Following the negative outcomes of three prior studies, newly published findings appear to confirm that heart patients prone to suffering dangerously irregular heart rhythms (arrhythmias) are simply too sick to be helped by fish oil supplements.
In June and September of last year, we published two reports on the results of studies designed to test the effects of omega-3s from fish on heart patients with implantable cardiac defibrillators (ICDs). (See "Fish Oil-Arrhythmia Study Sows Confusion” and "Misleading Headlines Distort Meaning of Research on Fish and Heart Rhythms”.)
These electronic devices are inserted into people’s chests to automatically restore suddenly-errant heart rhythms to normal.
In both cases (Rait MH 2005, Brouwer IA 2005), fish oil supplements failed to reduce the rate at which heart patients with ICDs experienced potentially heart-stopping arrhythmias. In fact, there was some indication that fish oil supplements might raise the risk of arrhythmias slightly in undefined subsets of patients with ICDs.
And last month, we scrutinized the meaning of a new analysis of lifestyle, diet and health outcomes data from the famed Physicians' Health Study (PHS): an ongoing landmark epidemiological investigation began in the fall of 1982.
The authors of that PHS data analysis (Aizer A 2006) found a correlation between higher fish intake—i.e., five or more meals per week—and a 55 percent increase in risk of atrial fibrillation, which is generally considered less dangerous than the other type (ventricular fibrillation).
But, critically, the recent PHS data analysis also showed that men who took fish oil supplements enjoyed a reduced risk of sudden cardiac death. As study lead author Dr. Anthony Aizer said (key point underlined), "It is important to recognize that within the same population as this current study, fish consumption was associated with lower risk of sudden cardiac death, which is the result of a much more life-threatening cardiac arrhythmia, ventricular fibrillation."
Neither the prior negative results—nor the new SOFA trial findings—undermine the enormous body of evidence indicating that, within the population as a whole, omega-3s substantially reduce the risk of three key threats:
- Sudden cardiac death in apparently healthy people, which accounts for half of all fatalities related to cardiovascular disease
- A second heart attack in heart attack survivors
- Sudden cardiac death in heart attack survivors
However, the latest findings (Brouwer IA 2006)—published this month in the Journal of the American Medical Association (JAMA)—appear to refute its authors’ hypothesis that supplemental omega-3s might reduce the risk of highly dangerous ventricular arrhythmias in patients with ICDs.
In September of 2005, when we reviewed the findings of earlier findings from the "Study on Omega-3 Fatty acids and ventricular Arrhythmia” (SOFA) trial (see "New Study Fogs Positive Picture”)—whose latest results we’re reviewing today—we noted that prior studies in apparently healthy people showed clear reductions in the risk of sudden cardiac death caused by unexpected arrhythmias.
The following week (see "Negative Studies Seen Irrelevant”), we received and published this enlightening letter from physician Adam B. Smith, M.D. which supported the accuracy of our own interpretation of the negative findings we’d just reviewed:
I read your article on the SOFA [Study on Omega-3 Fatty acids and ventricular Arrhythmia] trial, "New Study Fogs Positive Picture of Fish Oil and Arrhythmias", and would like to point out that the study population had, in all likelihood, cardiac electro-physiologic damage beyond the help of omega-3 supplements.
That is, many physiologic processes get to a point where they simply cannot be reversed or even attenuated, and it is likely that a study population requiring ICDs is simply beyond the help of omega-3s.
This in no way diminishes the power of earlier studies showing the undeniable benefit of omega-3s in preventing arrhythmia in less affected individuals.... I continue to recommend omega-3s in my practice with utmost confidence.
Adam B. Smith, M.D.
As we will see, one of the world’s leading fatty acid researchers endorses Dr. Smith’s well-informed perspective—as elaborated further in our own words—on the negative outcome of the new clinical trial we’ll address in this article, which was a continuation of the long-term SOFA study referenced by Dr. Smith.
The new "SOFA” study and what it shows
The new findings flowed from the European SOFA study, a well-designed (randomized, parallel, placebo-controlled, double-blind) trial conducted at 26 cardiology clinics across Europe.
This new phase of the SOFA study continued testing the ability of fish oil to reduce arrhythmias—and ensuing sudden cardiac death—in people with ICDs. It is important to stress, again, that virtually all people with ICDs are in an advanced stages of the various forms of cardiovascular disease, any of which is likely to induce dangerous arrhythmias.
The SOFA study team enrolled 546 patients with ICDs and prior documented incidents of ventricular arrhythmia: either ventricular tachycardia (VT) or ventricular fibrillation (VF). The participants were divided into two groups of 273 each.
Over the one-year study period, the test group received two grams of fish oil per day while the control group received identical placebo pills. The researchers then recorded the number of times that the patients’ ICDs intervened automatically to correct a ventricular arrhythmia, as well as the number of deaths from all causes.
By the end of the year, 27 percent of patients in the fish oil group and 30 percent in the placebo group experienced a ventricular arrhythmia that triggered a corrective intervention by their ICD. And survival rates did not substantially improve in the patients taking fish oil.
The authors concluded omega-3 essential fatty acids from fish oil did not have a strong protective effect against ventricular arrhythmia or death in this small subgroup of the population.
What do these negative outcomes mean?
In 2004, some of the authors of the new SOFA trial published a review of the available scientific literature, in which they complained of the conundrum that faces all cardiac researchers today:
"Results from two recent clinical trials do not support a protective effect of n-3 [omega-3] fatty acids. In light of the earlier published bulk of evidence that n-3 [omega-3] fatty acids reduce cardiovascular mortality and sudden cardiac death, it is hard to explain these findings" (Geelen A 2004).
To understand why this apparent paradox exists, we spoke with Vital Choice Science Advisor William E. Lands, Ph.D. Dr. Lands is leading figure in fatty acid research, who's published more than 250 scientific papers duringpublished more than 250 scientific papers during a career that included service as Professor of Biological Chemistry at the medical centers of the Universities of Michigan and Illinois, Director of the Division of Basic Research at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and Senior Scientific Advisor to the Institute’s Director.
In cases like this, he urges us all to consider research findings in their full context.
As Dr. Lands told us:
I want to urge you to avoid the quicksand trap of a too-narrow focus on arrhythmia—and a too-oversimplified a view of its onset. Before 1990, ischemia [insufficient blood flow to the heart] and thrombosis [excessive tendency toward blood clotting] were well established features to be prevented in [the effort to deter] CHD [coronary heart disease] death, but medical researchers wanted new funding for new research projects and they pressed hard for more narrow research funding for studies of arrhythmia.
That pressure (and its good funding) made arrhythmia a big "buzz-word" for over a decade, and we're now paying the price of the oversimplification. The etiology [underlying causes] and onset of arrhythmia have many origins. Remember that aspirin does still seem to prevent CHD deaths, not likely by direct action on arrhythmia!
Taking his advice to look at the bigger picture, we presented Dr. Lands with our own elaboration on the perspective voiced by Dr. Smith in his 2005 letter (above), based on what is proven—or widely hypothesized—about the impacts of omega-3s on relevant aspects of cardiovascular physiology.
We asked him whether he agreed that the following proposal represents a plausible explanation for the unexpectedly negative findings. As Dr. Lands replied, in his typically precise, understated style, "Your comment points readers toward a basically correct viewpoint about the subset of patients studied.”
Here’s the analysis/hypothesis we proposed to Dr. Lands:
The American Heart Association and other authorities endorse the protective power of omega-3s because the outcomes of the majority of clinical and epidemiological studies suggest that these under-consumed fatty acids reduce the risk of cardiac death, overall.
In that context, evidence that supplemental omega-3s may not reduce rates of arrhythmia in heart patients with ICD—-whose cardiovascular disease is, by definition, very advanced—is relevant only to that small, sick subpopulation.
Accordingly, the apparent inability of omega-3s to prevent arrhythmias in patients with ICDs doesn’t diminish to any degree the proven preventive value of omega-3s to the general public.
The critical point to remember is that the anti-inflammatory and triglyceride-lowering effects of omega-3s hamper development and progression of five underlying conditions that contribute to heart attacks, arrhythmias and sudden cardiac death:
- Elevated triglycerides
- Low HDL cholesterol levels
- Arteriosclerosis (clogged arteries) and resulting ischemia (insufficient blood supply to heart muscles)
- Thrombosis (dangerous tendency toward arterial blood clots).
The sinister, synergistic effects of this mutually reinforcing set of risk factors trigger most fatal arrhythmias and consequent sudden cardiac deaths.
Thus, if a person starts consuming higher levels of omega-3s relatively early and consistently—before cardiovascular disease gets far enough advanced to start triggering the arrhythmias that prompt placement of ICDs—this habit is likely to hinder the degenerative processes that yield arteriosclerosis, ischemia, and thrombosis, an arrhythmia will never occur.
In contrast, if the process is advanced enough to require implantation of a cardiac defibrillator, a late increase in intake of omega-3s cannot stop the inevitable— arrhythmias and attendant risk of sudden death—either certainly or indefinitely.
To summarize, people with ICDs cannot expect a regimen of fish oil allow them to remove their electronic aids. But, to reiterate the key point, the overwhelming majority of evidence indicates that marine omega-3s substantially reduce the risk of sudden cardiac death—the type responsible for half of all deaths related to cardiovascular disease—the risk of a second heart attack or sudden cardiac death among heart attack survivors.
While fish oil capsules remain highly valuable preventive health aids, endorsed by virtually all heart health medical bodies in the US and abroad, they are not miracle drugs.
The import of the negative studies published over the past two years seems obvious. We can’t expect fish or fish oil supplements to negate the consequences of damage done during the decades over which cardiovascular disease progresses: hidden injuries that can bring people to the point where they’re always at risk of a suffering fatal arrhythmia, and require surgical implantation of a cardiac defibrillator.
- Brouwer IA, Zock PL, Camm AJ, Bocker D, Hauer RN, Wever EF, Dullemeijer C, Ronden JE, Katan MB, Lubinski A, Buschler H, Schouten EG; SOFA Study Group. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA. 2006 Jun 14;295(22):2613-9.
- 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.
- Brouwer IA, Zock PL, Wever EF, Hauer RN, Camm AJ, Bocker D, Otto-Terlouw P, Katan MB, Schouten EG. Rationale and design of a randomised controlled clinical trial on supplemental intake of n-3 fatty acids and incidence of cardiac arrhythmia: SOFA. Eur J Clin Nutr. 2003 Oct;57(10):1323-30.
- Raitt MH, Connor WE, Morris C, Kron J, Halperin B, Chugh SS, McClelland J, Cook J, MacMurdy K, Swenson R, Connor SL, Gerhard G, Kraemer DF, Oseran D, Marchant C, Calhoun D, Shnider R, McAnulty J. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA. 2005 Jun 15;293(23):2884-91.
- Aizer A, Gaziano M, MansonJE, Buring JE, Albert CM. Relationship between fish consumption and the development of atrial fibrillation in men. Oral Abstract Sessions AB03, Abstract AB03-2, presented at the 27th annual meeting of the Heart Rhythm Society, Thursday, May 18, 2006, Boston, USA.
- Geelen A, Brouwer IA, Zock PL, Katan MB. Antiarrhythmic effects of n-3 fatty acids: evidence from human studies. Curr Opin Lipidol. 2004 Feb;15(1):25-30. Review.
- Hamer M, Steptoe A. Influence of specific nutrients on progression of atherosclerosis, vascular function, haemostasis and inflammation in coronary heart disease patients: a systematic review. Br J Nutr. 2006 May;95(5):849-59. Review.