Fish Oils In Heart Cells Can Block Dangerous Heart Rhythms

Epidemiologists have known for years that eating fish was associated with reduced risk of cardiovascular disease, but only recently have researchers had laboratory evidence to explain this effect, says review author Alexander Leaf, M.D., Jackson Professor of Clinical Medicine Emeritus, Harvard Medical School, Boston. Leaf and colleagues present a detailed explanation of how omega-3 (n-3) fish oils benefit the heart.

“Animal experiments show that fatty acids from n-3 fish oils are stored in the cell membranes of heart cells and can prevent sudden cardiac death or fatal arrhythmias,” Leaf says.

Arrhythmias are irregular heart rhythms. Leaf says that studies of individual heart cells demonstrated that the omega-3 essential polyunsaturated fatty acids (n-3 PUFAs) specifically block excessive sodium and calcium currents in the heart. Those excessive electrical discharges cause dangerous and erratic changes in heart rhythm.

The first clinical suggestion that n-3 PUFAs significantly benefited the heart came from a 1989 study in which 2,033 men with heart disease were given dietary advice on fat, fiber or fish. After two years the men who were told to eat fish at least twice a week had a 29 percent reduction in death. There was no benefit in either the fiber or fat groups.

Since about “50 percent to 60 percent of deaths in the setting of coronary heart disease are sudden cardiac death [deaths within one hour of symptoms of a heart attack] attributed to sustained ventricular arrhythmias” the authors write, the reduction in deaths reported in this early study is probably evidence of fewer fatal arrhythmias.

This initial study was followed by a series of observational studies and controlled clinical trials. All arrived at the same conclusion: A diet rich in fatty fish reduced fatal heart attacks. But Leaf says that this “protection” was still not completely understood.

In early animal experiments, researchers demonstrated that animals fed a diet in which 12 percent of the calories came from saturated fat died of sustained ventricular fibrillation, but animals that were also fed n-3 PUFAs did not develop these dangerous arrhythmias when their coronary arteries were tied off.

But then Leaf and other researchers still needed to find out if “there were any plausible biochemical or physiological effects of these n-3 fatty acids which could explain their antiarrhythmic action.” To do so, they cultured neonatal heart cells from rats and observed them under the microscope. The cells clump together and the clump beats spontaneously, rhythmically and simultaneously just like the whole heart.

Using a video camera, Leaf and his colleagues taped the action of the cells and the effect of different toxic agents on the cells. They discovered that adding n-3 PUFA prevented arrhythmias induced in the cells.

Leaf and his colleagues conclude that “n-3 fatty acids have been part of the human diet for some 2-4 million years during which our genes were adapting to our environment, including our diets. They are safe and have been listed on the GRAS list (‘generally regarded as safe’) according to the FDA.”

Leaf says that fresh or frozen fish are the best choices but canned tuna can be used if it is packed in water. “Tuna packed in oil is not a good choice because the extra oil will extract the beneficial n-3 oil from the fish,” he says.

According to a recent American Heart Association scientific statement a “dietary approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (about one gram per day) may be greater than what can readily be achieved through diet alone. These individuals, in consultation with their physician, could consider supplements for CHD risk reduction.”

The association recommends that individuals with certain cardiovascular conditions consult with their physician about fish oil supplements.

In an accompanying editorial, authors David S. Siscovick, M.D., Rozenn N. Lemaitre, Ph.D., and Dariush Mozaffarian, M.D. say the messages from Leaf and colleagues are clear.

“For clinicians, it is time to implement the current American Heart Association dietary guidelines . . . For policymakers, there is a need to consider a new indication for treatment with low-dose n-3 PUFA supplements – the prevention of sudden cardiac death in patients with a prior [heart attack]. For researchers, there is a need to continue both clinical studies and studies that explore the mechanism through which n-3 PUFAS influence the risk of sudden cardiac death,” they write.

The American Heart Association estimates that sudden cardiac death causes 250,000 deaths in the United States each year.

Co-authors are Jing X. Kang, M.D., Ph.D.; Yong-Fu Xiao, M.D., Ph.D.; and George E. Billman, Ph.D. The study was partly funded by the National Institutes of Health and the American Heart Association.