Omega-3
Fatty Acids Provide Protection Against Arrhythmia
Ventricular arrhythmias
are the leading cause of death from acute myocardial infarction
(AMI).1 In Canada, there were more than 12,000 deaths
from AMI in 1995.2 Each year in the United States,
about 250,000 people reportedly die within one hour of an AMI,
mostly due to arrhythmia. Developing simple methods of preventing
such fatal arrhythmias would provide a substantial benefit
to public health.3
There is growing evidence
that a simple dietary change-increasing the dietary intake
of omega-3 fatty acids-may help prevent arrhythmias. The major
omega-3 fatty acids are alpha-linolenic acid (ALA), the essential,
parent fatty acid of the omega-3 family, and the long-chain
derivatives of ALA-namely, eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA). ALA is found mainly in flaxseed
(the richest source of ALA in the North American diet),4 other
oilseeds such as soybean, canola and wheat germ, some nuts
(e.g., walnuts), and red and black currant seeds. EPA and DHA
are found mainly in cold-water fish such as mackerel, salmon,
herring, trout and blue fin tuna.5 (Most species
of fish contain very little ALA and low levels of EPA and DHA.)
The omega-3 fatty acids exhibit antiarrhythmic effects in cell
cultures and laboratory animals and are associated with a reduced
risk of fatal ventricular arrhythmia in humans.6
Normal Physiology of Cardiac
Muscle
Cardiac muscle fibres generate
electrical impulses and contract when stimulated. These actions
are the result of changes in the transmembrane potential gradient
that occur within each cardiac cell.
Nonpacemaker cells-that
is, the atrial and ventricular muscle cells that are not involved
in setting cardiac impulse or rhythm-must reach a threshold potential
before responding to electrical signals. The complex sequence
of depolarization and repolarization of cardiac cell membranes
depends on many mechanisms, including membrane permeability and
the actions of specialized molecular pumps that transfer sodium
out of the cell and potassium into the cell (the so-called Na+-K+ ATPase
pump).
Arrhythmias occur
when there is a disturbance in the electrophysiologic properties
of the cardiac muscle.7 During an ischemic episode,
for example, myocytes become slightly depolarized due to a
reduction in the Na+-K+ ATPase pump.
This change in the potential of the cell membrane makes it
sensitive to triggering an action potential prematurely, leading
to ventricular fibrillation and arrhythmias.8
Proposed Mechanism of Action of Omega-3's
Omega-3 fatty acids
appear to protect against arrhythmia by enhancing the electrical
stability of heart cells and increasing their resistance to
becoming "hyperexcitable".8 In cultured cardiac
myocytes of rats, for example, omega-3 fatty acids terminated
toxin-induced arrhythmias mainly by reducing the electrical
excitability of the heart cell.1, 9 Omega-3 fatty
acids also prolong the relative refractory period of the cardiac
cycle, thus reducing arrhythmia risk.8
Alpha-Linolenic Acid
Is As Effective as EPA and DHA
Pure preparations
of ALA, EPA and DHA are equally effective in protecting against
fatal arrhythmias in dogs. In one study, intravenous infusion
of pure ALA, EPA and DHA reduced significantly the incidence
of ventricular flutter-fibrillation and protected a majority
of dogs from fatal arrhythmias. Infusion of the control lipid
(soybean oil) failed to protect any animals from fatal arrhythmias.10
These findings suggest
that omega-3 fatty acids help regulate cardiac function. Furthermore,
it is the free, unesterified forms of ALA, EPA and DHA that
confers cardioprotective effects by virtue of their being readily
available to regulate ion channels and membrane excitability.11 In
other words, omega-3 fatty acids bound in membrane phospholipids
show no protective effect until they are released as free fatty
acids.12
Effectiveness of Dietary
Versus Pure Omega-3 Fatty Acids
The observation that only
free, unesterified omega-3 fatty acids are antiarrhythmic raises
an important question: Are dietary omega-3 fatty acids as effective
as infused, pure forms in reducing the risk of AMI? Dietary omega-3
fatty acids would not be expected to be as available as pure
infusions of fatty acids because they must first be absorbed,
transported to tissues, stored in membrane phospholipids, and
then released as free fatty acids and made available to cardiac
cells during times of stress.
Research among healthy male
volunteers provides a partial answer to the question: Dietary
omega-3 fatty acids are incorporated into the phospholipids of
cell membranes. For example, supplementing the diet with flaxseed
increases the ALA content of blood phospholipids, triglycerides
and/or cholesteryl esters 2-8 fold and significantly increases
the EPA and total omega-3 fatty acid content of platelet phospholipids.13,
14 Increasing the ALA, EPA and DHA
content of
cell membrane phospholipids theoretically makes more omega-3
fatty acids available to enhance the electrical stability of
cardiac cells.
Increasing Total Dietary
Omega-3 Fatty Acids Is the Key Action
Two lines of evidence
support the recommendation to increase total dietary intake
of omega-3 fatty acids. The first approach examined the cardioprotective
effects of ALA intake from all sources. Results of the Health
Professionals Follow-up Study,15 the Lyon Diet Heart
Study,16 the Multiple Risk Factor Intervention Trial
(MRFIT),17 and the Nurses' Health Study18 indicate
that populations with high intakes of ALA have a low risk of
AMI, non-fatal AMI, death from cardiovascular causes or all-cause
mortality. Indeed, in an extended follow-up of the participants
in the Lyon Diet Heart Study, the cardioprotective effect of
a Mediterranean diet high in ALA was maintained for up to four
years after the first infarction and confirmed the original
analysis. Only ALA was associated with an improved prognosis
for these survivors of a previous myocardial infarction.19
The second approach
examined the cardioprotective effects of EPA and DHA, mainly
from fish. One secondary prevention study compared the omega-3
fatty acid intakes from seafood of 334 patients with primary
cardiac arrest and 493 controls, matched for age and sex. Compared
with no seafood intake, an intake of 2.9 g of omega-3 fatty
acids or about two servings of fatty fish per month was associated
with a 30% reduction in risk of primary cardiac arrest. Subjects
who ate one fatty fish meal per week had a 50% reduction in
risk of primary cardiac arrest.20 In the Diet and
Reinfarction Trial (DART), men who had recovered from an MI
and who were advised to eat fatty fish twice a week had a 29%
reduction in 2-year all-cause mortality compared with those
who were not advised to eat fish weekly. [This study did not
record arrhythmic deaths.21] In the Physicians' Health
Study, a prospective cohort study, intake of omega-3 fatty
acids from seafood was associated with reduced risk of sudden
death. There was a threshold effect, with an intake of one
fish meal per week providing significant protection against
sudden death.22
Although these studies represent
a small body of evidence, they provide encouraging results. Populations
with high intakes of the omega-3 fatty acids enjoy some protection
against fatal arrhythmia.
Flaxseed Boosts Omega-3
Fatty Acid Intake
Health Canada recommends
an omega-3 fatty acid intake of at least 0.5% of total energy.
For persons consuming a 2,000 kcal diet, this represents an intake
of about 1 g of omega-3 fatty acids per day.23
(The United States has not
formulated a recommended intake of omega-3 fatty acids.) One
tablespoon of whole flaxseed provides about 2.5 g of ALA, thus
making a substantial contribution to total omega-3 fatty acid
intake.
Conclusions
Omega-3 fatty acids
appear to enhance the mechanical performance and electrical
stability of the heart and to protect against fatal arrhythmia
in both humans and animal models. Their mechanism of action
likely includes modifying the fatty acid composition of cell
membrane phospholipids, affecting cell signaling and controlling
ion transfers across the cell membrane.24 Evidence
is mounting that making a small dietary change-namely, eating
foods rich in omega-3 fatty acids on a regular basis-provides
protection against arrhythmia and is a simple means of improving
public health.25
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Flax Council of
Canada, 4654-167 Lombard Ave., Winnipeg, MB, Canada R3B
0T6, email: flax@flaxcouncil.ca
Web site: http://www.flaxcouncil.ca/
