An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial. Enteral absorption in man of eicosapentaenoic acid in different chemical forms Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Insulin-like growth factors (IGFs) and IGF binding proteins in active Crohn's disease treated with omega-3 or omega-6 fatty acids and corticosteroids. N-3 fatty acids only delay early relapse of ulcerative colitis in remission Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease--a randomized, placebo-controlled, double-blind cross-over trial. A double‐blind, randomized, placebo‐controlled trial of essential fatty acid supplementation in the maintenance of remission of ulcerative colitis Distal procto‐colitis and n‐3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition Dietary fat attenuates the benefits of an elemental diet in active Crohn's disease: a randomized, controlled trial Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids. Distal Proctocolitis and n-3 Polyunsaturated Fatty Acids (n-3 PUFAs): The Mucosal Effect In Situ Distal procto-colitis, natural cytotoxicity, and essential fatty acids Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis. Dietary supplementation with fish oil in ulcerative colitis. Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group). Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients Reduced joint pain after short-term duodenal administration of seal oil in patients with inflammatory bowel disease: comparison with soy oil Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study. A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis Nutritional Supplementation with N‐3 Fatty Acids and Antioxidants in Patients with Crohn's Disease in Remission: Effects on Antioxidant Status and Fatty Acid Profile Short-term efficacy of enteral nutrition in the treatment of active Crohn's disease: a randomized, controlled trial comparing nutrient formulas. Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials.
BACKGROUND & AIMS N-3 fatty acids from fish oil , antioxidants , and short-chain fatty acids ( SCFAs ) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis ( UC ) . We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil , fructooligosaccharides , gum arabic , vitamin E , vitamin C , and selenium on disease activity and medication use in adults with mild to moderate UC . METHODS A total of 121 patients with UC and a disease activity index ( DAI ) from 3 - 9 on a 12-point scale were block r and omized for extent of disease and smoking status . In addition to their usual diet , patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months . Clinical and histologic responses were assessed at 3 and 6 months or at the final visit . A change in average prednisone use between groups was tested by using a linear mixed-effects model . RESULTS Eighty-six patients completed the study . Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group ( 7.3 + /- 1.3 ; n = 36 ) compared with the placebo group ( 6.2 + /- 2.0 ; n = 50 ) ( P < .05 ) . Both groups showed significant and similar degree of improvement at 6 months in DAI ( -2.5 for oral supplement and -2.8 for placebo ) and histologic index ( -1.9 for oral supplement vs. -2.0 for placebo ) . Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001 ) . CONCLUSIONS The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC BACKGROUND Patients with Crohn 's disease may have periods of remission , interrupted by relapses . Because fish oil has antiinflammatory actions , it could reduce the frequency of relapses , but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects . METHODS We performed a one-year , double-blind , placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn 's disease who had a high risk of relapse . The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily . A special coating protected the capsules against gastric acidity for at least 30 minutes . RESULTS Among the 39 patients in the fish-oil group , 11 ( 28 percent ) had relapses , 4 dropped out because of diarrhea , and 1 withdrew for other reasons . In contrast , among the 39 patients in the placebo group , 27 ( 69 percent ) had relapses , 1 dropped out because of diarrhea , and 1 withdrew for other reasons ( difference in relapse rate , 41 percentage points ; 95 percent confidence interval , 21 to 61 ; P < 0.001 ) . After one year , 23 patients ( 59 percent ) in the fish-oil group remained in remission , as compared with 10 ( 26 percent ) in the placebo group ( P = 0.003 ) . Logistic-regression analysis indicated that only fish oil and not sex , age , previous surgery , duration of disease , or smoking status affected the likelihood of relapse ( odds ratio for the placebo group as compared with the fish-oil group , 4.2 ; 95 percent confidence interval , 1.6 to 10.7 ) . CONCLUSIONS In patients with Crohn 's disease in remission , a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse The effect of fish oil on the course of ulcerative colitis was investigated in a r and omised blinded controlled study . Eighty seven patients received supplements of 20 ml  HiEPA fish oil as triglyceride ( 4.5 g of eicosapentaenoic acid ) or olive oil placebo daily for one year . The oils were given in addition to st and ard drug therapy and trial entry was stratified for disease activity . Fish oil significantly increased the eicosapentaenoic acid content of rectal mucosa to 3.2 % of total fatty acids at six months , compared with 0.63 % for patients on olive oil . This was associated with increased synthesis of leukotriene B5 , and 53 % suppression of leukotriene B4 synthesis by ionophore -- stimulated neutrophils . Leukotriene B4 suppression persisted for at least two months after treatment was stopped . Treatment with fish oil result ed in measurable , but only limited clinical benefit . For patients entering the trial in relapse ( n = 53 ) , there was a significant reduction in corticosteroid requirement after one and two months treatment . There was a trend towards achieving remission ( off corticosteroids ) faster in the patients on fish oil , although differences were not significant . For patients in remission at trial entry or during the trial ( n = 69 ) , there was no significant difference in the rate of relapse by log rank analysis . We conclude that fish oil supplementation produces a modest corticosteroid sparing effect in active disease , but there is no benefit in maintenance therapy Crohn 's disease is associated with altered bone turnover that may be influenced by nutritional status , the systemic inflammatory response , cytokine production by circulating ( peripheral blood ) mononuclear cells ( P BMC ) and antioxidant micronutrient intake . High-dose fish oil is associated with reductions in disease relapse and inflammatory markers , and modulates P BMC function . The effect of fish oil plus antioxidants on bone turnover and P BMC function ( the production of interferon-gamma and prostagl and in E2 ) in Crohn 's disease was investigated in a r and omised-controlled trial . Patients with currently or recently raised biochemical markers of inflammation ( C-reactive protein > or = 6.9 mg/l or erythrocyte sedimentation rate > or = 18 mm/h ) received fish oil ( providing 2.7 g/d EPA and DHA ) and antioxidants ( vitamins A , C and E , and Se ) ( n 31 ) or placebo ( n 30 ) for 24 weeks . Bone turnover was assessed by measuring the concentrations of urinary deoxypyridinoline ( bone resorption ) and serum osteocalcin ( bone formation ) .  Fish oil plus antioxidants were associated with increases in EPA , DHA Se in plasma ( all P < 0.01 ) , and with a reduction in interferon-gamma production by mitogen-stimulated P BMC , which demonstrated a negative correlation with deoxypyridinoline/creatinine : osteocalcin ratio ( r - 0.33 , P = 0.009 ) . There were no differences between the groups at 24 weeks in the response of deoxypyridinoline or osteocalcin or their ratio , or in nutritional status . Dietary supplementation in Crohn 's disease with high intakes of EPA and DHA , as fish oil , plus antioxidants was associated with a modulated production of interferon-gamma by P BMC but not altered indices of bone turnover After administering the equivalent of 1 g of eicosapentaenoic acid ( EPA ) in four different chemical forms , the kinetics of EPA incorporation into plasma triglycerides ( TG ) were compared by gas liquid chromatography on a capillary column following separation of the lipid fraction by thin layer chromatography . EPA incorporation into plasma TG was markedly smaller and later when EPA was administered as an ethyl ester rather than as EPA free fatty acid , EPA arginine salt or 1,3-dioctanoyl-2-eicosapentaenoyl glycerol ( 2-EPA ) . Our results and the data in the literature are compatible with the hypothesis that 2-EPA is absorbed with minimum hydrolysis and escapes r and om distribution between the other positions of the glycerol molecule during the absorption process BACKGROUND Crohn disease ( CD ) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating ( peripheral blood ) mononuclear cells ( P BMC s ) . Fish oil rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters P BMC function . OBJECTIVE We investigated the effect of fish oil plus antioxidants on cytokine production by P BMC s from patients with CD with raised C-reactive protein concentrations ( > /=6.9 mg/L ) or erythrocyte sedimentation rates ( > /=18 mm/h ) . DESIGN A r and omized placebo-controlled trial of fish oil ( 2.7 g EPA and DHA/d ; n = 31 ) or placebo ( olive oil ; n = 31 ) for 24 wk was conducted in patients with CD . The fish-oil group additionally received an antioxidant preparation ( vitamins A , C , and E and selenium ) . Exclusion criteria included corticosteroid use . Fatty acid composition was measured by gas chromatography . Production of tumor necrosis factor alpha , interferon gamma ( IFN-gamma ) , and prostagl and in E(2 ) ( PGE(2 ) ) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin ( lipopolysaccharide ) . RESULTS Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into P BMC s ( P < 0.001 ) and lower arachidonic acid ( P = 0.006 ) and lower production of IFN-gamma by mitogen-stimulated P BMC s ( P = 0.012 ) and of PGE(2 ) by lipopolysaccharide-stimulated P BMC s ( P = 0.047 ) . CONCLUSION Dietary supplementation with fish oil plus antioxidants is associated with modified P BMC composition and lower production of PGE(2 ) and IFN-gamma by circulating monocytes or macrophages . The response of extraintestinal manifestations of CD should be investigated in a r and omized controlled trial Arachidonic acid metabolites formed by both the cyclooxygenase and lipoxygenase pathways may contribute to the clinical diarrhea and colitis of inflammatory bowel disease . Patients with active ulcerative colitis have increased levels of leukotriene B4 in their rectal mucosa , and these levels tend to correlate with severity of the disease . In this study , we evaluated the efficacy of ingestion of fish oil n-3-omega-fatty acids , inhibitors of leukotriene synthesis , in the treatment of ulcerative colitis . Eleven patients with ulcerative colitis of mild to moderate severity were studied in a 8-month , double-blind , placebo-controlled , crossover trial of dietary supplementation with fish oil , which provided about 4.2 g of omega-3- fatty acids per day . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mucosal leukotriene B4 production was measured by radioimmunoassay . Mean disease activity index declined 56 % for patients receiving fish oil and 4 % for patients on placebo ( p less than 0.05 ) . There were no statistically significant differences in histopathologic scores or colonic mucosal leukotriene B4 levels . All patients tolerated fish oil ingestion and showed no alteration in routine blood studies . No patient worsened ; anti-inflammatory drugs could be reduced or eliminated in eight patients ( 72 % ) while receiving fish oil . We conclude that fish oil dietary supplementation results in clinical improvement of active mild to moderate ulcerative colitis but is not associated with significant reduction in mucosal leukotriene B4 production , compared with placebo therapy . Further studies are needed to eluci date the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis OBJECTIVE Catabolism and growth impairment are well-known complications of inflammatory bowel disease ( IBD ) . This may be caused by the disease activity itself and /or the medical treatment , and both may lead to changes in the growth hormone (GH)/insulin-like growth factor I ( IGF-I ) axis . The aim of the present study was to examine the effects of enteral nutrition , Impact Powder , as adjuvant therapy to corticosteroid treatment on changes in the GH/IGF-I axis in patients with Crohn 's disease ( CD ) . MATERIAL AND METHODS The patients were r and omized to 3-IP ( omega-3-fatty acid ( FA ) , 3 g/day ) or 6-IP ( omega-6-FA , 9 g/day ) . Changes in total IGF-I ( tIGF-I ) and total IGF-II ( tIGF-II ) , free IGF-I ( fIGF-I ) , IGF binding proteins ( IGFBP-1 and IGFBP-3 ) , IGFBP-3 protease activity and insulin levels were examined in 31 patients with active CD ( CDAI : 186 - 603 ) during treatment with prednisolone ( 40 mg for 1 week ) and tapering the dose by 5 mg/week . Clinical and biochemical markers of inflammation were studied at day 0 , and after 5 and 9 weeks . RESULTS There were no differences at baseline between the two groups . During the treatment period , tIGF-I , fIGF-I and IGFBP-3 increased significantly in both groups compared to baseline ( p<0.05 ) without differences between the groups . Insulin and IGFBP-1 showed no significant changes throughout the treatment period . CONCLUSIONS There was no difference between 3-IP and 6-IP as adjuvant enteral nutrition on the GH/IGF-I axis . The changes observed in the GH/IGF-I axis are in line with previously published studies and may be explained by corticosteroid treatment ; however , we can not exclude an additional effect of omega3-/omega6 FA as adjuvant enteral nutrition Relapse prevention by dietary n-3 fatty acids ( 5.1 g/day ) was studied in a double-blind , placebo-controlled trial of 64 patients with ulcerative colitis in remission and off steroids . 5-ASA compounds were stopped three months after r and omization and clinical disease activity monitored for two years . Macroscopic and histologic activity and extension was assessed by colonoscopy at entry and at exit . Both treatment groups were well matched at start . Nine patients on placebo and eight on n-3 fatty acids  stopped taking their medication prematurely . Actuarial relapse-free survival was improved by n-3 fatty acids only during months 2 and 3 ( 2P<0.05−0.01 ) , but cumulative relapse rate at two years was similar for those taking placebo ( 18/33=55 % ) and n-3 fatty acids ( 18/31=58 % ) . There was also no consistent difference in clinical , macroscopic , and histologic disease activity between treatment groups . The n-3 fatty acids temporarily retard , but do not prevent , relapse of ulcerative colitis Thirty-nine patients with chronic inflammatory bowel disease were studied in a 7-month , double-blind , placebo controlled cross-over trial of dietary supplementation with fish oil , which provided about 3.2 g n-3 fatty acids per day . At control , biopsies from inflamed mucosa contained higher levels of arachidonic acid than uninvolved mucosa . Dietary n-3 fatty acids were well tolerated and incorporated into plasma and enteric mucosa phospholipids at the expense of n-6 fatty acids . The arachidonic acid-derived prostanoid generation was reduced by fish oil and the extension and severity of macroscopic bowel involvement was moderately improved . In patients with Crohn 's disease , clinical activity was unchanged by fish-oil supplementation . In patients with ulcerative colitis , clinical disease activity fell during fish oil supplementation and thereafter ; this was not significant however . Despite a moderate reduction in inflammatory lipid mediators by dietary n-3 fatty acids and limited morphological improvement in chronic inflammatory bowel disease , the clinical benefit seems to be confined to patients with ulcerative colitis Background : Essential fatty acid supplementation has been found to ameliorate certain  chronic inflammatory diseases . This effect is thought to be mediated through the modulation of eicosanoid synthesis . Pro‐inflammatory eicosanoids have been implicated in ulcerative colitis Altered natural killer ( NK ) and lymphokine‐activated killer ( LAK ) cell activities have been reported with ulcerative colitis ( UC ) . Previously , we have shown that in patients with UC , the n‐3 polyunsaturated fatty acids ( PUFAs ) , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , specifically inhibit natural cytotoxicity with clinical improvement in disease activity . The aim of this study therefore was to evaluate the possible mechanism(s ) involved in this inhibition , and in particular the alteration of production of interleukin 2 ( IL2 ) and the arachidonic acid metabolite leukotriene B4 ( LTB4 ) , both known to modulate NK cell activity Objectives Although an elemental diet has been established as the primary treatment for patients with Crohn 's disease , the influence of dietary fat on the elemental diet remains unclear . We have design ed the first r and omized , controlled trial for elemental diets containing different fat percentages in patients with active Crohn 's disease . Methods Each patient was r and omized to receive one of three dose levels of fat in an elemental diet ( Elental ) for 4 weeks : 10 patients received low fat ( 3.06 g/day ) , 10 patients received medium fat ( 16.56 g/day ) and eight patients received high fat ( 30.06 g/day ) . The additional fat was composed of long-chain fatty acids . All patients were evaluated using the International Organization of Inflammatory Bowel Disease rating , plus C-reactive protein level and erythrocyte sedimentation rate , which were measured at weekly intervals . Results Although the International Organization of Inflammatory Bowel Disease rating , C-reactive protein level and erythrocyte sedimentation rate in the low-fat group decreased , the values in the medium- and high-fat groups fluctuated during the study . The remission rate after 4 weeks in each group was 80 % , 40 % and 25 % for patients in the low- , medium- and high-fat groups , respectively . Conclusions When the fat consisted of long-chain triglycerides , a high amount of this fat in the elemental diet formula decreased its therapeutic effect against active Crohn 's disease OBJECTIVE The potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis . Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis ( UC ) , but the precise mechanism of the action of fish oil on oxidative stress is still controversial . The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress . METHODS Nine patients ( seven female and two male ; mean age = 40 + /- 11 y ) with mild or moderate active UC were studied in a r and omized crossover design . In addition to their usual medication ( 2 g/d of sulfasalazine ) , they received fish oil omega-3 fatty acids ( 4.5 g/d ) or placebo for 2-mo treatment periods that were separated by 2 mo , when they only received sulfasalazine .  Nine healthy individuals served as control subjects to study the oxidative stress status . Disease activity was assessed by laboratory indicators ( C-reactive protein , alpha1-acid glycoprotein , alpha1-antitrypsin , erythrocyte sedimentation rate , albumin , hemoglobin , and platelet count ) , sigmoidoscopy , and histology scores . Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation , both induced by tert butyl hydroperoxide ( t-BuOOH ) and by plasma malondialdehyde . Antioxidant status was assayed by total plasma antioxidant capacity ( TRAP ) and microsomal lipid peroxidation inhibition ( LPI ) . Superoxide dismutase ( SOD ) and catalase erythrocyte enzymatic activities were also determined . RESULTS No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores , with the exception of erythrocyte sedimentation rate , which decreased with both treatments . Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels , increased chemiluminescence induced by t-BuOOH , and higher SOD activity in patients with UC . Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine .  Levels of plasma malondialdehyde , erythrocyte lipid peroxidation , and catalase were not different from those in the control group . CONCLUSIONS The results indicated that plasma oxidative stress occurs in patients with UC , and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids . However , there was no improvement in most laboratory indicators , sigmoidoscopy , and histology scores . The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress It has been postulated that patients with ulcerative colitis ( UC ) have altered reactivity of gut-associated lymphoid tissue . In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage . We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids ( n-3 PUFAs ) , eicosapentaenoic acid ( EPA ) , and docosahexaenoic acid ( DHA ) results in significant systemic immune suppression . The aim of this study , therefore , was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis . Each patient received either fish oil extract ( EPA 3.2 g , DHA 2.4 g ) ( n = 9 ) or sunflower oil ( n = 9 ) daily in a double blind manner for six months . Monthly assessment included : ( 1 ) disease activity using clinical , sigmoidoscopic , and histological scores and ( 2 ) immunohistochemical analysis ( immunoglobulins , CD profiles ) of rectal biopsy specimens ( before and after six months supplementation ) using monoclonal antibodies and quantitative computer-assisted video image analysis . Prior to receiving supplementation , patients with proctocolitis ( n = 18 ) showed significantly higher numbers of cells expressing CD3 ( pan T cells ) and HLA-DR and IgM containing cells compared with non-colitic controls ( n = 8) . Six months supplementation with n-3 PUFAs result ed in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis . In patients receiving n-3 PUFA supplementation , there was improvement in the disease activity and histological scores , compared with pretreatment evaluation . This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation . This may have important implication for therapy in patients with ulcerative colitis Objective : Recently , it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity , in particular natural killer ( NK ) and lymphokine-activated killer ( LAK ) cell activities . These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process . We have shown previously that the essential fatty acids ( EFA ) eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) specifically inhibit natural cytotoxicity . Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis . Methods : In this pilot study patients were r and omized into two groups . Each patient received either fish oil extract ( EPA , 3.2 g , and DHA , 2.4 g ) ( n = 9 ) or sunflower oil ( placebo ) ( n = 9 ) daily in a double-blind manner for 6 months . Monthly assessment s of disease activity ( clinical and sigmoidoscopic scores ) and histological evaluation of mucosal biopsies were carried out . Also , the circulating levels and activities of NK and LAK cells , using flow cytometric analysis ( CD16 + CD56 + ) and in vitro 51 chromium release assays ( K562 ) , respectively , were monitored . Results : After 6 months ’ supplementation with EFA , there was improvement in the clinical activity compared with pretreatment evaluation . There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group . Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16 + and CD56 + cells and the cytotoxic activity of NK cells , compared with the placebo group . Conclusions : This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis . These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease Fish oil omega-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis . However , a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or omega-3 fatty acids has not been performed . We sought to detect changes in the inflammatory disease activity with the use of either fish oil omega-3 fatty acids or sulfasalazine in patients with ulcerative colitis . Ten patients ( five male , five female ; mean age = 48 + /- 12 y ) with mild to moderate active ulcerative colitis were investigated in a r and omized cross-over design . They received either sulfasalazine ( 2 g/d ) or omega-3 fatty acids ( 5.4 g/d ) for 2 m.o . Disease activity was assessed by clinical and laboratory indicators , sigmoidoscopy , histology , and whole-body protein turnover ( with 15N-glycine ) . Treatment with omega-3 fatty acids result ed in greater disease activity as detected by a significant increase in platelet count , erythrocyte sedimentation rate , C-reactive protein , and total fecal nitrogen excretion . No major changes in protein synthesis and breakdown were observed during either treatment . In conclusion , treatment with sulfasalazine is superior to treatment with omega-3 fatty acids in patients with mild to moderate active ulcerative colitis OBJECTIVE To determine the efficacy of fish oil supplementation in patients with active ulcerative colitis . DESIGN Multicenter , r and omized , double-blind , placebo-controlled , crossover trail with 4-month treatment periods ( fish oil and placebo ) separated by a 1-month washout . SETTING Four gastroenterology divisions . PATIENTS Twenty-four patients with active ulcerative colitis entered the study . Five dropped out , and one was noncompliant . Eighteen patients completed the study . All patients had active disease as manifested by diarrhea and rectal inflammation . INTERVENTIONS Treatment with prednisone and sulfasalazine was continued . Fish oil supplementation consisted of 18 Max-EPA ( eicosapentaenoic acid ) capsules daily ( eicosapentaenoic acid , 3.24 g ; and docosahexaenoic acid , 2.16 g ) . Placebo supplementation consisted of 18 identical capsules containing isocaloric amounts of vegetable oil . MEASUREMENTS Patients were evaluated at study entry and after each diet period . Evaluations included a review of symptoms , flexible sigmoidoscopy , rectal biopsy , and rectal dialysis to measure prostagl and in E2 and leukotriene B4 levels . RESULTS Fish oil supplementation result ed in a significant decrease in rectal dialysate levels of leukotriene B4 from 71.0 to 27.7 pg/mL ( average change , -43.3 pg/mL ; 95 % CI , -83 to -3.6 ) . Significant improvements were seen in acute histology index ( average change , -8.5 units from a baseline of 10.5 units ; CI , -12.9 to -4.2 ) and total histology index ( average change , -8.5 units from a baseline of 14.80 ; CI , -13.2 to -3.8 ) as well as significant weight gain ( average weight gain , 1.74 kg , CI , 0.94 to 2.54 ) . No significant changes occurred in any variable during the placebo period . Seven patients received concurrent treatment with prednisone . During the fish oil supplementation period , the mean prednisone dose decreased from 12.9 mg/d to 6.1 mg/d and rose from 10.4 mg/d to 12.9 mg/d during the placebo diet period ( P greater than 0.20 ) . CONCLUSIONS Four months of diet supplementation with fish oil in patients with inflammatory bowel disease result ed in reductions in rectal dialysate leukotriene B4 levels , improvements in histologic findings , and weight gain BACKGROUND There is no established therapy for maintaining remission in patients with Crohn 's disease . Following different suggestions from the literature , two potential interventions for maintaining remission were tested against placebo , using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet ( 84 g/day ) . METHODS A total of 204 patients were recruited after they had had an acute relapse . After remission ( CDAI < or = 150 ) was attained with steroid therapy , patients were r and omized to receive either omega-3 fatty acids ( n = 70 ) , placebo ( n = 65 ) , or diet ( n = 69 ) . Low-dose prednisolone was given to all patients for the first 8 weeks of intervention . CDAI and an acute-phase protein ( CRP ) were used as criteria for a relapse . RESULTS The proportion of patients without relapse within a year were similar in the placebo and active treatment group ( intention-to-treat analysis : placebo , 30 % ; active treatment , 30 % ; protocol -adhering patients , 29 % versus 28 % ) . Patients did gain benefit ( 53 % ; p = 0.023 ) for as long as they maintained the diet . However , intention-to-treat analysis ( diet group , 40 % ) did not show a noticeable difference when compared with placebo . CONCLUSIONS Omega-3 fatty acids did not show an effect on extending the remission in Crohn 's disease . For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease ( IBD ) ; however , a lot of annoying side effects ( ie , belching , halitosis , diarrhea , etc ) affect patient compliance . We carried out a study of patient tolerance in a group of Crohn 's disease ( CD ) patients with a new fish oil derivative  consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic ( EPA 40%-DHA 20 % ) , a free fatty acid mixture ( Purepa ) , and we also evaluated its incorporation into phospholipids , both in plasma and in red cell membranes . Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations ( A : uncoated , B : coated , pH 5.5 ; C : coated , pH 5.5 , 60 min time release ; D : coated , pH 6.9 ) and 12 × 1-g capsules daily of a triglyceride preparation ( Max-EPA , EPA 18%-DHA 10 % ) , respectively . We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects . After six weeks of treatment , the group taking Purepa capsules , coated , pH 5.5 , 60 min time release ( group C ) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes ( EPA from 0.2 to 4.4 % , DHA from 3.7 to 6.3 % ) , and no side effects were registered , whereas in all other groups side effects were experienced in 50 % or more of subjects . This new preparation will make it possible to treat patients for long periods Background : Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease ( IBD ) . Because the high ratio of n-6 to n-3 fatty acids ( FAs ) of the Western diet might promote rheumatic disorders , we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain . Methods : Nineteen patients with IBD-related joint pain were included in the study ; 9 had Crohn disease and 10 had ulcerative colitis .  Ten millilitres seal oil ( n = 10 ) or soy oil ( n = 9 ) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days . Results : Compared with soy oil treatment , seal oil significantly reduced the duration of morning stiffness ( P = 0.024 ) , number of tender joints ( P = 0.035 ) , intensity of pain ( P = 0.025 ) and the doctor 's scoring of rheumatic disease activity ( P = 0.025 ) at the end of the 10-day treatment period . Analysis of the effects as area under the curve ( area between the curve and baseline , zero ) for the entire period from start of treatment until 6 months ' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain , whereas soy oil tended ( not significantly ) to aggravate the condition . Consistently , the serum ratios of n-6 to n-3 FAs ( P ≪⃒ 0.01 ) and arachidonic acid to eicosapentaenoic acid ( P ≪⃒ 0.01 ) were reduced after treatment with seal oil . Conclusion : The results suggest distinctive , differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil ( significant improvement ) and n-6-rich soy oil ( tendency to exacerbation ) AIM To assess the value of long-chain omega-3 fatty acids ( FAs ) supplementation in addition to amino-salicylic-acid ( 5-ASA ) in pediatric patients with Crohn 's disease ( CD ) . METHODS Thirty-eight patients ( 20 males and 18 females , mean age 10.13 years , range 5 - 16 years ) with CD in remission were r and omized into two groups and treated for 12 mo . Group I ( 18 patients ) received 5-ASA ( 50 mg/kg/d)+ omega-3 FAs as triglycerides in gastro-resistant capsules , 3 g/d ( eicosapentanoic acid , EPA , 400 mg/g , docosahexaenoic acid , DHA , 200 mg/g ) . Group II ( 20 patients ) received 5-ASA ( 50 mg/kg/d)+olive oil placebo capsules . Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment . RESULTS The number of patients who relapsed at 1 year was significantly lower in group I than in group II ( P<0.001 ) . Patients in group I had a significant increase in the incorporation of EPA and DHA ( P<0.001 ) and a decrease in the presence of arachidonic acids . CONCLUSION Enteric-coated omega-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD In a placebo‐controlled study , 43 patients with stable ulcerative colitis were r and omized to receive either MaxEPA ( n= 16 ) , super evening primrose oil ( n= 19 ) , or olive oil as placebo ( n= 8) for 6 months , in addition to their usual treatment . Treatment with MaxEPA  increased red‐cell membrane concentrations of eicosapentaenoic acid ( EPA ) at 3 months by three‐fold and at 6 months by four‐fold ( both P < 0.01 ) , and doubled docosahexaenoic acid ( DHA ) levels at 6 months ( P < 0.05 ) . Treatment with super evening primrose oil  increased red‐cell membrane concentrations of dihomogamma‐linolenic acid ( DGLA ) by 40 % at 6 months ( P < 0.05 ) , whilst treatment with placebo reduced levels of DGLA and DHA at 6 months ( both P < 0.05 ) . Clinical outcome was assessed by patient diary cards , sigmoidoscopy and histology of rectal biopsy specimens . Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months , and this difference was maintained 3 months after treatment was discontinued ( P < 0.05 ) . There was however , no difference in stool frequency , rectal bleeding , disease relapse , sigmoidoscopic appearance or rectal histology in the three treatment groups . Despite manipulation of cell‐membrane fatty acids , fish oils do not exert a therapeutic effect in ulcerative colitis , while evening primrose oil may be of some benefit Summary : In patients with Crohn 's disease ( CD ) , malnutrition is frequently observed and is generally accepted to be an important issue . The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants ( AO ) or n‐3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue , respectively , in patients with long‐st and ing CD currently in remission . In a r and omized , double‐blind placebo‐controlled study , CD patients received either placebo , AO , or n‐3 fatty acids plus AO for 3 months in addition to their regular diet . In all , 25/37 CD patients completed the study . AO status was assessed by blood biochemical parameters . A statistical per‐ protocol analysis was performed . Serum concentrations of selenium , vitamin C , and vitamin E , the activity of superoxide dismutase and total antioxidant status were significantly ( p < 0.05 ) increased after AO supplementation . Furthermore , compared with controls , serum concentrations of & bgr;‐carotene , selenium , and vitamin C and the activity of glutathione peroxidase ( GPx ) were significantly ( p < 0.05 ) lower before supplemention ; however , after AO supplementation these levels were not significantly different from controls ( except for GPx ) . N‐3 fatty acids plus AO supplementation significantly ( p < 0.05 ) decreased the proportion of arachidonic acid , and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue . Supplementation with antioxidants improved antioxidant status in patients with CD in remission . In addition , supplementation with n‐3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile , which may lead to the production of eicosanoids with attenuated proinflammatory activity . This study indicates that an immunomodulating formula containing n‐3 fatty acids and /or AO may have the potential to play a role in the treatment of CD BACKGROUND The optimal dietary fat content to induce clinical remission in active Crohn 's disease has been the subject of controversy . We therefore performed a prospect i ve , r and omized , controlled study to compare the effects of nutrient formulas differing in the amount of medium-chain triglycerides ( MCT ) . METHODS Thirty-six patients with active Crohn 's disease whose Crohn 's disease activity index ( CDAI ) was > or = 150 were included in the study . A formula with 3.4 g of fat per 2000-kcal dose was used as the nutrient formula with a low-fat content ( ED group ) , and a formula with 55.6 g of fat per 2000-kcal dose was used as the nutrient formula with a high amount of MCT ( TL group ) . RESULTS The rate of short-term remission induction at 6 weeks was 67 % in the ED group and 72 % in the TL group ( p = NS ) . Therapy markedly reduced the high CDAI and van Hees activity index in both groups , with no significant difference in the pattern of the time-course changes . C-reactive protein levels , erythrocyte sedimentation rate , and low serum albumin and plasma prealbumin levels normalized over the course of therapy , with no significant difference between the 2 groups . The assessment of fatty acid fractions revealed that the triene/tetraene ratio began to increase at 2 weeks in the ED group . The serum levels of linoleic acid , an omega-6 fatty acid , almost always varied within the normal range during the treatment period in the TL group , but in the ED group , levels began to decrease significantly at 2 weeks . The levels of linolenic acid , an omega-3 fatty acid , decreased in both groups . CONCLUSIONS Both nutrient formulas induced clinical remission in about two-thirds of patients . The results of the present study suggest that it is not necessary to restrict the amount of MCT when given in liquid form to patients with active Crohn 's disease 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 r and omized , 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 r and omly 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 clinical trials.gov Identifiers : EPIC-1 : NCT00613197 , EPIC-2 : NCT00074542
The objective was to systematic ally 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 ) .