Prior studies say fish oil prevents sudden cardiac death; new study muddies the waters
by Craig Weatherby and Randy Hartnell
What’s up with fish oil's strong reputation for regularizing heart rhythms? Two clinical studies published in 2004 showed that fish oil may prevent dangerous abnormalities in heart rhythm called arrhythmias. However, two clinical studies published in the last several months seem to contradict those findings, at least when it comes to people with serious heart conditions.
Evidence from many earlier studies supports the hypothesis that the “marine” omega-3 fatty acids in fish oil reduce the risk of sudden death related to irregular heart rhythms. Sudden cardiac death is a leading killer in Western countries, and about half of these deaths are caused by arrhythmias.
But the two studies published this year call into question the benefits of fish oil for people who have existing problems with heart rhythms: problems serious enough to require an implantable cardioverter defibrillator (ICD). In addition to delivering rhythm-restoring electric impulses, ICDs contain a memory chip that registers all cardiac arrhythmias.
This past June, we reported on the first study, conducted at Oregon Health and Science University. In this issue, we review the results of the second negative study—called SOFA—led by Dutch researchers.
First, we’ll review the positive clinical track record of fish oil.
The positive evidence
The overwhelming preponderance of evidence from laboratory, animal, epidemiological, and clinical studies indicates that fish oil reduces the irregular heart beats that constitute the chief cause of sudden cardiac death, and also reduce rates of sudden cardiac death itself.
And as we reported in June, the results of several studies examining this issue were published in the past two years, all with positive results:
- “A large body of evidence suggests that n-3 fatty acids from fish prevent fatal heart disease. They may be an effective and safe alternative to drug treatment for reducing the risk of arrhythmia and sudden cardiac death.”
- “The data indicate an antiarrhythmic action of n-3 PUFA under conditions of clinical practice which might help to explain the reduced incidence of fatal myocardial infarction and sudden cardiac death in cohorts [groups] on a fish-rich diet or supplemented with n-3 PUFA.”
- “This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF [(atrial fibrillation, a common cardiac arrhythmia] (54.4%) and was associated with a shorter hospital stay.”
- “Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower incidence of AF (atrial fibrillation). Fish intake may influence risk of this common cardiac arrhythmia.”
However, as one research team wrote, “The available evidence still suggests that n-3 fatty acids may prevent fatal cardiac arrhythmia, but more conclusive studies are urgently needed.”
This plea for more evidence was answered when, three years ago, European researchers published the results of a very large clinical trial called GSSI-Prevention, which seemed to confirm the anti-arrhythmia benefits of fish and fish oil. The 11,323 cardiac patients participating in the GSSI study were randomly assigned to receive omega-3 fish oil supplements (one gram per day), vitamin E (300 mg per day), both, or no treatment (control), on top of optimal drug treatment and lifestyle advice.
The results, as expected from the positive findings of many prior animal, epidemiological (population-diet), and clinical trials, were very good. As the researchers said, “The early effect of low-dose [omega-3 supplements] on total mortality and sudden death supports the hypothesis of an anti-arrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes [heart-muscle cells], animal models, and epidemiological and clinical studies."
Contradictory conclusions: the current and prior study
As we reported in the June 20 issue of vital Choices (see “Fish Oil-Arrhythmia Study Sows Confusion”), a study published in the June 15 edition of the Journal of the American Medical Society came to confounding conclusions concerning the previously demonstrated benefits of fish oil, at least with regard to a very specific population.
The first negative clinical trial (Oregon Health and Science University, June 2005)
The JAMA study involved 200 elderly, omega-3-deficient arrhythmia patients with an ICD in their chest, who were not taking certain (class I or III) anti-arrhythmic medications. Among these people, fish oil supplementation did not reduce the risk of two common types of arrhythmia, and raised slightly the risk of arrhythmia in some categories of participating patients.
We pointed out the limitations of the JAMA study, and the highly positive history of research into the effects of omega-3s, and noted that the study had yet to be replicated: a caveat that no longer applies.
The second negative 2005 clinical trial (SOFA multi-center European study, September 2005)
With publication of the results of another large European trial, called SOFA (Study on Omega-3 Fatty acids and ventricular Arrhythmia), it appears that the results of the study conducted at the Oregon Health and Science University have now been replicated closely enough to support its negative conclusions; at least with regard to people with an ICD and a history of arrhythmia.
The Dutch researchers who authored the randomized, double-blind, placebo-controlled SOFA study recruited 546 patients in 26 cardiology centers throughout Europe, all of whom had implanted heart-rate monitors.
For periods ranging up to one year, patients were given either 2 grams of fish oil or a placebo oil every day, on top of their usual mediations and care.
After 12 months, there was no clear difference in the interval before another life-threatening arrhythmia occurred, in the percentage of patients who died after starting treatment (30 percent in the fish oil group, 33 percent in the placebo group).
The SOFA study: anomalous results with a silver lining
The findings of the SOFA trial do not contradict the findings of the many studies that show beneficial effects on heart rate and risk of sudden cardiac death among heart patients and the general population.
And, the SFOA study revealed a reduced risk of death for some of the sickest participants. Among the subgroup of 342 patients who’d suffered a previous heart attack, fewer of those on fish oil died or experienced either a serious arrhythmia compared to the patients on placebo oil (28 percent versus 35 percent).
Finally, unlike the Oregon study, the fish oil group did not show any increased risk of arrhythmia.
As lead researcher Ingeborg Brouwer said in a press release, “The SOFA trial does not indicate a strong beneficial effect of omega-3 PUFA [polyunsaturated fatty acid] from fish on life-threatening cardiac arrhythmia. However, patients with a previous myocardial infarction [heart attack] might still benefit from fish oil. In any case, we found no indications that fish oil would harm patients.”
- Brouwer IA. SOFA Study reveals no effect of fish oil on life-threatening cardiac arrhythmia (press release). European Society of Cardiology Congress. Stockholm, Sweden, 3-7 September 2005. Accessed online September 17, 2005 at http://www.escardio.org/vpo/ESC_congress_information/ConferenceReleases/CPreleases/Brouwer.htm
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