Randomized clinical trial Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery L. S. Sorensen 1 , O. Thorlacius-Ussing 1 , E. B. Schmidt 2 , H. H. Rasmussen 3 , S. Lundbye-Christensen 2 , P. C. Calder 5 and K. Lindorff-Larsen 4 1 Department of Surgical Gastroenterology, 2 Department of Cardiology, Centre for Cardiovascular Research, 3 Centre for Nutrition and Bowel Disease, and, 4 NordSim, Centre for Simulation, Skills Training, Science and Innovation, Aalborg University Hospital, Aalborg, Denmark, and 5 Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, and National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK Correspondence to: Mrs L. S. Sorensen, Department of Surgical Gastroenterology, Aalborg University Hospital, 9000 Aalborg, Denmark (e-mail: lss@rn.dk) Background: Omega-3 fatty acids (n-3 FAs) may have beneficial clinical effects, and n-3 FA supplements may improve outcome after surgery. Methods: In a randomized double-blind placebo-controlled trial in single centre, patients referred for elective colorectal cancer surgery received either an n-3 FA-enriched oral nutritional supplement (ONS) (Supportan  , 200 ml twice daily) providing 2·0 g eicosapentaenoic acid (EPA) and 1·0 g docosahexaenoic acid (DHA) per day, or a standard isocaloric and isonitrogenous ONS, for 7 days before and 7 days after surgery. The primary endpoint was infectious and non-infectious complications within 30 days of surgery. Secondary endpoints were length of hospital stay, intensive care unit admission, readmissions, and concentrations of marine n-3 FAs and arachidonic acid in granulocyte membranes. Results: Some 148 consecutive patients (68 women, 80 men; mean age 71 (range 41–89) years) were randomized. There was no significant difference between groups in infectious or non-infectious postoperative complications (P = 1·000). Granulocyte levels of EPA, DHA and docosapentaenoic acid (DPA) were significantly higher in the n-3 FA-enriched supplement group compared with the control group (P < 0·001). The arachidonic acid level in granulocytes was significantly lower in the enriched group than in the control group (P < 0·001). Conclusion: EPA, DHA and DPA were incorporated into granulocytes in patients receiving n-3 FAs, but this was not associated with improved postoperative outcomes. Registration number: NCT00488904 (http://www.clinicaltrials.gov). Presented in part to the European Society for Clinical Nutrition and Metabolism Congress 2011, Gothenburg, Sweden, September 2011 Paper accepted 27 September 2013 Published online 26 November 2013 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9361 Introduction Major surgery is associated with changes in the immune response 1 , initially with a hyperinflammatory response followed by a phase of relative immune incompetence 2 . Patients with colorectal cancer undergoing surgery have a considerable risk of developing complications in the postoperative period. Infectious complications occur in approximately 30 per cent, and anastomotic leakages in up to 15 per cent 3 , with increased mortality, morbidity and length of hospital stay 4 . Among factors known to influence the clinical course after surgery are nutritional status and availability of specific biologically active nutrients 4–9 that might include the marine omega-3 fatty acids (n-3 FAs), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and perhaps also docosapentaenoic acid (DPA). Increased intake of marine n-3 FAs results in increased concentrations of EPA, DPA and DHA in blood, cells and tissues 10,11 . This may alter the physical properties of cell membranes and functioning of membrane proteins, including receptors, transporters and signalling proteins 12 . EPA and DHA are incorporated into cells and mem- branes in competition with the more abundant omega-6 fatty acids (n-6 FAs) linoleic acid and arachidonic acid. Arachidonic acid may be liberated by phospholipases from cell membranes, and induces leucocytes to produce  2013 BJS Society Ltd BJS 2014; 101: 33–42 Published by John Wiley & Sons Ltd