In a large-scale study of UK Biobank participants published in BMJ Medicine, researchers found regular fish oil supplementation was associated with an increased likelihood of first-time incidence of atrial fibrillation (Afib) and stroke.
 
However, for participants who were diagnosed with cardiovascular disease, regular use of fish oil supplements was beneficial in slowing down the transition from atrial fibrillation to major adverse cardiovascular events or myocardial infarction, or heart failure to death.
 
These findings led the authors to conclude that fish oil supplementation might be a risk factor for cardiovascular issues among the general population, but could be beneficial for preventing cardiovascular disease progression to major adverse events and death, in those who are already diagnosed with heart disease.
 
Subject matter experts within the omega-3s industry noted that the results of this observational study pertaining to the healthy participants contradict the overwhelming majority of clinical research examining the cardiovascular effects of fish oil on healthy populations.
 
Study Details
 
The authors of the present study tracked the health outcomes of 415,737 UK Biobank participants who enrolled between the ages of 40 and 69 with a median follow-up of 11.9 years. The main outcomes assessed were incident cases of AFib, major adverse cardiovascular events, and death, as well as fish oil supplementation. Participants were divided into regular users and non-users of fish oil supplements based on a touch screen questionnaire or face-to-face interview which asked whether or not they were regular users of fish oil supplements. 
 
By the end of the observation period, 18.367 patients developed incident AFib, 22,636 had major adverse cardiovascular events, and 22,140 deaths during follow-up were identified.
 
For people without heart disease, regular use of fish oil was associated with having a 13% higher risk of developing AFib and a 5% heightened risk of having a stroke. Meanwhile, for people with existing heart disease at baseline, it was linked to a 15% lower risk of progressing from AFib to heart attack, and a 9% lower risk of progressing from heart failure to death.
 
Within the healthy arm of the study, women who took fish oil were slightly more at risk of developing heart attack, stroke, or death than men. In the arm of participants who had heart disease at baseline, both men and older participants saw elevated risk reduction than the overall heart disease population.
The authors of the study noted that inconsistent results of the studies could be related to dosages or compositions of fish oil supplements. In research, particularly high dosages of fish oil seem to be related to incident AFib. Further, there are differences in how EPA and DHA influence cardiovascular disease outcomes, so ratios of the two fatty acids may be important.
 
“Despite these differences in risk estimates, our findings do not support the use of fish oil or omega-3 fatty acid supplements for the primary prevention of incident atrial fibrillation or other specific clinical cardiovascular disease events in generally healthy individuals,” the authors wrote.  
 
Industry Takeaways
 
The Fatty Acid Research Institute (FARI) noted that it is concerned over headlines it considers misleading in the broader context of research.
 
“Headlines around the world are blaring, ‘Fish oil supplements cause heart disease!’ which is a serious misrepresentation of not only this specific study but of the field at large,” said William S. Harris, PhD, president of FARI.
 
Aside from mainstream media coverage, FARI had multiple points of contention with the study itself, such as that it is in contrast with the body of evidence relating fish oil supplementation to the evaluated heart issues.
 
Further, 16 previous studies associated fish oil use with positive outcomes, which the present study failed to mention. This included the most recent study which tracked cardiovascular outcomes.  “In Li et al., every CVD outcome except death from stroke, including total mortality, was statistically significantly and beneficially associated with [fish oil] use. The findings by Li et al. were from the same cohort as Chen et al. (the present study) using the same exposure, also published in BMJ, and yet Chen et al. said nothing about why their results directly contradicted those of Li et al.,” FARI said in a statement.
 
Finally, FARI noted that self-reported fish oil supplementation is far less reliable than measuring actual blood levels of omega-3 fatty acids. “A recent report from O’Keefe et al. in the UKBB looked at the association between plasma omega-3 levels and risk for death from all causes and from CVD, cancer and remaining other causes. They found significant inverse associations between DHA levels and risk for all four mortality outcomes. Why did this report receive virtually no attention by either Chen et al. or the press?” FARI stated.
 
“This new study seemingly takes omega-3 research a step back, especially given the sensational headlines it has generated,” Harris said. “The mainstream press conclusions from this study are simply overblown, disappointing, and reckless. Fish oil isn’t the danger. These headlines are.”

In emails to its membership, the Global Organization for EPA and DHA Omega-3s (GOED) similarly found the findings to be “difficult to reconcile” in the broader context of research.
 
Like FARI, they found it concerning that the present study didn’t mention the 2020 BMJ study which used the same dataset but yielded different outcomes for the healthy population that took fish oil supplements. “Li et al. uses survival analysis, a standard statistical analysis tool, while Chen et al. uses multi-states regression models, a newer technique with less history of use,” the association reported. “The recent article failed to provide the necessary explanation of the reasons why its results might be different from the entire body of interventional research and the results of a study on the same data, using more established statistical techniques.”
 
Additionally, given that this was an observational study, no conclusion can be drawn about causal factors. Another limitation was that everyone taking fish oil was pooled into one group regardless of the dosage they took. “While concerns have been raised about the effects of EPA/DHA to increase the risk of atrial fibrillation, little or no increase has been seen with typical daily supplementation dosages (less than one gram),” GOED noted. “It’s also important to point out that estimating the real risk of developing atrial fibrillation that can be attributed to EPA and DHA is challenging.”