ω-3 fatty acids, γ-linolenic acid, and antioxidants: immunomodulators or inert dietary supplements?
1 Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
2 The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh, Pittsburgh, PA, USA
Critical Care 2012, 16:325 doi:10.1186/cc11863Published: 23 November 2012
Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock, P. Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury. JAMA. 2011; 306(14):1574-1581. PubMed PMID: 21976613.
The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.
Objective: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.
Design: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. All participants had complete follow-up.
Setting: This trial occurred at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.
Subjects: Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition.
Intervention: Twice-daily enteral supplementation of n-3 fatty acids, γ -linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.
Outcomes: Ventilator-free days to study day 28.
The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P=.02) (difference, −3.2 [95% CI, −5.8 to −0.7]) and intensive care unit-free days (14.0 vs 16.7; P=.04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P=.02). Sixty-day hospital mortality was 26.6% in the n 3 group vs 16.3% in the control group (P=.054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P=.11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P=.001).
Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.