Dietary supplementation with fish oil in ulcerative colitis. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Distal procto-colitis, natural cytotoxicity, and essential fatty acids. Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis.
To determine the efficacy of fish oil supplementation in patients with active ulcerative colitis.
                Multicenter, randomized, double-blind, placebo-controlled, crossover trail with 4-month treatment periods (fish oil and placebo) separated by a 1-month washout.
                Four gastroenterology divisions.
                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.
                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.
                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 prostaglandin E2 and leukotriene B4 levels.
                Fish oil supplementation resulted 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).
                Four months of diet supplementation with fish oil in patients with inflammatory bowel disease resulted in reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain. 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 elucidate the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis. 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.
                In this pilot study patients were randomized 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 assessments 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.
                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.
                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 randomized 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 resulted 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.
The current data does not allow for a definitive conclusion regarding the efficacy of fish oil. There is no adequate information to make recommendations for clinical practice. More research is required.