Study lends to weight hypothesis that fish and fish oil can benefit a very sick subset of heart patients 08/27/2007
Fish and fish oil keep looking better and better when it comes to heart health.
The results of a landmark study published last summer went unreported by the media and just came to our attention.
In the first study of its kind, researchers at the University of Maryland and New Orleans' Ochsner Clinic Foundation, conducted a randomized, placebo-controlled clinical trial in 14 patients with advanced congestive heart failure (CHF).
They reported that the CHF patients randomized to receive fish oil enjoyed two major benefits versus the placebo group:
- They gained weight, thereby reversing the dangerous weight loss--called cardiac cachexia--that often occurs in advanced CHF.
- Blood levels of pro-inflammatory, cachexia-promoting immune-system chemicals (cytokines) dropped very substantially.
The pro-inflammatory cytokines suppressed by fish oil included TNF-alpha, elevated levels of which are risk factors for congestive heart failure and cardiac cachexia.
As the Maryland/New Orleans team wrote, “Fish oil therapy may represent a novel therapeutic approach in late-stage heart failure characterized by cardiac cachexia” (Mehra MR et al 2006).
What about fish-oil warnings to people with arrhythmias and CHF?
Following a series of studies published in 2005 and 2006, we cautioned that fish oil might be contraindicated in two overlapping groups:
- People with congestive heart failure (CHF), whose hearts have a high proportion of “hyper-excitable” cells, which are prone to trigger the arrhythmias
- Arrhythmia-prone heart patients with implanted cardioverter defibrillators (ICDs), which are used to stopp arrhythmias when they occur.
Out of concern for affected readers, we may have overdone our warnings, based on the new findings in patients with advanced CHF and the conclusions of an evidence review conducted at Columbia University Medical Center (Reiffel JA, McDonald A 2006).
Omega-3s, implanted cardioverter defibrillators (ICDs), and arrhythmias
Studies in patients with implanted cardioverter defibrillators have been mixed. Some reported a trend toward an increased risk of ventricular arrhythmias—although not an increased risk of death—in patients taking fish oil (Cleland JG et al 2004).
As we reported last summer, this may simply due the plausible possibility that, as our headline suggested, “Fish Oil Can't Rescue the Sickest Cardiac Patients' Heart Rhythms”: a position supported by a leading omega-3 researcher and a physician, both of whom are quoted in the article.
Dietary omega-3s present a hypothetical risk to people with CHF, whose few functional heart cells are starved for blood flow, making them hyper-excitable and prone to trigger the arrhythmias that cause most cases of sudden cardiac death.
Omega-3s selectively quiet hyper-excitable cells, bringing anti-arrhythmia benefits to most heart patients… and to the many outwardly healthy people who die from unexpected arrhythmias daily.
Thus, taking omega-3 fish oil—even eating fatty fish—could represent a hypothetical risk to people with congestive heart failure by suppressing pumping action in the hyper-excitable cells that account for an unusually large proportion of their blood-pumping power.
The Columbia University authors set the scene succinctly:
- “Sudden cardiac death is the most common cause of mortality among patients surviving a myocardial infarction [heart attack], accounting for 50 percent to 60 percent of all deaths due to coronary artery disease.
- “Post-infarction [heart attack] treatment of patients with fish oil supplements is now considered one component of an effective approach to preventing mortality due to sudden cardiac death in this group at high risk.” (Reiffel JA, McDonald A 2006)
The recommendation that heart patients take fish oil—made by the American Heart Association, among others—is supported by evidence from studies of post-heart-attack patients treated with fish oil supplements and from studies following healthy adults who consume fish regularly.
In the studies conducted to date, the overall reduction in risk of heart-related deaths ranged from 29 percent to 52 percent, while the reductions in risk of for sudden cardiac death ranged from 45 percent to 81 percent.
How does this relate to our caution about fish oil in people with CHF or ICDs?
As the Columbia University team noted, these positive findings are supported by studies in patients with ischemic heart disease—that is, hearts starved for blood flow by clogged arteries, which leads to CHF—and in subgroups of patients with implantable cardioverter defibrillators or who are susceptible to heart arrhythmias.
And they made one very key point: “In those studies that verified the level of omega-3 fatty acid intake by measuring plasma phospholipid fatty acid content, the antiarrhythmic effects associated with fish and fish oil have been confirmed.”
Their review goes on to detail the types of arrhythmias—ventricular ectopy, atrial fibrillation, and ventricular tachyarrhythmias—that appear beneficially affected by fish oil, and how the omega-3s in fish oil are believed to exert their positive effects.
And the Columbia authors suggest four plausible explanations for the mixed results of fish oil studies in people with ischemic heart disease (IHD), congestive heart failure (CHF) resulting from IHD, and implanted cardioverter defibrillators (ICFs):
- The human studies have varied widely in terms of the diagnostic criteria for incliding subjects: that is, different clinical criteria were used to determine eligibility for enrollment.
- Fish oils were either administered as supplements or obtained from consumption of fish. Doses of omega-3 fatty acids from supplements were not the same across clinical studies.
- Dietary intakes of omega-3s from fish were based on people's unreliable memories.
- The relation between intake of omega-3s and risk of death may be, as the authors suggest, “non-linear, dose-limited, and non-incremental”. In other words, the well-documented ability of omega-3s to help prevent arrhythmias, second heart attacks, and sudden cardiac death occurs up to a certain, as yet undefined omega-3-intake threshold, with little extra benefit seen above that level. Thus, someone enrolled in a trial who is already consuming the maximum beneficial amount of omega-3s will appear have received no benefits from the fish oil they take during the study.
We would add another confounding factor, often overlooked in such analyses: namely, dietary context.
As leading researchers in the field reported last year—see “New Report Finds Americans Need Far More Omega-3s”—the ratio of omega-6 fatty acids to omega-3 fatty acids in people's diets plays an enormous role in setting their risk for depression and heart trouble.
- Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant. 2006 Jul;25(7):834-8. Epub 2006 May 24.
- Reiffel JA, McDonald A. Antiarrhythmic effects of omega-3 fatty acids. Am J Cardiol. 2006 Aug 21;98(4A):50i-60i. Epub 2006 May 26. Review.
- Lombardi F, Terranova P. Anti-arrhythmic properties of N-3 poly-unsaturated fatty acids (n-3 PUFA). Curr Med Chem. 2007;14(19):2070-80.
- Yndestad A, Damas JK, Oie E, Ueland T, Gullestad L, Aukrust P. Role of inflammation in the progression of heart failure. Curr Cardiol Rep. 2007 May;9(3):236-41. Review.