Interest in omega-3 fatty acids
began some 30 years ago and there are now several thousand papers in the
scientific literature supporting their benefits.
There is little doubt that
omega-3 fatty acids are important in human nutrition. They are significant
structural components of the cell membranes of tissues throughout the
body and are especially rich in the retina, brain, and sperm, in which
docosahexaenoic acid (DHA) constitutes 36.4% of total fatty acids
Membrane fluidity is essential
for proper functioning of these tissues. In the retina, where omega-3
fatty acids are especially important, deficiency can result in decreased
vision and abnormal electroretinogram results.
Fatty acids are essential fatty acids, necessary from conception through
pregnancy and infancy and, undoubtedly, throughout life.
The ratio of omega-6 to omega-3
fatty acids has increased in industrialized societies because of increased
consumption of vegetable oils rich in omega-6 fatty acids, ie, linoleic
acid, and reduced consumption of foods rich in omega-3 fatty acids.
Another important feature of
omega-3 fatty acids is their role in the prevention and modulation of
certain diseases that are common in Western civilization.
The following is a partial
list of diseases that may be prevented or ameliorated with omega-3 fatty
acids, in descending order of the strength of the available evidence as
perceived by this reviewer:
- Coronary heart disease and
- Essential fatty acid deficiency
in infancy (retinal and brain development);
- Autoimmune disorders (e.g.,
lupus and nephropathy);
- Crohn disease;
- Cancers of the breast, colon,
- Mild hypertension; and
- Rheumatoid arthritis.
Benefits Of Omega-3 Fatty Acids
The strongest evidence of a
relation between omega-3 fatty acids and disease is the inverse relation
between the amount of omega-3 fatty acids in the diet and in blood and
tissues and the occurrence of coronary heart disease and its many complications.
Effects of omega-3 fatty acids
on coronary heart disease have been shown in hundreds of experiments in
animals, humans, tissue culture studies, and clinical trials.
Omega-3 fatty acids from fish
have been shown to be protective of heart disease and, by a variety of
mechanisms, prevent deaths from coronary disease, particularly cardiac
The unique properties of these
fatty acids in coronary heart disease first became apparent in the investigations
of the health status of Greenland Eskimos who consumed diets very high
in fat from seals, whales, and fish and yet had a low rate of coronary
Further studies clarified this
paradox. The fat the Eskimos consumed contained large quantities of the
very-long-chain and highly polyunsaturated fatty acids of EPA and DHA,
which are abundant in fish, shellfish, and sea mammals and are scarce
or absent in land animals and plants. EPA and DHA are synthesized by phytoplankton,
which are the plants of the waters and the base of the food chain for
Dietary omega-3 fatty acids
act to prevent heart disease through a variety of actions. They:
- Prevent arrhythmias (ventricular
tachycardia and fibrillation),
- Prostaglandin and leukotriene
- Have anti-inflammatory properties,
- Inhibit synthesis of cytokines
- Stimulate endothelial-derived
- Have hypolipidemic properties
with effects on triglycerides and VLDLs, and
- Inhibit atherosclerosis.
EPA and DHA have strong antiarrhythmic
action on the heart. In experimental animals and tissue culture systems,
EPA and DHA prevent the development of ventricular tachycardia and fibrillation.
Even total mortality has been
improved in several studies in which the omega-3 fatty acid intake was
increased. In one study, men who consumed salmon 1 time/wk had a 70% less
likelihood of cardiac arrest.
In another study overall mortality
was decreased by 29% in men with overt cardiovascular disease who consumed
omega-3 fatty acids from fish or fish oil, probably because of the reduction
in cardiac arrests.
The most recent data on fish
consumption and risk of sudden cardiac death were from the Physician's
Health Study in the United States in 20551 male physicians. Consumption
of 1 fish meal/week was associated with a 52% lower risk of sudden cardiac
death compared with consumption of <1 fish meal/month.
Death Rate Was Also Lower In Those Who Ate Fish.
Thrombosis, or the tendency
to form blood clots, is a major complication of coronary atherosclerosis
that can lead to heart attacks.
The omega-3 fatty acids from
fish oil have powerful antithrombotic actions. EPA inhibits the synthesis
of thromboxane A2 from arachidonic acid in platelets. This prostaglandin
causes platelet aggregation and vasoconstriction.
As a result, fish oil ingestion
by humans increases the bleeding time and decreases the stickiness of
the platelets for aggregation to glass beads. In addition, the administration
of fish oil enhances the production of prostacyclin, a prostaglandin that
produces vasodilation and less sticky platelets.
The EPA and DHA contained in
fish oil fed to experimental animals actually inhibited development of
atherosclerosis. There is evidence in both pigs and monkeys that dietary
fish oil prevents atherosclerosis by actions other than reducing plasma
Atherosclerotic plaque formation
may also be lessened by the reduction in growth factors after fish-oil
consumption. Not only is platelet-derived growth factor diminished by
fish oil consumption, but its messenger RNA is reduced. Because atherosclerosis
begins with cellular proliferation in response to the influx of cholesterol-rich
lipoproteins, the inhibition of this proliferation would greatly reduce
the growth of the atherosclerotic plaque.
The pronounced effect of fish
oil on high blood fats or elevated cholesterol levels is especially well
documented and is supported by results of precise dietary studies in which
the effects of a diet rich in salmon oil were compared with those of a
vegetable oil and a diet high in saturated fat.
Fish oil in particular was
shown to lower plasma cholesterol and triglyceride concentrations. Apolipoprotein
B production is reduced by consumption of fish oil in comparison with
vegetable oils such as safflower or olive oil.
Fatty Acids Essential Components Of Cell Membranes In Infancy
There are 2 critical periods
for the acquisition of these essential omega-3 fatty acids: during fetal
development and after birth until the biochemical development in the brain
and retina is completed.
As already noted, the omega-3
fatty acid DHA is an important constituent of the cell membrane of these
Omega-3 fatty acid deficiency
is manifested in both the blood and in tissue biochemistry. Of note is
a strikingly low concentration of DHA, which may fall to as much as one-fifth
of the normal amount.
In addition, the body attempts
to replace the deficient DHA with another highly polyunsaturated fatty
acid of the omega-6 series. In rhesus monkeys, omega-3 fatty acid -- deficient
diets fed to pregnant animals and then continued after birth induce profound
functional changes such as reduced vision, abnormal electroretinograms,
impaired visual evoked potential, more stereotypic behavior (e.g., pacing),
and, perhaps, disturbances of cognition.
Some of these findings have
been replicated in infants fed formulas deficient in omega-3 fatty acids.
Most studies of premature infants have shown visual impairment and abnormal
A recent study in full-term
infants, in which a standard infant formula was compared with human milk
and with formulas enriched with DHA, provided unequivocal evidence of
considerable differences in visual evoked potential.
In all of the human studies,
the biochemical evidence in plasma, red blood cells, and, occasionally,
in tissues from autopsied infants has substantiated the omega-3 fatty
acid deficiency state. The lower concentrations of DHA in plasma and erythrocytes
are mirrored by lower concentrations in the brain and retina. Formula-fed
infants have lower concentrations of brain DHA than do infants fed human
milk. They also have lower intelligence quotients.
During pregnancy, both maternal
stores and dietary intake of omega-3 fatty acids are of importance in
insuring that the baby has adequate amounts of omega-3 fatty acids at
the time of birth.
All the polyunsaturated fatty
acids, including DHA, are transferred across the placenta into fetal blood.
In addition, EPA and DHA in maternal adipose tissue can be mobilized as
free fatty acids bound to albumin and be made available to the developing
fetus via placenta transport.
Several studies in monkeys
have indicated that when the maternal diet is deficient in omega-3 fatty
acids, the infant at birth is likewise deficient as evidenced by low DHA
concentrations in their plasma and red blood cells.
In humans, it was shown that
the administration of fish oil or sardines to pregnant women led to higher
DHA concentrations in both maternal plasma and red blood cells and in
cord blood plasma and red blood cells at the time of birth.
Once membrane phospholipids
have adequate concentrations of DHA, there is an avid retention of these
fatty acids in the brain and the retina, even though the diet may subsequently
be deficient. Several studies illustrate clearly the effects of omega-3
deficiency in both animals and humans.
Journal of Clinical Nutrition, Vol. 71, No. 1, 171S-175S, January