Association between Omega-3 fatty acids and autoimmune disease: Evidence from the umbrella review and Mendelian randomization analysis

Abstract

Background: Autoimmune diseases are a group of disorders characterized by abnormal immune responses that mistakenly target and attack healthy cells, tissues, and organs, resulting in inflammation and tissue damage. Omega-3 fatty acids possess anti-inflammatory activities and may decrease abnormal immune activity. However, the role of omega-3 fatty acids in various autoimmune diseases is still unclear. This umbrella review and Mendelian randomization (MR) study aims to summarize the highest available evidence on omega-3 fatty acids and autoimmune disease.

Methods: We conducted an umbrella review by searching electronic databases to identify systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis, which evaluated omega-3 fatty acids as the exposure and autoimmune disease as the outcome variable. Two authors independently assessed the overlapping and quality of the reviews using the AMSTAR-2 tool. We also performed MR studies to investigate the potential causal effect of fatty acids on the risk of various autoimmune diseases, utilizing data from the meta-analysis of the UKB-TOPMed and FinnGen cohorts.

Result: The umbrella review identified 21 studies (8 systematic reviews and 13 meta-analyses) on 9 autoimmune diseases and 30 diseases in the MR study. AMSTAR 2 categorized the quality of evidence in six studies as critically low, six studies as low, eight studies as moderate, and one as high-quality evidence. The consistent result between the review and the MR study demonstrated the benefit of omega-3 fatty acids on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Additionally, in our summary review, omega-3 fatty acids can improve disease activity and inflammation biomarkers; however, MR studies provided no consistent evidence for the causal effects of omega-3 fatty acids on psoriasis, multiple sclerosis (MS), type 1 diabetes (T1D), IgA nephropathy (IgAN), juvenile idiopathic arthritis (JIA), Crohn's disease (CD), and ulcerative colitis (UC).

Conclusion: The current study presented solid evidence highlighting the advantageous impact of omega-3 fatty acids on SLE and RA. This was achieved through the reduction of disease risk, the decrease of disease activity, and the mitigation of inflammatory biomarkers. To stratify another autoimmune illness, it is necessary to carry out rigorous evaluations to surpass the existing findings and enhance understanding in this domain.

Keywords: Autoimmune disease; DHA; EPA; Mendelian randomization; Omega-3 fatty acids; Umbrella review.