Olive Oil_Fact Sheet 04

Scientific Basis for Olive Oil, Monounsaturated Fatty Acids, Antioxidants, and
LDL Oxidation
Introduction
Low density lipoprotein (LDL) is the major cholesterol carrying particle in plasma.
There is wide agreement that increased levels of LDL are causally related to
atherosclerosis and the development of coronary heart disease (CHD). There is
increasing evidence that LDL in its native state is not harmful, but when it becomes
altered by a process called oxidation, it becomes a real threat within the arterial wall.
The susceptibility of LDL to become oxidised is determined by both internal
(endogenous) and external (exogenous) factors. Among the latter, nutritional factors
are extremely important, particularly the types of fatty acids and antioxidant vitamins
in the diet. This Fact Sheet reviews the mechanisms of LDL oxidation and the role of
nutritional factors in its prevention.
LDL oxidation (in atherogenesis)
Half of the cholesterol in the blood is carried in LDL which is a spherical fat-protein
particle, consisting of an outer monolayer containing the protein apolipoprotein B
(apo B) which surrounds a core containing triglycerides and/or cholesterol esters
(non-polar fats). One LDL particle contains about 3600 fatty acids, half of which are
polyunsaturated fatty acids (PUFAs). LDL also contains antioxidants, the most
important being (alpha) a-tocopherol (vitamin E).
LDL oxidation (peroxidation) is a chain reaction initiated by free radicals, a mainly
reactive oxygen species. PUFAs are very susceptible to lipid peroxidation and
breakdown to a variety of byproducts which bond to LDL apo B. LDL can be
oxidised in vitro by exposing them to smooth muscle and endothelial cells,
macrophages (derived from large cells called monocytes), or metal ions (Copper or
Iron). LDL oxidation in vivo is poorly understood, and it may be reduced by the
presence of antioxidants in plasma such as ascorbic acid (vitamin C). It is therefore
likely that LDL oxidation occurs in the artery wall rather than in the blood stream.
Vitamin E-enriched LDL is significantly more difficult to oxidise. LDL oxidation is
likely to occur when the antioxidant defences are down, especially when atocopherol is depleted.
LDL oxidation and atherosclerosis
The essential step in the development of atherosclerosis begins as LDL filter into the
arterial wall and become entrapped in the intima where they may undergo oxidative
modification. Macrophages (cells formed when monocytes permeate the artery wall
from the bloodstream) avidly take up this modified LDL, which contributes to their
transformation to foam cells. The accumulation of foam cells in the intima results in
the formation of fatty streaks. These do not produce significant obstruction of the
artery, but they are gradually converted into fibrous plaques by a mechanism similar
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to scar formation. These, in turn are gradually transformed into atherosclerotic

lesions which underlie most clinical events.
Olive oil and LDL oxidation
There are several potential ways by which dietary fatty acids may influence the
oxidation of LDL. The amount and composition of dietary fats affects the amount of
LDL in the artery wall. Replacement of dietary saturated fats with monounsaturated
fats (MUFAs) or PUFAs lowers LDL levels, thereby decreasing the amount of LDL
entering the artery wall and so reducing the amount (and composition) available for
oxidation. Because of its high MUFA content, olive oil appears to protect against
LDL oxidation (see Section entitled "Effects of dietary fatty acids on LDL
oxidation"). Olive oil may afford additional protection by supplying LDL with potent
antioxidants, such as vitamin E and phenolic compounds, which will be described
later.
Effects of dietary fatty acids on LDL oxidation.
Various studies have investigated the role of MUFA and PUFA in reducing
susceptibility to LDL oxidation. Studies in the rabbit model show that oleate-rich
(oleic acid is the predominant fatty acid of olive oil) LDL is remarkably resistant to
oxidation. Dietary studies in humans support this finding and show that the linoleic
acid (the major dietary PUFA which is predominant in vegetable oils) content of LDL
is strongly related to the rate and extent of oxidation, with LDL oxidation rate being
increased during the PUFA diet compared to the MUFA diet. Further studies have
tried to address whether such effects are due to PUFA caused enhancement or a
MUFA caused inhibition of LDL oxidation. Dietary supplementation of olive oil
suggests that the linoleic acid content of LDL is reduced and that there is less cellular
uptake by macrophages and reduced susceptibility of LDL to oxidation.
Pro-oxidant activities of dietary fatty acids
Certain dietary fatty acids can change the monocyte membrane composition, thereby
enhancing free radical production, and producing pro-oxidant effects. A study
compared the effects of dietary supplementation with MUFA, and n-3 (found in fish
oils) or n-6 (linoleic acid) PUFA on superoxide anion, (a free radical), generation in
monocytes and macrophages. Only n-3 fatty acids reduced free radical production,
while the monocytes from the MUFA or n-6 PUFA showed no change or increased
levels. The mechanisms for this are unknown, and these results have not been
reproduced. More studies on the role of different fatty acids on cellular pro-oxidant
activity are needed; however MUFA enriched cells are less susceptible to oxidative
damage (in direct comparison to n-6 PUFA) probably as a result of cell membrane
fatty acid composition.
Antioxidant constituents of olive oil
Oxidative stress may play an important role in the development of several chronic
diseases such as CHD and cancer. The possibility that dietary antioxidants, such as
those found in olive oil, may protect against LDL oxidation has led to
epidemiological and intervention studies.
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Vitamin E (a-tocopherol)
Epidemiological studies have shown that high doses of vitamin E over at least two
years, significantly reduce CHD risk (31-65%). Short term studies using lower doses
have not shown this however. This is also the finding from the majority of
randomised intervention trials with vitamin E. But these trials were not designed to
assess cardiovascular end-points, their treatment duration was too short, and they
employed sub-optimal doses of the vitamin. Several on-going large scale trials may
help to resolve this issue. To date only the Cambridge Heart Antioxidant Study
(CHAOS) has been completed. This double-blind, placebo-controlled study of 2000
patients with established CHD, reported that high-dose vitamin E supplementation
significantly reduced the incidence of non-fatal heart attacks but had no impact on
cardiovascular or all-cause mortality.
Intervention trials have been criticised on the grounds that a few years treatment may
be inadequate to demonstrate benefit of antioxidants, and that antioxidant
supplementation may be needed over 20 or more years, before any clinical benefit
ensues.
Several studies have demonstrated that vitamin E supplementation results in
increased levels of a-tocopherol both in plasma and in LDL particles. Furthermore
LDL showed a higher resistance against in-vitro oxidation compared to the pre-study
baseline. The degree of resistance was closely related to the vitamin dose received.
Oxidative resistance is also higher in non-supplementing individuals who have
higher plasma levels of a-tocopherol, than those with naturally occurring lower
levels.
Phenolic compounds
In addition to vitamin E, olive oil contains a variety of constituents which are
responsible for its unique taste. Among these (comprising 2-3% of unrefined oil) are
phenolic compounds, which are also found in vegetable foods and are biologically
extremely important. These include simple phenols and phenolic acids e.g.
flavonoids. These play a vital role to scavenge and detoxify free radicals, and can
provide increased resistance to LDL oxidation and inhibit lipid peroxidation.
Phenolic compounds have additional anti-inflammatory and anti-haemorrhagic
effects.
Health benefits derived from potent phenolic flavonoids, also present in fruits and
beverages such as tea and wine, have been observed in the Seven Countries and the
Zutphen Elderly studies, where the average intake of flavonoids was inversely and
independently correlated with CHD mortality. Although, more studies are needed to
confirm the cardioprotective properties of flavonoids.
Summary and conclusions
There is extensive evidence that oxidative modifications of LDL play a crucial role in
atherogenesis. Oxidation of LDL begins with peroxidation of PUFA in the LDL
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particle. Thus the LDL fatty acid composition undoubtedly contributes to LDL
oxidation. LDLs fatty acid composition (and therefore, susceptibility to oxidation) is
influenced by dietary fatty acids. Diets rich in MUFA render LDL more resistant to
LDL oxidative modification compared with diets rich in PUFA such as linoleic acid.
In addition, the fatty acid composition of cell membranes is diet-dependent, and
MUFA-rich diets also lead to a higher MUFA content of cell membranes and
therefore higher cellular resistance to oxidative damage.
Dietary antioxidants such as vitamins E and C, flavonoids etc, provide additional
protection against oxidative stress. Recent studies indicate that not only a-tocopherol,
but also phenolic compounds in olive oil may inhibit LDL oxidation and reduce risk
of atherosclerosis. Further research is needed to fully elucidate the mechanisms of
action of phenolic compounds in vivo.
Much of the focus of attention of the Mediterranean diet has been on the
cardiovascular benefits associated with a reduced saturated fat intake, and its high
MUFA levels, as well as complex carbohydrate and fibre. Current evidence suggests
that additional components, in abundance in the Mediterranean diet, namely
antioxidants derived from fruit and vegetables, but additionally, from olive oil may
contribute to protection from CHD, cancer and other chronic disorders.
High intakes of MUFA from olive oil consumption in the Mediterranean diet, may
combine the advantages of lowering cholesterol and decreasing LDL and cell
susceptibility to oxidation.