Step/zen
M Prescott
The fish
finding
in some
products
rosis
were
epidemiologic
correlated
led to investigations
(1-3).
The
bosis
central
ofthe
role
suggested
studies
with
risk
mechanism
ofplatelets
the hypothesis
that
a lowered
diets
by which
that
in
this occurs
in atherosclerosis
and
a fish-enriched
ticularly the fatty acids from fish, ease by altering platelet function
high
of atheroscle-
diet,
par-
prevented cardiovascular dis( I , 3). Other epidemiologic
oil on platelets
might
be due
acid (EPA), and suggested that the to alterations
fatty
with
acids
platelet that
alter
isolated
platelet
aggregation eat
diets
has been
no clear
in vitro
but
Additionally,
secretion
were
shown
in different
fatty
acids.
demonstration
ofa
been more extensive analyses showed that there is a modest
platelet
aggregation
when
subjects marine platelet
were on diets containing moderate oils ( 1 , 3, 4). There is also evidence function in vivo. Platelet turnover,
thesis, and fl-thromboglobulin viduals with atherosclerosis 8). However, each of these served only Increasing inhibit
for relatively concentrations
eicosanoid
are examined
doses of EPA
cx vivo while
metabolism
in platelets,
but
were additive of fish oils was
Thus,
this
observation
effects recent
of these fatty acids study demonstrated
its receptor
is inhibited
a variety are more that the
by these
fatty
of others
acids
(9).
Another
synthesis
because
tight
of platelet-acti-
autacoid
was discovered
it is a potent
cells and
is found
activator
at the vas-
by endothelial cells themselves synthesize
Essential fatty as do diets rich
and rel-
acid deficiency in EPA. This
is
linkage between PAF synthesis which probably occurs because of
substrate.
phospholipase
A2 step: a is pre-
This
half-life that
leading
and
to decreased
PAF.
This
pro-
is potentially
dietary changes in fatty acid composition inflammatory and thrombotic responses.
in which made.
thereby product
hypothesis
the
product
1. Goodnight
can
has
not
direct
been
tested
measurements
will
be a difficult
of PAF
in vivo
of PAF
and
experiment is short
unequivocally
in a nutritional
establish
and
its
to conthere
the prior
is no pres-
13
SH. Fisher
of the therapeutic
M. FitzGerald
GA,
Levine
PH. Assessment
use of dietary fish oil in atherosclerotic
disease and thrombosis.
recent
© 1992 American
more
Chest
vascular
1989:95:195-255.
a to
Printed
in USA.
in a much
synthesis
rep-
because
References
the
Am
1992:56:801S-2S.
were
enceofPAF.
eight individuals who were reassessment of platelet adhesion stress found a marked decrease
Nuir
this
that
pleiotropic. For example, binding of thromboxane
of PAF. of PAF,
eicosanoid
in humans
specific
that
the
and other
amounts synthesis
a suitable
However, trial
are exerted these acids one study on platelet
suggest
results
( 1 1). Nonetheless,
a mechanism by which might lead to decreased
duct
it is not clear
usually
likely
metabolism
phospholipid
platelets,
of the
acid
study examined platelets from ceiving 6 g EPA/d. An cx vivo under conditions of low shear i C/in
duction
(5). This would not be expected if the at the level of eicosanoid metabolism.
and
in inflammation
no longer
or high amounts of that fish oils alter thromboxane syn-
this is the mechanism by which the antiplatelet effects in vivo. In general, it takes large concentrations of in vitro to totally inhibit eicosanoid metabolism. In it was shown that the effects of fish oil and aspirin
This
( 10). This
diet
ferred. When this substrate is depleted, by replacement of arachidonate moiety with EPA or 20:3n-9, the phospholipid is
done for fish inhibition of
of fish oil ( 10 g/d). and docosahexaenoic
fish-oil
on eicosanoid
the use ofa common precursor at the l-O-alkyl-2-arachidonyl-sn-glycero-3-phosphocholine
this
secretion are decreased in mdiwho consume a fish-oil-rich diet (4effects is modest and usually is ohhigh
aggregation only effect
there
by which
aspirin
thought to be due to the and eicosanoid metabolism,
in populations
mechanism
with
(PAF).
atively small decreases the in
However,
than
cular surface because it is synthesized expressed on their surface. Platelets
many
differences
occurs. There have oils. Several groups
platelets
that
factor
of leukocytes,
metab-
showed
function.
and
enriched
platelets
the
other
as a factor that induced platelet activation, but more recent studies have suggested that its main role is not in thrombosis
olism.
Experiments
during
inhibition
vating
its structural effects of fish
in eicosanoid
an effect
modest effect on adhesion. Dietary changes also influence
observations regarding intake of saturated vs unsaturated fatty acids also suggested this possibility. One ofthe major components of fish oils is eicosapentaenoic homology to arachidonic acid
adhesion
resents total
thromand
in such
‘From the Departments of Utah, Salt Lake City. 2 Address reprint requests 500-CVRTI. Society
for Clinical
Salt Lake City. Nutrition
of Medicine to SM Prescott,
and
Biochemistry.
University
of Utah.
University Building
UT 84112.
801S
Downloaded from https://academic.oup.com/ajcn/article-abstract/56/4/801S/4715621 by guest on 11 February 2019
What are the effects of dietary fatty acid modification on platelet eicosanoid metabolism, platelet-activating factor, and platelet function? How might these metabolic alterations influence thrombosis?1’2
802S 2. Kromhout
between
PRESCOTT D, Bosschieter
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EB, Coulander C. The inverse relationship and 20-year mortality from coronary heart
boxane
formation
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7. von Schacky
with marine
8.
B, Bohlig B, Roth P, Kurzmann fatty acids, platelet aggregation,
during
a mackerel
omega-
diet.
I, Weber PC. and thromLancet 1980;l:
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44 1-4.
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10. 11.
5, Weber
PC. Long-term
effects
of dietary
tion, and eicosanoid formation in humans. I Clin Invest l985;76: 1626-31. Knapp HR, Reilly lAG, Alessandrini P, FitzGerald GA. In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis. N Engl I Med 1986;314:937-42. Swann PG, Parent CA, Croset M, et al. Enrichment of platelet phospholipids with eicosapentaenoic acid and docosahexaenoic acid inhibits thromboxane A2/prostaglandin H2 receptor binding and function. I Biol Chem 1990;265:2l 692-7. Li X, Steiner M. Fish oil: a potent inhibitor of platelet adhesiveness. Blood l990;76:938-45. Prescott SM, Zimmerman GA, McIntyre TM. Platelet-activating factor. I Biol Chem 1990:265:17 381-4.
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A. Effects of 11-week increase in dietary eicosapentaenoic acid on bleeding time, lipids, and platelet aggregation. Lancet 198 l;2:l 190-3. 6. Goodnight SH, Harris WS, Connor WE. The effects of dietary i3 fatty acids on platelet composition and function in man: a prospective, controlled study. Blood 1981:58:880-5.
C, Fischer
fatty acids upon plasma and cellular lipids, platelet func-