Clinical Briefs: Something's Fishy — A Supplement for UC?
Clinical Briefs: Something's FishyA Supplement for UC?
With Comments from Russell H. Greenfield, MD Dr. Greenfield is Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, and Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC.
Source: Seidner DL, et al. An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: A randomized, controlled trial. Clin Gastroenterol Hepatol 2005;3: 358-369.
Goal: To assess the efficacy of a balanced nutritional supplement on disease activity and medication use in adults with mild-to-moderate ulcerative colitis (UC).
Design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter (five clinical centers) trial over six months in which participants were stratified based on extent of disease and smoking status.
Subjects: Adults older than age 18 (n = 121) with documented UC for at least six months, active inflammation on endoscopic evaluation, and mild-to-moderate symptomatology as determined by a disease activity index (DAI) of 3-9 at time of enrollment.
Methods: Eligible subjects underwent endoscopy and mucosal biopsy to confirm the presence of active disease, as well as a variety of blood tests, at study entry and at three and six months of treatment. Subjects were to maintain their normal diet, but also received a placebo formula (drink containing water, sucrose, flavoring, and color) or the UC nutritional supplement (UCNS) containing a combination of fish oil, fructooligosaccharide, gum Arabic, and a mixture of vitamins and minerals. Subjects maintained a daily diary recording formula intake, bowel movements, and medication use. The primary efficacy endpoint measured was daily dose of medication used, while secondary endpoints included disease severity.
Results: Of the 121 subjects randomized, 86 completed all aspects of the trial. There was no significant difference between the two groups with respect to clinical improvement, including bowel function; however, subjects in the UCNS group were able to decrease the dose of prednisone required to control clinical symptoms at a greater rate, as well as control symptoms with a lower total dose of steroid (35-65% lower), as compared with the placebo group.
Conclusion: A formula containing a mixture of fish oil, fermentable oligosaccharides, and antioxidants provides a corticosteroid sparing effect for patients with mild-to-moderate UC over a period of six months.
Study strengths: Stratification scheme to ensure equal distribution of characteristics among study groups; means of determining compliance; intention-to-treat analysis; duration of trial.
Study weaknesses: Significant withdrawal rate (29%); inequality of groups with respect to DAI (the UCNS group had a higher mean DAI score at baseline compared with the placebo group).
Of note: Use of antibiotics and non-steroidal anti-inflammatory drugs was not allowed within two weeks of study entry, while use of immunosuppressive agents was not permitted within four weeks of enrollment (but prednisone and/or mesalamine derivatives were permitted during the course of the study, as were antibiotics, but for no more than 10 days); the DAI is based on four clinical parameters (stool frequency, rectal bleeding, appearance of the rectal mucosa, and physician assessment of disease activity); subjects were instructed to discontinue outside supplementation during the course of the study; almost 50% of participants had stopped smoking before the onset of UC; intolerance rates were similar with both formulas (uncommon); the UCNS contained significantly more calories than the placebo drink, though there was no significant difference in body weight change at study's end between the two groups; levels of arachidonic acid (AA) were significantly decreased only in the UCNS group; bleeding time was not prolonged in the UCNS group, and there was no difference between the two groups in erythrocyte sedimentation rate (a nonspecific measure of inflammation).
We knew that: Corticosteroids are very effective for the treatment of moderate-to-severe UC, but side effects are prominent, and a significant number of patients relapse once treatment is discontinued; fish oils appear to decrease the production of pro-inflammatory eicosanoids; phospholipase A2 causes release of AA, which is metabolized by cyclooxygenase and lipoxygenase into 2-series prostaglandins and thromboxanes, resulting in a variety of processes that can lead to mucosal damage; fructooligosaccharides and gum Arabic are prebiotics that enteric bacteria metabolize into short-chain fatty acids (SCFAs), the primary fuel of the colon; SCFAs do not reach the colon when taken orally due to small bowel absorption and hepatic metabolism; fish oils have shown benefit in animal models of UC; fish oils have been studied previously in the setting of UC with inconsistent results, while studies focusing on the use of SCFAs have shown more consistent benefit; reactive oxygen species are produced by activated neutrophils and macrophages, and contribute to mucosal damage in UC, leading to the hypothesis that antioxidants might ameliorate some pathophysiology seen with UC; the clinical relevance of the dose decrease of steroid employed by those in the UCNS group remains a topic for discussion.
Clinical import: Inflammatory bowel disease can be problematic for the practitioner aiming to relieve suffering and prevent complication, and maddeningly frustrating for the person with the disease. Treatment options include the use of corticosteroids that, while often effective, are associated with the potential for significant side effects as well as adverse effects on quality of life. An adjunct that could safely lessen the dose of steroid required to control disease activity should prove a welcome addition to the physician armamentarium. Studies addressing Crohn's disease and impact on long-term sequelae will be welcomed, but until such time the unique form of supplementation employed in this study can be considered a viable adjunct in the treatment of people with UC.
What to do with this article: Keep a hard copy in your file cabinet.Greenfield RH. Something's fishy--a supplement for UC? Altern Med Alert 2006;9(1):10-11.
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