Full text of DOI:10.1002/1438-9312(200107)103:7<483::AID-EJLT483>3.0.CO;2-Q

Eur. J. Lipid Sci. Technol. 103 (2001) 483–489
483
Riitta Freese
Low-erucic acid rapeseed oil and platelet function
Division of Nutrition,
University of Helsinki,
Finland
Keywords: Rapeseed oil, canola oil, blood platelets, oleic acid, linoleic acid, α-lino-
lenic acid.
realized decades ago. Diet FA composition is not only an
important determinant of serum cholesterol concentra-
tions, but it also influences hemostatic factors of which
platelets have been studied most frequently.
Platelet function and CHD
The classical risk factors – elevated serum cholesterol,
high blood pressure and tobacco smoking – only partly
predict coronary heart disease (CHD) risk [1, 2]. Imbal-
ance in the function of hemostatic factors may account for
part of the morbidity. Hemostasis is the delicate process
which regulates the fluidity of blood. It is the result of in-
terplay of four components: platelets, blood coagulation
system, fibrinolytic system, and endothelium. These form
a network by interacting with each other. The physiologi-
cal role of this system is to arrest bleeding and promote
wound healing. However, imbalance in hemostasis may
contribute to atherosclerosis and thrombosis.
The mechanisms by which dietary FAs can modulate
platelet function may be either direct or indirect. Platelets
are surrounded by plasma membrane and they have in-
tensive intracellular membrane systems like the dense
tubular system. The phospholipid FA composition in these
membranes can be modified by dietary FAs. Phospholipid
FA composition may have effects on the physicochemical
properties of the cell membranes which can cause alter-
ations in receptor activities and intracellular signalling.
The function of receptor proteins and enzymes linked
to the membrane are modified by membrane FAs [9, 10].
Phospholipid FAs are also the precursor pool for
eicosanoids. Thromboxane A2 (TXA2), synthesized from
arachidonic acid (C20:4 n-6) by cyclooxygenase, is one of
the most important activators of platelet aggregation and
its synthesis can be modified by dietary FAs, either due to
an altered precursor pool, competition for or inhibition of
cyclooxygenase [11]. Alterations in the precursor FA pool
may also affect platelet function via lipoxygenase prod-
ucts [12]. Indirectly dietary FAs can affect platelets via
alterations in serum lipoprotein concentrations [6].
Platelets are the smallest cellular particles in blood. They
form the primary plug which arrests bleeding from a
wounded blood vessel. In this process platelets are acti-
vated by adhesion to exposed subendothelial molecules.
Activated platelets change their shape, spread on the site
of injury, and release their granule contents. Platelet-
platelet interactions lead to formation of platelet aggre-
gates which temporarily seal the break in the blood vessel
[3–5]. Eicosanoids synthesized in platelets as well as
molecules secreted from platelet granules have several
effects on cells in the platelet environment (e.g. endothe-
lial cells, monocytes and other platelets) and on the blood
coagulation and fibrinolysis cascades [3, 6]. Platelets may
participate in atherosclerosis by several mechanisms and
play a central role in thrombosis [see 6–8]. The impor-
tance of platelet function in the development and outcome
of human CHD and stroke is demonstrated by the effec-
tiveness of antiplatelet drugs like aspirin and antagonists
of the platelet fibrinogen receptor in both primary and sec-
ondary prevention of thrombotic events [6, 8].
In dietary studies the different aspects of platelet function
and activation have been studied by several ways, sum-
marized in Fig. 1. Of all tests, ex vivo platelet aggregation
has been used most frequently.
After the reports showing low ex vivo platelet aggregabili-
ty and long bleeding times in Greenland Eskimos [13],
many diet-related hemostatic studies have been centered
on the effects of fish oils and long-chain n-3 FAs eicosa-
pentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic
acid (C22:6 n-3, DHA) on platelet function. A general out-
come of the fish or fish oil studies has been a prolongation
of bleeding time and decreased platelet TXA2 production,
findings interpreted to indicate decreased thrombosis ten-
dency. The results from ex vivo platelet aggregation stud-
ies are controversial. However, in the majority of the well-
controlled studies platelet aggregation in response to var-
ious activators was either decreased or not changed by
Dietary fatty acids and platelet function
The importance of diet, and in particular dietary fatty acid
(FA) composition, in the development of CHD has been
Correspondence: Riitta Freese, Division of Nutrition, P.O. Box
27 (Viikki, Latokartanonkaari 9), FIN-00014 University of Helsin-
ki, Finland. Phone: +358-9-191-58202, Fax +358-9-191-58269;
e-mail: riitta.freese@helsinki.fi
© WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
0931-5985/2001/0707-0483 $17.50+.50/0

484
Freese
Eur. J. Lipid Sci. Technol. 103 (2001) 483–489
fish oils or long-chain n-3 FAs [14, 15]. Less information is
available on the effects of the FAs found in vegetable oils
on platelet function.
sociated with thrombosis or cardiac arrhythmias. Plasma
ALA was inversely associated with myocardial infarction
and cardiac death in the study [21, 22]. Although the re-
sults indicate that rapeseed oil can have favorable ef-
fects, one has to keep in mind that the experimental and
control groups also differed in their intake of bread,
legumes, fruit, and vegetables.
Rapeseed oil and platelet function
Very low-erucic acid rapeseed oil (erucic acid <1% of
FAs) or canola oil are low in saturated fatty acids (SFA),
rich in oleic acid (C18:1 n-9, OA), and contain substantial
amounts of both the essential FAs linoleic (C18:2 n-6, LA)
and α-linolenic acid (C18:3 n-3, ALA). When rapeseed oil
replaces other fat sources in the diet, the total dietary FA
intake is modified accordingly. Based on epidemiological
data [16–18] and experimental studies focusing on
lipoprotein metabolism [19, 20] this kind of dietary FA
composition is considered to prevent CHD.
In addition to FAs, rapeseed oil contains also other com-
pounds which may affect platelets, e.g. phytosterols [23]
and γ-tocopherol [24]. Thus far, however, the human stud-
ies related to platelet function have been focused on FAs.
When the specific effects of oils or FAs are studied, one
has to be careful not to change the total amount of fat or
other nutrients in the diet. Thus, the studies focusing on
the effects of certain edible oils or FAs are principally
comparisons between oils or FAs and no “absolute” ef-
fects can be studied. In the case of rapeseed oil the com-
parisons have most often been carried out with sunflower
oil. No comparisons e.g. with another rich source of OA,
olive oil, have been published thus far.
The Lyon Diet Heart study was a secondary prevention
trial in which the diet of the experimental group was
changed in the direction of a Mediterranean diet (re-
viewed in this special issue, see p. 490). The dietary mod-
ifications were carried out by increasing the consumption
of vegetables, fruit, legumes and bread and by replacing
saturated fats by a canola oil-based margarine and using
olive and canola oils for salads and cooking [21, 22]. The
survival curves for cardiac death of the experimental and
control groups separated early (under 1 year) in favor of
the experimental group. The fast protective effect of the
experimental diet is most probably not due to decreased
atherogenesis, but rather due to alterations in factors as-
Rapeseed oil vs. sunflower/safflower oil
One of the earliest interventions on the effects of veg-
etable oils on platelet function is a study of Renaud et al.
[25] in which the SFA-rich habitual diet of Moselle farmers
was modified by replacing butter and cream with either
margarine based on sunflower oil or rapeseed oil for one
year. Platelet aggregation in response to ADP, collagen
Fig. 1. Events related to platelet activation and measurements of platelet activation/function used in dietary studies.

Eur. J. Lipid Sci. Technol. 103 (2001) 483–489
Rapeseed oil and platelet function
485
and thrombin decreased in both groups. The dietary mod-
ifications tended to decrease total fat intake from the
habitual level, which may have had some effect on the
results [25].
at the end of the 8-week study period. In our highly-con-
trolled cross-over dietary intervention study [28], a diet
with rapeseed oil did not differ from that with sunflower oil
in its effects on platelet aggregation to ADP. Both diets in-
creased platelet aggregation to ADP and collagen as well
as TXB2 production in collagen-activated platelets in com-
parison with baseline dairy fat diet [28]. These three stud-
ies suggest thus that rapeseed/canola oil diets rich in OA
+ ALA and sunflower/safflower oil diets rich in LA do not
differ from each other in their effects on platelet function.
In smaller-scale controlled settings the effects of rape-
seed/canola oil diets rich in OA+ALA and sunflower or
safflower oil rich in LA on platelet function have been
compared in three studies (Fig. 2) [26–28]. In the cross-
over study of McDonald et al. [26] canola oil increased
bleeding time and sunflower oil decreased the concentra-
tion of the metabolite of the vasoconstrictive eicosanoid
TXA2, thromboxane B2 (TXB2) in blood collected during
the determination of bleeding time in comparison with a
high-SFA baseline diet. The effects of the oil diets did not
differ. Kwon and colleagues [27] carried out a parallel di-
etary study with canola and safflower oil and found that
both diets slightly decreased platelet aggregation to colla-
gen in whole blood. The effects of the diets did not differ
Rapeseed oil vs. saturated fatty acids
Although it is feasible to think that increased consumption
of rapeseed oil could replace SFA in the diet, controlled
studies focusing on such a comparison have not been
carried out. The comparisons between the run-in diets
rich in SFA and the rapeseed oil diets in the above-men-
tioned studies give conflicting results by indicating de-
creased [26, 27] or increased [28] platelet activation after
the experimental oil diets. The differences in the SFA
intakes during the experimental diets (5–7 vs. 12% of en-
ergy, en%) may partly explain the discrepancy [26–28].
Also the fact that the studies were designed to compare
the two oils instead of SFA and oils may complicate the
results.
In the intervention of Hunter et al. [29] controlled experi-
mental diets rich in stearic acid, OA or LA did not differ in
respect of platelet aggregation, membrane fluidity or the
binding of anti-aggregatory eicosanoid, prostaglandin E2
to platelet membranes.
Oleic acid vs. linoleic acid
Because rapeseed oil is a good source of OA while many
other vegetable oils are good sources of LA, it is of inter-
est to compare the effects of these two main unsaturated
FAs in our diet. In controlled settings these kind of studies
can be carried out e.g. by using high-OA and high-LA sun-
flower oils which contain very small amounts of ALA.
Three published and one unpublished (R. Freese, unpub-
lished results) study show that controlled high-OA and
high-LA diets both low in ALA do not differ in their effects
on platelet function [29–31]. The fatty acid composition of
these diets is presented in Fig. 2.
Fig. 2. Dietary fatty acid composition (% of energy) of ex-
perimental diets in platelet function studies comparing
low-erucic acid rapeseed/canola oil and other vegetable
oils or relevant fatty acids. Data partly calculated by the
author. SFA – saturated fatty acids, MUFA – monounsatu-
rated fatty acids, OA – oleic acid, LA – linoleic acid, ALA –
α-linolenic acid, CAN – canola oil, SO – sunflower oil,
SFO – safflower oil, RO – rapeseed oil, HOSO – high-OA
sunflower oil, OO – olive oil, SBO – soybean oil, FSO –
flaxseed oil. References: McDonald [26], Kwon [27],
Mutanen [28], Freese (a) [36], Chan [35], Burri [30],
Turpeinen [31], Hunter [29], Freese (b) (unpublished
results).
α
-Linolenic acid
Recent findings from two cohort studies [32, 33] support
the hypothesis that ALA may exert a protective role on its
own with regard to myocardial infarction or coronary mor-
tality. The correlation analyses of the Lyon Diet Heart
study [34] also indicate that plasma ALA is associated
with protective effects. The effects of ALA on platelet func-

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Freese
Eur. J. Lipid Sci. Technol. 103 (2001) 483–489
tion have been investigated using various experimental
designs.
duced aggregation remained unchanged. Sunflower oil
had no effects on platelet aggregation. Unfortunately,
comparisons between the two oils were not reported [42].
In a parallel intervention among vegetarian men moder-
ate (2.0en%) or high (6.3en%) intake of ALA after a low-
ALA diet (0.6–0.8en%) were not associated with differ-
ences in platelet aggregation or urinary 11-dehydro-TXB2
excretion [43].
The effects of ALA in rapeseed oil on platelet function
have been examined in two intervention studies. Chan et
al. [35] studied the effects of isocaloric diets with different
amounts and ratios of LA to ALA on bleeding time and on
the formation of TXB2 in blood lost during the determina-
tion of bleeding time (bleeding time blood collected). The
ratio of LA to ALA varied in the diets from 2.7 to 27.4. No
significant differences in bleeding time or TXB2 formation
were seen between the diets. However, when comparing
two diets with similar OA intake (for composition see
Fig. 2), bleeding time tended to be longer (5.3 vs. 5.0 min)
and TXB2 production lower (3.8 vs. 5.0 µg/l) after the
canola oil diet which contained more ALA than a diet
based on sunflower oil+olive oil [35]. We used rapeseed
oil and high-OA sunflower oil in a partly controlled cross-
over study to compare the effects of two high-OA diets dif-
fering only in their LA to ALA ratio (2.8 an 28, respective-
ly) (Fig. 2) [36]. In this study, platelet aggregation at the
end of the rapeseed oil diet did not differ from that at
baseline (habitual diet), but sunflower oil diet enhanced
aggregation to ADP, collagen and thrombin. Platelet ag-
gregation responses were lower during the rapeseed oil
diet than during the sunflower oil diet [36]. These results
indicate that dietary LA to ALA ratio or the absolute in-
takes of ALA and LA affect platelet function if intakes of
SFAs and OA are kept constant.
ALA is a n-3 FA and it can be elongated to EPA in the
body. It is therefore of interest to see whether ALA differs
from the longer-chain n-3 FAs in its effects on platelets.
When the effects of ALA from linseed oil and EPA+DHA
from fish oil were compared in a controlled parallel sup-
plementation study [44] no differences between the two
treatments were seen in bleeding time, platelet aggrega-
tion to collagen or thromboxane-analogue I-BOP, or in
the urinary excretion of β-thromboglobulin or 11-dehydro-
TXB2 [44]. ADP-induced aggregation was, however, en-
hanced during fish oil feeding, an effect not seen with lin-
seed oil. Different results were obtained by Adam et al.
[45] who compared the effects of ALA and EPA in formula
diets with 4en% LA in female subjects. Bleeding time
lengthened and platelet aggregation to ADP and collagen
decreased only with very high ALA intakes (12 or
16en%). Similar effect was obtained already with 1.7en%
EPA.
In summary, the data concerning the effects of ALA on
platelet function are contradictory. There are some indica-
tions of favorable effects but whether ALA can have an
independent role or whether its possible effects are medi-
ated via elongation to EPA is still not resolved.
A controlled long-term study carried out in 1960’s and 70’s
showed lower platelet ex vivo aggregation at the end of a
long-term high-polyunsaturated fat (PUFA) diet (16en%
LA) in comparison with a high-SFA diet (4en% LA) [37,
38]. The treatment effect has been attributed mainly to LA
[38] although the high-PUFA diet was carried out by re-
placing habitual milk and margarine with soybean oil-filled
skim-milk and soybean oil-based margarine and was thus
also rich in ALA [39, 40].
Dietary ratio of n-6 and n-3 polyunsaturated
fatty acids
As already pointed out, there are data from intervention
studies that indicate that dietary LA to ALA ratio may
modulate platelet function in humans [36]. These results
are at least partly in line with those from Salo et al. [46]
who studied the correlations between platelet aggregabil-
ity with FAs in platelets, plasma lipids, and adipose tissue
in middle-aged Finnish men. ADP-induced platelet aggre-
gation was inversely correlated with platelet n-3 FAs, n-3
to n-6 ratio, and EPA to AA ratio while positive associa-
tions were found between platelet aggregation and LA in
plasma triglycerides, cholesterol esters, and in adipose
tissue. The authors concluded that the positive correlation
between platelet function and LA in tissues may be due to
imbalance in the dietary n-6 to n-3 ratio. Thus attention
should be paid to the n-6 to n-3 ratio when SFAs are sub-
stituted with PUFAs [46].
The effects of ALA on hemostatic factors have also been
investigated by supplementing linseed or flaxseed oil to
subjects whose dietary intake has been controlled. In
such studies the intake of ALA can be increased to a
clearly higher level than in rapeseed oil-based mixed di-
ets. Kelley et al. [41] saw no changes in bleeding time
when a low-fat (23en%) baseline diet was supplemented
with flaxseed oil (ALA 6.3en%). Flaxseed or sunflower oil
(40g/day) was supplemented to a basal low-fat diet in a
study of 10 male subjects [42]. The flaxseed oil supple-
mentation increased n-3 FA intake (mainly ALA) from 0.4
to 8.5en% and sunflower oil supplementation increased
n-6 FA intake (mainly LA) from 2.7 to 11.7en%. Collagen-
induced aggregation in whole blood (cell-counting
method) decreased in the flaxseed oil group, but ADP-in-
In the Lyon Diet Heart study [22] the substitution of SFAs
by fatty acids from canola and olive oil together with an in-

Eur. J. Lipid Sci. Technol. 103 (2001) 483–489
Rapeseed oil and platelet function
487
creased consumption of fish in the experimental group
was reflected not only in plasma fatty acids but also in
platelet phospholipid fatty acids. There was a significant
decrease in plasma and platelet n-6 to n-3-ratio in com-
parison with the control group [22]. The ratio of total n-3 to
n-6 FAs in the diet was inversely related to cardiovascular
mortality in the Multiple Risk Factor Intervention Trial [18,
47]. These results may indicate that, at least to a certain
level, increasing the relative intake of n-3 FAs may reduce
coronary risk. The effects of dietary n-6 to n-3 ratio on
platelet function should be studied further.
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