Higher Omega 3 Predicts Lower Mortality

BOSTON —The observational, prospective Cardiovascular Health Study (CHS) >2500 older adults initially without coronary heart disease or a history of stroke showed that the highest levels of plasma phospholipid omega-3 polyunsaturated fatty acids (PUFA) predicted the lowest mortality rates. Comparing the highest quintile of omega-3 PUFA levels vs the lowest quintile, all-cause mortality fell by 27%, mostly due to a reduction in cardiovascular death. Deaths due to arrhythmias fell by nearly 50%. Dr Dariush Mozaffarian (Harvard School of Public Health, Boston, MA), who led the study, and published their findings in the April 2, 2013 issue of the Annals of Internal Medicine. He and his researchers noted that such cardiovascular-outcome effects are consistent with abundant evidence from laboratory and clinical studies that omega-3 PUFA intake may benefit heart rate, blood pressure, myocardial contractile function and electrical stability, and endothelial, autonomic, and hemostatic function. Not only did this data link plasma omega-3 PUFA levels with survival, it also allowed them to estimate the benefit: in this population, starting at age 65, about 2.2 extra years for people in the highest compared with the lowest plasma-level quintile.

Outcomes also varied by individual omega-3 PUFAs. For a number of end points, importantly heart-disease mortality and arrhythmic mortality, there appeared to be greater benefit from highest levels of docosahexaenoicacid (DHA) vs highest levels of eicosapentaenoic acid (EPA) and even more benefit from highest levels of total omega-3 PUFA. Consuming both EPA and DHA together is probably wise, as there appear to be “complementary effects,” Mozaffarian said. Based on the current analysis, “If you’re going to consume omega-3s, you should at least be sure you’re getting DHA. EPA alone might not have the same benefit; I think that’s fair to say.”

This goes along with our current knowledge that not all Omega-3 is created equally. Importantly, these two main omega 3 fatty acids studied are derived mainly from fish and not flax seed or plants.It is well-known that there are major differences in the quality and potency of over-the-counter and nutraceutical preparations of omega-3 PUFA, many of which may be tainted with heavy metals including mercury, which are commonly found in the fish.

Clinical Outcomes Hazard Ratio* (HR, 95% CI) for Quintile 5 vs Quintile 1 of Plasma Phospholipid Omega-3 PUFA Levels, by PUFA Type

End point EPA DHA Total omega-3 PUFA
Total mortality 0.83 (0.71–0.98) 0.80 (0.67–0.94) 0.73 (0.61–0.86)
Total CV mortality 0.72 (0.54–0.96) 0.66 (0.49–0.89) 0.65 (0.48–0.87)
Total CHD mortality 0.77 (0.54–1.11) 0.60 (0.41–0.87) 0.60 (0.42–0.87)
Arrhythmic CHD mortality 0.76 (0.47–1.23) 0.55 (0.33–0.93) 0.52 (0.31–0.86)
Stroke mortality 0.84 (0.47–1.48) 0.62 (0.32–1.20) 0.60 (0.32–1.12)
Ischemic stroke 1.09 (0.76–1.57) 0.74 (0.50–1.10) 0.63 (0.43–0.94)
Hemorrhagic stroke 0.70 (0.30–1.67) 1.24 (0.52–2.94) 1.23 (0.53–2.89)
PUFA=polyunsaturated fatty acid

EPA=eicosapentaenoic acid

DHA=docosahexaenoic acid

*Adjusted for age, sex, race, education, enrollment site, fatty-acid-measurement batch (1994–1996 or 2007–2010), smoking status, diabetes, atrial fibrillation, drug-treated hypertension, physical activity, body-mass index, waist circumference, alcohol use, and consumption of tuna or other broiled or baked fish, fried fish, red meat, fruits, vegetables, and dietary fiber

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Several large-scale studies and programs, including a patient registry, have assessed treatment.

“The LDL-raising effect of omega-3s is very modest.” If there is any such effect, he said, “it’s to make the particles larger and fluffier and therefore potentially less atherogenic.” According to Mozaffarian, “it’s just hype” to say that an omega-3 PUFA supplement that delivers only EPA should be preferred over a mixed EPA/DHA supplement because of a difference in LDL effects.

The CHS was funded by the National Institutes of Health; disclosures for Mozaffarian et al are available here.