The study, published in JAMA, contrasts the findings of previous research in patients with acute lung injuries (ALI) – such as from pneumonia or sepsis – by finding that those who received dietary supplements including omega-3 fatty acids, gamma-linolenic acid, and antioxidants have more days on a ventilator, more days in an intensive care unit (ICU), and a slightly increased (though not statistically significant) rate of death.
As a result the study was terminated early.
The researchers explained that patients at risk of developing acute lung injury have omega-3 levels around 25% below normal, whilst those with established lung injury have levels as low as 6% of normal, which prompted the researchers to investigate “a potential role for omega-3 dietary supplementation."
“This study suggests that twice-daily enteral supplementation of omega-3 fatty acids, GLA, and antioxidants change plasma levels of omega-3 fatty acids but do not improve clinical outcomes or biomarkers of systemic inflammation in patients with ALI and in fact may be harmful," said the authors, led by Dr Todd Rice of Vanderbilt University School of Medicine, USA.
Chance or harm?
Rice and his colleagues explained that an independent data and safety monitoring board recommended terminating the study at the first interim analysis “because the primary end point [of ventilator free days] and the major secondary end point (mortality) crossed the predefined futility boundaries, making the probability of a positive trial going forward very low.”
However, they added that despite data to suggest negative outcomes for ventilator free days and mortality, respectively, “we cannot confidently conclude there was harm in the omega-3 group, because this may have been a chance observation.”
The researchers said that previous research had suggested that the omega-6 gamma-linolenic acid (GLA), in conjunction with the omega-3 fatty acid eicosapentaenoic acid (EPA), may be beneficial in acute lung injury. They noted that three previous randomized controlled studies, conducted in patients with ALI or sepsis-induced respiratory failure, showed an association between the administration of an oral formula of omega-3s, GLA, and antioxidants, and improved outcomes on some measures.
The suggestion for such benefits, Rice and his team said, is that the supplements may modulate systemic inflammatory responses, increase oxygenation, and therefore improve outcomes in patients with ALI. The team therefore conducted a study to examine the effects of supplementation of omega-3 fatty acids, GLA, and antioxidants on clinical outcomes in patients with ALI in a phase 3 trial.
They hypothesized that a twice-daily dose of such supplements would increase the ratio of omega-3 to omega-6 fatty acids, reduce inflammatory mediators, and improve certain clinical outcomes.
However, Rice and his team explained that the study – known as the OMEGA study – was stopped early for ‘futility’, after 143 and 129 patients were enrolled in the omega-3 and control groups.
“Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the omega-3 supplement had fewer ventilator-free days (14.0 vs 17.2;P = .02) and intensive care unit–free days (14.0 vs 16.7;P = .04),” wrote the researchers.
They said that patients in the omega-3 group also had fewer non-pulmonary organ failure–free days (12.3 vs 15.5;P = .02), after sixty days the adjusted mortality was 25.1% and 17.6% in the omega-3 and control groups, respectively (P = .11) – adding that use of the omega-3 supplement also resulted in significantly more days with diarrhea (29% vs 21%; P = .001).
Another Dr Rice - Harry Rice, PhD, VP of regulatory & scientific affairs for the Global Organization for EPA and DHA Omega-3s (GOED) - told NutraIngredients that the present results conflict with previous investigations, including a meta-analysis.
"Considering the totality of the scientific evidence, not to mention the use of a questionable control formula in the present investigation, the authors’ conclusions that the enteral formula used provided no benefits, as well as potentially being harmful are not only premature, but outrageous," said GOED's Dr RIce. "Further well-designed research is warranted."
Published online ahead of print: doi: 10.1001/jama.2011.1435
“Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury”
Authors: T.W. Rice, A.P. Wheeler, B.T. Thompson, B.P. deBoisblanc, J. Steingrub, P. Rock