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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.
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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
Abstract
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.
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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
Abstract
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.
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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
Abstract
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
Abstract
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
Abstract
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
Abstract
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
Abstract
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
Abstract
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. |
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