Monday, June 18, 2007
Omega-3
William E Connor
The steps in the development of important medical discoveries
rest first on intuition and then on associations of a certain
factor with a disease, followed by scientifically designed experiments.
The history of the importance of the n3 polyunsaturated
fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) illustrates this point beautifully. Early Arctic explorers
commented on the rarity of coronary artery disease in Eskimos
despite their consumption of a very-high-fat, high-cholesterol
diet. This finding was indeed a paradox until it was resolved
by 2 Danish scientists, Bang and Dyerberg (1). When these
investigators looked at the coronary mortality statistics in Greenland
Eskimos and in Danish persons living in Greenland but
having a vastly different lifestyle, they found few deaths from
coronary artery disease in Greenland Eskimos but many deaths in
Danes. The answer to this riddle came from an analysis of the diet
of the Eskimos compared with that of the Danes (1). The latter
group ate a diet high in saturated fat and cholesterol from meat
and dairy products similar to the diet eaten in the homeland of
Denmark. The Eskimos, on the other hand, ate seal, whale, and
fish, all of which are extremely rich in EPA and DHA. This was
in contrast with the lower n3 fatty acid content of the typical
Danish diet. In the Greenland Eskimos also, the content of these
same n3 fatty acids in the blood was high (2), and the tendency
of the blood to form thrombi was lessened because the n3 fatty
acids were taken up by the blood platelets (3).
The same situation prevails in present-day Eskimos, as illustrated
by the study by Dewailly et al (4) in this issue of the Journal.
The Nunavik Inuit of Quebec, despite some Westernization,
still partly consume the diet of their ancestors, which is rich in
fish and marine mammals. Mortality from coronary artery disease
in the Inuit is 50% less than that in the Quebec province as
a whole. The Inuit’s high blood content of EPA and DHA reflects
their consumption of these foods from the sea.
Why the n3 fatty acids from fish and marine oils prevent
coronary artery disease has now been delineated in hundreds of
experiments in animals and tissue culture cells and in population
and clinical trials (5). Of the nutritional modalities thought to
prevent heart disease, the evidence for the efficacy of n3 fatty
acids is strong. This evidence may be best summarized in Table 1
and by answering the following question: have other population
studies and clinical trials shown that fish consumption is associated
with a lowered incidence of coronary artery disease? Japanese,
Dutch, and US studies indicate that deaths from coronary
artery disease are reduced by ≥50% by the consumption of 1–2 fish
meals/wk (6–8). The most important finding is of a reduction in
sudden death from ventricular fibrillation and tachycardia. About
300 000 such deaths occur in the United States each year. Direct
clinical trials of fish and fish oil have also shown a striking
reduction in sudden deaths (9, 10); these findings have great public
health significance. Furthermore, animal studies and experiments
in isolated myocytes showed that ventricular arrhythmias
are inhibited by EPA, which affects sodium and calcium ion
channels in the heart (11).
Thrombosis is a major complication of coronary atherosclerosis
and leads to myocardial infarction. The n3 fatty acids from
fish oil have powerful antithrombotic actions. EPA inhibits the
synthesis of thromboxane A2 from arachidonic acid in platelets.
Thromboxane A2 causes platelet aggregation and vasoconstriction.
By blocking thromboxane A2 synthesis, fish oil ingestion by
humans increases the bleeding time and decreases the number of
platelets that stick to glass beads (12). In addition, administration
of fish oil enhances the production of prostacyclin, a
prostaglandin that produces vasodilation and less sticky platelets.
In an in vivo baboon model, dietary fish oil prevented platelet
deposition in a plastic vascular shunt (13). Injury to the intima of
the carotid artery of the baboon invariably caused a marked proliferative
and inflammatory lesion, greatly thickening the wall.
When the animals were fed fish oil, this damage and intimal
thickening were completely blocked.
The EPA and DHA contained in fish oil inhibit the development
of atherosclerosis. There is evidence in both pigs and monkeys that
dietary fish oil prevents atherosclerosis by actions other than the
lowering of plasma cholesterol concentrations (14). These actions
may be associated with the inhibition of monocyte migration into
the plaque, with less cytokine and interleukin 1 production, and
with stimulation of the endothelial production of nitric oxide.
Dyerberg and Bang also found that the blood of Greenland
Eskimos had lower triacylglycerol and cholesterol concentrations,
particularly triacylglycerol, than the blood of Danes (2).
Dewailly et at (4) found that n3 fatty acids in the plasma
phospholipids of Nunavik Inuit were positively associated with
HDL-cholesterol concentrations and inversely associated with
Am J Clin Nutr 2001;74:415–6. Printed in USA. © 2001 American Society for Clinical Nutrition
The steps in the development of important medical discoveries
rest first on intuition and then on associations of a certain
factor with a disease, followed by scientifically designed experiments.
The history of the importance of the n3 polyunsaturated
fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) illustrates this point beautifully. Early Arctic explorers
commented on the rarity of coronary artery disease in Eskimos
despite their consumption of a very-high-fat, high-cholesterol
diet. This finding was indeed a paradox until it was resolved
by 2 Danish scientists, Bang and Dyerberg (1). When these
investigators looked at the coronary mortality statistics in Greenland
Eskimos and in Danish persons living in Greenland but
having a vastly different lifestyle, they found few deaths from
coronary artery disease in Greenland Eskimos but many deaths in
Danes. The answer to this riddle came from an analysis of the diet
of the Eskimos compared with that of the Danes (1). The latter
group ate a diet high in saturated fat and cholesterol from meat
and dairy products similar to the diet eaten in the homeland of
Denmark. The Eskimos, on the other hand, ate seal, whale, and
fish, all of which are extremely rich in EPA and DHA. This was
in contrast with the lower n3 fatty acid content of the typical
Danish diet. In the Greenland Eskimos also, the content of these
same n3 fatty acids in the blood was high (2), and the tendency
of the blood to form thrombi was lessened because the n3 fatty
acids were taken up by the blood platelets (3).
The same situation prevails in present-day Eskimos, as illustrated
by the study by Dewailly et al (4) in this issue of the Journal.
The Nunavik Inuit of Quebec, despite some Westernization,
still partly consume the diet of their ancestors, which is rich in
fish and marine mammals. Mortality from coronary artery disease
in the Inuit is 50% less than that in the Quebec province as
a whole. The Inuit’s high blood content of EPA and DHA reflects
their consumption of these foods from the sea.
Why the n3 fatty acids from fish and marine oils prevent
coronary artery disease has now been delineated in hundreds of
experiments in animals and tissue culture cells and in population
and clinical trials (5). Of the nutritional modalities thought to
prevent heart disease, the evidence for the efficacy of n3 fatty
acids is strong. This evidence may be best summarized in Table 1
and by answering the following question: have other population
studies and clinical trials shown that fish consumption is associated
with a lowered incidence of coronary artery disease? Japanese,
Dutch, and US studies indicate that deaths from coronary
artery disease are reduced by ≥50% by the consumption of 1–2 fish
meals/wk (6–8). The most important finding is of a reduction in
sudden death from ventricular fibrillation and tachycardia. About
300 000 such deaths occur in the United States each year. Direct
clinical trials of fish and fish oil have also shown a striking
reduction in sudden deaths (9, 10); these findings have great public
health significance. Furthermore, animal studies and experiments
in isolated myocytes showed that ventricular arrhythmias
are inhibited by EPA, which affects sodium and calcium ion
channels in the heart (11).
Thrombosis is a major complication of coronary atherosclerosis
and leads to myocardial infarction. The n3 fatty acids from
fish oil have powerful antithrombotic actions. EPA inhibits the
synthesis of thromboxane A2 from arachidonic acid in platelets.
Thromboxane A2 causes platelet aggregation and vasoconstriction.
By blocking thromboxane A2 synthesis, fish oil ingestion by
humans increases the bleeding time and decreases the number of
platelets that stick to glass beads (12). In addition, administration
of fish oil enhances the production of prostacyclin, a
prostaglandin that produces vasodilation and less sticky platelets.
In an in vivo baboon model, dietary fish oil prevented platelet
deposition in a plastic vascular shunt (13). Injury to the intima of
the carotid artery of the baboon invariably caused a marked proliferative
and inflammatory lesion, greatly thickening the wall.
When the animals were fed fish oil, this damage and intimal
thickening were completely blocked.
The EPA and DHA contained in fish oil inhibit the development
of atherosclerosis. There is evidence in both pigs and monkeys that
dietary fish oil prevents atherosclerosis by actions other than the
lowering of plasma cholesterol concentrations (14). These actions
may be associated with the inhibition of monocyte migration into
the plaque, with less cytokine and interleukin 1 production, and
with stimulation of the endothelial production of nitric oxide.
Dyerberg and Bang also found that the blood of Greenland
Eskimos had lower triacylglycerol and cholesterol concentrations,
particularly triacylglycerol, than the blood of Danes (2).
Dewailly et at (4) found that n3 fatty acids in the plasma
phospholipids of Nunavik Inuit were positively associated with
HDL-cholesterol concentrations and inversely associated with
Am J Clin Nutr 2001;74:415–6. Printed in USA. © 2001 American Society for Clinical Nutrition
# posted by roodbont @ 3:41 AM 
