Most media coverage of a large new clinical trial claims that fish oil didn't live up to its heart-healthy reputation.
The five-year trial involved 12,513 people who showed evidence of atherosclerosis or had multiple cardiovascular risk factors … but who'd not suffered a heart attack.
Although the results were disappointing in some regards, they were positive in other ways, and the negative outcomes were both unsurprising and explicable.
The Italian trial tested the ability of omega-3 fish oil to do either of two things:
  • Reduce death rates from cardiovascular causes.
  • Reduce hospital admissions related to cardiovascular health.
After five years, there was no drop in death rates, or reduction in overall hospital admissions related to cardiovascular health, overall.
The results seemed disappointing, compared with those of some prior trials ... but there are reasons why we added the qualifier, “overall”.
In fact, the trial results showed these significant benefits … a fact overlooked by most media reports:
  • HDL (“good”) cholesterol rose slightly.
  • Women were 18 percent less likely to die from heart-related causes.
  • Triglyceride levels dropped 28 percent more than in the control group.
  • Hospital admissions for heart failure dropped by 34 percent among men and women.
The authors wrote this about the drops in death risk for women and the drop in hospital admissions for heart failure:
“Both may be due to chance, although they are consistent with two findings from other studies: the beneficial effect of omega-3 fatty acids in patients with heart failure in the GISSI-HF [trial] and the decrease in non-fatal coronary events … in the JELIS [trial].”
Before we analyze the mixed outcomes of the new trial – see “New Italian study yields mixed outcomes”, below – let's probe the clinical evidence collected to date, including the landmark GISSI and JELIS trials.
Why do doctors recommend fish and fish oil for heart health?
Physicians and public health authorities worldwide recommend fish and omega-3 supplements to guard heart health.
That guidance is detailed in two sections of our Omega-3 Facts & Sources page: “Omega-3 EPA and DHA: Key heart-health allies” and “Official Omega-3 Intake Recommendations, Worldwide”.
For example, the American Heart Association (AHA) advises healthy people to eat fish twice a week, and tells heart patients to take one gram (1,000mg) of long-chain, marine-source omega-3 fatty acids (EPA and DHA) daily.
And in 2004, the U.S. FDA approved this qualified health claim for omega-3 supplements: “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.”
Why does this general consensus still hold, despite the mixed-to-negative outcomes of this and other recent clinical trials testing omega-3 supplements for heart health?
Evidence on omega-3s forms a solid foundation
Harvard researchers summarized the evidence last year (Hu FB, Manson JE 2012):
  • “Omega-3 fatty acids are among the most extensively studied nutrients for their potential cardiovascular benefits.”
  • “A large body of evidence from experimental, clinical, and epidemiologic research has demonstrated the potential benefits of EPA-rich and DHA-rich fish oil on cardiovascular health.”
  • “Consistent findings from prospective observational cohort investigations indicate that regular consumption of fatty fish (two times per week) is associated with a significantly lower risk of cardiovascular death.”
This record explains why the American Heart Association and public health authorities worldwide recommend eating fatty fish and/or taking fish oil supplements on a routine basis.
We'd add these reasons for believing that omega-3s aid heart health:
  • They exert a moderating influence on chronic inflammation … a proven promoter of cardiovascular disease.
  • Thousands of cell, animal, and clinical studies detail the biological effects of long-chain omega-3s (EPA and DHA) ... almost all considered good for heart health.
  • Clinical trials generally find that omega-3 fish oil supplements produce beneficial vascular, lipid-profile, heart-rhythm, and inflammation-damping effects.
  • Most reviews of controlled trials conclude that fish-rich diets or omega-3 fish oil reduce the risk of heart-related deaths and/or adverse cardiac events (Wang C et al. 2006; León H et al. 2008; Marik PE et al. 2009).
  • Several large clinical trials found that omega-3 fish oil reduced the risk of sudden cardiac death, which makes up half of all heart-related deaths.
As the Harvard duo noted, most of the extant trials have involved people already diagnosed with and being treated for cardiovascular disease, thus putting omega-3s to a very tough test: “… almost all RCTs [randomized clinical trials] were conducted in secondary prevention settings” (Hu FB, Manson JE 2012).
Prior, positive clinical trials
Chief among the large, high-quality, persuasively positive clinical trials were two conducted in Italy Marchioli R et al. 2001; Gissi-HF Investigators et al. 2008):
  • GISSI-HF involved patients with congestive heart failure
  • GISSI-Prevenzione, which involved people who'd had a heart attack (myocardial infarction)
Both GISSI trials found that fish oil supplements reduced the risk of sudden cardiac death, which is usually caused by a risky irregular heart rhythm (ventricular arrhythmia).
Doctors also rely on the results of a large, five-year Japanese trial called JELIS, which tested omega-3 EPA as an adjunct to statin drugs in 18,645 older women and men with high cholesterol, hypertension, diabetes, and/or coronary artery disease (Yokoyama M et al. 2003; Saito Y et al. 2008).
The JELIS trial showed that adding EPA to statin therapy cut major coronary events (heart attack, stroke, death) by 19 percent, compared with the no-EPA control group, which took only statins and other cardiac drugs.
Not every subsequent trial has shown the benefits seen in the GSSI and JELIS trials ... but many suffered from limitations or confounding factors that muddied the waters:
  • Trial was small or short.
  • Omega-3 doses were low.
  • Participants were very sick.
  • Participants were taking cardiac drugs (e.g., statins) proven to reduce heart risks.
Accordingly, medical authorities worldwide remain persuaded by the overwhelmingly positive body of epidemiological evidence, and the positive outcomes of most high-quality clinical trials.
The results of a large, five-year clinical trial raise questions ... but must be weighed against a huge preponderance of positive evidence supporting a clear medical consensus that omega-3s from fish and fish oil help hearts.
New Italian study yields mixed outcomes  Back to top
The New England Journal of Medicine just published a large, five-year clinical trial from Italy.
The trial involved 12,513 people who showed evidence of atherosclerosis or had multiple cardiovascular risk factors … but had who had not suffered a heart attack (myocardial infarction).
Most were taking cardiac drugs (statins and others), with even more participants taking drugs as the trial went on, which makes it harder to detect any added benefits from supplemental omega-3s.
The trial was designed to test the ability of omega-3 fish oil to do either of two things within five years:
  • Reduce death rates from cardiovascular causes.
  • Reduce hospital admissions related to cardiovascular health problems.
The patients were randomly assigned to one of two groups, and took their assigned supplement every day for five years:
  • Placebo (olive oil) capsule.
  • Fish oil capsule providing one gram of omega-3 fatty acids (mostly EPA and DHA).
Overall, the omega-3 group showed no significant drop in the death rate from cardiovascular causes, or in the rate of admissions to the hospital for cardiovascular causes.
Nor were there were any overall differences in any of the pre-specified secondary outcomes (blood pressure, heart rate, total and LDL cholesterol levels, blood glucose).
However, as we noted, the omega-3 fish oil group enjoyed some significant benefits:
  • HDL (“good”) cholesterol rose slightly.
  • Women were 18 percent less likely to die from heart-related causes.
  • Triglyceride levels dropped 28 percent more than in the control group.
  • Hospital admissions for heart failure dropped by 34 percent among men and women.
The trial authors discussed their results in relation to the two GISSI trials, in which supplemental fish oil reduced sudden cardiac deaths, usually caused by arrhythmias:
“It is conceivable that the effects of omega-3 fatty acids become manifest primarily in patients who are particularly prone to [adverse] ventricular arrhythmic events.”
They noted that, compared with the volunteers in the successful GISSI trials, the population in their trial was much less prone to arrhythmias.
It's worth quoting from comments made to by Harvard's famed omega-3/heart researcher, Dariush Mozaffarian, M.D.
Given the overwhelming body of positive evidence, his measured reaction to the new trial seems spot on: “Recommendations to eat fish, in the context of an overall healthy diet, increasing activity, and stopping smoking, should remain the priority for reducing risk [and] for patients who won't eat fish or wish to be sure they are getting their omega-3′s, there is no reason to stop taking fish oil supplements ...”.
We suspect that many omega-3/heart researchers will express similar views, as they digest the trial results in depth.
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