Fish oil supplements provide cardiovascular benefits in randomised trials, but is this benefit undermined by an increased risk of atrial fibrillation and does this risk also apply to eating oily fish? Rod Tucker finds out more, in our Review series

Danish researchers first observed how Greenland Eskimos had a fatty acid plasma profile that showed a higher content of long-chain polyunsaturated fatty acids – known as omega-3 fatty acids – derived from marine mammals, in 1976. The two key fatty acids perceived as being physiologically most important were docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). With a lower incidence of cardiovascular disease mortality compared to the wider Danish population among the indigenous Eskimos, researchers speculated that this effect was due to consumption of large amounts of oily fish containing these omega-3 fatty acids.

Over the ensuing years, observational data also implied that eating fish may confer a cardiovascular benefit. For instance, one study from 1985 showed that among men without coronary heart disease followed for 20 years, coronary heart disease mortality was more than 50% lower among those who consumed at least 30 g of fish per day. More robust evidence came in 1989, when a randomised dietary trial of fatty fish intake in men who had sustained a myocardial infarction found a 29% reduction in two year all-cause mortality compared with those not advised to eat it. More recently, a 2021 meta-analysis of 38 randomised controlled trials with nearly 150,000 participants, confirmed that there were important cardiovascular benefits in patients receiving EPA and DHA.

But there was a problem lurking within the data. It seemed that these fish oils also increased the risk of arrythmias, in particular, atrial fibrillation (AF).

Fish oil supplements and atrial fibrillation

A recent analysis of the cardiovascular benefits of different doses of fish oil supplement intake, concluded that higher doses significantly increased the risk of both bleeding events and AF compared to lower doses. This was re-affirmed in a 2021 meta-analysis. showing a 37% higher risk of incident AF compared with placebo in randomised trials of fish oil supplementation in patients with cardiovascular disease.

Is it EPA or DHA?

As with most things in life, it was never that simple. In fact, some evidence pointed the AF finger of blame at DHA, because those with the highest levels of EPA had a 45% lower risk of AF. But other work muddied the waters even further, showing no effect of either type of fish oil on incident AF; another suggested that incident AF was significantly lower with higher levels of DHA but not for either EPA or a combination of the two oils.

Does eating oily fish increase AF risk?

A prospective analysis published in June 2023 assessed whether dietary marine omega-3 fatty acid intake was associated with the risk of AF. Among over 300,000 individuals who had a median intake of omega-3 fatty acids of 219 mg per day, there was a nonlinear and inverse relationship with incident AF. As the authors somewhat reassuringly stated, 'consumption of marine omega-3 fatty acids was not associated with a higher incidence of AF'. There was also no detectable difference in risk between EPA and DHA. Another very recent analysis found that blood levels of both EPA and DHA, from eating fish, were not associated with increased risk of incident AF.

But what about plant-based sources of EPA and DHA?

Good news it seems. It has been found that intake of the plant-based omega-3 fatty acid alpha-linolenic acid (ALA) for example, in flaxseed and rapeseed oils, is associated with cardiovascular benefits. In fact, the Cardiovascular Health Study, which was a community-based longitudinal cohort of adults aged 65 or older, found no association of plasma phospholipid or dietary ALA and incident AF.

What’s the best advice for those wanting to purchase fish oils?

It does seem that consuming large doses of fish oil capsules, increases the risk of AF. But it is also important to note that the fish oil supplement trials were not designed to specifically look at the risk of AF, so the findings need to be interpreted with caution. Nevertheless, pharmacists and patients need to weigh up the observed cardiovascular benefits from supplementing with fish oils against the potential risk of not only arrythmias such as AF but also a higher risk of bleeding.

For patients worried about the risk of AF, pharmacists can reassure them that eating oily fish confers cardiovascular benefits and is unlikely to increase the risk of AF and might even reduce the risk. If patients don’t like fish, they can increase their intake of ALA. In both cases, patients are likely to achieve cardiovascular benefits that are not eroded by an associated greater risk of atrial fibrillation.

Rod Tucker is a clinical writer