• Deo Narayan, Caitlyn Vlasschaert, Andrew G Day, Patrick Norman, Michael J Rauh, and David M Maslove.
• Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
• Crit. Care Med. 2025 Feb 3.

ObjectivesSepsis is a life-threatening condition characterized by a dysregulated host response to infection. Despite decades of clinical trials, there are no specific treatments; care of the nearly 50 million annual cases worldwide is limited to antimicrobials and supportive measures. A primary prevention strategy may therefore be of value. We hypothesized that higher premorbid omega-3 fatty acid levels would be associated with a reduced incidence of sepsis.DesignPopulation-based cohort study.SettingRetrospective data from the United Kingdom (U.K. Biobank).PatientsTwo hundred seventy-three thousand three hundred twenty-five participants from the U.K. Biobank.InterventionsNone.Measurements And Main ResultsOur exposure was baseline estimated omega-3 index (eO3I), modeled both categorically in quartiles, and continuously with restricted cubic splines. Our outcome measure was hospital admission with an International Classification of Diseases, 10th Edition code consistent with sepsis. The median (interquartile range) baseline eO3I was 6.0% (4.8-7.3%). Over a mean follow-up period of 13 years, 9241 participants experienced hospitalization with sepsis. In our adjusted model, compared with the lowest eO3I quartile, participants had lower risks of sepsis incidence in the second quartile (hazard ratio [HR], 0.88; 95% CI, 0.86-0.91; p < 0.001), third quartile (HR, 0.80; 95% CI, 0.78-0.83; p < 0.001), and fourth quartile (HR, 0.75; 95% CI, 0.73-0.77; p < 0.001). When analyzed as a continuous variable, increasing eO3I was associated with a decreasing risk of sepsis (p < 0.001).ConclusionsIn this population-based cohort study, baseline eO3I was inversely associated with subsequent sepsis incidence. Given that omega-3 levels can be increased with dietary supplementation, primary prevention should be explored to mitigate the burden of sepsis.Copyright © 2025 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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