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Fish Oil Adds Extra Heart Benefits to Fish-Heavy Diets
4/2/2007
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Japanese people with high cholesterol and heart disease enjoy reduced risk of heart attacks, surgery and other adverse but non-fatal events
by Craig Weatherby


The positive results of a large clinical trial from Japan reinforce the value of supplemental fish oil, and show that it can add heart-health benefits even to people who already enjoy diets rich in fish.

The trial, called the Japan EPA Lipid Intervention Study or JELIS, involved 18,645 Japanese people with high cholesterol levels, all of whom were taking cholesterol-lowering, anti-inflammatory statin drugs.

Key Points

  • Omega-3 EPA from fish oil reduces risk of heart attacks and surgeries by 19 percent in 18,000 fish-loving Japanese taking statin drugs to treat high cholesterol.
  • Omega-3 EPA likely reduced the risk of heart problems by cutting blood triglycerides and inflammation and enhancing vascular health, since, as expected, supplemental EPA did not lower cholesterol levels further than the statin therapy already had (25 percent).

  • Death rates were unaffected, probably because the Japanese already consumed enough omega-3 EPA from dietary fish to reduce the risk of fatal arrhythmias very sharply.

  • EPA is not necessarily more beneficial than DHA—the other major omega-3 in fish oil—which exerts overlapping, complementary effects. Most trials successful studies used oils containing both omega-3s.

As the Japanese researchers noted, “Epidemiological and clinical evidence suggests that an increased intake of long-chain omega-3 fatty acids protects against mortality from coronary artery disease.”

Their stated goal was to test the hypothesis that long-term use of omega-3 EPA supplements would prevent major coronary events in Japan with high cholesterol levels who already consume lots of fish.

By “major coronary events” they meant sudden cardiac death, fatal and non-fatal heart attacks, unstable angina pectoris, or surgical interventions (e.g., angioplasty, stents, and coronary bypasses).

(Reductions in surgical interventions might be less meaningful as markers of reduced risk of “major coronary events” in the US, where their excessive use persists despite clear evidence that drug and diet/lifestyle therapies are comparably effective.)

The Japanese team wanted so see whether high daily doses of omega-3 EPA (1.8 grams per day) would provide further help to patients with elevated cholesterol levels, who were already taking cholesterol-lowering, anti-inflammatory statin drugs.

This goal is logical, since it’s certain that supplemental omega-3s do three things, all to very substantial extents:
  • Lower high blood triglyceride levels (a major cardiac risk factor).
  • Reduce risk of arrhythmias: the fatally erratic heart beats responsible for fully half of all heart-related deaths.
  • Reduce inflammation—a major cardiac risk factor—more than statin therapy alone.
Half of the volunteers took 1,800 milligrams of omega-3 EPA from fish oil per day, plus a standard statin dosage. The other half, who took only statin-type drugs, constituted the control group.

(NOTE: EPA is probably not more valuable to cardiovascular health than DHA, the other major omega-3 in fish oil. The two exert overlapping, complementary effects. The EPA-only omega-3 supplements were donated, so that's what the researchers used.)

The participants were followed for an average of 4.6 years, with interesting results for those who already enjoy lots of fish.

Omega-3s add heart benefits to fish-rich diets
Only a few participants in either group had major heart problems during the study period. This is probably because, like the average Japanese person, they ate lots of fish, whose inherent omega-3 content works to blunt the three major risk factors listed above.

But there were substantial benefits:
Compared with those only taking statins, the participants who also took omega-3 EPA supplements enjoyed a hefty 19 percent reduction in the risk of suffering a non-fatal adverse heart event ( 2.8 percent in the EPA-plus-statin group versus 3.5 percent in the statin-only control group).

“We must curb our infatuation with downstream risk factors and treatments, and focus on the fundamental risk factors for cardiovascular disease: dietary habits, smoking, and physical activity.” -Mozaffarian, M.D.

This substantial risk reduction occurred only in those among the EPA-plus-statin group who had a diagnosis of coronary artery disease (i.e., clogged arteries or other symptoms) in addition to high cholesterol levels.

The EPA-plus-statin group did not experience any greater reduction in fatal heart events, another effect likely due to the fact that the Japanese participants—like their countrymen—consumed so many omega-3s from their fish-rich diets.

As the researchers said, their results indicate that “EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events...” (Yokoyama M et al 2007).

Since these benefits occurred in fish-loving Japanese with high cholesterol levels, it is reasonable to propose that similarly afflicted Americans—who eat much less fish on average—should benefit from omega-3 supplements even more.

A renowned heart researcher's cogent commentsDariush Mozaffarian, M.D.
Readers of Vital Choices may recall our coverage of studies led by Harvard’s Dariush Mozaffarian, M.D.: a leading researcher into the connections between dietary factors (especially omega-3s) and cardiovascular disease, who we heard and spoke with at the Seafood & Health scientific conference in 2005.

He penned some incisive expert comments about the new study for The Lancet: the British medical journal that published the JELIS study.

Dr. Mozaffarian contrasted the outcome of the JELIS trial—in which fish oil did not reduce the subject's very low cardiac death rates any further—against those of Italy's landmark GISSI-Prevenzione trial, in which fish oil supplements reduced cardiac death rates by a whopping 45 percent.

This large trial of fish oil supplements involved more than 11,000 Italians, who would have eaten far less fish on average than the Japanese in the JELIS trial likely did (Marchioli R et al 2005).

The key difference, as he pointed out, was that the Italian trial involved subjects who ate much less fish than the Japanese in the JELIS trial would have, and were therefore more likely to enjoy dramatic reductions in risk of death as the result of taking supplemental fish oil.


As he noted, the average Japanese person eats one 3 oz serving of fish, containing about  900 mg of omega-3s per day, while 90 percent of Japanese individuals eat fish at least once a week.

This places most Japanese people's omega-3 intake above the level shown to provide a major drop in the risk of cardiac death.

Consuming more omega-3s than the average Japanese person doesn’t seem to reduce the risk of heart-related death any further, but the new trial's results indicates that adding more dietary omega-3s via supplements may reduce the rate of adverse but non-fatal cardiac events.

Dr. Mozaffarian expressed some appropriately vinegar-tinged views on the state of modern cardiology practice, in light of the new trial's positive results, and the pro-omega-3 findings of most of the well-designed clinical trials and virtually all population studies (Mozaffarian D 2007):

“If any placebo effect could reduce total mortality by [about] 20% [as in the JELIS trial] and sudden death by 45% (the results of GISSI-Prevenzione), we should all be taking such a placebo.”

“Compared with drugs, invasive procedures, and devices, modest dietary changes are low risk, inexpensive, and widely available.”

“We must curb our infatuation with downstream risk factors and treatments, and focus on the fundamental risk factors for cardiovascular disease: dietary habits, smoking, and physical activity.”

We couldn’t agree more with his wish that more doctors will act on the evidence in favor of fish oil and other easy nutritional interventions.


*Note: As we’ve reported, patients with implanted cardiac defibrillators or diagnosed with congestive heart failure should discuss omega-3 fish oils with a cardiologist experienced in their use. Higher omega-3 intake—whether from fish or fish oil—could increase the risk of arrhythmia or sudden cardiac death.


Sources

  • Yokoyama M et al for the Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. The Lancet 2007; 369:1090-1098; DOI:10.1016/S0140-6736(07)60527-3. Accessed online March 31, 2007 at http://www.thelancet.com/journals/lancet/article/PIIS0140673607605273/fulltext.
  • Mozaffarian D. JELIS, fish oil, and cardiac events. The Lancet 2007; 369:1062-1063  DOI:10.1016/S0140-6736(07)60504-2. Accessed online March 31, 2007 at http://www.thelancet.com/journals/lancet/article/PIIS0140673607605042/fulltext.
  • Yokoyama M, Origasa H; JELIS Investigators. Effects of eicosapentaenoic acid on cardiovascular events in Japanese patients with hypercholesterolemia: rationale, design, and baseline characteristics of the Japan EPA Lipid Intervention Study (JELIS). Am Heart J. 2003 Oct;146(4):613-20.
  • Marchioli R, Levantesi G, Macchia A, Maggioni AP, Marfisi RM, Silletta MG, Tavazzi L, Tognoni G, Valagussa F; GISSI-Prevenzione Investigators. Antiarrhythmic mechanisms of n-3 PUFA and the results of the GISSI-Prevenzione trial. J Membr Biol. 2005 Jul;206(2):117-28.
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