Does omega-3 reduce your risk of a heart attack or stroke?

A recent analysis of all the available evidence concluded that taking omega-3 does reduce the risk of adverse cardiovascular events (such as heart attack and stroke), but only by 5%. However, a highly-purified pharmaceutical form of the omega-3 fat eicosapentaenoic acid (EPA) reduces risk by 25%, when added to statin therapy.

Unfortunately, then, your regular off-the-shelf fish oil may not have much impact on your risk of heart attack or stroke.

In the late 1970s, a group of hardy Danish researchers made several visits to the frozen expanse of Greenland to study the health of the indigenous Inuit people. They discovered that the Inuit had an unusually low incidence of cardiovascular disease (CVD) and – due to their diet rich in seal meat and fish – high levels of EPA in the blood.

Since then, this early finding has been confirmed and expanded by multiple studies across different populations:

Over the past couple of decades, this striking observational evidence has been used by the supplement industry to sell omega-3/fish oil to everyone who doesn’t want to die of a heart attack.

However, as always, the picture is more complicated than that. The observational data doesn’t tell us whether or not taking omega-3/fish oil supplements causes a reduction in the risk of these cardiovascular outcomes. To decipher that, we need randomised controlled trials.

Fortunately for us, there are quite a few (38 to be precise). But unfortunately for us, there is no clear answer. Some trials report a benefit from omega-3, some don’t. How can we sort through the noise?

A recent study, thankfully, has done the sorting for us. It’s a meta-analysis, giving us a weighted average of the results from all 38 randomised controlled trials – a statistical synthesis of all the available data.

And what does it say? With moderate certainty, the authors found that supplementing with omega-3 reduced major adverse cardiac events (MACE) – a composite endpoint which usually includes non-fatal heart attack, non-fatal stroke and cardiovascular death – by 5%.

While every little helps when it comes to health, this result is a little disappointing, and perhaps not what you were expecting. 

However, that’s not the whole story.

The two major omega-3 fats are EPA and docosahexaenoic acid (DHA). The EPA to DHA ratio in your typical omega-3/fish oil supplement is around 60:40. Most (34) of the omega-3-CVD trials included in the meta-analysis tested a combination of EPA and DHA. And, on average, this had no effect on MACE (although it did have a small impact on cardiovascular death and non-fatal heart attack).

On the contrary, EPA alone reduced MACE by 23%. That is meaningful.

But there’s more.

The EPA effect size seen here was largely attributable to two trials – the REDUCE-IT trial from 2019 and the JELIS trial from 2007, which showed a 25% and 19% reduction in MACE respectively. It’s worth noting that the EPA dose used in REDUCE-IT was 4g per day, and the dose used in JELIS was 1.8g per day.

Both trials used a highly purified form of EPA called EPA ethyl ester (or icosapent ethyl). This is not an off-the-shelf omega-3 supplement – you can’t buy it at your local health store. It’s a pharmaceutical grade EPA drug currently not available in the UK (although an appraisal by NICE is in progress).

The participants in both trails were also receiving statins. So, while the EPA drug was shown to meaningfully reduce MACE over and above the effect of statins, we don’t know if the same effect would be seen without statins in play.

To conclude: Supplementing with EPA + DHA (the composition of a typical omega-3/fish oil supplement) doesn’t appear to have much impact on cardiovascular risk. Purified EPA ethyl ester (such as Vascepa), on the other hand, reduces the risk of major adverse cardiac events by 23% in people already taking statins.

We may soon see Vascepa in the UK, but, if we do, it will likely be prescribed alongside statins.

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