Summary
Crohn's disease is a gastrointestinal condition, with symptoms including abdominal pain, diarrhea, fatigue, and weight loss. Moreover, many patients with Crohn's disease are affected by malnutrition, contributing weight loss, micronutrient deficiencies and loss of muscle mass. Omega-3 fatty acids have been shown to reduce markers of inflammation, decrease disease activity, and increase quality of life in Crohn's disease patients 

Introduction
Crohn's disease is a chronic inflammatory disorder, characterized by periods of inflammation that can affect any segment of the gastrointestinal tract. The disease is idiopathic, meaning that patients often have periods of symptomatic relapse and remission. Symptoms include fatigue, fever, abdominal pain, diarrhea, and weight loss that may lead to hospitalization and severely impact quality of life. Because the gastrointestinal system malfunctions during disease flare-ups, common complications include malnutrition and improper absorption of nutrients, sometimes leading to weight loss and decline in muscle mass. This can be a direct consequence of the disease pathology, but may also occur because affected individuals have a reduced food intake to avoid making their symptoms worse during disease flare ups. Furthermore, repetitive flare ups can cause irreparable damage to the gastrointestinal system. Together, these factors make it so that people with Crohn’s disease can have severe decreases in quality of life during flare ups, but also during remission stages where anything that might trigger the disease must be meticulously avoided. As no cure exists for Crohn’s disease, current management strategies commonly focus on exercise training and diet. In certain cases where disease flare ups have caused irreparable damage to affected sections of the gastrointestinal system, a bowel resection (removal of certain segments) may have to be performed. Because of the anti-inflammatory properties of Omega-3 fatty acids such as EPA and DHA, studies have investigated their role in Crohn’s disease risk and management, as well as beneficial effects . 

Research findings
Chan and collaborators conducted a large-scale prospective cohort study to investigate the association between dietary DHA intake and the development of Crohn's disease (Chan et al., 2014). Dietary intakes of DHA and other fatty acids were measured of 229,702 participants using validated food frequency questionnaires. The cohort was followed for up to 13 years to identify participants who developed incident Crohn's disease. The study employed a nested case-control analysis in which each case of Crohn's disease was matched with four control participants. Odds ratios were calculated for quintiles of DHA intake, with adjustments made for total energy intake, smoking status, other dietary fatty acids, dietary vitamin D intake, and body mass index. During the follow-up period, 73 participants developed Crohn's disease. All higher quintiles of DHA intake showed inverse associations with the development of Crohn's disease, meaning that higher DHA consumption was associated with lower risk of developing the disease. The highest quintile of DHA intake demonstrated the strongest protective effect, with an odds ratio of 0.07, indicating a 93% reduction in Crohn's disease risk compared to the lowest quintile. The trend analysis across all quintiles of DHA intake showed an odds ratio of 0.54. When body mass index was included in the multivariate analysis due to its correlation with dietary fat intake, similar protective associations were observed. Notably, no associations were found with other dietary fatty acids studied. On the basis of these findings, the authors concluded that there were inverse associations with a biological gradient between increasing dietary DHA intakes and incident Crohn's disease. 

Haskey and colleagues conducted a cross-sectional analysis to investigate the effects of a Crohn's disease treatment-directive diet intervention (CD-TDI) on dietary fatty acid intake and markers of inflammation (Haskey et al., 2025). The CD-TDI is low in vegetable oils (high in omega-6 fatty acids), red meat, dairy products, and other foods that are rich in linoleic acid and high in mono-unsaturated fatty acids and poly-unsaturated fatty acids such as DHA.The analysis included 24 participants (13 receiving CD-TDI and 11 following their normal diet as controls) enrolled in a 13-week randomized controlled trial assessing the efficacy of CD-TDI in inducing clinical and biomarker remission in Crohn's disease. The primary outcome measurements were dietary fatty acid intake patterns, red blood cell fatty acid content, and correlations between dietary intake and inflammatory markers. 
After the 13-week intervention period, the CD-TDI group demonstrated a significant increase in dietary omega-3 polyunsaturated fatty acid intake compared to baseline, while no changes were observed in the control group. Participants following the CD-TDI also showed significant reductions in circulating levels of total fat, saturated fat, and arachidonic acid. Analysis of red blood cells revealed lower percentages of (pro-inflammatory) arachidonic acid and higher levels of DHA in the CD-TDI group compared to controls. This was associated with a positive change in markers of inflammation and oxidative stress. On the basis of these results, the authors concluded that the CD-TDI significantly increased dietary omega-3 polyunsaturated fatty acid intake, reduced certain pro-inflammatory omega-6 polyunsaturated fatty acids, and improved markers of oxidative stress, supporting its potential role in Crohn's disease management. 

Ge and fellow scientists investigated whether postoperative parenteral omega-3 polyunsaturated fatty acid supplementation could improve recovery outcomes in Crohn's disease patients following bowel resection (Ge et al., 2024). They recruited 268 patients with Crohn's disease who underwent bowel resection and received parenteral nutrition after the operation. These were randomly assigned to receive either standard parenteral nutrition (134 patients, receiving long-chain and medium-chain fats at 1.0 g/kg/d) or omega-3 enriched parenteral nutrition (134 patients, receiving long-chain, medium-chain, and Omega-3 fatty acids at 1.2 g/kg/d) for 5 days after the operation. The primary outcome measurements were postoperative complications and length of hospital stay, while secondary outcomes included complete blood count, serum biochemical values, and inflammatory cytokine concentrations.  
After the 5-day supplementation period, significant differences were observed between the two groups. The omega-3 supplementation group showed a marked reduction in overall post-operative complication rates compared to the control group, 21.8% versus 38.2% respectively. Additionally, patients receiving omega-3 supplementation had shorter postoperative hospital stays (8.7 ± 4.0 days) compared to the control group (11.5 ± 7.3 days). Regarding inflammatory markers measured on postoperative day 5, the omega-3 supplementation group demonstrated substantially lower levels of inflammatory markers interleukin-6, interleukin-1β, tumor necrosis factor-α, and C-reactive protein compared to the control group. On the basis of these results, the authors concluded that parenteral omega-3 polyunsaturated fatty acid supplementation promotes postoperative recovery in Crohn's disease patients following bowel resection, with fewer complications and reduced inflammatory cytokine levels.

Conclusion
The association between omega-3 fatty acids and Crohn's disease has been investigated through multiple clinical studies. These found that high dietary DHA intake was strongly associated with reduced risk of developing Crohn's disease, with the highest intake quintile showing a very large risk reduction compared to the lowest quintile. In addition, a Crohn's disease treatment-directive diet intervention that was low in omega-6 fatty acids and high in omega-3 fatty acids including DHA, lower arachidonic acid and higher DHA levels correlated with improvements in inflammatory and oxidative stress markers. Finally, Crohn’s disease patients who underwent a bowel resection and received omega-3 enriched parenteral nutrition showed substantially lower levels of inflammatory markers, experienced significantly fewer complications and shorter hospital stays compared to those receiving standard parenteral nutrition. Collectively, these studies suggest that omega-3 fatty acids, particularly DHA, may play important roles in both preventing Crohn's disease development and improving clinical outcomes in patients currently burdened by the disease.

References
Chan, S. S. M., Luben, R., Olsen, A., Tjonneland, A., Kaaks, R., Lindgren, S., Grip, O., Bergmann, M. M., Boeing, H., Hallmans, G., Karling, P., Overvad, K., Venø, S. K., van Schaik, F., Bueno-de-Mesquita, B., Oldenburg, B., Khaw, K.-T., Riboli, E., & Hart, A. R. (2014). Association between high dietary intake of the n−3 polyunsaturated fatty acid docosahexaenoic acid and reduced risk of Crohn’s disease. Alimentary Pharmacology & Therapeutics, 39(8), 834–842. https://doi.org/10.1111/apt.12670 
Ge, X., Liu, H., Wu, Y., Liu, W., Qi, W., Ye, L., Cao, Q., Lian, H., Bai, R., & Zhou, W. (2024). Parenteral n–3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn’s disease after bowel resection: A randomized, unblinded controlled clinical trial. The American Journal of Clinical Nutrition, 119(4), 1027–1035. https://doi.org/10.1016/j.ajcnut.2023.12.022 
Haskey, N., Letef, C., Sousa, J. A., Yousuf, M., Taylor, L. M., McKay, D. M., Ma, C., Ghosh, S., Gibson, D. L., & Raman, M. (2025). Exploring the connection between erythrocyte membrane fatty acid composition and oxidative stress in patients undergoing the Crohn’s disease Therapeutic Diet Intervention (CD-TDI). Therapeutic Advances in Gastroenterology, 18, 17562848251314827. https://doi.org/10.1177/17562848251314827