The association between plasma omega-3 fatty acids and suicidal ideation/self-harm in the United Kingdom Biobank

Lipids in Health and Disease Franco et al. Lipids in Health and Disease (2025) 24:364 https://doi.org/10.1186/s12944-025-02689-1 Open Access RESEARCH The association between plasma omega-3 fatty acids and suicidal ideation/self-harm in the United Kingdom Biobank W. Grant Franco1, Nathan L. Tintle2,3, Jason Westra2, Evan L. O’Keefe1, James H. O’Keefe1 and William S. Harris2,4* Abstract Background Self-harm is a significant public health concern, with increasing prevalence globally. Omega-3 fatty acids (FAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known for their health benefits, including potential mental health improvements. This study explores the association between omega-3 FAs and self-harm behaviors using data from the UK Biobank (UKBB). Objectives To investigate the relationship between plasma levels of omega-3 FAs and various measures of self-harm, including passive suicidal ideation and deliberate self-harm, within a large cohort study. Methods This observational study analyzed data from a random subset of 258,012 participants with plasma omega-3 FA levels, covariate data, and self-harm records. Omega-3 levels were measured using Nuclear Magnetic Resonance (NMR) and are expressed as a percent of total FAs. Self-harm outcomes were assessed through self-reported questionnaires and medical records. Covariates included demographic, health, and lifestyle factors. Statistical analyses involved logistic regression and Cox proportional hazards models, adjusting for relevant covariates. Adjusted odds ratios (aORs) are presented and 95% confidence intervals. Results Higher levels of DHA, non-DHA (ALA+EPA+DPA) and total omega-3 were generally inversely associated with passive suicidal ideation, history of self-harm, and future self-harm, with both DHA and non-DHA showing some of the strongest associations. Participants in the highest quintile of non-DHA had a 14% lower risk of passive suicidal ideation in the last year (aOR = 0.86; 95% CI 0.75, 0.99), and the highest DHA levels were associated with a 33% lower odds of history of self-harm (aOR = 0.67; 95% CI 0.55, 0.83). These associations were generally stronger for medical record-based outcomes than for self-reported data. Conclusions This study provides evidence that higher omega-3 FA levels, both DHA and non-DHA, are associated with reduced risks of self-harm and suicidal ideation. These findings suggest that omega-3 FAs may play a protective role in mental health, highlighting the potential of dietary interventions to mitigate self-harm behaviors. Keywords Omega-3, Self-harm, suicide, Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA) *Correspondence: William S. Harris 1 Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, MO, USA 2 Fatty Acid Research Institute, 4600 W. Nobel Street, Suite 123, Sioux Falls, SD 57107, USA 3 Department of Population Health Nursing Science, College of Nursing, University of Illinois – Chicago, Chicago, IL, USA 4 Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creati vecommons.org/licenses/by-nc-nd/4.0/. Franco et al. Lipids in Health and Disease (2025) 24:364 Introduction The prevalence of self-harm, a significant public health concern globally, has increased over recent years. A recent report from England showed a two-fold increase in reported self-harm from 2.4% prevalence to 6.4% between 2000 and 2012 with a particularly notable increase among females aged 16–24 years, where prevalence jumped from 6.5 to 19.7% [1]. Deliberate self-harm, which includes non-suicidal self-injury involves behaviors such as cutting, burning, or self-poisoning and is often a manifestation of psychological distress [2–4]. Studies have reported varying rates of self-harm across different populations, with lifetime prevalence of this form of self-harm of 22% [5–8]. These findings underscore the urgency of addressing self-harm and its underlying causes to mitigate its impact on individuals and society. Omega-3 fatty acids (FAs), in particular eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), are bioactive constituents of certain fish and seafoods and have well-documented health benefits. These include protective effects against cardiovascular disease (CVD) and cognitive decline [9]. Recent evidence suggests that omega-3 FAs may also offer significant mental health benefits, potentially reducing the risk of depression, and anxiety, and possibly influencing self-harm behaviors [10]. The etiology of these benefits is believed to be linked to the anti-inflammatory properties of these FAs and to their crucial role in brain function [11]. Specifically, EPA and DHA are integral to maintaining neuronal cell membrane fluidity and function, which in turn supports neurotransmission and may mitigate mood disorders [12]. Supporting evidence for the impact of omega-3 FAs on mental health is growing, with studies linking higher levels of these nutrients to reduced symptoms of depression and anxiety [13–15]. For instance, the Women’s Health Initiative Memory Study found that higher omega-3 index levels (erythrocyte EPA+DHA) were associated with significantly lower risks of major depressive disorder (MDD) and other psychiatric conditions [16]. A recent report from the National Health And Nutrition Examination Survey found that higher intakes of omega-3 FAs (and of the omega-6 FA, linoleic acid) were linked to lower rates of suicidal ideation [17]. Plasma levels of omega-3 FAs were lower in US service personnel who ultimately committed suicide than in controls [18]. However, a study among individuals admitted to Emergency Department for attempted (or planned) suicide did not find an association with lower plasma omega-3 levels, but with lower arachidonic acid levels (another omega-6 FA) [19]. Beyond these observational studies, omega-3 supplementation has shown promise in reducing the s (...truncated)