An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health

Abstract

Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released-these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.

Keywords: cardiovascular disease; omega 3 index; omega 3 polyunsaturated fatty acid.

Figure 1

Pooled results from meta-analysis. This figure showed the pooled estimate of relative risk and 95% CI, as well as the number of studies and combined number of participants. CHD = coronary heart disease; CVD = cardiovascular disease; MI = myocardial infarction. Reproduced with permission from: Bernasconi, A.A., Wiest, M.M., Lavie, C.J., Milani, R.V., Laukkanen, J.A. Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials. Mayo. Clin. Proc. 2020; S0025-6196(20)20985-X.

Figure 2

Dose–effect relationship for the prevention of CVD events. The horizontal axis shows the EPA + DHA dosage in grams per day. The vertical axis shows the treatment effect (log-relative risk). The area of each study square is proportional to its regression weight (inverse-variance of relative risk estimate). Reproduced with permission from: Bernasconi, A.A., Wiest, M.M., Lavie, C.J., Milani, R.V., Laukkanen, J.A. Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials. Mayo. Clin. Proc. 2020; S0025-6196(20)20985-X.

Figure 3

Hypothetical omega-3 supplementation dose and threshold effect.