Omega-3: Fakten - Therapie und Dosierung
Rheuma: < 2,8g/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 bei Rheuma festgelegt werden kann.
Dietary modification of inflammation with lipids.
Calder PC: Institute of Human Nutrition, University of Southampton, Bassett Crescent East, UK
Proc Nutr Soc 2002 Aug 61:345-58
The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in high proportions in oily fish and fish oils. The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA. Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation. Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators. This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA. However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity. For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFB). Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.
n-3 polyunsaturated fatty acids inhibit the antigen-presenting function of human monocytes.
Hughes DA: Diet, Health and Consumer Science Division, the Institute of Food Research, Norwich Research Park, Colney, Norwich, Norfolk, UK; Pinder AC
Am J Clin Nutr 2000 Jan 71:357S-60S
Diets rich in n-3 polyunsaturated fatty acids (PUFAs) are associated with suppression of cell-mediated immune responses, but the mechanisms are unclear. We hypothesized that n-3 PUFAs can inhibit the function of human antigen-presenting cells. A prerequisite for this role of blood monocytes is the cell surface expression of major histocompatibility complex (MHC) class II molecules [human leukocyte antigen (HLA)-DR, -DP, and -DQ], aided by the presence of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function associated antigens 1 and 3. We showed previously that the n-3 PUFA eicosapentaenoic acid (EPA) inhibits the expression of HLA-DR on unstimulated human monocytes in vitro, but that docosahexaenoic acid (DHA) enhances its expression. However, both n-3 PUFAs suppress the expression of HLA-DR, HLA-DP, and ICAM-1 on interferon-gamma-activated monocytes. We also established that dietary fish-oil supplementation can inhibit the expression of these surface molecules on circulating human monocytes. We subsequently showed that when EPA and DHA were combined in the same ratio as is commonly found in fish-oil-supplement capsules (3:2), there was no significant effect in vitro on the expression of HLA-DR on unstimulated monocytes, but the expression on activated monocytes remained significantly inhibited. In the same in vitro system, the ability of activated monocytes to present antigen to autologous lymphocytes was significantly reduced after culture with the combined n-3 PUFAs. These findings provide one potential mechanism for the beneficial effect of fish oil in the treatment of rheumatoid arthritis, a disorder associated with elevated expression of MHC class II and adhesion molecules on monocytes present within affected joints.
Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects.
Kremer JM: Department of Medicine, Albany Medical College, NY, USA; Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M
Arthritis Rheum 1990 Jun 33:810-20
Forty-nine patients with active rheumatoid arthritis completed a 24-week, prospective, double-blind, randomized study of dietary supplementation with 2 different dosages of fish oil and 1 dosage of olive oil. Clinical evaluations were performed at baseline and every 6 weeks thereafter, and immunologic variables were measured at baseline and after 24 weeks of study. The 3 groups of patients were matched for age, sex, disease severity, and use of disease-modifying antirheumatic drugs (DMARDs). Subjects continued receiving DMARDs and other background medications without change during the study. Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 mg/kg eicosapentaenoic acid (EPA) and 18 mg/kg docosahexaenoic acid (DHA) (low dose), 17 patients ingested 54 mg/kg EPA and 36 mg/kg DHA (high dose), and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid. Significant improvements from baseline in the number of tender joints were noted in the low-dose group at week 24 (P = 0.05) and in the high-dose group at week 18 (P = 0.04) and 24 (P = 0.02). Significant decreases from baseline in the number of swollen joints were noted in the low-dose group at weeks 12 (P = 0.003), 18 (P = 0.002), and 24 (P = 0.001) and in the high-dose group at weeks 12 (P = 0.0001), 18 (P = 0.008), and 24 (P = 0.02). A total of 5 of 45 clinical measures were significantly changed from baseline in the olive oil group, 8 of 45 in the low-dose fish oil group, and 21 of 45 in the high-dose fish oil group during the study (P = 0.0002). Neutrophil leukotriene B4 production decreased by 19% from baseline in the low-dose fish oil group (P = 0.0003) and 20% in the high-dose group (P = 0.03), while macrophage interleukin-1 production decreased by 38.5% in the olive oil group (P not significant), 40.6% in the low-dose group (P = 0.06), and 54.7% in the high-dose group (P = 0.0005). Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks, compared with baseline values. We conclude that the clinical benefits of dietary supplementation with omega-3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil for time intervals that are longer than those previously studied. Dietary supplementation with olive oil is also associated with certain changes in immune function, which require further investigation.
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Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis.
Fortin PR: Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston MA, USA; Lew RA, Liang MH, Wright EA, Beckett LA, Chalmers TC, Sperling RI
J Clin Epidemiol 1995 Nov 48:1379-90
The purpose of this study was to validate the results of a meta-analysis showing the efficacy of fish oil in rheumatoid arthritis with the results of a re-analysis of the complete primary data set. A Medline search yielded seven published papers. Three additional trials were found by contacting authorities in the field. Inclusion criteria included (1) a double-blind, placebo-controlled study, (2) use of at least one of seven predetermined outcome measures, (3) results reported for both placebo and treatment groups at baseline and follow-up, (4) randomization, and (5) parallel or cross-over design. Papers were scored for quality. Demographic and outcomes variables were collected. For the re-analysis of the primary data, the same variables were abstracted for the 395 individual patients randomized. The meta-analysis demonstrated that dietary fish oil supplementation for 3 months significantly reduced tender joint count (rate difference [RD] [95% CI] = -2.9 [-3.8 to -2.1] [p = 0.001]) and morning stiffness (RD [95% CI] = -25.9 [-44.3 to -7.5] [p < 0.01]) as compared with heterogeneous dietary control oils. The re-analysis of the primary data confirmed a significant reduction in tender joint count (p = 0.001) and in morning stiffness (p < 0.02) in the parallel analysis that ignored interaction terms. The analyses that included an interaction term between site and treatment again confirmed a significant reduction in tender joint count. The results for morning stiffness were similar to the meta-analysis, but did not quite reach statistical significance (p = 0.052-0.083). The relative improvements in the other outcome variables did not reach statistical significance. Use of fish oil improved the number of tender joints and duration of morning stiffness at 3 months as analyzed by both meta- and mega-analysis. The fuller mega-analysis confirmed the results of the meta-analysis. The advantages of mega-analysis were as follows: (1) the ability to analyze the homogeneity of the patient populations, (2) the ability to make clinically sensible adjustments in the form of the comparison, and (3) the ability to examine subsets of the data.
Dietary n-3 fatty acids and therapy for rheumatoid arthritis.
James MJ: Rheumatology Unit, Royal Adelaide Hospital, Australia; Cleland LG
Semin Arthritis Rheum 1997 Oct 27:85-97
OBJECTIVE: To examine the potential for dietary n-3 fats to be component of therapy for rheumatoid arthritis (RA). METHODS: Studies of encapsulated fish oil use in RA were reviewed and critiqued, and possible biochemical mechanisms for fish oil effects were examined. The potential for use of n-3 fats was evaluated within a dietary framework rather than a quasi-pharmaceutical framework. RESULTS: There is consistent evidence from double-blind, placebo-controlled clinical trials that dietary n-3 fats, supplied as fish oil, can have beneficial effects in RA. The beneficial effects appear modest, but their size and extent may have been moderated by common trial design factors such as high n-6 polyunsaturated fat diets and concurrent antiinflammatory drug use. Mechanisms for the clinical effects of n-3 fats in RA may involve their ability to suppress production of inflammatory mediators, including n-6 eicosanoids and proinflammatory cytokines. Suppression of n-6 eicosanoid and cytokine production will be possible using foodstuffs that are rich in n-3 fats and poor in n-6 fats. CONCLUSIONS: There are many overlapping biochemical effects of n-3 fatty acids and antiinflammatory pharmaceuticals that could explain the clinical actions of n-3 fats in RA. They suggest that there is the potential for complementarity between drug therapy and dietary choices that increase intake of n-3 fats and decrease intake of n-6 fats. In particular, there is the potential for drug-sparing effects. Future studies with n-3 fats in RA need to address the fat composition of the background diet and the issue of concurrent drug use.
Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study.
Geusens P: Arthritis and Metabolic Bone Disease Research Unit, K. U. Leuven, U. Z. Pellenberg, Belgium; Wouters C, Nijs J, Jiang Y, Dequeker J
Arthritis Rheum 1994 Jun 37:824-9
OBJECTIVE. To study the long-term effects of supplementation with omega-3 fatty acids (omega 3) in patients with active rheumatoid arthritis. METHODS. Ninety patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementations with either 2.6 gm of omega 3, or 1.3 gm of omega 3 + 3 gm of olive oil, or 6 gm of olive oil. RESULTS. Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of omega 3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of omega 3. CONCLUSION. Daily supplementation with 2.6 gm of omega 3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication.
Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study.
Lau CS: Department of Medicine, Ninewells Hospital, Dundee, Scotland; Morley KD, Belch JJ
Br J Rheumatol 1993 Nov 32:982-9
Maxepa contains eicosapentaenoic acid (EPA) (171 mg/capsule) and docosahexaenoic acid (DHA) (114 mg/capsule). EPA acts as an alternative substrate to arachidonate, leading to the formation of the less proinflammatory prostaglandins ('3' series) and leukotrienes ('5' series). If Maxepa has anti-inflammatory properties it could be expected to reduce the requirement for NSAIDs in patients with RA. This has not been investigated nor has Maxepa therapy been studied over a full 1-yr period. Sixty-four patients with stable RA requiring NSAID therapy only were studied. Patients received either 10 Maxepa or air-filled placebo capsules per day for 12 months. All then received placebo capsules for a further 3 months. Patients were reviewed at 3-monthly intervals. NSAID requirement at entry visit for each patient was assigned as 100%. Patients were instructed to slowly reduce their NSAID dosage providing there was no worsening of their symptoms. Clinical and laboratory parameters of RA activity were also measured. There was a significant reduction in NSAID usage in patients on Maxepa when compared with placebo from month 3 [mean (95% C.I. for mean) requirement--71.1 (55.9-86.2)% and 89.7 (73.7-105.7)%, respectively]. This effect reached its maximum at month 12 [40.6 (24.5-56.6)% and 84.1 (62.7-105.5)%, respectively] and persisted to month 15 [44.7 (27.6-61.8)% and 85.8 (60.5-111.1)%, respectively] (P < 0.001, ANOVA). These patients were able to reduce their NSAID requirement without experiencing any deterioration in the clinical and laboratory parameters of RA activity.
Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis.
Kremer JM, Bigauoette J, Michalek AV, Timchalk MA, Lininger L, Rynes RI, Huyck C, Zieminski J, Bartholomew LE
Lancet 1985 Jan 1:184-7
The effects of manipulation of dietary fatty acids in patients with rheumatoid arthritis were investigated in a 12-week, prospective, double-blind, controlled study. 17 patients took an experimental diet high in polyunsaturated fat and low in saturated fat, with a daily supplement (1.8 g) of eicosapentaenoic acid. 20 patients took a control diet with a lower polyunsaturated to saturated fat ratio and a placebo supplement. Compliance was monitored by plasma lipid gas-chromatographic analysis, Ivy bleeding time, and diet diaries. Results favoured the experimental group at 12 weeks for morning stiffness and number of tender joints. On follow-up evaluation 1-2 months after stopping the diet, the experimental group had deteriorated significantly in patient and physician global evaluation of disease activity, pain assessment, and number of tender joints. The control group had improved in morning stiffness and number of tender joints on follow-up.