Writing in the Journal of the American Heart Association, researchers at the Fatty Acid Research Institute, the University of Illinois, Stanford University, University of Missouri, and Saint Luke’s Mid America Heart Institute found that when the confounding effects of age in the statistical models were accounted, fish oil supplement use did not increase the risk of atrial fibrillation.
The study contradicts previous accounts from UK Biobank data that concluded supplementation heightened the risk for AF.
“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,” said Bill Harris, PhD, president of the Fatty Acid Research Institute (FARI) and senior investigator on the paper. “In properly adjusted models, supplement use showed no increase in AF risk.”
The researchers added that the biomarker-based approach they carried out offers a more nuanced understanding than studies that rely solely on self-reported supplement usage or dose, aligning with a greater body of evidence demonstrating cardiovascular benefits of omega-3 fatty acids.
Contradicting studies
More than 37 million people worldwide have atrial fibrillation with greater than three million new cases documented every year. The condition can lead to hospitalization, premature mortality, heart failure and thromboembolic events like stroke.
Consuming omega-3 fatty acids has been linked to a lower likelihood of AF, heart failure and all-cause mortality, though pharmaceutical omega-3 products that contain 2 to 4 grams of daily eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) may increase risk of AF, according to randomized controlled trials. However, findings from these trials contradict a meta-analysis that explored 17 biomarker-based cohort studies of nearly 55,000 people which observed a reduced risk for AF when EPA and DHA were found in blood samples.
Additionally, two reports that used UK Biobank data noted that self-reported consumption of over-the-counter fish oil supplements increased AF incidents.
The authors of the study that appeared in the American Heart Association sought to investigate the relationship between omega-3 levels and AF risk in individuals participating in the UK Biobank by testing omega-3 levels and reexamining the purported link between self-reported FOS and AF risk.
Study details
The researchers conducted a retrospective analysis of UK Biobank data and found connections between omega-3 levels and fish oil supplement use with AF risk. A random sample of over 261,000 people in the Biobank did not have prevalent AF and more than 466,000 reported FOS use. AF incidents were followed for 12.7 years.
“The UK Biobank includes data on two serum omega-3 metrics: DHA and total omega-3s,” the researchers noted. “We constructed a third metric, other omega-3 fatty acids (i.e., the sum of alpha linolenic acid, EPA, and docosapentaenoic acid [DPA]), as the difference between these two. Serum samples were collected at baseline and analyzed for omega-3 fatty acids by nuclear magnetic resonance.”
The study also accounted for sex, body mass, race or ethnicity and education differences as well as individual exercise habits and alcohol consumption. Levels of serum linoleic acid, omega-6 acid and use of β-blockers were also assessed. Researchers noted self-reported treatment for hypertension, high cholesterol and whether individuals were diagnosed with diabetes, cardiovascular disease or heart failure.
The study found the following:
- Higher circulating levels of omega-3s were associated with reduced risk for AF in the UK Biobank, in both FOS users and nonusers;
- When added to a previous meta-analysis by Qian et al, their conclusion that higher omega-3 levels were linked with lower risk for AF was further supported;
- Earlier reports from two prior UK Biobank studies that fish oil supplement users were at increased risk for AF were nullified when age was adjusted for continuously.
The findings showed higher blood levels of DHA, EPA, DPA, and EPA + DHA were associated with a 6% to 10% lower risk of AF. The only signal for increased AF 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 atrial fibrillation.
“This very large, methodologically sound and statistically robust study finds that higher omega-3 blood levels correlate with lower risks for atrial fibrillation during long-term follow up,” said study co-author James O’Keefe, MD, director of preventive cardiology at St. Luke’s Mid-America Heart Institute, professor of medicine at University of Missouri. “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…For the vast majority of people, omega-3 intake is a safe and effective nutrient for supporting long-term heart and brain health.”
Source: Journal of the American Heart Association. doi: 10.1161/JAHA.125.043031. “Associations Between Plasma Omega-3 and Fish Oil Use With Risk of Atrial Fibrillation in the UK Biobank”. Authors: E. O’Keefe, et al.
