Clarifying the Role of EEN Diet as Ulcerative Colitis Therapy

Despite being well tolerated with low discontinuation rates, there is a lack of strong evidence to confirm that exclusive enteral nutrition (EEN) is effective as an add-on therapy for active ulcerative colitis, highlighting the need for more robust research, according to a systematic review.1

EEN is a liquid dietary therapy that involves consuming only specialized nutrition shakes and water for 6 to 12 weeks to reduce inflammation and promote intestinal healing, primarily in individuals with Crohn disease. | Image credit: eldarnurkovic - stock.adobe.com

EEN is a liquid dietary therapy that involves consuming only specialized nutrition shakes and water for 6 to 12 weeks to reduce inflammation and promote intestinal healing, primarily in individuals with Crohn disease, which, along with ulcerative colitis, is a subtype of inflammatory bowel disease (IBD).2 EEN helps manage flares, relieve symptoms, and prepare for surgery by replacing all foods and beverages with a specialized formula, followed by a gradual reintroduction of solid foods under medical supervision.

While EEN has shown success in managing Crohn disease, its effectiveness in ulcerative colitis remains unclear, despite emerging research suggesting potential benefits, particularly in acute severe cases. With growing interest in diet-based therapies and recent clinical trials hinting at EEN’s efficacy, more research was needed to assess existing evidence, clarify its role, and guide future research on safe and effective treatment alternatives for ulcerative colitis.1

The present review, published in Alimentary Pharmacology and Therapeutics, sought to investigate the current data on EEN to determine whether it is effective for helping adults specifically with the ulcerative colitis. The investigators also examined how variations in treatment protocol, safety, tolerability, and adherence influence EEN efficacy.

Researchers conducted a comprehensive search of multiple databases, trial registries, and Google Scholar to identify relevant studies. Inclusion criteria required studies to focus on adult patients with ulcerative colitis, use EEN as an intervention, and report disease activity outcomes. Two independent reviewers screened and extracted data, with a third reviewer resolving discrepancies. Statistical analyses, including meta-analysis where applicable, were conducted, and study quality was assessed using established tools such as Cochrane’s risk-of-bias tool and the GRADE system.

In total, 17,287 records were identified, which investigators narrowed down to 70 studies after screening and eligibility assessment, with 10 studies focusing on ulcerative colitis. The assortment included various designs: 4 randomized controlled trials (RCTs), 2 prospective cohort studies, 2 retrospective cohort studies, and 4 conference abstracts.

A total of 334 patients were analyzed, with 94.3% having moderate to severe disease. Among them, 26.6% were corticosteroid-refractory, and 75.7% met the criteria for acute severe ulcerative colitis (ASUC). Most studies investigated EEN as an adjunctive therapy to standard care, particularly for ASUC (60% of studies).

Comparators varied, including hospital diets, nonexclusive liquid diets, total parenteral nutrition, and historical controls. Concurrent medical therapy included corticosteroids, sulfasalazine, and infliximab, with 4 studies using medical rescue therapy before considering colectomy.

Regarding efficacy, clinical remission was assessed in 3 studies, showing no significant difference between patients following EEN and the control group. Corticosteroid failure was reported in 6 studies, with meta-analysis showing no significant reduction in failure risk with EEN. Additionally, EEN did not significantly impact medical rescue therapy outcomes in patients with ASUC.

The reviewed studies showed significant variation in EEN protocols for ulcerative colitis. Eight studies (80%) specified EEN formulas: 4 (40%) used polymeric, 1 (10%) semielemental, and 3 (30%) elemental. EEN duration ranged from 5 to 14 days, depending on disease severity, with some studies adjusting based on clinical response. One study used EEN for up to 4 weeks, though it's unclear if this applied to both IBD subtypes.

Caloric needs were determined using methods like Long’s equation and body mass index-based calculations. Two studies (20%) calculated protein needs without specifying methods, and none reported fluid intake requirements. Dietitian involvement was noted in 2 studies (20%), primarily for prescribing and monitoring. One study (10%) allowed limited foods, while 3 (30%) restricted all non-EEN foods and fluids.

Administration routes varied: 2 studies (25%) used nasogastric tubes, and 6 (60%) administered EEN orally. Adjustments were made for poor tolerability, with 1 study (10%) reducing nasogastric feeding and 2 (20%) switching to nasogastric feeding if oral intake was intolerable.

Post-EEN dietary transitions included normal diets (20%) and low-residue diets (10%), but transition pace and partial enteral nutrition details were unclear. Disease activity was monitored via clinical, biochemical, radiological, and endoscopic methods. Only 1 study (10%) measured nutritional indices.

Adherence and tolerability were assessed differently, with 3 studies (30%) reporting adherence. Treatment completion was reported in 9 studies (90%), with a pooled discontinuation rate of 3%, varying by formulation (2% polymeric, 16% semielemental, 1% elemental).

Adverse effects, including worsening diarrhea, were reported in 70% of studies. Researchers highlighted the need for standardized EEN protocols and monitoring as an ulcerative colitis treatment. However, the authors determined that there was insufficient evidence linking therapy completion to improved clinical outcomes.

Although EEN did not improve clinical outcomes, it was associated with higher serum albumin levels, which may reflect reduced inflammation rather than directly improving disease.

The authors called for more research going forward: “Further high-quality trials utilising harmonised protocols for prescribing and monitoring EEN are needed, capturing contemporary clinical, biomarker and endoscopic trial endpoints at appropriate timepoints, as well as standardised measurement of adherence, tolerability and duration of therapy.”

References

1. Chu MKW, Day AS, Broad L, Costello SP, Edwards S, Bryant RV. Meta‐analysis: exclusive enteral nutrition in adults with ulcerative colitis. Aliment Pharmacol Ther. 2025;61(5):756-775. doi:10.1111/apt.18495

2. Crohn’s disease: exclusive enteral nutrition. American Gastroenterological Association GI Patient Center. 2021. Accessed March 12, 2025. https://patient.gastro.org/exclusive-enteral-nutrition-een-for-crohns-disease/