REVIEWThe role of eggs, margarines and ﬁsh oils in the nutritional
management of coronary artery disease and strokes
Jules ConstantState University of New York at Buffalo(Received for publication on November 26, 2003)

Abstract. Although egg yolk is a rich source of cholesterol, the effect of eggs in raising serum cholesterol is variable and in some subjects there is no effect whatsoever. However, oxidized cholesterol
can increase atherosclerosis even with normal serum cholesterol. In order to attenuate oxidation ofcholesterol in eggs, it is necessary to limit the degree of heat applied. This means that we should use
only soft-boiled eggs which should be almost like water. We can also avoid egg yolk altogether and geta highly nutritious egg food from the egg white alone. The saturated fats from milk products, especiallybutter, are highly atherogenic. There are available many butter substitutes in the form of margarines.
But many of these margarines have hydrogenated vegetable oils which result in the production oftrans-fatty acids. The trams-fatty acids are as atherogenic as saturated fats. There are available, however, margarines without the trans-fatty acids. These are found only in large supermarkets. Fish oils
contain N3 fatty-acids which, unlike vegetable oils which contain N6 fatty-acids, can prevent atherosclerosis and sudden death by counteracting ventricular arrhythmias, acting as antioxidants, antithrombotic, anti-inﬂammatory agents, and decreasing triglycerides and blood pressure. (Keio J Med
53 (3): 131–136, September 2004)
Key words: cholesterol, eggs, ﬁsh oil, margarine, trans-fatty acids

The Nutritional Management of Coronary Artery
Disease and Strokes
How to minimize the dangers of egg cholesterol: theegg story
In 1912 Anitchkow in Germany fed egg yolk cholesterol to rabbits and produced aortic atherosclerosis.1
This was the ﬁrst widely publicized proof that there
was a connection between atheromas and cholesterol.
The word ‘‘atheroma’’ comes from the Greek ‘‘athero’’
which means porridge or gruel plus ‘‘oma’’ which means
tumor. This is the fatty cholesterol-rich lump found in
the lining of the blood vessels. When calcium is added
to the lump it is called ‘‘plaque’’ and the condition iscalled ‘‘atherosclerosis’’ (sclerosis is Greek for ‘‘hard’’).
When the lining of the plaque or atheroma ruptures,the fats burst through into the lumen. These fats arevery thrombogenic and the clot can cause a complete
obstruction known in lay term as ‘‘heart attack’’ but inmedical terms as a ‘‘myocardial infarction.’’

About 65 years after Anitchkow’s experiments,
three American groups fed puriﬁed cholesterol to
rabbits and could produce no atheroma.2–4 When
Anitschknow’s methods were analyzed, it was apparent
that his egg yolk cholesterol had had ample time to be
exposed to air which allowed the cholesterol to be oxidized. Oxidized cholesterol when fed to rabbits produces angiotoxic effects in the coronary arteries within
24 hours and ultimately results in atheromas.
In 1904, Schutze had described the oxidation ofcholesterol by air.5 Improperly stored cholesterol in
air contains at least 32 auto-oxidization products,
some of which have lethal toxic effects on the arterial
walls that can lead to atheroma.4 Atheromas removed from human aortas contain these oxidization
products.
Half of the cholesterol in the blood is due to diet andhalf comes from the liver and other tissues. The endogenous cholesterol produced by the liver and other tissues does not cause atheromas because endogenously
produced cholesterol is probably protected from auto-

Presented at the 1316th Meeting of the Keio Medical Society in Tokyo, May 9, 2003.
Reprint requests to: Dr. Jules Constant, 57 Tillinghast Place, Buffalo, NY 14216-3408, USA
131

132

oxidation by antioxidants present in most animalorganisms.2,6
Because egg yolk is a major source of cholesterol, it
is natural to assume that we should avoid eggs as muchas possible in order to lower our serum cholesterol. The
assumption that eggs should raise serum cholesterol
was ﬁrst tested in 1960. On the usual high saturated
fat Western diet, it was found that six to twelve weeks
of two to fourteen eggs/day had no effect on cholesterol.7,8 However, on a low saturated fat diet, Connor
found that although he could raise the cholesterol with
six to eight eggs/day, to his surprise, six eggs/day produced no greater increase in serum cholesterol than two
yolks. This suggests that the G.I., tract has a limited
capacity for cholesterol absorption. Another surprise
was that when taken with polyunsaturated fats (mostly
vegetable oils) the cholesterol rose higher than without
those polyunsaturated fats.9,10
The studies on the effect of egg intake on serum
cholesterol is confounded by the presence of hyperresponders and hypoerresponders to cholesterol intake, an inheritable condition. They may account forthe ﬁnding by Kummerow, et al.11 that two eggs/day inthree different countries resulted in an increase in cholesterol in some and a decrease in others. Usually whena study was carried on over a period of at least eightweeks there was no difference in cholesterol levels.
When a reduced fat diet was used together with two toseven egg/week, hyperresponders to cholesterol showedno effect at eight weeks, i.e., the hyperresponse effect isonly temporary.12
The above research suggests that we should not
be concerned with the amount of cholesterol ingested
in high cholesterol foods but we should be more concerned with whether or not the cholesterol is oxidized,
especially now that it is widely known that oxidized
LDL is the culprit in causing atherosclerosis. Oxidizedcholesterol can not only result in ulceration and ruptureof plaques which can lead to thrombosis13 but someoxidized cholesterol products have also been found tobe carcinogenic.14,15
Aside from autooxidization in air, the most powerful
method of oxidizing cholesterol is by heat. Heated egg
yolk and milk can produce atheromas in hamsters,
an animal known to be resistant to atherosclerosis.16
Today’s egg industry puts out eggs free of oxidation
products. In rabbit feeding, fried or hard-boiled eggs
produced the highest serum cholesterol (10 to 14 times
the experimental level). Scrambled eggs increase cholesterol six to seven times above the preexperimental
level, and soft boiled eggs increase it by only three tofour times.4 Other high cholesterol foods such as milk
fat become oxidized during the pasteurization process.
Powdered milk is exceptionally high in oxidization
products. Cheeses exposed to air for long periods dur-Constant J: Oxidized cholesterol and trans-fatty acids

ing processing and stored at room temperature arelikely to contain signiﬁcant toxic cholesterol oxidation
products.
Thus, if we wish to minimize the ingestion of oxidized cholesterol, we should prepare our eggs to be soft
boiled or soft fried (‘‘sunny side up’’). These eggs still
have small amounts of oxidized cholesterol and they
are therefore a compromise. Our milk products shouldbe either non-fat or contain 1% fat. For those whose
fear of the small amount of cholesterol in a minimallyheated egg yolk is too strong for comfort, there areavailable whole egg substitutes. The egg yolk is removed and the egg white is sold with yellow color
added in the form of beta-carotine which our bodies
turn into vitamin A. These are available in all supermarkets and in many American restaurants, the mostpopular being ‘‘Eggbeaters.’’ Egg whites are a highprotein food that contains all the vitamins and mineralsof the whole egg. One-quarter cup contains even agreater vitamin A, thiamine, riboﬂavin, vitamin E, B6,
and B12 content than the whole egg. They may also be
preferred by the calorie conscious person because they
have only about one-third the calories of the whole egg.
Butter substitutes: the margarine story
It is well known that saturated fats (all animaderived fats) are the strongest method of raising serum
cholesterol. In order to avoid butter which is very highin saturated fat we naturally turn to margarines which
are made of vegetable oils which have no signiﬁcantamounts of saturated fat or cholesterol. The problem
with margarines is that the wrong ones can have thesame effect as saturated fat, depending on how hard
they are. In order to make the vegetable oils hardenough to spread on bread, hydrogen must be added.
The more hydrogenation, the more saturated and themore atherogenic they are. The stick margarines are thehardest. Therefore, soft tub margarines are preferable.
If the ﬁrst ingredient on the label is the oil, then it has
the least hydrogenation.
Unfortunately, the more hydrogenation, the more
it produces atherogenic fatty acids called transfatty
acids.16 They may be worse than saturated fats in thatthey not only equal saturated fats in increasing the badcholesterol known as LDL, but also decrease the goodcholesterol known as HDL. Saturated fats do not lower
HDL.17 It is helpful for the memory to think of the ﬁrst‘‘ll’’ in LDL as ‘‘lethal’’ and to think of the ﬁrst letter in
HDL as ‘‘healthy.’’ The soft tub margarines have about
one-third of the amount of the amount of transfatty
acids as the hard stick margarines. To make mattersworse, transfats are not usually listed as saturated fatson product labels, although new legislation is promising
to change that. Replacing butter by soft margarines wasKeio J Med 2004; 53 (3): 131–136

found to favorably affect blood lipids, and may reduce
the risk of coronary artery disease, but hard margarines
conferred no beneﬁt whatsoever over butter.16 Merely
switching from butter to margarine without regard to
the degree of hydrogenation is counterproductive assuggested by the ﬁnding that in 1950 Norway launcheda cholesterol-lowering campaign in which soy margarine replaced butter. In the next 20 Years, there was asteep rise in deaths from coronary thrombosis.18
There are now available margarines that have notransfatty acids. Some also have added stanol esters
which are products of vegetable oils that can actually
lower serum cholesterol. The trade names in the USA
are Benecol, Smart Balance Plus, and Take Control. In
almost every supermarket in Europe or North America
you can ﬁnd margarine that has no transfatty acids.
Those that have stanol esters added are probably preferable.
o-3 (N3 ) Fatty Acids: the Fish Story
Epidemiologic studies
Greenland Eskimos rarely have coronary artery disease despite their high fat diet. They were found tohave low cholesterol, low triglycerides, and high HDLs.
Eskimos who repatriated to Dermark lost their beneﬁcial lipid proﬁle. The diet of the Greenland Eskimos is
low in saturated fat and high in a kind of polyunsaturated fat known as o-3 or N3 fatty acids. This is in contrast to the N6 fatty acids which are preponderant invegetable oils that contain linoleic acid such as corn,
soy and safﬂower oil.
Mortality from coronary artery disease and strokein a Japanese ﬁshing village where ﬁsh supplied a highamount N3 fatty acids was much lower than in a nearby
farming village where the consumption was only lessthan one-half of the farming village N3 fatty acids perday. In the Netherlands a 20-year study showed that
two ﬁsh dishes (even ﬂounder or cod) a week resulted
in a 50% less likelihood of dying from coronary disease
than those who ate no ﬁsh.19 This is surprising because
ﬂounder and cod have the lowest percent of N3 fatty
acids of all the ﬁsh. The fattier the ﬁsh, the more N3
fatty acids are present. The fatty ﬁshes are those fromcold ocean water; the highest being Norwegian sardines, Chinook salmon and Atlantic mackerel. The
lowest is haddock which has about one-ﬁfth of the N3
that is in salmon. Tuna has one-half of that in salmon.
This suggests that the Netherland study was successful
not because of the ﬁsh intake per se, but probably because at least two meals a week were devoid of meatand its saturated fat.
Three other studies: one Swedish (14 Years) and two
USA (20 years and 25 years) showed an inverse rela-133

tion between ﬁsh consumption and the risk of coronary
artery disease.20
The N3 fatty acids and sudden cardiac death
One study found that coronary occlusion and ventricular ﬁbrillation that occurs during reperfusion canbe prevented in animals by feeding them tuna ﬁsh oil.21
Patients with heart disease who had the highest levelsof N3 fatty acids had the lowest incidence of myocardial
infarctions and sudden death.22 In one study if they ate
fatty ﬁsh only once a week, there was a 50% decrease in
primary cardiac arrest. However, this did not include
fried ﬁsh or ﬁsh sandwiches.23,24
Fish oil
The commonest ﬁsh oils used in research contained
two N3 fatty acids, eicosapentanoic (EPA) and docosahexanoic acid (DHA). The commerical capsules usedhave usually been either Max EPA or Promega whichhave both EPA and DHA fatty acids. Humans canmanufacture N3 fatty acids from linolenic acid which isfound in some vegetable oils. There may be enoughlinolenic acid in a normal Western diet to equal one totwo ﬁsh oil capsules per day.25 The liver can adjust theconversion rate to equal what the body needs, thus wecan prevent overdosing with ﬁsh oils.
N3 fatty acids as antioxidants
Fish oil can decrease the oxidation products generated by the inﬂammatory cells which accompany
ischemic reperfusion. But ﬁsh oils themselves may beoxidized. Antioxidants such as vitamin E and vitamin C
can prevent ﬁsh oil oxidation. Fish oil feeding is a classical method of producing vitamin E deﬁciency in animals.26 Cod liver oil capsules usually come with a suboptimal amount of vitamin E added as an antioxidant.27
When concentrated N3 such as Max EPA is fed to animals no peroxides are produced, and so no antioxidants
are necessary.
N3 effect on platelets, thrombosis, and bleeding
Thromboxane from platelets causes vasconstriction,platelet aggregation and thrombosis. Prostacycline isderived from vascular endothelial cells and causes vasodilation and decreases platelet aggregation. N3 fatty
acids decrease thrombosis by decreasing the output ofthromboxane from platelets and increasing prostacycline and ﬁbrinolysis.28,29 Although only large doses ofﬁsh oils can decrease ﬁbrinogen levels and increaseﬁbrinolysis,30 even moderate doses of cod liver oil can

134

increase bleeding time.31 Long term ﬁsh oil feeding or ahigh intake of ﬁsh can increase bleeding time by producing platelet changes. These changes in Greenland
Eskimos are so marked that they bruise easily, haveprofuse nosebleeds and cerebral hemorrhages. They
usually often die of internal hemorrhage from moderate
injuries after falling into a hole in the ice.22,27 However, there have been no reports of bleeding or increased cerebral vascular hemorrhage in Japan ﬁshingvillages or in clinical trials with ﬁsh oil supplements.27
The inhabitants of a ﬁshing village in Japan showed alower blood viscosity.32 Many studies have shown thatﬁsh oil supplements can decrease whole blood but not
plasma viscosity suggesting that the N3 fatty acids makethe red blood cells more deformable. This would help
attenuate ischemia.32–34
One study suggested that the decrease in thrombosis
by N3 fatty acids is not due to a fall in thromboxane
decreased platelet aggregability35 but probably due tothe effect of N3 on tPA. tPA is a tissue plasminogenactivator, the inhibition of which would cause thrombosis. N3 can block the inhibition of tPA.36 N3 in large
doses can also cause a fall in antithrombin III.37
Selenium supplements have been known to prolong
bleeding time and low selenium levels are associatedwith an increased risk of coronary artery disease.38 Fishcontains selenium which is rare in other foods.
Fish oil and atherosclerosis
In The Greenland Eskimos myocardial infarction
was one-tenth that of the nearby Danes. In patientswith coronary artery disease those with higher levelsof N3 had fewer myocardial infarctions and sudden
death.22 A ﬁshing village in Japan had a lower incidence of myocardial infarction and strokes than the
nearby dairy farming village who also had one-third ofﬁsh had the N3 .34
Those Swedes who eat little or no higher incidenceof myocardial infarction and angina than those who atemuch ﬁsh.40 Fish oil fed to rabbits and two species ofmonkeys all of whom were placed on atherogenic diets
decreased the degree of aortic atheromas and had
smaller induced infarction size.39,40
Fish oils, cholesterol, trigicerides and HDL
Moderately high ﬁsh diet, i.e., fatty ﬁsh twice a week,
produced a non-signiﬁcant effect on cholesterol, LDL
and HDL. However, the triglycerides do decreasesigniﬁcantly.41–43 Although ﬁsh oil does not increasecholesterol much, it does prevent it from rising if thepatient has a very high cholesterol intake.44,45 In moststudies where ﬁsh oil did decrease LDL or cholesterol,the patients were also on a low saturated fat diet.6

Constant J: Oxidized cholesterol and trans-fatty acids

Some ﬁsh oil capsules can actually increase cholesteroland LDL because they contain relatively large amountsof cholesterol and saturated fats. Other capsules whichcontain no cholesterol and only a small amount ofsaturated fats may decrease LDL. Therefore you must
look at the ingredients to know the effect of ﬁsh oils
on lipids.41,46 In studies using very fatty ﬁsh such as
mackerel and sardines for as little as two weeks, there isa depression of triglycerides and an elevation of HDL.
The conclusion must be that ﬁsh oil capsules can only
be recommended for severe hypertriglyceridemia witha danger of pancreatitis. Otherwise, only increasing ﬁshintake is recommended.47
N3 fatty acids’ inﬂammation, allergy and vasospasm
Interleukin 1, tumor necrosis factor, and leukotriene
4 are stimulated by inﬂammation. All three are inhibited by N3 fatty acids.22 N3 fatty acids also increase theresponsiveness of T lymphocytes to inﬂammation anddecrease their adherence to neutrophils. Some of theadvantages to the above are that they may decrease theinﬂammatory response to rheumatoid arthritis,48 andmay beneﬁt patients with psoriasis and atopic dermatitis.49 The nephrotoxicity of cyclosporine decreased withﬁsh oils.50
Primary Raynaud’s symptoms completely resolvedin 50% of patients over 12 weeks of ﬁsh oil ingestion.
The other 50% could keep their hands in cold water
50% longer. Secondary Raynaud patients received
no help from ﬁsh oils.51 Fish oils are also effective
for refractory migraine.52 However, cardiac allographs
in rabbits given ﬁsh oil develop accelerated coronary
atherosclerosis.53
Fish and ﬁsh oils on blood pressure
A daily intake of fatty ﬁsh, i.e., mackerel, for two
weeks can diminish systolic pressure by about 10
mmHg.54 However, ﬁsh oil had more questionableeffects in other studies. In one study ﬁsh oil supplements had no effect on blood pressure55 while in another study large doses of Max EPA lowered the bloodpressure.34 In diabetic patients on hemodialysis low
dose ﬁsh oils can lower systolic blood pressure by about
10 mmHg.56–58 Cod liver oil may be more speciﬁc forblood pressure because even one or two capsules daily(which will yield about 100 international units of vitamin D) can produce a modest fall in blood pressure.31
In vegetable oils the N3 polyunsaturated fats areof three types: 1. Twelve carbon chains as in alphalinolenic acid, 2. Twenty carbon chains as in EPA, 3.
Twenty-two carbon chains as in DHA. The alpha linolenic acid comes from plant oils, especially canola, ﬂaxseed, soy bean, walnut and evening primrose oil.

Keio J Med 2004; 53 (3): 131–136

Humans can convert a portion of alpha linolenic acid to
EPA and DHA.59 If enough alpha linolenic acid isconsumed, the body will form enough EPA and DHA
without the need for ﬁsh oils.60 Even in the normal diethumans can get enough linolenic acid to produce
enough N3 to equal one to two ﬁsh oil capsules daily.25

135

20.

21.

22.

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