Omega-3 fatty acids are quite well established as a secondary preventative treatment for cardiovascular disease. Guidelines both in the US and Europe recommend the use of omega-3s following an MI. But now, a large meta-analysis questions this intervention by failing to find a significant effect of omega-3s on several cardiac-related outcomes. 

 In the analysis, published September 12, 2012 in JAMA, the authors tried to avoid the problem of small numbers by including data from several types of studies. Previous studies and even earlier meta-analyses have come to conflicting conclusions based on different methodologies used and outcomes examined. In this analysis, the authors included all methodologies, doses, prevention settings (primary and secondary), supplementation methods (food or nutraceuticals), and study designs. Three of the studies included patients with ICDs. The studies only had to be include treatment times that lasted at least one year.

Using data from 20 studies and more than 68,000 patients, the researchers found no significant effects of omega-3 supplementation on all-cause mortality, cardiac death, sudden death, MI, or stroke. This was true both when they examined relative risk and absolute risk. Relative risks (with confidence intervals) were:

  • All-cause mortality 0.96 (0.91–1.02)
  • Cardiac death 0.91 (0.85–0.98)
  • Sudden death 0.87 (0.75–1.01)
  • MI 0.89 (0.76–1.04)
  • Stroke 1.05 (0.93–1.18)

The p value for significance was set at a miniscule 0.0063 based on the fact that the researchers performed multiple comparisons.

It is interesting to note that four of the five results show a nearly significant trend toward risk reduction, and the risk reduction in cardiac death is especially noteworthy. It seems likely that some subset of patients is benefiting from omega-3 supplementation, but the all-inclusive nature of the analysis masks this effect by including data from patient populations who may not benefit from omega-3s.

There is also no examination of patients’ baseline omega-3 status (or omega-6:omega-3 ratio), which could certainly impact who benefits and who does not. The study also lumps food sources with supplements, and looksat all doses of supplementation as the same (the average dose used across all the studies was 1.51 grams/day).

Also there is no distinction between primary and secondary prevention, which data from other interventions suggest may be a critical difference.

The lead author of the study notes that there were few trials included in the meta-analysis that used the high-dose omega-3 fatty-acid supplements (2 to 4 g per day as approved by the FDA) so more studies are needed to study the benefit of using the high-dose supplements.

The authors write, "Randomized evidence will continue to accumulate in the field, yet an individual patient data meta-analysis would be more appropriate to refine possible associations related to, among others, dose, adherence, baseline intake, and cardiovascular disease risk group."

I certainly agree with the authors that the factors mentioned should not be neglected in future analyses, and I would caution from drawing any solid conclusions based on the present meta-analysis beyond that giving different doses of omega-3s to several populations under varying circumstances may not significantly lower cardiac risk for all patients. At the very least, they do no harm.



Rizos EC, et al. Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-analysis. JAMA 2012;308(10):1024-1033.