Change of heart: Mixed evidence on omega-3 FAs

Integrative medicine

In 2010, Americans spent more than $1 billion on nonprescription fish oil products. These dietary supplements remain the most commonly used natural products. Fish oil can be used as a source of long chain omega-3 polyunsaturated fatty acids (FAs), but data for their cardiovascular benefits are conflicting.

Omega-3 FAs may have antiplatelet activity and may lower triglyceride concentrations and decrease the risk of arrhythmias. In the past 12 months, clinical trials, observational studies, and a meta-analysis have evaluated the potential value of omega-3 FAs on cardiovascular outcomes and all-cause mortality, with varying results.

Research highlights

In July 2012, results from the Outcome Reduction With an Initial Glargine Intervention (ORIGIN) study were published.1 The study evaluated the potential benefits of long-term use of omega-3 FA 1 g/d in patients with type 2 diabetes or at high risk of developing diabetes. Researchers followed more than 12,000 patients for 6 years. Between 50% and 70% of participants were taking statins, antiplatelet agents, beta blockers, and ACE inhibitors or angiotensin-receptor blockers.

The study’s primary outcome, death from cardiovascular causes, was not reduced by omega-3 FA, despite a 14.5 mg/dL decrease in triglyceride concentrations. The negative results may have been due to patients already being on optimal therapy, an inadequate dosage of omega-3 FA, or patients not at high enough cardiovascular risk.

In September 2012, a group of researchers conducted a meta-analysis of omega-3 FA studies including 20 randomized clinical trials involving almost 70,000 people.2 The studies included primary or second prevention trials of at least 1 year in duration and assessed the effects of omega-3 FA through either diet or supplements on all-cause mortality, sudden death, myocardial infarction (MI), or stroke. Two-thirds of studies were secondary prevention, and the mean dosage of omega-3 FA was 1.51 g/d. Overall, the meta-analysis identified no benefits from omega-3 FA.

In April 2013, researchers published data from the Cardiovascular Health Study.3 Unlike most other studies, in which participants eat a diet supplemented with omega-3 FA or use dietary supplements, this study’s investigators used measurements of plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid from almost 2,700 adults 74 years and older without documented cardiovascular disease. Their analysis also incorporated assessments of cardiovascular risk factors first measured in 1992 and data on outcomes collected until 2008. The researchers found that individuals with the highest concentrations of omega-3 FA were associated with a 27% reduction in risk of all-cause death. The decrease was due primarily to a reduced risk of cardiovascular death—specifically, death due to arrhythmias. DHA concentrations had the strongest inverse association with arrhythmic deaths, and EPA levels were inversely correlated with risk of nonfatal MI.

The ingestion of fish oil and omega-3 FA supplements has increased dramatically in the past 24 years since the first reports of their benefits. The original studies demonstrating large benefits predated the current widespread use of statins, however. Newer studies have yielded contradictory data due to different designs and populations (primary vs. secondary prevention), concomitant use of drugs, self-reports of dietary omega-3 FA ingestion, and variable dosages and quality of some fish oil products.

What to tell patients

Encourage patients interested in omega-3 FA supplementation to substitute fish such as salmon or sea trout, in appropriately sized portions, for red meat once or twice a week. For secondary prevention of cardiovascular disease, omega-3 FA supplements likely have little additional benefit when combined with optimal therapies, including statins and ACE inhibitors. For primary prevention, especially in older patients, omega-3 FA supplementation may offer some benefits, although evidence remains conflicting.

As always, patients interested in effective primary and secondary prevention should focus on reducing cardiovascular risk factors, especially smoking cessation.


  1. ORIGIN trial investigators. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367:309–18.
  2. Rizos EC, Ntzani EE, Bika E, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024–33.
  3. Mozaffarian D, Lemaitre RN, King IB et al. Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med. 2013;158:515–25.