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Issue #81 (July 2021)

From the Editor

In this issue, we shine our safety spotlight on the recent evidence surrounding the increased risk of atrial fibrillation caused by omega-3 supplementation. There, we also briefly mention a meta-analysis of the most recent evidence about its efficacy for reducing cardiovascular disease risk. We’re probably not going to cover that meta-analysis in a more detailed Deep Dive because we’ve covered fish oil’s impact on cardiovascular disease several times already. But since the evidence is a bit confusing and the 2021 meta-analysis has some interesting findings, I thought I’d use my soapbox this month to give you a quick overview.

The meta-analysis took a look at 38 randomized controlled trials involving a total of close to 150,000 participants. The main takeaway is that omega-3 fatty acid supplementation reduced the risk of serious cardiovascular events by about 5–13%. Furthermore, the evidence quality was rated as moderate for some of the more serious outcomes, including heart attacks, coronary heart disease, cardiovascular death, and major cardiovascular adverse events overall. Most of these effects remained significant even when studies with only a low risk of bias were explored.

The authors found that EPA tended to do better than a combination of EPA and DHA. Notably, the effect of supplementation on stroke risk and the risk of dying from any cause was not statistically significant. And, perhaps surprisingly, there was very little evidence to suggest that high risk people benefited more from supplementation than low or moderate risk people. However, the authors rightly note that even though the relative risk of avoiding bad cardiovascular outcomes wasn’t different between the two risk categories, people with a higher baseline absolute risk may still benefit more. That’s because taking 10% off a bigger number will lead to more risk being shaved off, compared to taking 10% off a smaller number.

Despite these positive results, there are still plenty of unanswered questions, and room for uncertainty. One major concern I have is that the benefits of EPA-only formulations are largely being driven by the results of the REDUCE-IT trial. This could be a problem because that trial may have yielded exaggerated benefits due to its choice of mineral oil as a placebo. Since mineral oil raises CRP levels, its use may have led to a bigger performance gap between the EPA treatment group and the placebo.

We should also keep the small effect sizes in mind. Combined with the possibility of boosting the risk of atrial fibrillation and maybe bleeding (with very low certainty evidence and borderline statistical significance), small effect sizes mean that the question of whether fish oil is worth taking for cardiovascular disease prevention is far from settled.

See other articles in Issue #81 (July 2021) of Study Deep Dives.