Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease

Fish oil contains omega 3 fatty acids that may be beneficial in reducing inflammation, such as seen in the bowel of Crohn's disease patients. Randomized placebo-controlled studies that evaluated the effect of daily intake of capsules containing omega-3 fatty acids to maintain remission in Crohn's disease were reviewed. Six studies including 1039 patients were included in the review. A pooled analysis of six studies suggests a marginal benefit for omega 3 fatty acids over placebo (i.e. fake medicine) in preventing relapse of disease at one year. However, these results need to be interpreted with caution due to differences across the studies in terms of induction of remission regimens (e.g. surgical remission versus drug therapy) patients (e.g. adult versus pediatric patients) and medication regimens (e.g. some studies used different placebos), the possibility of publication bias (i.e. only studies with positive results are published) and low methodological quality in four studies in the pooled analysis. When the two largest and highest quality studies were pooled the results showed no benefit to omega-3 treatment over placebo. There were no serious side effects in any of the studies. Common side effects included unpleasant taste, bad breath, heartburn, nausea and diarrhea. Evidence from two large high quality studies suggests that omega 3 fatty acids are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids appear to be safe although they may cause diarrhea and upper gastrointestinal tract symptoms.

Authors' conclusions: 

Evidence from two large high quality studies suggests that omega 3 fatty acids are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids appear to be safe although they may cause diarrhea and upper gastrointestinal tract symptoms.

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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. This review is an update of a previously published Cochrane review.

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 inception to November 2013 without language restriction: CENTRAL, MEDLINE, EMBASE, HealthSTAR, PubMed, and ACP journal club.

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.

Data collection and analysis: 

The primary outcome was the relapse rate and secondary outcomes included change in disease activity scores, time to first relapse and adverse events. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary and selected secondary outcomes was reassessed for the current update using the GRADE system. We used the RevMan software for analyses. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes and the hazard ratio and 95% CI for time-to-event outcomes. Random-effects or fixed-effect models were used according to degree of heterogeneity and sensitivity analyses were performed in an attempt to explore possible sources of heterogeneity.

Main results: 

Six studies with a total of 1039 patients were eligible for inclusion. The two largest studies were rated as low risk of bias for all assessed items. Four studies were rated as unclear risk of bias for randomization and allocation concealment. Two studies were rated as high risk of bias for incomplete outcome data and selective reporting. There was a marginal significant benefit of n-3 therapy for maintenance of remission. Thirty-nine per cent of patients in the n-3 group relapsed at 12 months compared to 47% of placebo patients (6 studies, 1039 patients; RR 0.77, 95% CI 0.61 to 0.98). A GRADE analysis rated the overall quality of the evidence for the primary outcome (i.e. relapse) as very low due to unexplained heterogeneity (I2 = 58%), publication bias, and a high or unknown risk of bias in four studies in the pooled analysis. When two large studies at low risk of bias were considered the benefit was no longer statistically significant. Thirty-seven per cent of patients in the n-3 group relapsed at 12 months compared to 42% of placebo patients (2 studies, 738 patients; RR 0.88, 95% CI 0.74 to 1.05). No significant heterogeneity was identified for this pooled analysis ( I2 = 0%). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (294 events). No serious adverse events were recorded in any of the studies but in a pooled analyses there was a significantly higher rate of diarrhea (4 studies, 862 patients; RR 1.36 95% CI 1.01 to 1.84) and upper gastrointestinal tract symptoms (5 studies, 999 patients; RR 1.65, 95% CI 1.25 to 2.18) in the n-3 treatment group.

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