Posted on 10 November 2021
Omega-3 polyunsaturated fatty acids, abbreviated to n3FAs, are a type of fatty acid with a specific chemical structure, and are found almost exclusively in seafood. In 1995, a study was published suggesting that consumption of n3FAs in seafood was associated with a significant reduction in mortality from cardiovascular disease. This sparked enthusiasm around omega-3 and fish oil supplementation (specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main fish n3FAs involved in human biology). Today, many dietary guidelines recommend intake of n3FAs to reduce the risk of cardiovascular disease, yet their effectiveness is sometimes called into question.
n3FAs influence many aspects of cellular function in different tissues, for example by altering the expression of genes or interacting with receptors and channels on the cell’s surface. In the heart, this can potentially alter the conduction of the electrical signals responsible for cardiac contraction, and so it has been proposed that one of the ways in which n3FAs might protect the heart is by reducing the risk of arrhythmia, a condition in which the heart beats with an irregular rhythm. However, there have been some studies (including a recent meta-analysis) suggesting that not only do n3FAs fail to reduce the risk of arrhythmias, they actually make them more likely. What’s going on here? Let’s take a closer look at this study.
In the meta-analysis, researchers set out to study the nature of the relationship between the consumption of omega-3 fatty acids and atrial fibrillation, a specific type of arrhythmia that begins in the smaller, upper chambers of the heart (the atria). They analysed 5 randomised, placebo controlled trials of n3FA supplementation in a total of 25 000 people at high risk of cardiovascular disease and with elevated triglyceride levels. They then compared incidence of atrial fibrillation and of stroke (which is a complication associated with atrial fibrillation) between the experimental and the placebo groups.
The table above summarises the association between n3FA supplementation and atrial fibrillation events across the 5 studies. Even though all of the studies found either a favourable or no association between supplementation and the risk of cardiovascular disease, those taking n3FAs were about 37% more likely to experience atrial fibrillation when compared with the placebo group. Despite this, the group taking n3FAs was not significantly more likely to experience stroke.
n3FAs might increase the risk of atrial fibrillation, at least in people who are already at significant risk of cardiovascular disease. Supplementation with n3FAs didn’t significantly increase the risk of stroke on average, possibly because of their reported anti-clotting effects. However, that’s not to say that n3FAs don’t do more harm than good for certain individuals: there may be a trade-off between cardioprotective and pro arrhythmic effects of n3FAs, and whether that trade-off is beneficial might depend on the specifics of one’s cardiac and overall health status.
As mentioned earlier, other studies have investigated the possible link between n3FA supplementation and atrial fibrillation, but are by no means unanimous in their findings. This study reported an up to 40% increase in atrial fibrillation for those taking EPA and 30% for those taking DHA, this study reported no significant effect, and this study reported a protective effect. Even when studying the direct effects of n3FAs on cardiac parameters, such as heart rate variability (the variability in the time interval between successive heart beats), results can vary depending on the population studied. For example, in the general population and in most chronic diseases, supplementation increases heart rate variability (this is usually a good thing). However, a study found that in people with chronic kidney disease, there was no change in heart rate variability in those assigned n3FAs. This hints at the possibility that the favourable effects of n3FAs aren’t universal and might depend on individual health factors.
Omega-3 fatty acids might increase the risk of atrial fibrillation in those at high risk of cardiovascular disease under certain conditions, but we need more research to figure out what those conditions are so that the benefits and risks can be weighed for each patient. Several organisations are currently conducting further analysis of data relating to this subject, and should provide more insights in the not-too-distant future.
Does fish oil cause cardiac arrhythmia in high-risk individuals?: https://peterattiamd.com/does-fish-oil-cause-cardiac-arrhythmia/
Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials: https://doi.org/10.1093/ehjcvp/pvab008
Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA: https://doi.org/10.1161/jaha.121.021431
Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: doi:10.1001/jama.2021.1489
The Effect of n-3 Fatty Acids on Heart Rate Variability in Patients Treated With Chronic Hemodialysis: https://doi.org/10.1053/j.jrn.2007.02.004
Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation: https://doi.org/10.1111/eci.13649
Anticoagulant Effect of Dietary Fish Oil in Hyperlipidemia: https://doi.org/10.1161/ATVBAHA.107.156992
Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest: https://doi.org/10.1001/jama.1995.03530170043030