Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial

Ann Surg. 2017 Nov;266(5):720-728. doi: 10.1097/SLA.0000000000002390.


Objective: This randomized controlled trial (RCT) hypothesized that prolonged enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3 fatty acid with immune and anabolic properties, may impact on clinical and nutritional outcomes.

Background: Esophagectomy is associated with significant weight loss and catabolism, and negatively impacts quality of life (QL). Strategies to counter sustained catabolism have therapeutic rationale.

Methods: This multicenter, double-blind, placebo-controlled RCT was powered on a 5% difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and at 1, 3, and 6 months included weight, body mass index (BMI), body composition, muscle strength, cytokines, complications, and QL.

Results: The median (range) nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For the entire cohort, a significant (P < 0.005) decrease in weight (-7.4 ± 6.6 kg), BMI (-2.6 ± 2.2 kg/m), LBM (-2.5 ± 8.7 kg), and fat mass (-3.4 ± 5.8 kg) was evident from preoperatively to 6 months. The mean (±SD) loss of LBM (kg) at 1 month was -3.7 ± 8.7 in the EN-S group, compared with -5.6 ± 12.1 in the EN-EPA group (P = 0.355). Per-protocol analysis revealed no difference between the EN-EPA and EN-S in any clinical, nutritional, functional, QL or immune parameter at any time point.

Conclusions: The thesis that EPA impacts on anabolism, immune function, and clinical outcomes post-esophagectomy was not supported. Compliance with home EN was excellent, but weight, muscle, and fat loss was significant in 30% of patients, highlighting the complexity of postoperative weight loss.

Trial registration: NCT00790140.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dietary Supplements*
  • Double-Blind Method
  • Eicosapentaenoic Acid / therapeutic use*
  • Enteral Nutrition / methods*
  • Esophagectomy*
  • Follow-Up Studies
  • Humans
  • Malnutrition / diagnosis
  • Malnutrition / etiology
  • Malnutrition / prevention & control*
  • Postoperative Care / methods*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / prevention & control*
  • Prospective Studies
  • Quality of Life
  • Time Factors
  • Treatment Outcome
  • Weight Loss


  • Eicosapentaenoic Acid

Associated data