Omega-3 Studien: Arteriosklerose

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.

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
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).

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
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.

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
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
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.

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
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.

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
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.

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
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.