tissue as a result of inflammation, and when combined with SCS, this technique accurately differentiated the inflamed colonic mucosa based on the severity of the inflammation. This indicates that MRS could serve as a valuable adjunct to histology in accurately assessing colonic inflammation. Our data also suggest that both the type and the amount of fatty acids in the diet are critical in modulating IBD.
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PMID: 20721632 [PubMed - in process]10: Photochem Photobiol Sci. 2010 Sep 24;9(9):1244-51. Epub 2010 Aug 12.
Kello M, Mikes J, Jendzelovsky R, Koval J, Fedorocko P.
Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01, Kosice, Slovakia.
Since many studies have suggested the impact of dietary polyunsaturated fatty acids on cancer progression and prognosis, there is an assumption of possible pre-sensitizing effects of their application in combined treatment. The present work evaluates modulation of photodynamic therapy (PDT) with hypericin by pre-treatment with n-3 and n-6 fatty acids in HT-29 and HeLa tumour cells. We observed stimulation of cytotoxic effects by docosahexaenoic acid (n-3) and arachidonic acid (n-6) in several stages of action in both cell lines. Treatment with either fatty acids or photodynamic therapy alone induced apoptosis in a dose- and time-dependent manner; however the effect was even more striking in mutual combination applied as pre-treatment with fatty acids prior to photodynamic therapy. Moreover, the combination also induced changes in membrane lipid composition leading to alteration in cell membrane fluidity. Increased toxicity of combined treatment was also confirmed by the presence of oxidative stress demonstrated by ROS production, RNS accumulation and increased presence of lipoperoxides. In conclusion, we suggest that pre-treatment with polyunsaturated fatty acids may contribute to cytotoxic effects induced by photodynamic therapy with hypericin.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20714672 [PubMed - in process]11: Biochimie. 2010 Aug 4; [Epub ahead of print]
Blouin JM, Bortoli S, Nacfer M, Collinet M, Penot G, Laurent-Puig P, Forest C.
Institut National de la Sante et de la Recherche Medicale UMR-S 747, Universite Paris Descartes, Pharmacologie Toxicologie et Signalisation Cellulaire, 45 rue des Saints-Peres, 75006 Paris, France.
The polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) reduces proliferation of several cell types, including colon tumor cells, and regulates gene expression in a cell- and gene-selective manner. In hepatocytes, the fatty acid synthase (FAS) gene is down-regulated by DHA whereas the carnitine palmitoyltransferase-1 (CPT-1) gene is up-regulated. In adipocytes but not in hepatocytes, the expression of the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) gene is stimulated by unsaturated FA, including DHA. We monitored the expression of the FAS, CPT-1 and PEPCK-C genes in rat and human colon and in colonic tumors from humans. The ratio of PEPCK-C to FAS transcripts was in favor of PEPCK-C in human and rat colon, whereas the opposite occurred in Caco2 tumoral cells. FAS gene expression declined from proliferative to differentiated Caco2 cells, while in contrast the expression of PEPCK-C and CPT-1 genes increased. DHA strongly induced expression of the PEPCK-C and CPT-1 genes, in correlation with decreased cell growth, while, as expected, it reduced FAS mRNA. We assessed the relative expression of PEPCK-C, CPT-1 and FAS genes in fragments of colonic tumors and adjacent non-tumoral tissue from a series of 10 patients. PEPCK-C and CPT-1 mRNAs are more abundant in non-tumoral tissues than in the tumoral counterpart, whereas the opposite occurred for the FAS gene. Therefore, the PEPCK-C gene can be defined as a new negative marker for colonic tumors and a target for the anti-tumorigenic action of omega-3 PUFAs. Copyright (c) 2010. Published by Elsevier Masson SAS.
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PMID: 20691246 [PubMed - as supplied by publisher]12: J Agric Food Chem. 2010 Sep 8;58(17):9579-86.
Owczarek-Fendor A, De Meulenaer B, Scholl G, Adams A, Van Lancker F, Yogendrarajah P, Uytterhoeven V, Eppe G, De Pauw E, Scippo ML, De Kimpe N.
Department of Food Safety and Food Quality, nutriFOODchem unit, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
The formation of the possibly carcinogenic process contaminant furan was studied in starch-based emulsions during heat treatments as applied for sterilization. Fresh and oxidized soybean, sunflower, high-oleic sunflower, olive, linseed, and rapeseed oils were compared. Results indicated that both the oil type, in particular, the fatty acid composition, and the oxidation degree of the oil determined the susceptibility of the oils to generate furan upon heating. Thus, oils containing the nutritionally relevant omega-3 unsaturated alpha-linolenic acid proved to be able to generate significant amounts of furan if the oils were oxidized. No clear relationship between p-anisidine values of various oils and the amount of generated furan could be observed. However, in the case of soybean oil, significantly more furan was produced upon an increase in oxidation degree. Surprisingly, furan formation in food-relevant systems containing fresh lipids proved to be a minor route (up to 1.5 ppb furan) compared to a previously studied vitamin C containing model system (up to 13 ppb furan).
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20690672 [PubMed - in process]13: Neoplasia. 2010 Aug;12(8):618-27.
Hawcroft G, Loadman PM, Belluzzi A, Hull MA.
Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom. medgha@leeds.ac.uk
The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), in the free fatty acid (FFA) form, has been demonstrated to reduce adenoma number and size in patients with familial adenomatous polyposis. However, the mechanistic basis of the antineoplastic activity of EPA in the colorectum remains unclear. We tested the hypothesis that EPA-FFA negatively modulates synthesis of and signaling by prostaglandin (PG) E(2) in human colorectal cancer (CRC) cells. EPA-FFA induced apoptosis of cyclooxygenase (COX)-2-positive human HCA-7 CRC cells in vitro. EPA-FFA in cell culture medium was incorporated rapidly into phospholipid membranes of HCA-7 human CRC cells and acted as a substrate for COX-2, leading to reduced synthesis of PGE(2) and generation of PGE(3). Alone, PGE(3) bound and activated the PGE(2) EP4 receptor but with reduced affinity and efficacy compared with its "natural" ligand PGE(2). However, in the presence of PGE(2), PGE(3) acted as an antagonist of EP4 receptor-dependent 3',5' cyclic adenosine monophosphate induction in naturally EP4 receptor-positive LoVo human CRC cells and of resistance to apoptosis in HT-29-EP4 human CRC cells overexpressing the EP4 receptor. We conclude that EPA-FFA drives a COX-2-dependent "PGE(2)-to-PGE(3) switch" in human CRC cells and that PGE(3) acts as a partial agonist at the PGE(2) EP4 receptor.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20689756 [PubMed - in process]14: Cardiol Res Pract. 2010;2010:824938. Epub 2010 Jun 29.
Singh RB, Demeester F, Wilczynska A.
Tsim Tsoum Institute, Ul. Golebia 2, 31-007 Krakow, Poland.
The Tsim Tsoum Concept means that humans evolved on a diet in which nature recommends to ingest fatty acids in a balanced ratio (polyunsaturated(P) : saturated(S) =w-6 : w-3 = 1 : 1)as part of dietary lipid pattern where monounsaturated fatty acids(MUFA) is the major fatty acid(P : M : S = 1 : 6 : 1) in the background of other dietary factors; antioxidants, vitamins, minerals and fiber as well as physical activity and low mental stress. Several hundred years ago, our diet included natural foods; fruits, vegetables, green vegetables, seeds, eggs and honey. Fish, and wild meat were also available to pre-agricultural humans which shaped modern human genetic nutritional requirement. Cereal grains (refined), and vegetable oils that are rich in w-6 fatty acids are relatively recent addition to the human diet that represent dramatic departure from those foods to which we are adapted. Excess of linoleic acid, trans fatty acids (TFA), saturated and total fat as well as refined starches and sugar are proinflammatory. Low dietary MUFA and n-3 fatty acids and other long chain polyunsarurated fatty acids (LCPUFA) are important in the pathogenesis of metabolic syndrome. Increased sympathetic activity with greater secretion of neurotransmitters in conjunction of underlying long chain PUFA deficiency, and excess of proinflammatory nutrients, may damage the neurons via proinflammatory cytokines, in the ventromedial hypothalamus and insulin receptors in the brain.Since, 30-50% of the fatty acids in the brain are LCPUFA, especially omega-3 fatty acids, which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may be protective.Blood lipid composition does reflect one's health status: (a) circulating serum lipoproteins and their ratio provide information on their atherogenicity to blood vessels and (b) circulating plasma fatty acids, such as w-6/w-3 fatty acid ratio, give indication on proinflammatory status of blood vessels, cardiomyocytes, liver cells and neurones; (a) and (b) are phenotype-related and depend on genetic, environmental and developmental factors. As such, they appear as universal markers for holistic health and these may be important in the pathogenesis of cardiovascular diseases and cancer, which is the main consideration of Tsim Tsoum concept.
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PMID: 20671994 [PubMed - in process]15: Neuropsychopharmacology. 2010 Jul 28; [Epub ahead of print]
Lu DY, Tsao YY, Leung YM, Su KP.
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
Accumulating evidence suggests that the pathophysiology of depression might be associated with neuroinflammation, which could be attenuated by pharmacological treatment for depression. Omega-3 polyunsaturated fatty acids (PUFAs) are anti-inflammatory and exert antidepressant effects. The aim of this study was to identify the molecular mechanisms through which docosahexaenoic acid (DHA), the main omega-3 PUFA in the brain, modulates oxidative reactions and inflammatory cytokine production in microglial and neuronal cells. The results of this study showed that DHA reduced expressions of tumor necrosis factor-alpha, interleukin-6, nitric oxide synthase, and cyclo-oxygenase-2, induced by interferon-gamma, and induced upregulation of heme oxygenase-1 (HO-1) in BV-2 microglia. The inhibitory effect of DHA on nitric oxide production was abolished by HO-1 inhibitor zinc protoporphyrin IX. In addition, DHA caused AKT and ERK activation in a time-dependent manner, and the DHA-induced HO-1 upregulation could be attenuated by PI-3 kinase/AKT and MEK/ERK inhibitors. DHA also increased IKKalpha/beta phosphorylation, IkappaBalpha phosphorylation, and IkappaBalpha degradation, whereas both nuclear factor-kappaB and IkappaB protease inhibitors could inhibit DHA-induced HO-1 expressions. The other major n-3 PUFA, eicosapentaenoic acid, showed similar effects of DHA on inflammation and HO-1 in repeated key experiments. In connecting with inflammation hypothesis of depression and clinical studies supporting the antidepressant effects of omega-3 PUFAs, this study provides a novel implication of the antidepressant mechanisms of DHA.Neuropsychopharmacology advance online publication, 28 July 2010; doi:10.1038/npp.2010.98.
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PMID: 20668435 [PubMed - as supplied by publisher]16: In Vivo. 2010 Jul-Aug;24(4):561-5.
Higashihara E, Itomura M, Terachi T, Matsuda T, Kawakita M, Kameyama S, Fuse H, Chiba Y, Hamazaki T, Okegawa T, Tokunaga M, Murota T, Kawa G, Furuya Y, Akashi T, Hamazaki K, Takada H.
Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo. 181-8611 Japan. Fax: +81 422477553, ehigashi@ks.kyorin-u.ac.jp.
Aim: To study the effects of eicosapentaenoic acid (EPA) on prostate-specific antigen (PSA) failure in prostate cancer patients who underwent prostatectomy. PATIENTS AND METHODS: Sixty-two prostate cancer patients whose PSA levels were less than 0.2 ng/ml 3 months after surgery were randomized to either an EPA group (n=32) or a control group (n=30). EPA (2.4 g/day) was administered in the EPA group for 2 years. PSA was measured every two months. RESULTS: The EPA concentration increased but the docosahexaenoic acid concentration decreased significantly (P<0.001) in erythrocytes. The PSA recurrence rates during a mean follow-up of 53.8 months were not different between the two groups (p=0.16). CONCLUSION: A longer and/or larger intervention or docosahexaenoic acid supplementation might be necessary to identify significant preventive effects of mega-3 polyunsaturated fatty acids on PSA recurrence.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20668324&dopt=ExternalLink
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PMID: 20668324 [PubMed - in process]17: In Vivo. 2010 Jul-Aug;24(4):553-60.
Lai YC, Hamazaki K, Yoshizawa K, Kawanaka A, Kuwata M, Kanematsu S, Hamazaki T, Takada H, Tsubura A.
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. tsubura@takii.kmu.ac.jp.
Aim: Short-term oestrogen and progesterone treatment (STEPT) mimics the pregnancy hormone milieu. This study compared the development of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Lewis rats that received STEPT in early or later life. MATERIALS AND METHODS: Rats in Groups 1 and 2 received a single intraperitoneal injection of 50 mg/kg MNU at 4 weeks old. Pellets containing 0.5 mg 17beta-estradiol and 32.5 mg progesterone (EP) were subcutaneously implanted in rats in Group 1 during 6-9 weeks old. Rats in Groups 3 and 4 received 50 mg/kg MNU at 22 weeks old and again at 23 weeks old. EP pellets were implanted in rats in Group 3 during 24-27 weeks old. At the time of EP removal and 8 weeks afterward, 4 randomly selected rats in each group were sacrificed for blood sampling. The fatty acid composition of serum phospholipids was measured by capillary gas chromatography. The remaining rats were sacrificed when they developed mammary tumours >/=1 cm in diameter or at the termination of the experiment, which was at 18 weeks old for Groups 1 and 2 and at 64 weeks old for Groups 3 and 4. Mammary cancer was histologically confirmed. RESULTS: Group 1 had a significantly suppressed incidence of mammary cancer compared to Group 2 (7% vs. 90%), whereas the cancer incidence in Group 3 was similar to that of Group 4 (50% vs. 56%). Rats in Group 1 had significantly smaller n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and higher levels of docosahexaenoic acid (DHA) than those in Group 2 at the time of EP removal but not 8 weeks after EP removal. Neither the PUFA ratios nor the DHA levels differed between Groups 3 and 4 at any time. These data suggest that the age at which STEPT is administered is important, since its mammary cancer-suppressing potential was lost in aged animals. CONCLUSION: DHA and the n-6/n-3 PUFA ratio may play a crucial role in mammary cancer suppression by STEPT.
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PMID: 20668323 [PubMed - in process]18: Carcinogenesis. 2010 Sep;31(9):1584-91. Epub 2010 Jul 25.
Brown I, Cascio MG, Wahle KW, Smoum R, Mechoulam R, Ross RA, Pertwee RG, Heys SD.
Cancer Medicine Research Programme, Translational Medical Sciences, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Polwarth Building, Aberdeen, AB25 2ZD, UK. i.brown@abdn.ac.uk
The omega-3 fatty acid ethanolamides, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), displayed greater anti-proliferative potency than their parent omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in LNCaP and PC3 prostate cancer cells. DHEA and EPEA activated cannabinoid CB(1) and CB(2) receptors in vitro with significant potency, suggesting that they are endocannabinoids. Both LNCaP and PC3 cells expressed CB(1) and CB(2) receptors, and the CB(1)- and CB(2)-selective antagonists, AM281 and AM630, administered separately or together, reduced the anti-proliferative potencies of EPEA and EPA but not of DHEA or DHA in PC3 cells and of EPA but not of EPEA, DHEA or DHA in LNCaP cells. Even so, EPEA and EPA may not have inhibited PC3 or LNCaP cell proliferation via cannabinoid receptors since the anti-proliferative potency of EPEA was well below the potency it displayed as a CB(1) or CB(2) receptor agonist. Indeed, these receptors may mediate a protective effect because the anti-proliferative potency of DHEA in LNCaP and PC3 cells was increased by separate or combined administration of AM281 and AM630. The anandamide-metabolizing enzyme, fatty acid amide hydrolase (FAAH), was highly expressed in LNCaP but not PC3 cells. Evidence was obtained that FAAH metabolizes EPEA and DHEA and that the anti-proliferative potencies of these ethanolamides in LNCaP cells can be enhanced by inhibiting this enzyme. Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20660502&dopt=ExternalLink
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PMID: 20660502 [PubMed - in process]19: J Nutr. 2010 Sep;140(9):1602-6. Epub 2010 Jul 14.
Murphy RA, Mourtzakis M, Chu QS, Reiman T, Mazurak VC.
Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alberta, Canada.
Upwards of 50% of newly diagnosed advanced lung cancer patients have severe muscle wasting (sarcopenia). Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in advanced cancer has been shown to attenuate lean tissue wasting. However, the relationship between muscle mass and plasma (n-3) fatty acids in the absence of supplementation is unclear. We aimed to determine how plasma phospholipid (n-3) fatty acids relate to sarcopenia and change in muscle mass in non-small cell lung cancer patients receiving chemotherapy. Computed tomography images were used to measure muscle mass. Patients were classified as sarcopenic or nonsarcopenic based on sex-specific cutpoints. Change in muscle mass during chemotherapy (2.5 mo) was calculated and patients were divided into quartiles based on the rate of muscle loss or gain. Patients with sarcopenia had lower plasma EPA (16.7 +/- 2.1 micromol/L vs. 31.6 +/- 4.4 micromol/L; P = 0.001), DHA (36.6 +/- 4.0 micromol/L vs. 55.3 +/- 4.0 micromol/L; P = 0.003), and Sigma(n-3) fatty acids (63.6 +/- 5.6 micromol/L vs. 95.0 +/- 7.7 micromol/L; P = 0.002) than nonsarcopenic patients. Patients with maximal muscle loss (mean - 3.5 kg) had lower plasma EPA (12.2 +/- 3.3 micromol/L vs. 35.0 +/- 7.1 micromol/L; P = 0.03), DHA (26.9 +/- 8.7 micromol/L vs. 59.6 +/- 5.3 micromol/L; P = 0.01), and Sigma(n-3) fatty acids (57.8 +/- 13.5 micromol/L vs. 104.6 +/- 11.1 micromol/L; P = 0.005) compared with patients who were gaining muscle (mean +1 kg). Plasma (n-3) fatty acids are depleted in cancer patients with sarcopenia, which may contribute to accelerated rates of muscle loss.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20631325&dopt=ExternalLink
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PMID: 20631325 [PubMed - in process]20: Prostaglandins Leukot Essent Fatty Acids. 2010 Jul 12; [Epub ahead of print]
Erythrocyte fatty acids and prostate cancer risk: A comparison of methods.
Shannon J, O'Malley J, Mori M, Garzotto M, Palma AJ, King IB.
Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA; Portland Veterans Affairs Medical Center, 2710 US Veterans Hospital Road, Portland, OR 97239-9823, USA.
The role of fatty acids (FA) in prostate carcinogenesis is unclear. Interest in the inter-relationship among different types of FA has resulted in new analytic approaches to FA and their role in cancer development. We evaluated the association between erythrocyte FA and prostate cancer in 127 prostate cancer patients and 183 screen negative controls. We present three approaches to the analyses of the FA and prostate cancer association; (1) individual or common groups of FA, (2) biologically meaningful FA ratios and (3) principal components analysis. Monounsaturated FA and the alpha-linolenic:eicosapentaenoic ratio were associated with reduced risk of prostate cancer. However, Factor 1, which was strongly correlated with some long chain saturated FA, was associated with an increased risk of prostate cancer. We provide an example of modeling FA and their inter-relationships on the risk of prostate cancer. Comparing three approaches suggests the importance of considering the impact of the entire fatty acid profile in disease prevention. Published by Elsevier Ltd.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20630734&dopt=ExternalLink
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PMID: 20630734 [PubMed - as supplied by publisher]