Effects of perioperative intravenous ω-3 fatty acids in colon cancer patients: a randomized, double-blind, placebo-controlled clinical trial

Background: The postoperative inflammatory response contributes to tissue healing and recovery but overwhelming inflammation is associated with postoperative complications. n-3 (omega-3) PUFAs modulate inflammatory responses and may help to prevent a proinflammatory cascade. Objective: We aimed to investigate the effects of perioperative intravenous n-3 PUFAs on inflammatory cytokines in colon cancer surgery. Methods: This study is a randomized, double-blind, placebo-controlled clinical trial. Forty-four patients undergoing elective colon resection for nonmetastasized cancer were randomly assigned to 2 intravenous n-3 PUFA or saline control infusions the night before and the morning after surgery. Blood was sampled at 6 perioperative time points for changes in cytokines in serum and in LPS-stimulated whole blood samples and leukocyte membrane fatty acid profiles. Results: Twenty-three patients received saline and 21 patients received n-3 PUFAs. Patient and operation characteristics were equal between groups, except for open resection (saline n = 5 compared with n-3 PUFA n = 0, P = 0.056). Ex-vivo IL-6 after LPS stimulation was significantly higher in the n-3 PUFA group at the first day after surgery (P = 0.014), but not different at the second day after surgery (P = 0.467). White blood cell count was higher in the n-3 PUFA group at the fourth day after surgery (P = 0.029). There were more patients with infectious complications in the n-3 PUFA group (8 compared with 3, P = 0.036). There were no overall differences in serum IL-6, IL-10, C-reactive protein, and length of stay. The administration of n-3 PUFAs resulted in rapid increases in leukocyte membrane n-3 PUFA content. Conclusions: In the n-3 PUFA group a clear relation with serum and LPS-stimulated cytokines was not found but, unexpectedly, more infectious complications occurred. Caution is thus required with the off-label use of a perioperative intravenous n-3 PUFA emulsion as a standalone infusion in the time sequence reported in the present study in colon resections with primary anastomosis. This trial was registered at clinicaltrials.gov as NCT02231203.