Rapid Review Alert April 4, 2013
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 In EPA & DHA Research
Abstract (as published in Ann Intern Med)

Background: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention.

Objective: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements.

Design: Prospective cohort study.

Setting: 4 U.S. communities.

Participants: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline.

Measurements: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed.

Results: During 30,829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile.

Limitation: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding.

Authors’ Conclusion: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults.
Rapid Review Alert
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ω3-PUFAs and Mortality

Review of:
Mozaffarian D Lemaitre RN King IB Song X Huang H Sacks FM Rimm EB Wang M and Siscovick DS (2013). Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. Ann Intern Med 158:515-525. http://www.ncbi.nlm.nih.gov/pubmed/23546563

GOED Take-Away

ω3-PUFA levels were associated with a lower total mortality (27% lower risk when comparing lowest intakes to highest intakes) which translated into living an extra 2 plus years.   

What Else Should You Know? 

  • It has been estimated that low ω3-PUFA intakes account for 72,000-96,000 deaths per year from CVD in the United States alone (Danaei et al., 2009).
  • According to the authors, the present findings support an average target dietary range of 250-400 mg of EPA + DHA per day.
  • Prospective associations of plasma phospholipid ω3-PUFAs with total mortality were adjusted for leisure-time physical activity, helping to dismiss the notion that the ω3-PUFA effect is just a result of a healthier lifestyle.
  • According to the authors, while the present findings do not support major effects of circulating ω3-PUFA levels on mortality from non-CVD conditions later in life, the present results do not exclude potential benefits on incidence or severity of these conditions or on mortality due to more specific subtypes of these diseases. 

Suggested Citation

Global Organization for EPA and DHA Omega-3s (2012). Omega-3s and Mortality [Peer commentary on the paper “Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study” by Mozaffarian D Lemaitre RN King IB Song X Huang H Sacks FM Rimm EB Wang M and Siscovick DS (2013). Ann Intern Med 158:515-525.].


Danaei G Ding EL Mozaffarian D Taylor B Rehm J Murray CJ and Ezzati M (2009). The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 6: e1000058. 
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