Effect of dietary cholesterol content on plasma cholesterol levels
Fat intake is well known to influence the levels of plasma cholesterol
and certain fats promote marked increases in cholesterol levels and hence,
are positive factors in contributing to atherosclerosis risk. Dietary sources
of cholesterol have a minor impact on cholesterol, particularly when intake
of cholesterol rich foods provides less than 200 mg of cholesterol in the
diet. 
As shown in Figure 1 (dietchol.gif), a threshold level of cholesterol intake in the range of 100 - 200 mg/day represents the level at which the resulting plasma levels of cholesterol remain within the normal range for people without a genetic predisposition for elevated plasma lipoprotein levels.
Beyond a 200 mg daily intake the change in plasma levels increases sharply
and reaches maximum, or "ceiling" levels with intakes beyond
400 mg/day. This represents the maximum rate of cholesterol assimilation
by the intestines and processing by the liver. Decreased rates of uptake
and increased biliary clearance accounts for elimination of cholesterol
at higher intake rates. Dietary cholesterol generally increases the levels
of chylomicrons and chylomicron remnants (also
triglyceride rich lipoproteins), and as expected, increases hepatic cell
cholesterol content. The consequences of this are that there is decreased
liver cholesterol synthesis in normal individuals, compensated by increased
biliary excretion to lessen hepatic cholesterol. Coordinately, there is
a reduction in hepatic LDL receptors which results in less clearance of
plasma LDL by the liver and elevated levels of plasma LDL, the major carrier
of plasma cholesterol. The consequences of this are that plasma cholesterol
levels tend to remain elevated with increased deposition of cholesterol
into artery walls (30 Kb) and production of atherosclerotic
plaques. A coronary angiogram (30 Kb) can be used to visualize the vessels that have significant
narrowing.
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The influence of polyunsaturated vs saturated fats
on plasma cholesterol
Intake of fat together with cholesterol will influence the plasma levels
of cholesterol with a clearly different effect for saturated
vs unsaturated fats. This effect of fats extends beyond the influence
on dietary cholesterol since the type of fat also influences endogenous
cholesterol production and resulting plasma levels. 
Figure 2 (fat_chol.gif 11Kb) compares the effects of diets enriched in three types of fatty acids on the plasma cholesterol levels after 10 weeks of feeding. In individuals with low plasma cholesterol (< 150 mg/dL) there is little difference in effect for diets enriched in palmitic acid (saturated - 16:0) vs oleic acid (monounsaturated - 18:1) vs linoleic acid (polyunsaturated - 18:2). For individuals with starting plasma cholesterol of 200 mg/dL, a diet enriched in saturated fat causes elevated cholesterol compared to a diet of unsaturated fatty acids. Beyond plasma levels of 200 mg/dL, the strong cholesterol raising effect of saturated fat becomes clearly apparent, while the polyunsaturated and monounsaturated fats appear to be about equally suppressive towards elevations in cholesterol levels over the 10 week period. The suppressive effect of unsaturated fats can also be revealed by examining the plasma levels of cholesterol produced on the basis of a diet consisting of various percentages of calories derived from dietary polyunsaturated fats.
Figure 3 (lin_chol.gif 3.2Kb) shows that as the amount of linoleic
acid in the diet approaches 5% of total fat calories there is a sharp reduction
in the plasma cholesterol levels with maximum reduction taking place at
10% total fat calories or greater. Moreover, switching from diets rich
in polyunsaturated fats to diets rich in saturated fats causes a marked
increase in plasma cholesterol levels and in LDL cholesterol and the opposite
effect is produced when the diet is switched back to one rich in polyunsaturated
fats. This favorable effect of unsaturated fats has been demonstrated for
the fish oils which represent a popular form of cholesterol lowering "heart
smart" polyunsaturated fats. Fish oils, also known as w-3 fatty acids,
are hypolipidemic, ie. they decrease the levels of plasma lipoproteins
in general, and in turn lower plasma cholesterol levels.
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Cardiovascular disease-related deaths and fat intake
A strong positive correlation has long been known for cardiovascular-related
deaths and intake of total fats, however, this relationship only remains
if fats are considered in terms of being saturated and cardiovascular deaths
categorized as related to atherosclerotic lesions. Despite the cholesterol
lowering effects of unsaturated fats, the trend for increased risk of cardiovascular
disease remains in the United States. The epidemiological data, combined
with clinical trials indicates that factors other than consumption of fats
and plasma levels of cholesterol have a strong influence on the progression
of atherosclerosis. A widely held view is that modification of lipoprotein
structure, particularly of LDL, has a strong impact on atherogenic potential,
augmenting the effects of high plasma cholesterol. The inability of polyunsaturated
fats to lower atherosclerosis risk in proportion to the lowering of cholesterol
levels may be linked to the propensity of polyunsaturated fatty acid enriched
lipoproteins to undergo oxidative modification. This modification in structure
and composition alters the properties of LDL from the standpoint of its
uptake and processing by vascular cells and in terms of its immunological
characteristics. These features are believed to account, in part, for the
rapid and unregulated uptake of the lipoproteins by macrophages and endothelial
cells leading to foam cell formation and elaboration of the fatty streak.
The importance of antioxidants is most apparent from the standpoint of
their ability to inhibit oxidation of unsaturated lipids and suppress lipoprotein
oxidation. This inhibition is strongly associated with the ability to inhibit
various biochemical processes associated with atherosclerosis lesion development
and with a lower incidence of cardiovascular disease. The protective effects
of certain antioxidants, most notably vitamin E, has been documented in
several epidemiological and clinical trials over the last decade.
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Intake of foods and/or supplements with antioxidant
vitamins and its impact on CHD
The tendency of unsaturated lipids to undergo oxidation is related to the number of double bonds in the fatty acid molecule. Each additional double bond after the initial double bond found in monounsaturated fatty acids increases susceptibility to peroxidation by forty fold while a fatty acid with one double bond is about fifty times more susceptible to peroxidation than a saturated fatty acid. Hence, a fatty acid with three double bonds is oxidized eighty times as readily as a fatty acid with only one double bond. This oxidative susceptibility of fatty acid is reflected by the tendency of various oils to oxidize.
Figure
4
Figure 4 describes the stability of major types of oils consumed throughout
the world based on their shelf life before rancidification, ie. oxidative
deterioration. Safflower oils, consisting largely of triglycerides containing
polyunsaturated fatty acids is least stable whereas olive oil, rich in
monounsaturated fats, is most stable to oxidation. These comparisons are
only valid, of course, when the oils are devoid of their natural antioxidants
(found only in highly refined oils).
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The fat soluble vitamins - the special relationship
to fat intake
In their natural (or virgin) state, these oils contain a compliment
of antioxidants, key among which are the tocopherols (vitamin E). Indeed,
the content of tocopherols in unprocessed oils is proportionate to the
amount of polyunsaturated fatty acids, natures way of preserving the oils.
Ordinarily, consumption of polyunsaturated fatty acid enriched oils provides
a proportionate intake of lipid associated (lipophilic or fat soluble)
antioxidants. However, this proportionality breaks down when more refined
oils are consumed and may not apply to other lipid rich foods or foods
prepared or fortified with polyunsaturated fats. It is widely held that
the major natural sources of lipophilic antioxidants are vegetable oils
with all other food sources providing far less amounts of major antioxidants
such as tocopherols, carotenoids and polyphenolic compounds. Thus, it is
possible to ingest the recommended daily allowance (RDA) levels of lipophilic
antioxidants, such as tocopherols by consuming three helpings of fresh
mixed vegetables and/or natural vegetable oils per day, however, levels
much above the RDA are difficult to consume unless large amounts of vegetable
oils are ingested. This is not a desirable way to obtain the fat soluble
antioxidants as the caloric intake of such foods is enormous, leading to
rapid weight gain.
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