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Omega-3: Fakten
- Therapie und Dosierung
Arteriosklerose:
3 - 6 g/Tag EPA & DHA
In
Fachzeitschriften wurden folgende Artikel über Omega-3 publiziert.
Die Liste dieser Publikationen wurde im April 2003 kompiliert
und erhebt keinen Anspruch auf Vollständigkeit. Quelle: MEDLINE.
Die Daten dienen als Referenz für
Ärzte und Therapeuten, damit eine therapeutische Dosis für
Arteriosklerose festgelegt werden kann.
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n-3
fatty acid ethyl ester administration to healthy subjects and
to hypertriglyceridemic patients reduces tissue factor activity
in adherent monocytes.
Tremoli E: Institute of Pharmacological
Sciences, E. Grossi Paoletti Center, University of Milan, Italy;
Eligini S, Colli S, Maderna P, Rise P, Pazzucconi F,
Marangoni F, Sirtori CR, Galli C
Arterioscler Thromb 1994 Oct 14:1600-8
Abstract
n-3 Fatty acids are known to influence several functions
of monocytes, including adhesion, cytokine synthesis, and superoxide
generation. Monocytes express tissue factor, a membrane-bound
glycoprotein, that acts as a catalyst in the coagulation cascade.
In this study we evaluated the effects of administration of n-3
fatty acid ethyl esters to healthy volunteers and to hypertriglyceridemic
patients on tissue factor activity (TF activity) in adherent
monocytes. n-3 Fatty acids containing 75% eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) (ratio
of EPA to DHA, 1.34) were administered (3
g/d) to normal volunteers for 18 weeks. In addition,
the effects of this treatment were evaluated in 30 hypertriglyceridemic
patients for 24 weeks by using a double-blind, placebo-controlled
study. TF activity in adherent monocytes was evaluated with a
one-stage clotting assay. Plasma and monocyte fatty acid compositions
were determined by gas-liquid chromatography. In healthy volunteers,
n-3 fatty acids significantly reduced TF activity in adherent
monocytes either in the unstimulated condition or after exposure
to endotoxin. The inhibitory effect was
observed after 12 weeks of treatment and was more pronounced
after 18 weeks (> 70%, P < .001 versus baseline). Concomitantly,
levels of EPA and DHA increased in plasma and monocyte lipids.
Interestingly, after stopping treatment, monocyte TF activity
remained inhibited for at least 14 weeks. Treatment
with n-3 fatty acids for 24 weeks also resulted in a significant
reduction of TF activity in adherent monocytes from hypertriglyceridemic
patients (-31% and -40% in unstimulated and endotoxin-stimulated
cells; P < .05 versus baseline).
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Comparison
between dietary monounsaturated and polyunsaturated fatty acids
as regards diet-related diseases.
Mutanen M: Department of Applied Chemistry
and Microbiology (Nutrition), University of Helsinki, Finland.
Biomed Pharmacother 1997 51:314-7
Abstract
We have studied the effects of dietary fatty acid (FA)
composition on lipids and lipoproteins, platelet function and
other hemostatic variables as well as on the endogenous formation
of DNA adducts of malonaldehyde (MA) in healthy subjects in controlled
dietary experiments. The FAs studied were monounsaturated oleic
acid (OA, 18:1 n-9), n-6-polyunsaturated linoleic acid (LA, 18:2
n-6), n-3 polyunsaturated alpha-linolenic acid (ALA, 18:3 n-3),
and two long-chain, n-3 polyunsaturated FAs, eicosapentaenoic
acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3).
The results indicated that a high OA and high LA diet had comparable
effects on lipids and lipoproteins when they replaced saturated
FAs in a diet. Furthermore, the effect of ALA did not differ from
that of LA in this respect. Both diets also similarly increased
in vitro platelet aggregation when compared with high saturated
FA baseline diet. In another study the effect of LA and ALA on
platelet function was studied. In this study ALA decreased in
vitro platelet aggregation when compared with LA. When ALA was
compared with EPA + DHA it was found that platelet function and
some coagulation and fibrinolysis parameters were mainly affected
in a similar manner by ALA and EPA + DHA treatments. The high
LA diet increased the levels of DNA adducts of MA when compared
with the effect of the high OA diet. Our findings indicate that
the interpretation of the effect of diet, dietary fat or a specific
FA on the development of chronic disease is extremely complex.
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Eicosanoid
precursors: potential factors for atherogenesis in diabetic CAPD
patients?
Holler C: Ludwig Boltzmann Institute
for Nutrition, City Hospital Linz, Vienna, Austria; Auinger M,
Ulberth F, Irsigler K
Perit Dial Int 1996 16 Suppl 1:S250-3
Abstract
Prostaglandins, thromboxanes, and other eicosanoids represent
a widespread lipid-mediator system for intercellular signalling,
and, hence, have multiple cellular actions. Thus it is not surprising
that numerous events in the pathogenesis of atherosclerosis are
associated with an altered formation of eicosanoids. To reconsider
the availability of eiconsanoid precursors as one possible cause
of atherogenesis, the dietary intake and the serum concentrations
of arachidonic acid (AA) and eicosapentaenoic acid (EPA) were
determined in patients with high risk for atherosclerosis on continuous
ambulatory peritoneal dialysis (CAPD) with and without diabetes
in comparison to healthy controls and diabetic patients without
late complications. The factor AA/EPA in serum was created as
a marker for the atherosclerosis risk. The setting was in a CAPD
unit in one city hospital. There were 26 CAPD patients [9 with
insulin-dependent diabetes mellitus (IDDM), 9 with noninsulin-dependent
diabetes mellitus (NIDDM), and 8 without diabetes], 27 IDDM without
late complications, and 41 healthy control persons. The AA levels
in serum were significantly higher in all of the CAPD groups.
In contrast, the EPA concentrations in serum were significantly
lower in the CAPD groups, with the lowest EPA levels found in
the CAPD-IDDM group. Therefore, the factors AA/EPA in serum were
significantly higher in all of the CAPD groups, and again significantly
higher in the CAPD-IDDM group than in the other CAPD groups. No
differences in the amount of dietary intake of AA existed between
the groups. The daily intake of EPA was significantly highest
in the control group. Higher concentrations of AA and a lack of
n-3 fatty acids lead in the presence of a reduced prostaglandin
I2 biosynthesis, to a higher formation rate of potentially proatherogenic
metabolites such as thromboxane A2, a vasoconstricting and platelet
aggregating agent. Thus, the quotient AA/EPA could possibly be
used as a marker of atherogenicity in the future.
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Fish
oil in thrombosis and arteriosclerosis.
Tschopp TB: Pharmaforschung und Abteilung
für Gesundheit und Ernährung, F. Hoffmann-La Roche AG,
Basel;Muggli R
Schweiz Med Wochenschr 1990 Mar 120:372-8
Abstract
In the past few years interest in the use of fish oil as
a dietetic approach in the management of thromboarteriosclerotic
diseases has increased. This is based on epidemiological studies
which indicate that people living mainly on a fish diet have a
low incidence of coronary heart disease (CHD). The beneficial
effect is attributed to the high content of polyunsaturated n-3
fatty acids (PUFA), especially eicosapentaenoic acid (C20:5n-3)
(EPA), in the marine diet. These fatty acids are built into the
phospholipids of various cell membranes, changing their biological
reactivity. EPA and docosahexaenoic acid (C22:6n-3) are also metabolized
into specific eicosanoids (e.g. prostaglandin I3, thromboxane
A3 and leukotriene B5). In contrast to the mediators originating
from the n-6 fatty acids, these n-3 autocoids exhibit stronger
antiaggregant, vasodilatory and anti-inflammatory activities.
When given to volunteers, n-3 PUFAs inhibit platelet aggregation
and lower plasma triglycerides. However, first clinical studies
in patients with angina pectoris are equivocal. Furthermore, restenosis
of coronary arteries in patients after PTCA was not clearly reduced.
Therefore, more prospective clinical studies are needed to establish
the efficacy of these fish oils before their use in thromboarteriosclerotic
CHD can be recommended.
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Dose
response of dietary fish oil supplementations on platelet adhesion.
Li XL: Division of Hematology/Oncology,
Memorial Hospital of Rhode Island, Pawtucket 02860, USA; Steiner M
Arterioscler Thromb 1991 Jan-Feb 11:39-46
Abstract
A dose-response study of dietary fish oil supplementation
on platelet adhesion was performed in three groups of five normal
individuals each. Fish oil equivalent
to 3, 6, or 9 g eicosapentaenoic acid (EPA)/day was
administered for 3 weeks, and platelet adhesion was evaluated
under high and low shear rate conditions in a laminar flow chamber
before, during, and after termination of fish oil administration.
Platelet adhesion to collagen I and fibrinogen, the two
test surfaces in this study, was greatly reduced in response to
fish oil. The inhibitory effect was similar whether platelet adhesion
was evaluated at high or low shear rates. Maximal
inhibitory activity was noted at 6 g EPA/day. A delayed
onset and prolonged washout period characterized the response.
The washout period of the fish oil effect was inversely related
to the level of dietary supplementation. Measurement of total
fatty acid distribution in platelets showed a dose-related increase
in n-3 polyunsaturated fatty acids. From
these studies, it is concluded that fish oil is an effective inhibitor
of platelet adhesion, which reaches its maximum effect at approximately
6 g EPA/day.
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Serum
non-esterified very long-chain PUFA are associated with markers
of endothelial dysfunction.
Yli-Jama P: Institute for Nutrition
Research, University of Oslo, PO Box 1046, Blindern, N-0316, Oslo,
Norway; Seljeflot I, Meyer HE, Hjerkinn EM, Arnesen H,
Pedersen JI
Atherosclerosis 2002 Oct 164:275-81
Abstract
The objective of this study was to investigate the pattern
of serum non-esterified fatty acid (NEFA) fraction in association
with atherosclerosis development. We have studied possible relationships
between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)
and arachidonic acid (AA) in the NEFA fraction and biochemical
markers of endothelial activation or dysfunction. The study population
consisted of 152 elderly men with high risk for coronary heart
disease. The composition of fasting serum NEFA was analysed by
gas-liquid chromatography. Endothelial activation was evaluated
using biochemical analyses of some markers of endothelial function.
A significant inverse linear association was found between serum
non-esterified EPA and DHA, and soluble vascular cell adhesion
molecule-1 (sVCAM-1) (P=0.02 and 0.001, respectively). An inverse
linear association was found between serum non-esterified AA and
sVCAM-1 (P=0.001) and von Willebrand Factor (P=0.005). The significant
inverse associations for DHA and AA were independent from the
serum content of other NEFAs. Taken together, negative associations
were found between sVCAM-1 and the serum levels of non-esterified
DHA, EPA and AA. The inverse relation between the levels of sVCAM-1
and very long-chain n-3 fatty acids might indicate an anti-inflammatory
effect of the latter.
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Supplementation
of postmenopausal women with fish oil does not increase overall
oxidation of LDL ex vivo compared to dietary oils rich in oleate
and linoleate.
Higdon JV: Department of Nutrition
and Food Management, Oregon State University, Corvallis, OR 97331,
USA; Du SH, Lee YS, Wu T, Wander RC
J Lipid Res 2001 Mar 42:407-18
Abstract
Although replacement of dietary saturated fat with monounsaturated
and polyunsaturated fatty acids (MUFA and PUFA) has been advocated
for the reduction of cardiovascular disease risk, diets high in
PUFA could increase low density lipoprotein (LDL) susceptibility
to oxidation, potentially contributing to the pathology of atherosclerosis.
To investigate this possibility, 15 postmenopausal women in a
blinded crossover trial consumed 15 g of sunflower oil (SU) providing
12.3 g/day of oleate, safflower oil (SA) providing 10.5 g/day
of linoleate, and fish oil (FO) providing 2.0 g/day of eicosapentaenoate
(EPA) and 1.4 g/day of docosahexaenoate (DHA). During CuSO(4)-mediated
oxidation, LDL was depleted of alpha-tocopherol more rapidly after
FO supplementation than after supplementation with SU (P = 0.0001)
and SA (P = 0.05). In LDL phospholipid and cholesteryl ester fractions,
loss of n-3 PUFA was greater and loss of n-6 PUFA less after FO
supplementation than after SU and SA supplementation (P < 0.05
for all), but loss of total PUFA did not differ. The lag phase
for phosphatidylcholine hydroperoxide (PCOOH) formation was shorter
after FO supplementation than after supplementation with SU (P
= 0.0001) and SA (P = 0.006), whereas the lag phase for cholesteryl
linoleate hydroperoxide (CE18:2OOH) formation was shorter after
FO supplementation than after SU (P = 0.03) but not SA. In contrast,
maximal rates of PCOOH and CE18:2OOH formation were lower after
FO supplementation than after SA (P = 0.02 and 0.0001, respectively)
and maximal concentrations of PCOOH and CE18:2OOH were lower after
FO supplementation than after SA (P = 0.03 and 0.0006, respectively).
Taken together, our results suggest that FO supplementation does
not increase the overall oxidation of LDL ex vivo, especially
when compared with SA supplementation. Consequently, health benefits
related to increased fish consumption may not be offset by increased
LDL oxidative susceptibility.-- Higdon, J. V., S. H. Du, Y. S.
Lee, T. Wu, and R. C. Wander. Supplementation of postmenopausal
women with fish oil does not increase overall oxidation of LDL
ex vivo compared to dietary oils rich in oleate and linoleate.
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