125 articles - 10.09.10
1: 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]2: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14298-303. Epub 2010 Jul 26.
Campbell EL, MacManus CF, Kominsky DJ, Keely S, Glover LE, Bowers BE, Scully M, Bruyninckx WJ, Colgan SP.
Mucosal Inflammation Program, Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
Resolvin-E1 (RvE1) has been demonstrated to promote inflammatory resolution in numerous disease models. Given the importance of epithelial cells to coordination of mucosal inflammation, we hypothesized that RvE1 elicits an epithelial resolution signature. Initial studies revealed that the RvE1-receptor (ChemR23) is expressed on intestinal epithelial cells (IECs) and that microarray profiling of cells exposed to RvE1 revealed regulation of inflammatory response gene expression. Notably, RvE1 induced intestinal alkaline phosphatase (ALPI) expression and significantly enhanced epithelial ALPI enzyme activity. One role recently attributed to ALPI is the detoxification of bacterial LPS. In our studies, RvE1-exposed epithelia detoxified LPS (assessed by attenuation of NF-kappaB signaling). Furthermore, in epithelial-bacterial interaction assays, we determined that ALPI retarded the growth of Escherichia coli. To define these features in vivo, we used a murine dextran sulfate sodium (DSS) model of colitis. Compared with vehicle controls, administration of RvE1 resulted in significant improvement of disease activity indices (e.g., body weight, colon length) concomitant with increased ALPI expression in the intestinal epithelium. Moreover, inhibition of ALPI activity resulted in increased severity of colitis in DSS-treated animals and partially abrogated the protective influence of RvE1. Together, these data implicate a previously unappreciated role for ALPI in RvE1-mediated inflammatory resolution.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
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PMID: 20660763 [PubMed - indexed for MEDLINE]3: Inflamm Bowel Dis. 2010 Jun 17; [Epub ahead of print]
Turner D, Shah PS, Steinhart AH, Zlotkin S, Griffiths AM.
Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Israel.
The objective was to systematically review the efficacy and safety of n-3 (omega-3 fatty acids, fish oil) for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Electronic databases were searched systematically for randomized controlled trials of n-3 for maintenance of remission in inflammatory bowel disease (IBD). Studies of patients of any age group who were in remission at the time of recruitment and were followed for at least 6 months were included. The primary outcome was relapse rate at the end of the follow-up period. Nine studies were eligible for inclusion; six studies of CD (n = 1039) and three of UC (n = 138). There was a statistically significant benefit for n-3 in CD (relative risk [RR] 0.77; 95% confidence interval [CI] 0.61-0.98); however, the studies were heterogeneous (I(2) = 58%). The absolute risk reduction was -0.14 (95% CI: -0.25 to -0.02). Opinions may vary on whether this is a clinically significant effect. Two well-done studies with a larger sample size reported no benefit. A sensitivity analysis excluding a small pediatric study resulted in the pooled RR being no longer statistically significant. A funnel plot analysis suggested publication bias for the smaller studies. For UC, there was no difference in the relapse rate between the n-3 and control groups (RR 1.02; 95% CI: 0.51-2.03). The pooled analysis showed a higher rate of diarrhea (RR 1.36; 95% CI: 1.01-1.84) and symptoms of the upper gastrointestinal tract (RR 1.96; 95% CI: 1.37-2.80) in the n-3 treatment group. There are insufficient data to recommend the use of omega 3 fatty acids for maintenance of remission in CD and UC. (Inflamm Bowel Dis 2010;).
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PMID: 20564531 [PubMed - as supplied by publisher]4: Nutr Hosp. 2010 Mar-Apr;25(2):181-92.
[Article in Spanish]
Ballesteros Pomar MD, Vidal Casariego A, Calleja Fernandez A, Lopez Gomez JJ, Urioste Fondo A, Cano Rodriguez I.
Seccion de Endocrinologia y Nutricion, Complejo Asistencial de Leon, Leon, Espana. mdballesteros@telefonica.net
Inflammatory bowel disease is an entity with not wellknown pathogenesis, and important nutritional and metabolic implications because of the high prevalence of malnutrition, the possible implication of dietary factors in its pathogenesis and because of the hypothesis that nutritional intervention could be a primary treatment for the disease. Some nutrients could induce a low antigenic stimuli, regulate inflammatory and immunological responses and stimulate intestinal mucosal trophism. Present available evidence supports enteral nutrition in Crohn's disease as a primary treatment if treatment with steroids is not possible (failure or contraindication) (grade of recommendation A) or either combined treatment with drugs in malnourished patients or those with inflammatory bowel stenosis. In those patients with sustained clinical remission, no benefit of either enteral nutrition or supplements in the absence of nutritional deficits has been shown. Elemental or modified formula (glutamine, omega 3 fatty acids) could not be recommended. In ulcerative colitis, nutritional influence over the activity of the disease has not been shown, although there are some promising results regarding enteric coated W3 fatty acids and a possible role for probiotics. In the treatment and prevention of pouchitis, there could be a role for probiotics (VSL#3). Nutritional treatment should be considered an integral component in the Management of patients with inflammatory bowel disease.
Publication Types: English Abstract Review
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PMID: 20449527 [PubMed - indexed for MEDLINE]5: Nutrition. 2010 Apr 2; [Epub ahead of print]
Vieira de Barros K, Gomes de Abreu G, Navarro Xavier RA, Real Martinez CA, Ribeiro ML, Gambero A, de Oliveira Carvalho P, Flor Silveira VL.
Department of Physiology, Federal University of Sao Paulo, Sao Paulo, SP, Brazil.
OBJECTIVE: High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. METHODS: Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. RESULTS: The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). CONCLUSION: The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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PMID: 20363597 [PubMed - as supplied by publisher]6: Eur J Gastroenterol Hepatol. 2010 May;22(5):602-6.
John S, Luben R, Shrestha SS, Welch A, Khaw KT, Hart AR.
Norfolk and Norwich University Hospital NHS Trust, Norwich, UK.
OBJECTIVES: The aetiology of ulcerative colitis (UC) is largely unknown, although it is plausible that dietary n-3 polyunsaturated fatty acids (PUFAs) may be protective. Metabolites derived from n-3 PUFAs are less proinflammatory than those from n-6 PUFAs. Earlier, no prospective cohort studies have investigated this hypothesis, using dietary information collected from food diaries. The aim of this study was to investigate the total dietary intake of n-3 PUFAs and the specific n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the risk of developing incident UC. METHODOLOGY: Twenty-five thousand six hundred and thirty-nine participants, living in Norfolk UK, aged 45-74 years (median age at recruitment of 59.2 years), completed 7-day food diaries. These were interpreted using a computer programme, which converted food items into nutrients, including n-3 PUFAs. The cohort was monitored for participants who developed UC. Each case was matched with four controls and an analysis performed using conditional logistic regression. RESULTS: In the cohort, 22 incident cases of UC were identified after a median follow-up time of 4.2 years (range 1.8-8.3 years). A statistically significant protective odds ratio (OR) for the trend across tertiles was found for DHA [OR = 0.43, 95% confidence interval (CI)=0.22-0.86, P = 0.02] and borderline statistically significant differences for trends for total total n-3 PUFAs (OR = 0.56, 95% CI=0.28-1.13, P = 0.10) and EPA (OR = 0.53, 95% CI=0.27-1.03, P = 0.06) after adjusting for age, sex, total energy intake, smoking, and other fatty acids. CONCLUSION: Total dietary n-3 PUFAs, EPA, and DHA, particularly DHA were associated with protection from UC in a cohort aged over 45 years. If the association is causal, then increasing the population's intake of n-3 PUFAs from oily fish may help prevent UC.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20216220 [PubMed - indexed for MEDLINE]7: Curr Pharm Des. 2009;15(36):4135-48.
Ruggiero C, Lattanzio F, Lauretani F, Gasperini B, Andres-Lacueva C, Cherubini A.
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. ruggieroc07@hotmail.it
Inflammation is part of the normal host response to infection and injury. However, inappropriate inflammation contributes to several diseases, including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Both conditions are characterized by the excessive production of inflammatory cytokines, arachidonic acid (AA)-derived eicosanoids, and other inflammatory agents (e.g., reactive oxygen species, adhesion molecules). By virtue of their anti-inflammatory action, omega-3 polyunsaturated fatty acids (PUFA) may be beneficial in inflammatory diseases. A large body of evidence supports a protective effect of omega-3 PUFA in experimental animal and ex-vivo models of Crohn's disease (CD), Ulcerative colitis (UC) and Rheumatoid arthritis (RA). Although fish oil supplementation in patients with IBD results in omega-3 PUFA incorporation into gut mucosal tissue and modification of inflammatory mediator profiles, the evidence of clinical benefits of omega-3 PUFA is weak. On the other hand, more convincing data support the efficacy of omega-3 PUFA in reducing pain, number of tender joints, duration of morning stiffness, use of non-steroidal anti-inflammatory drugs and improving physical performance in RA patients. In both IBD and RA further clinical trials with large sample size are needed to clarify the efficacy of omega-3 PUFA as a treatment.
Publication Types: Review
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PMID: 20041815 [PubMed - indexed for MEDLINE]8: Inflamm Bowel Dis. 2010 Jan;16(1):87-95.
Ishida T, Yoshida M, Arita M, Nishitani Y, Nishiumi S, Masuda A, Mizuno S, Takagawa T, Morita Y, Kutsumi H, Inokuchi H, Serhan CN, Blumberg RS, Azuma T.
Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
BACKGROUND: Resolvin E1 (RvE1), an endogenous lipid mediator derived from eicosapentaenoic acid, has been identified in local inflammation during the healing stage. RvE1 reduces inflammation in several types of animal models including peritonitis and retinopathy and blocks human neutrophil transendothelial cell migration. The RvE1 receptor ChemR23 is expressed on myeloid cells such as macrophages and dendritic cells. The aim of this study was to determine whether RvE1 regulates colonic inflammation when the innate immune response of macrophages plays a key role in pathogenesis and tissue damage. METHODS: The RvE1 receptor ChemR23 was expressed in mouse peritoneal macrophages as defined by flow cytometry. Peritoneal macrophages were pretreated with RvE1, followed by lipopolysaccharide stimulation, whereupon transcriptional levels of proinflammatory cytokines were analyzed. RESULTS: RvE1 treatment led to inhibition of proinflammatory cytokines including TNF-alpha and IL-12p40. In HEK293 cells, pretreatment with RvE1 inhibited TNF-alpha-induced nuclear translocation of NF-kappaB in a ChemR23-dependent manner. These results suggested that RvE1 could regulate proinflammatory responses of macrophages expressing ChemR23. Therefore, we investigated the beneficial effects of RvE1 in dextran sulfate sodium-induced colitis. RvE1 treatment led to amelioration of colonic inflammation. CONCLUSIONS: These results indicate that RvE1 suppresses proinflammatory responses of macrophages. RvE1 and its receptor may therefore be useful as therapeutic targets in the treatment of human inflammatory bowel disease and other inflammatory disorders.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
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PMID: 19572372 [PubMed - indexed for MEDLINE]9: Nutr Clin Pract. 2009 Feb-Mar;24(1):91-7.
El-Matary W.
Faculty of Medicine, University of Alberta, Pediatric Gastroenterology, 11402 University Ave, Edmonton, Alberta, Canada, T6G 2J3. wael.elmatary@capitalhealth.ca
Nutrition therapy of Crohn's disease is considered the first-line of treatment for Crohn's disease in children, especially in Europe. This article discusses the role, mechanism, and the available updated evidence supporting use of this treatment to induce and maintain remission of Crohn's disease. It also highlights the importance of the team approach in achieving success using this treatment. Future research-related topics are briefly summarized.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19244154&dopt=ExternalLink
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PMID: 19244154 [PubMed - indexed for MEDLINE]10: Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006320.
Turner D, Zlotkin SH, Shah PS, Griffiths AM.
Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, P.O.B 3235, Jerusalem, Israel, 91031. turnerd@szmc.org.il
BACKGROUND: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil) have been suggested to be beneficial in chronic inflammatory disorders such as inflammatory bowel disease. OBJECTIVES: To systematically review the efficacy and safety of n-3 for maintenance of remission in Crohn's disease (CD). SEARCH STRATEGY: The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for unpublished data. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT) of n-3 for maintenance of remission in CD were included. Studies must have enrolled patients of any age group, who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil or n-3 given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was the relapse rate and secondary outcomes included change in disease activity scores, time to first relapse and adverse events. DATA COLLECTION AND ANALYSIS: Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. Meta-analyses were performed using RevMan 4.2 software weighted by the Mantel-Haenszel method. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed in an attempt to explore possible sources of heterogeneity. MAIN RESULTS: Six studies were eligible for inclusion. There was a marginal significant benefit of n-3 therapy for maintaining remission (RR 0.77 0.; 95%CI 0.61 to 0.98; P = 0.03). However, the studies were both clinically and statistically heterogeneous (P = 0.03, I(2) = 58%). Two large studies showed negative results. When considering the estimated rather than the observed 1-year relapse rate of these two studies, the benefit was no longer statistically significant (RR 0.59; 95% CI 0.34 to 1.03; P=0.06). A funnel plot suggested publication bias. No serious adverse events were recorded in any of the studies but in a pooled analyses there was a significantly higher rate of diarrhea (RR 1.36 95% CI 1.01 to 1.84) and symptoms of the upper gastrointestinal tract (RR 1.98 95% CI 1.38 to 2.85) in the n-3 treatment group. AUTHORS' CONCLUSIONS: Omega 3 fatty acids are safe but probably ineffective for maintenance of remission in CD. The existing data do not support routine maintenance treatment of Crohn's disease with omega 3 fatty acids.
Publication Types: Meta-Analysis Review
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PMID: 19160277 [PubMed - indexed for MEDLINE]11: Korean J Gastroenterol. 2008 Jul;52(1):1-8.
[Article in Korean]
Lee KM.
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Suwon, Korea. drmaloman@catholic.ac.kr
Nutrition, as a definite environmental factor, has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Although low-fiber, high-sugar, and high-animal fat diets have been proposed as a risk factor, the role of nutrition in IBD still needs more conclusive evidence. Nutritional deficiency is a common problem in IBD patients. The goals of nutritional intervention are the prevention and correction of malnutrition, the prevention of osteoporosis, and the promotion of optimal growth and development in childhood. Enteral nutrition is effective in induction and maintenance of the clinical remission in adults and promoting growth in children with Crohn's disease. The n-3 polyunsaturated fatty acids contained in fish oil may provide short-term benefit to patients with IBD.
Publication Types: English Abstract Review
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PMID: 19077484 [PubMed - indexed for MEDLINE]12: Mol Nutr Food Res. 2008 Aug;52(8):885-97.
Calder PC.
Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton, UK. pcc@soton.ac.uk
With regard to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid (AA), which is the precursor of inflammatory eicosanoids like prostaglandin E(2) and leukotriene B(4), and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are found in oily fish and fish oils. EPA and DHA inhibit AA metabolism to inflammatory eicosanoids. They also give rise to mediators that are less inflammatory than those produced from AA or that are anti-inflammatory. In addition to modifying the lipid mediator profile, n-3 PUFAs exert effects on other aspects of inflammation like leukocyte chemotaxis and inflammatory cytokine production. Some of these effects are likely due to changes in gene expression, as a result of altered transcription factor activity. Fish oil has been shown to decrease colonic damage and inflammation, weight loss and mortality in animal models of colitis. Fish oil supplementation in patients with inflammatory bowel diseases results in n-3 PUFA incorporation into gut mucosal tissue and modification of inflammatory mediator profiles. Clinical outcomes have been variably affected by fish oil, although some trials report improved gut histology, decreased disease activity, use of corticosteroids and relapse.
Publication Types: Review
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PMID: 18504706 [PubMed - indexed for MEDLINE]13: Inflamm Bowel Dis. 2008 Oct;14(10):1348-57.
Matsunaga H, Hokari R, Kurihara C, Okada Y, Takebayashi K, Okudaira K, Watanabe C, Komoto S, Nakamura M, Tsuzuki Y, Kawaguchi A, Nagao S, Itoh K, Miura S.
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
BACKGROUND: Although the immunoregulatory effects of omega-3 fatty acid and adiponectin have been postulated, their role in intestinal inflammation is controversial. The aim of this study was to determine whether dietary fat intake influences activity of colonic inflammation through modulating this system. METHODS: C57BL/6 mice received dextran sulfate sodium for induction of colitis. Mice were fed a control diet, omega-3 fat-rich diet, omega-6 fat-rich diet, or saturated fat-rich diet. Some mice were administered a peroxisome proliferator activated receptor-gamma; agonist, pioglitazone. Messenger RNA expression of adiponectin and its receptors were analyzed. Adiponectin expression in colonic mucosa of ulcerative colitis patients was also analyzed. RESULTS: The receptors for adiponectin were found to be ubiquitously expressed in epithelial cells, intraepithelial lymphocytes, lamina proprial mononuclear cells, and subepithelial myofibroblasts from colonic tissue, but adiponectin was only expressed in myofibroblasts. Induction of colitis significantly decreased the expression of adiponectin in colonic mucosa. The omega-3 fat diet group, but not the other fat diet groups, showed exacerbated colitis with a further decrease of adiponectin expression. Pioglitazone treatment ameliorated the level of decrease in adiponectin expression and improved colonic inflammation induced by the omega-3 fat-rich diet. In patients with ulcerative colitis, the expression level of adiponectin in colonic mucosa was also decreased compared with that in control mucosa. CONCLUSIONS: Adiponectin was found to be expressed in myofibroblasts. Adiponectin expression was significantly suppressed by induction of colitis, and aggravation of colitis after exposure to omega-3 fat may be due to a further decrease in the expression level of adiponectin.
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PMID: 18484673 [PubMed - indexed for MEDLINE]14: JAMA. 2008 Apr 9;299(14):1690-7.
Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D'Haens G, Bradette M, Cohen A, Dallaire C, Ponich TP, McDonald JW, Hebuterne X, Pare P, Klvana P, Niv Y, Ardizzone S, Alexeeva O, Rostom A, Kiudelis G, Spleiss J, Gilgen D, Vandervoort MK, Wong CJ, Zou GY, Donner A, Rutgeerts P.
Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, 100 Perth Dr, London, ON, Canada N6A 5K8. bfeagan@robarts.ca
CONTEXT: Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. OBJECTIVE: To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. DESIGN, SETTING, AND PATIENTS: Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. INTERVENTIONS: Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. MAIN OUTCOME MEASURE: Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. RESULTS: For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. CONCLUSION: In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.
Publication Types: Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't
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PMID: 18398081 [PubMed - indexed for MEDLINE]15: Clin Nutr. 2008 Aug;27(4):614-22. Epub 2008 Apr 18.
Brunborg LA, Madland TM, Lind RA, Arslan G, Berstad A, Froyland L.
National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029, Nordnes, N-5817 Bergen, Norway. linn.anne.brunborg@nifes.no
BACKGROUND: Very long chain n-3 polyunsaturated fatty acids have modulating effects on inflammatory mechanisms. Seal and fish oils are rich in n-3 polyunsaturated fatty acids, and possibly therefore high doses of nasoduodenally administered seal oil rapidly relieved inflammatory bowel disease (IBD)-associated joint pain in two recent studies. In the present study, we compared the effects of short-term oral administration of seal oil and cod liver oil on IBD-related joint pain, leucotriene B(4) level, serum fatty acid profile and IBD activity. METHODS: Thirty-eight patients with IBD-related joint pain were included in the study; 21 had Crohn's disease and 17 ulcerative colitis. Ten milliters of seal oil (n=18) or cod liver oil (n=20) was self-administered orally 3 times a day for 14 days before meals in a double-blind setting. RESULTS: There were no significant differences between the two intervention groups or between Crohn's disease and ulcerative colitis patients. There was a tendency toward improvement in several joint pain parameters after both seal oil and cod liver oil administration. Further, plasma leucotriene B(4) concentration, serum Sigma n-6 to Sigma n-3, and arachidonic acid (20:4n-6) to eicosapentaenoic acid (20:5n-3) ratios were similarly reduced after administration of seal oil and cod liver oil. CONCLUSION: No significant differences in the two treatment groups were seen; in both groups, the changes in several joint pain parameters, leucotriene B(4) level of plasma, and serum fatty acid profile were putatively favourable.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
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PMID: 18374458 [PubMed - indexed for MEDLINE]16: Biochem Biophys Res Commun. 2008 Mar 14;367(3):566-72. Epub 2008 Jan 10.
Yamamoto K, Ninomiya Y, Iseki M, Nakachi Y, Kanesaki-Yatsuka Y, Yamanoue Y, Itoh T, Nishii Y, Petrovsky N, Okazaki Y.
Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
(5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid (4-OHDHA) is a potential agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma) and antidiabetic agent as has been previously reported. As PPARgamma agonists may also have anti-inflammatory functions, in this study, we investigated whether 4-OHDHA has an inhibitory effect on expression of inflammatory genes in vitro and whether 4-OHDHA could relieve the symptoms of dextran sodium sulfate (DSS)-induced colitis in a murine model of inflammatory bowel disease. 4-OHDHA inhibited production of nitric oxide and expression of a subset of inflammatory genes including inducible nitric oxide synthase (Nos2/iNOS) and interleukin 6 (Il6) by lipopolysaccharide (LPS)-activated macrophages. In addition, 4-OHDHA-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of 4-OHDHA-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). These results suggest that 4-OHDHA has potentially clinically useful anti-inflammatory effects mediated by suppression of inflammatory gene expression.
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=18191038&dopt=ExternalLink
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PMID: 18191038 [PubMed - indexed for MEDLINE]17: J Food Sci. 2007 Jan;72(1):S049-54.
Borneo R, Kocer D, Ghai G, Tepper BJ, Karwe MV.
Dept. of Food Science, Rutgers, the State Univ. of New Jersey, 65 Dudley Rd., New Brunswick, NJ 08901, USA.
We formulated a filling for sandwich cookies containing 400 mg of eicosapentaenoic acid, 20:5, n-3 (EPA) + docosahexaenoic acid, 22:6, n-3 (DHA) encapsulated in a matrix of starch and gelatin. Cookies were stored at 2 different temperatures (18 degrees C and 35 degrees C) and under 2 different packaging conditions (atmospheric and vacuum packed) for 28 d. At regular intervals, cookies were analyzed for moisture, water activity, and concentrations of EPA, DHA, and dienes. Results showed that there were no significant losses of EPA and DHA during storage under the conditions of study. A maximum loss of 5% was observed after 28 d of storage. The concentration of dienes obtained under different conditions were low (< 25 mmol/kg) as compared to a salmon oil sample with appreciable signs of oxidation (600 mmol/kg). Sensory evaluation of cookies by an untrained panel of healthy consumers and ulcerative colitis patients revealed no aftertaste and high acceptability of the cookies. Our results demonstrated that it is possible to make shelf-stable fortified foods with high levels of long-chain omega3FA.
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=17995897&dopt=ExternalLink
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PMID: 17995897 [PubMed - indexed for MEDLINE]18: J Gastrointest Surg. 2008 Feb;12(2):279-87. Epub 2007 Oct 23.
Scarpa M, Romanato G, Manzato E, Ruffolo C, Marin R, Basato S, Zambon S, Filosa T, Zanoni S, Pilon F, Polese L, Sturniolo GC, D'Amico DF, Angriman I.
Clinica Chirurgica I, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Policlinico Universitario, University of Padova, Padova, Italy. marcoscarpa73@yahoo.it
The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids in patients with ulcerative colitis after restorative proctocolectomy. Fifteen consecutive patients and 15 sex- and age-matched healthy controls were enrolled. Disease activity, diet, inflammatory parameters, plasma lipoprotein concentrations, and fatty acids (FA) of serum phospholipids and of the subcutaneous adipose tissue were assessed at colectomy and at ileostomy closure. In ulcerative colitis patients, total cholesterol and docosahexaenoic acid were lower than in healthy subjects (p < 0.01 and p < 0.05). The median interval between colectomy and ileostomy closure was 6 (range 2-9) months. During that interval, the inflammatory parameters improved, high-density lipoproteins (HDL) cholesterol increased (p < 0.01), and low-density (LDL) cholesterol decreased (p = 0.01). At ileostomy closure, serum arachidonic acid levels were increased (p = 0.04), whereas serum oleic acid level was decreased (p = 0.02). In this interval, no significant alteration, either in serum n-3 FA precursors or in the FA of subcutaneous adipose tissue, was observed. The increase of serum arachidonic acid after colectomy might suggest a lower utilization for inflammatory process. The reduction of LDL cholesterol is an index of malabsorption probably due to the accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17955308&dopt=ExternalLink
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PMID: 17955308 [PubMed - indexed for MEDLINE]19: Aliment Pharmacol Ther. 2008 Jan 1;27(1):11-8. Epub 2007 Oct 5.
Akobeng AK.
Department of Paediatric Gastroenterology, Booth Hall Children's Hospital, Central Manchester and Manchester Children's University Hospitals, Manchester, UK. tony.akobeng@cmmc.nhs.uk
BACKGROUND: Crohn's disease is characterised by recurrent flare-ups alternating with periods of remission. A number of interventions are currently used in clinical practice to try and maintain remission in Crohn's disease but the evidence base for some of them may be questionable. AIM: To review the available evidence on interventions, which are currently used to maintain remission in Crohn's disease. METHODS: The Cochrane Library and Medline (Pubmed) were searched for level 1 evidence on specific interventions. Search terms included 'Crohn's disease or synonyms', 'remission or synonyms' and the names of specific interventions. RESULTS: Azathioprine, infliximab and adalimumab are effective at maintaining remission in Crohn's disease. Natalizumab is also effective, but there are concerns about its potential association with progressive multifocal leukoencephalopathy. Long-term enteral nutritional supplementation, enteric-coated omega-3 fatty acids and intramuscular methotrexate may also be effective but the evidence for these is based on relatively small studies. The available evidence does not support the use of oral 5-aminosalicylates agents, corticosteroids, anti-mycobacterial agents, probiotics or ciclosporin as maintenance therapy in Crohn's disease. CONCLUSION: A better understanding of the evidence base of existing interventions could result in the use of treatments, which are more likely to lead to improved patient outcomes.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17919275&dopt=ExternalLink
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PMID: 17919275 [PubMed - indexed for MEDLINE]20: Bangladesh Med Res Counc Bull. 2006 Dec;32(3):72-7.
Mahmood B, Higgs N, Howl L, Warhurst G.
Deptt. of Microbiology, North East Medical College, Sylhet, UK.
Recent studies primarily in man have shown that cod fish oil rich in polyunsaturated fatty acids (PUFA) are beneficial to certain inflammatory diseases such as ulcerative colitis. This study was undertaken to observe any change in intestinal secretion where the tissues have been treated with cod fish and sunflower oils. Male Sprague Dawley rats weighing 200 gms were fed omega-3 fatty acids for 50 days. Changes in colonic secretion (fed with PUFA) were studied in-vitro in an Ussing chamber. Rat colon which were not fed with PUFA served as controls. Basal intestinal short circuit in PUFA group were comparable with control group in stripped rat colon. The results showed significant high short circuit current in cod fish oil and sunflower oil treated tissues. When stripped colonic tissues (fed with PUFA) were stimulated by EC50 of carbachol, bradykinin and prostaglandin; there was no significant changes in Short circuit current. PGE2 and LTB4 levels were measured in rat colon fed with PUFA by using radioimmunoassay. Biochemical changes in PGE2 and LTB4 levels showed LTB4 were significantly raised in both cod fish oil group and sunflower oil group. This study reveals that intestinal permeability increases in the rat colon (fed with PUFA) as indicated by high short circuit current. The high levels of leukotriene in colonic tissues also explains the high basal short circuit current in the present study.
Publication Types: In Vitro
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17867271&dopt=ExternalLink
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PMID: 17867271 [PubMed - indexed for MEDLINE]