Despite numerous studies, the effect of omega-3 fatty acids (n-3 FA) on cardiovascular disease (CVD) has remained controversial.1 n-3 FA are important for the composition of cell membranes and include alphalinolenic acid (ALA), stearidonic acid (SDA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA).  Although most people obtain n-3 FA from dietary sources, supplements such as “fish oil” and flaxseed oil have become increasingly popular.

In 2004, the Agency for Healthcare Research and Quality (AHRQ) published a review analyzing the effect of n-3 FA on CVD outcomes.1 Since this report, many other studies have also evaluated this subject, however the topic has remained controversial. Recently, the AHRQ was commissioned to provide updates regarding the effects of n-3 FA on CVD. The goal of this review was to address the effect or association of n-3 FA intake on CVD outcomes and risk factors, the n-3 FA variables and modifiers that may affect treatment, and adverse events experienced with n-3 FA intake. Figure 1 details the framework of the study and key questions addressed in this review.

In this analysis, 61 randomized controlled trials (RCT) and 37 prospective longitudinal studies met criteria for inclusion.1 The majority of RCTs analyzed compared marine oil (primarily EPA + DHA) to placebo in patients with known CVD or increased risk of CVD. Conversely, most observational studies compared individual n-3 FA and were conducted in the general population. The authors also stated that there were few risk of bias concerns among the RCTs and fairly few risk of bias concerns across the observational studies.

Results obtained in this analysis regarding the effect of n-3 FA intake on CV outcomes generally remained unchanged from previous data.1 The majority of RCTs analyzed found that n-3 FA intake did not have a statistically significant effect on CVD outcomes or there was not sufficient evidence to draw conclusions. These results are summarized in Table 1. This review also found that there were no serious adverse events associated with n-3 FA intake, and that most adverse events reported were mild gastrointestinal effects. 

One important observation seen in this analysis was a high level of evidence indicating that marine oil supplementation decreased triglyceride (Tg) levels and the total:HDL-c ratio.1 In addition, supplementation was found to increase HDL-c and LDL-c levels by a small amount (≤2 mg/dL) as well. A low strength of evidence also found that higher dietary intake of marine oil is associated with a lower risk of ischemic stroke.

The results of this study regarding various patient populations and potential confounders are summarized in Table 2.1 In general, no significant differences in effects between different patient populations were found. However, evidence did indicate strong RCT evidence that n-3 FA had a protective effect for Tg in healthy patients, those with risk factors for CVD, and patients with known CVD. In addition, n-3 FA had a protective effect for HDL-c in patients with known CVD.

Based on evidence obtained in this review, n-3 FA intake does not have a statistically significant effect on CVD.1 However, evidence found n-3 FA intake produced a reduction in Tg levels and the total:HDL-c ratio, and an increase in HDL-c and LDL-c levels. No significant difference in outcomes for various patient populations was seen in this study.


1. Agency for Healthcare Research and Quality (AHRQ). Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review: Executive Summary. Evidence Report/Technology Assessment Number 223. 2016 Aug