Meta-analysis finds higher blood omega-3 levels linked to lower atrial fibrillation risk

A recently published meta-analysis examined the link between fish oil supplements (FOS) for omega-3 supplementation and atrial fibrillation (AF), finding an inverse relationship between the two.¹ Earlier randomized controlled trials on pharmaceutical products as well as reports using self-reported data from the UK Biobank have demonstrated an increased risk in AF, the study explains, while higher blood levels of omega-3s have also been previously associated with a lower risk of AF and other conditions such as stroke and heart failure. The current analysis aimed to further investigate the discrepancies between study results and the link between AF and omega-3s. The study, “Associations Between Plasma Omega‐3 and Fish Oil Use With Risk of Atrial Fibrillation in the UK Biobank,” was published in the Journal of the American Heart Association in December 2025.

Study design

This retrospective analysis examined blood serum omega-3 metrics of DHA and total omega‐3s using data from the UK Biobank, as well as self-reported FOS use. Within the Biobank data was a random sample of 261,108 individuals with omega-3 level data, and a sample of 466,169 with reports on FOS use. Follow up was 12.7 years on average. Models were adjusted for multiple behavioral, biomarker, and health‐related variables.

The researchers also replicated the two previous reports on AF and self-reported FOS use, and adjusted for age as a variable.

Study results: AF and FOS relationship

Levels of omega-3 and incidence of AF were inversely related and after adjustment of variables, and no link was seen between AF risk and FOS use, the study demonstrated.

“In agreement with recent biomarker‐based meta‐analyses, higher circulating blood levels of omega‐3 were associated with reduced risk of AF in the UK Biobank,” the researchers concluded. “In addition, this study reassessed the relationship between FOS use and risk of AF in the UK Biobank and found no evidence of an association between FOS use and AF.”

More randomized controlled trials would clarify the inconsistencies between the trials and the observational studies, they added.

“This very large, methodologically sound and statistically robust study finds that higher omega-3 blood levels correlate with lower risks for atrial fibrillation (AFIB) during long-term follow up,” stated study co-author James O’Keefe, MD, in a December 16 press release from OmegaQuant.² “This is in line with other recent studies our group has done, which show that omega-3 in doses typically achieved with consumption of fish/seafood and/or omega-3 over-the-counter supplements reduce risk of AFIB. The only signal for increased AFIB risk comes in people treated with very high-dose omega-3, such as pharmacologic, prescription-strength omega-3 products, used in people at high risk for AFIB. For the vast majority of people, omega-3 intake is a safe and effective nutrient for supporting long-term heart and brain health.”

Impact on omega-3 supplementation

“From a clinical standpoint, these findings help clarify an important misconception,” explained study author Bill Harris, PhD, president of the Fatty Acid Research Institute (FARI).² “When we look at objectively measured blood omega-3 levels, higher status is associated with lower risk of atrial fibrillation—not higher. This reinforces the importance of evaluating physiology, not assumptions about supplements. Concerns raised by earlier reports linking fish oil use to atrial fibrillation were likely driven by methodological limitations. When age is modeled appropriately, fish oil supplement use does not increase atrial fibrillation risk.”

“These results reinforce that it’s the physiologic status of omega-3 in the blood — not simply supplementation per se — that correlates with AF risk. In properly adjusted models, supplement use showed no increase in AF risk,” he added.

References

1. O’Keefe, E.; O’Keefe, JH.; Tintle, NL.; Franco, WG.; Westra, J.; Harris, WS. Associations Between Plasma Omega‐3 and Fish Oil Use With Risk of Atrial Fibrillation in the UK Biobank. Journal of the American Heart Association. 2025.14(24). DOI: 10.1161/JAHA.125.043031
2. OmegaQuant. Higher Blood Omega-3 Levels Linked With Significantly Lower Atrial Fibrillation Risk. December 16, 2025. https://omegaquant.com/higher-blood-omega-3-levels-linked-with-significantly-lower-atrial-fibrillation-risk/ (Accessed 2025-12-22).