inflammatory bowel

Mozaffari H, Daneshzad E, Larijani B, Bellissimo N, Azadbakht L. European Journal of Nutrition. 2020;59(1):1–17. DOI: 10.1007/s00394-019-01901-0

Background & Rationale

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), has shown increasing incidence globally, with the highest rates reported in Europe and North America. While genetic factors contribute approximately 25% to IBD pathophysiology, environmental and lifestyle factors, including diet, appear to play a substantial role in disease aetiology. Polyunsaturated fatty acids, particularly omega-3, have established roles in regulating inflammatory processes and may therefore influence IBD risk. Previous studies examining associations between fish consumption, dietary omega-3 intake, and IBD risk have yielded inconsistent results. While some investigations identified protective associations, others found positive associations or no relationship. A recent meta-analysis of randomised controlled trials did not support omega-3 supplementation for maintaining remission in IBD; however, the authors noted that dietary omega-3 in the context of foods such as fish might exert different effects, and the role of omega-3 in disease onset may differ from its role in treatment.

Study Design

This systematic review and meta-analysis followed PRISMA guidelines and included observational studies examining associations between fish consumption or dietary omega-3 intake and IBD risk. Three databases (PubMed, Scopus, Web of Science) were searched for articles published prior to January 2019. Eligible studies were observational designs including cohort, case-control, and nested case-control studies, published in English, involving participants aged 15 years or older, and reporting odds ratios, hazard ratios, or relative risks with 95% confidence intervals. The primary exposures were fish consumption and dietary omega-3 intake, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The primary outcomes were CD, UC, or IBD incidence. Fixed-effects or random-effects models were applied to pool effect sizes. The Cochrane Q test and I² statistic assessed heterogeneity. Study quality was evaluated using the Newcastle-Ottawa Scale.

Patient Population

Twelve studies (five prospective and seven case-control) were included in the systematic review, with ten eligible for meta-analysis. The combined sample comprised 282,610 participants, including 2,002 IBD cases (1,061 CD and 937 UC). Participants were aged 15 years or older. Five studies were conducted in Europe, five in Asia, and two in the United States. Three studies included only women, while nine included both sexes. Study sample sizes ranged from 186 to 170,805 participants. Follow-up duration in cohort studies ranged from 10.4 to 26 years. Dietary assessment was predominantly conducted using food frequency questionnaires.

Key Findings

For fish consumption, the fixed-effects model showed no significant association with overall IBD risk. However, when using a random-effects model due to substantial heterogeneity, a marginally inverse association emerged with IBD risk. When analysed by disease subtype, fish consumption demonstrated a significant inverse association with CD risk under the random-effects model, with those in the highest consumption category showing approximately 46% lower risk compared with the lowest category. No association was found between fish consumption and UC.

For total dietary omega-3 intake, no association was observed with IBD, CD, or UC under either statistical model.

For long-chain omega-3 (EPA plus DHA), a significant inverse association was found with overall IBD risk, with those in the highest intake category showing approximately 22% lower risk. This association was driven primarily by UC, where high long-chain omega-3 intake was associated with approximately 25% lower risk. No significant association was observed between long-chain omega-3 and CD.

For ALA intake, no association was found with IBD risk.

Subgroup analyses indicated the inverse association between fish consumption and CD was significant in Asian populations, in studies adjusted for body mass index and smoking, in high-quality studies, and in studies where IBD was confirmed by physician diagnosis.

Discussion

The authors noted that the protective effect of omega-3 on IBD appears to be driven primarily by long-chain omega-3 rather than ALA. They proposed several mechanisms for these findings, including the competitive action of long-chain omega-3 against arachidonic acid, inhibition of inflammatory eicosanoid production, reduction of leukotriene B4 levels in intestinal membranes, and inhibition of nuclear factor kappa beta activation. The authors suggested that pretreatment with long-chain omega-3 may be more effective at preventing disease onset than treating established disease.

The regional differences observed, with stronger associations in Asian populations, were attributed to variations in dietary patterns, intestinal microflora composition, and genetic factors including CARD-15/NOD-2 mutations.

Regarding safety, this meta-analysis of observational studies did not report adverse event data as this was not within the study scope.

The authors acknowledged several limitations, including incomplete adjustment for confounders across studies, inability to examine EPA and DHA effects separately, variation in dietary assessment methods, and the observational nature of the evidence.

Authors’ Conclusions

The authors concluded that fish consumption was inversely associated with CD risk, and dietary long-chain omega-3 intake was inversely associated with UC incidence. They emphasised that while the meta-analysis provided a comprehensive review of associations between fish consumption and dietary omega-3 intake with IBD, additional well-designed studies considering subtypes of fish and omega-3 are needed to strengthen these findings.

Reference

Mozaffari H, Daneshzad E, Larijani B, Bellissimo N, Azadbakht L. Dietary intake of fish, n-3 polyunsaturated fatty acids, and risk of inflammatory bowel disease: a systematic review and meta-analysis of observational studies. Eur J Nutr. 2020;59(1):1–17.

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This Scientific Publication Summary is an objective summary of the published trial for personal and educational use. It does not constitute clinical advice, endorsement of the intervention, or a recommendation to alter clinical practice.