A 5-year study of 510 older Spanish adults found no consistent connection between omega-3 intake and circulating markers of atrial fibrillation risk, challenging the premise that dietary omega-3 levels reliably reflect protective changes in AF-related pathways.
Researchers in the PREDIMED-Plus trial tracked five circulating biomarkers associated with atrial fibrillation mechanisms across a half-decade in participants with metabolic syndrome. These biomarkers included NT-pro-BNP (a marker of cardiac stress), high-sensitivity troponin T (cardiac damage), high-sensitivity CRP (inflammation), PICP (collagen turnover), and 3-nitrotyrosine (oxidative stress). The team stratified participants by their omega-3 intake levels, measured via detailed food-frequency questionnaire, and looked for associations both at baseline and over the 5-year follow-up period.
The headline result: total omega-3 fatty acid intake showed no meaningful relationship with any of the five biomarkers, either in cross-sectional analysis or when tracking changes over time. The median dietary omega-3 intake was 2.0 grams per day, suggesting adequate consumption in this Mediterranean-diet-heavy Spanish population. This null finding held whether researchers examined total omega-3, marine-derived omega-3 (from fish and seafood), or non-marine omega-3 (from plant sources).
One exception emerged in the cross-sectional data: marine omega-3 intake was associated with a 28% higher level of 3-nitrotyrosine, a marker of oxidative stress. Notably, this association did not persist in longitudinal analysis, meaning it was present at baseline but did not predict biomarker trajectories over 5 years. A separate non-linear finding appeared with non-marine omega-3 intake, where moderate baseline intake predicted lower PICP levels at 5 years, but this effect was inconsistent across intake categories. The authors describe these sporadic associations as warranting further investigation rather than confirming a protective effect.
The study adds a layer of nuance to omega-3 research. While oily fish consumption has broad evidence supporting cardiovascular and inflammatory markers in other contexts, this trial suggests that habitual omega-3 intake may not reliably shift the specific biomarkers implicated in atrial fibrillation pathogenesis. This does not mean omega-3 has no role in atrial fibrillation risk, but rather that circulating levels of these five markers may not be the mechanism through which omega-3 exerts effects, or that the effect size is too small to detect in a cohort of 510 people.
If you consume adequate omega-3 from dietary sources, this study does not suggest a need to drastically increase intake based on atrial fibrillation prevention alone. The null findings argue against treating omega-3 supplementation as a targeted intervention for shifting AF-related biomarkers. However, omega-3 remains supported by broader evidence for other cardiovascular and metabolic outcomes; this study simply shows that the AF-biomarker pathway may not be where those benefits primarily manifest.
The cross-sectional finding linking marine omega-3 to higher oxidative stress markers is unexpected and unexplained. One possibility is reverse causation or confounding, where people with early signs of cardiac stress consumed more fish. Another is that the association is spurious. Do not use this single finding to reduce fish consumption, which has established benefits in Mediterranean and DASH-style diets.
For individuals at risk of atrial fibrillation, validated lifestyle interventions like maintaining normal weight, managing blood pressure, controlling alcohol intake, and preserving physical fitness have stronger evidence than omega-3 supplementation specifically for AF prevention. This study suggests that biomarker-chasing with omega-3 supplementation is unlikely to be a reliable proxy for atrial fibrillation risk reduction.
| Attribute | Details |
|---|---|
| Study type | Randomized controlled trial (secondary biomarker analysis) |
| Sample size | 510 participants |
| Population | Older Spanish adults (mean age ~65) with metabolic syndrome |
| Duration | 5 years |
| Intervention | Dietary omega-3 intake (observational stratification, not randomized supplementation) |
| Biomarkers measured | NT-pro-BNP, hs-TnT, high-sensitivity CRP, PICP, 3-nitrotyrosine |
| Measurement timepoints | Baseline, 3 years, 5 years |
| Dietary assessment | 143-item food-frequency questionnaire |
| Primary finding | No consistent association between total omega-3 intake and any AF-related biomarker over 5 years |
| Journal | Nutrients |
| PubMed ID | 42280313 |
Diaz-Lopez A, et al. Effect of Omega-3 Fatty Acid Intake on Circulating Biomarkers of Atrial Fibrillation-Related Pathways in the PREDIMED-Plus Study. Nutrients. 2024. PubMed: 42280313
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