(fatty acids, omega 3 [majr]) & (arthritis [majr]) (only with abstract)

54 articles - 08.09.10


1: JPEN J Parenter Enteral Nutr. 2010 Mar-Apr;34(2):151-5.

omega-3 Fatty acids infusions as adjuvant therapy in rheumatoid arthritis.

Bahadori B, Uitz E, Thonhofer R, Trummer M, Pestemer-Lach I, McCarty M, Krejs GJ.

Internal Medicine, State Hospital Muerzzuschlag, Muerzzuschlag, Austria.

BACKGROUND: The present study investigated the efficacy and safety of parenteral omega-3 fatty acids (omega-3 FA) in patients with active rheumatoid arthritis (RA). METHODS: We performed a double-blind, randomized, placebo-controlled study in 23 patients with moderate to severe RA. Patients received either 0.2 g of fish oil emulsion/kg (active) or 0.9% saline (placebo) infusion intravenously for 14 consecutive days, followed by 20 weeks of 0.05 g of fish oil/kg (active) or paraffin wax (placebo) ingested orally as capsules. A decrease in swollen and tender joint counts was the primary efficacy measure. RESULTS: At baseline, both swollen and tender joint counts were not significantly different between patients in the treatment and placebo groups. Twenty patients completed the infusion portion of the study, and 13 completed the oral portion. Swollen joint count was significantly lower in the omega-3 FA group compared with the placebo group after 1 week of infusion (P = .002) as well as after 2 weeks of infusion (P = .046). Tender joint count also tended to be lower in the omega-3 FA group, although this did not reach statistical significance. Both swollen and tender joint counts were significantly lower in the omega-3 FA group compared with the placebo group during and at the end of oral treatment. CONCLUSION: Our pilot study indicates that parenteral omega-3 FAs are well tolerated and improve clinical symptoms of RA. Subsequent oral administration of omega-3 FAs may prolong the beneficial effects of the infusion therapy. These results warrant validation in larger multicenter studies.

Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20375422&dopt=ExternalLink

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PMID: 20375422 [PubMed - indexed for MEDLINE]

2: J Vet Intern Med. 2010 May-Jun;24(3):487-95. Epub 2010 Mar 22.

Evaluation of a therapeutic diet for feline degenerative joint disease.

Lascelles BD, DePuy V, Thomson A, Hansen B, Marcellin-Little DJ, Biourge V, Bauer JE.

Comparative Pain Research Laboratory, Department of Clinical Science, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. duncan_lascelles@ncsu.edu

BACKGROUND: Feline degenerative joint disease (DJD) is common and there are no approved therapies for the alleviation of the associated pain. OBJECTIVE: To test a diet high in eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate (test-diet) for its pain-relieving and activity-enhancing effects in cats with painful, mobility-impairing DJD over a 9-week period. ANIMALS: Forty client-owned cats. METHODS: Randomized, controlled, blinded, parallel group, prospective clinical study. Cats with no detectable systemic disease, and with at least 1 appendicular joint with radiographic evidence of DJD where manipulation elicited an aversive response were included. Cats were randomly allocated to the test-diet or control diet (C-diet). Outcome measures were subjective owner and veterinarian assessments, and objective activity monitoring (accelerometry). Nonparametric statistics were used to evaluate changes within and between groups for both subjective and objective data, and locally weighted scatterplot smoothing regression analysis was used to predict activity changes. RESULTS: The primary objective outcome measures indicated that activity declined significantly (P < .001) in the C-diet group, significantly increased (P < .001) in the test-diet group and there was a significant difference between the groups (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: A diet high in EPA and DHA and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate improved objective measures of mobility. Dietary modulation might be 1 method to use to improve mobility in cats with DJD-associated pain.

Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20337921&dopt=ExternalLink

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PMID: 20337921 [PubMed - indexed for MEDLINE]

3: Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):315-8. Epub 2010 Mar 1.

Dietary fatty acids and arthritis.

Hurst S, Zainal Z, Caterson B, Hughes CE, Harwood JL.

School of Biosciences, Cardiff University, Cardiff, UK.

Musculoskeletal complaints are the second most frequent reason for medical treatments. Within these diseases rheumatoid arthritis (RA) and, especially, osteoarthritis (OA) are common. Although the causes of arthritis are multifactorial and not fully understood, clinical trials have generally shown benefit from dietary n-3 polyunsaturated fatty acids. This has usually been attributed to their anti-inflammatory properties. Recently we have used in vitro model systems to study the molecular mechanism(s) by which n-3 PUFAs may act to alleviate the symptoms of arthritis. These experiments showed that n-3 PUFAs reduce expression of cartilage-degrading proteinases, cyclooxygenase-2 and inflammatory cytokines. Eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) or alpha-linolenic acid. The data provide a scientific rationale for the consumption of n-3 fatty acids as part of a healthy diet and perhaps in treating arthritis. Copyright 2010 Elsevier Ltd. All rights reserved.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20189789&dopt=ExternalLink

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PMID: 20189789 [PubMed - indexed for MEDLINE]

4: Bangladesh Med Res Counc Bull. 2009 Aug;35(2):63-8.

Role of omega-3 fatty acid supplementation with indomethacin in suppression of disease activity in rheumatoid arthritis.

Das Gupta AB, Hossain AK, Islam MH, Dey SR, Khan AL.

Department of Pharmacology, Sylhet M. A. G. Osmani Medical College, Sylhet 3100, Bangladesh.

A study was conducted to see the disease activity suppression role of omega-3 fatty acids with indomethacin in patients with rheumatoid arthritis. One group received indomethacin (75 mg) only daily while another group received indomethacin (75 mg) along with omega-3 fatty acids (3 g) daily for 12 weeks. The main outcome measures were DAS 2-28 joints score, number of swollen joints, number of tender joints, duration of morning stiffness, grip strength, pain VAS, patients global VAS, erythrocyte sedimentation rate and C-reactive protein. In terms of outcome both the groups experienced a modest improvement in disease activity after 12 weeks of treatment. However, compared to indomethacin-treated group, omega-3 plus indomethacin-treated group achieved a better improvement in terms of reducing disease activity. Physical functioning, physical role, bodily pain, general health, vitality, social functioning, grip strength, duration of morning stiffness improved significantly better in the combination group compared to indomethacin only group. The safety measures included liver and kidney function tests done didn't differ between the study groups. This study suggests that omega-3 fatty acid supplementation with indomethacin might ameliorate disease activity and be non-steroidal anti-inflammatory drugs (NSAIDs) sparing in rheumatoid arthritis.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20120782&dopt=ExternalLink

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PMID: 20120782 [PubMed - indexed for MEDLINE]

5: J Am Vet Med Assoc. 2010 Jan 1;236(1):67-73.

Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis.

Roush JK, Cross AR, Renberg WC, Dodd CE, Sixby KA, Fritsch DA, Allen TA, Jewell DE, Richardson DC, Leventhal PS, Hahn KA.

Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

OBJECTIVE: To evaluate the effects of a food supplemented with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 38 client-owned dogs with osteoarthritis examined at 2 university veterinary clinics. PROCEDURES: Dogs were randomly assigned to receive a typical commercial food (n = 16) or a test food (22) containing 3.5% fish oil omega-3 fatty acids. On day 0 (before the trial began) and days 45 and 90 after the trial began, investigators conducted orthopedic evaluations and force-plate analyses of the most severely affected limb of each dog, and owners completed questionnaires to characterize their dogs' arthritis signs. RESULTS: The change in mean peak vertical force between days 90 and 0 was significant for the test-food group (5.6%) but not for the control-food group (0.4%). Improvement in peak vertical force values was evident in 82% of the dogs in the test-food group, compared with 38% of the dogs in the control-food group. In addition, according to investigators' subjective evaluations, dogs fed the test food had significant improvements in lameness and weight bearing on day 90, compared with measurements obtained on day 0. CONCLUSIONS AND CLINICAL RELEVANCE: At least in the short term, dietary supplementation with fish oil omega-3 fatty acids resulted in an improvement in weight bearing in dogs with osteoarthritis.

Publication Types: Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20043801&dopt=ExternalLink

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PMID: 20043801 [PubMed - indexed for MEDLINE]

6: J Am Vet Med Assoc. 2010 Jan 1;236(1):59-66.

Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs.

Roush JK, Dodd CE, Fritsch DA, Allen TA, Jewell DE, Schoenherr WD, Richardson DC, Leventhal PS, Hahn KA.

Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

OBJECTIVE: To assess the effect of food containing high concentrations of fish oil omega-3 fatty acids and a low omega-6-omega-3 fatty acid ratio on clinical signs of osteoarthritis in dogs. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 127 client-owned dogs with osteoarthritis in 1 or more joints from 18 privately owned veterinary clinics. PROCEDURES: Dogs were randomly assigned to be fed for 6 months with a typical commercial food or a test food containing a 31-fold increase in total omega-3 fatty acid content and a 34-fold decrease in omega-6-omega-3 ratio, compared with the control food. Dog owners completed a questionnaire about their dog's arthritic condition, and investigators performed a physical examination and collected samples for a CBC and serum biochemical analyses (including measurement of fatty acids concentration) at the onset of the study and at 6, 12, and 24 weeks afterward. RESULTS: Dogs fed the test food had a significantly higher serum concentration of total omega-3 fatty acids and a significantly lower serum concentration of arachidonic acid at 6, 12, and 24 weeks. According to owners, dogs fed the test food had a significantly improved ability to rise from a resting position and play at 6 weeks and improved ability to walk at 12 and 24 weeks, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of the test food raised blood concentrations of omega-3 fatty acids and appeared to improve the arthritic condition in pet dogs with osteoarthritis.

Publication Types: Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20043800&dopt=ExternalLink

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PMID: 20043800 [PubMed - indexed for MEDLINE]

7: Curr Pharm Des. 2009;15(36):4135-48.

Omega-3 polyunsaturated fatty acids and immune-mediated diseases: inflammatory bowel disease and rheumatoid arthritis.

Ruggiero C, Lattanzio F, Lauretani F, Gasperini B, Andres-Lacueva C, Cherubini A.

Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. ruggieroc07@hotmail.it

Inflammation is part of the normal host response to infection and injury. However, inappropriate inflammation contributes to several diseases, including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Both conditions are characterized by the excessive production of inflammatory cytokines, arachidonic acid (AA)-derived eicosanoids, and other inflammatory agents (e.g., reactive oxygen species, adhesion molecules). By virtue of their anti-inflammatory action, omega-3 polyunsaturated fatty acids (PUFA) may be beneficial in inflammatory diseases. A large body of evidence supports a protective effect of omega-3 PUFA in experimental animal and ex-vivo models of Crohn's disease (CD), Ulcerative colitis (UC) and Rheumatoid arthritis (RA). Although fish oil supplementation in patients with IBD results in omega-3 PUFA incorporation into gut mucosal tissue and modification of inflammatory mediator profiles, the evidence of clinical benefits of omega-3 PUFA is weak. On the other hand, more convincing data support the efficacy of omega-3 PUFA in reducing pain, number of tender joints, duration of morning stiffness, use of non-steroidal anti-inflammatory drugs and improving physical performance in RA patients. In both IBD and RA further clinical trials with large sample size are needed to clarify the efficacy of omega-3 PUFA as a treatment.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20041815&dopt=ExternalLink

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PMID: 20041815 [PubMed - indexed for MEDLINE]

8: Lipids. 2009 Oct;44(10):889-96. Epub 2009 Sep 26.

Contrasting effects of n-3 and n-6 fatty acids on cyclooxygenase-2 in model systems for arthritis.

Hurst S, Rees SG, Randerson PF, Caterson B, Harwood JL.

Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.

Cyclooxygenase-2 (COX-2) is intimately involved in symptoms of arthritis while dietary n-3 polyunsaturated fatty acids (PUFA) are thought to be beneficial. In these experiments, using both bovine and human in vitro systems that mimic features of arthritis, we show that the n-3 PUFA eicosapentaenoic acid (EPA) is able to reduce mRNA and protein levels of COX-2. Activity, as assessed through prostaglandin E(2) formation, was also reduced in a dose-dependent manner. These effects of EPA contrasted noticeably with the n-6 PUFA, arachidonic acid. The data provide direct evidence for a molecular mechanism by which dietary n-3 PUFA, such as EPA, can reduce inflammation and, hence, associated symptoms in arthritis.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19784684&dopt=ExternalLink

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PMID: 19784684 [PubMed - indexed for MEDLINE]

9: Adv Ther. 2009 Sep;26(9):858-71. Epub 2009 Sep 4.

Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis.

Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ.

Analyze & Realize AG, Berlin, Germany. jgruenwald@analyze-realize.com

INTRODUCTION: A total of 177 patients with moderate-to-severe hip or knee osteoarthritis (OA) were tested over a period of 26 weeks in a two-center, two-armed, randomized, double-blind, comparison study. The aim was to see if a combination of glucosamine sulfate (1500 mg/day) and the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (group A), showed equivalence (noninferiority) or superiority as opposed to glucosamine sulfate alone (group B). METHODS: The primary therapy evaluation was performed using the Western Ontario and McMaster Universities Arthrosis index (WOMAC) score. At the end of the study, a reduction in the pain score of > or =20% was required (primary target criterion) and the quantitative difference in the WOMAC subscores pain, stiffness, and function were analyzed (secondary target criteria). RESULTS AND CONCLUSION: When a minimal pain reduction of > or =20% was chosen, there was no statistically significant difference in the number of responders between the two groups (92.2% group A, 94.3% group B). A higher responder criterion (> or =80% reduction in the WOMAC pain score) was chosen. Therefore, the frequency of responders showed a therapeutic and statistical superiority for the combination product of glucosamine sulfate and the omega-3 polyunsaturated fatty acids in patients who complied with the study protocol (group A 44%, group B 32%; P=0.044). OA symptoms (morning stiffness, pain in hips and knees) were reduced at the end of the study: by 48.5%-55.6% in group A and by 41.7%-55.3% in group B. The reduction was greater in group A than in group B. There was a tendency toward superiority shown in the secondary target criteria and concurrent variables. In the global safety evaluation, both products have been demonstrated to be very safe in long-term treatment over 26 weeks. To our knowledge, this is the first clinical trial in which glucosamine was given in combination with omega-3 fatty acids to patients with OA.

Publication Types: Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19756416&dopt=ExternalLink

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PMID: 19756416 [PubMed - indexed for MEDLINE]

10: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1322-31. Epub 2009 Sep 9.

Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors.

Castillero E, Martin AI, Lopez-Menduina M, Villanua MA, Lopez-Calderon A.

Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that has anti-inflammatory and anticachectic actions. The aim of this work was to elucidate whether EPA administration is able to prevent an arthritis-induced decrease in body weight and muscle wasting in rats. Arthritis was induced by intradermal injection of Freund's adjuvant; 3 days later, nine rats received 1 g/kg EPA or coconut oil daily. All rats were killed 15 days after adjuvant injection. EPA administration decreased the external signs of arthritis and paw volume as well as liver TNF-alpha mRNA. EPA did not modify arthritis-induced decrease in food intake or body weight gain. However, EPA treatment prevented arthritis-induced increase in muscle TNF-alpha and atrogin-1, whereas it attenuated the decrease in gastrocnemius weight and the increase in MuRF1 mRNA. Arthritis not only decreased myogenic regulatory factors but also increased PCNA, MyoD, and myogenin mRNA in the gastrocnemius. Western blot analysis showed that changes in protein content followed the pattern seen with mRNA. In the control rats, EPA administration increased PCNA and MyoD mRNA and protein. In arthritic rats, EPA did not modify the stimulatory effect of arthritis on these myogenic regulatory factors. The results suggest that in experimental arthritis, in addition to its anti-inflammatory effect, EPA treatment attenuates muscle wasting by decreasing atrogin-1 and MuRF1 gene expression and increasing the transcription factors that regulate myogenesis.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19741054&dopt=ExternalLink

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PMID: 19741054 [PubMed - indexed for MEDLINE]

11: Br J Nutr. 2009 May;101(10):1517-26. Epub 2009 Feb 27.

Long-term moderate intervention with n-3 long-chain PUFA-supplemented dairy products: effects on pathophysiological biomarkers in patients with rheumatoid arthritis.

Dawczynski C, Schubert R, Hein G, Muller A, Eidner T, Vogelsang H, Basu S, Jahreis G.

Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Jena, Germany.

n-3 long-chain PUFA (n-3 LC-PUFA) may improve cardiovascular and inflammatory diseases. The effects of n-3 LC-PUFA-supplemented dairy products on inflammation and immunological parameters, biomarkers of oxidative stress, serum lipids, and on disease activity were determined in patients with rheumatoid arthritis (RA). Forty-five subjects (forty-three females and two males) were randomly divided into two groups in a double-blind, placebo-controlled cross-over study. Both groups received placebo or verum products consecutively for 3 months with a 2-month washout phase between the two periods. Blood samples were taken at the beginning and at the end of each period. The dairy products generally improved serum lipids by increasing HDL and lowering lipoprotein a. The n-3 LC-PUFA supplements act to lower TAG. Additionally, a decreased lipopolysaccharide-stimulated cylo-oxygenase-2 expression was found in patients who had consumed the enriched dairy products. The majority of the CD analysed were not influenced, although n-3 LC-PUFA did suppress the immune response as lymphocytes and monocytes were found to be significantly decreased. The n-3 LC-PUFA did not increase the biomarkers of oxidative stress such as 8-iso-PGF(2alpha) and 15-keto-dihydro PGF(2alpha), and DNA damage like 7,8-dihydro-8-oxo-2'-deoxyguanosine. The long-term consumption of dairy products (2 x 12 weeks) diminished the excretion of hydroxypyridinium crosslinks, and favoured the diastolic blood pressure. The consumption of moderate doses of n-3 LC-PUFA in combination with dairy products did not improve the disease activity. However, there is evidence of cardioprotective effects. Furthermore, the long-term consumption of dairy products acts against the cartilage and bone destruction in RA.

Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19245735&dopt=ExternalLink

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PMID: 19245735 [PubMed - indexed for MEDLINE]

12: Osteoarthritis Cartilage. 2009 Jul;17(7):896-905. Epub 2009 Jan 13.

Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis.

Zainal Z, Longman AJ, Hurst S, Duggan K, Caterson B, Hughes CE, Harwood JL.

School of Biosciences, Cardiff University, Cardiff, UK.

OBJECTIVE: To assess the relative efficacy of three different omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in suppressing the mRNA levels for important proteins involved in the etiology of osteoarthritis (OA). METHODS: A model cell culture system (bovine chondrocytes) was used. Inflammatory factors and enzymes involved in OA were induced by exposure of the chondrocyte cultures to interleukin-1alpha (IL-1alpha). The effect of pre-incubating cultures with various amounts of exogenous fatty acids on subsequent levels of mRNAs was assessed by reverse transcription-polymerase chain reactions (RT-PCR). RESULTS: Exposure of cultures to IL-1alpha induced expression of the cartilage proteinases A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS)-4 and ADAMTS-5, cyclooxygenase (COX)-2, the matrix metalloproteinase (MMP)-3 and the inflammatory cytokines IL-1alpha, interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). n-3 PUFAs were able to reduce the levels of mRNA for ADAMTS-4, ADAMTS-5, MMP-3, MMP-13, COX-2 (but not COX-1), IL-1alpha, IL-1beta and TNF-alpha. Eicosapentaenoic acid (EPA) was the most effective, followed by docosahexaenoic (DHA) and then alpha-linolenic (ALA) acid. The n-6 PUFA, arachidonic acid (AA) had no effect. CONCLUSION: These results show that omega-3 (n-3) PUFAs cause a reduction in the mRNA levels for various proteins known to be important in the pathology of OA. They provide a molecular explanation, at least in part, for beneficial effects of dietary omega-3 PUFAs for the amelioration of symptoms of the disease. The relative efficacy of EPA suggests that this omega-3 PUFA may be especially useful for dietary supplementation in patients with OA.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19217322&dopt=ExternalLink

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PMID: 19217322 [PubMed - indexed for MEDLINE]

13: Proc Nutr Soc. 2008 Nov;67(4):409-18.

Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on 'Nutrition and autoimmune disease' PUFA, inflammatory processes and rheumatoid arthritis.

Calder PC.

Institute of Human Nutrition, School of Medicine, University of Southampton, IDS Building, MP887, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. pcc@soton.ac.uk

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18847518&dopt=ExternalLink

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PMID: 18847518 [PubMed - indexed for MEDLINE]

14: Rheum Dis Clin North Am. 2008 May;34(2):469-79.

Dietary omega-3 fats for treatment of inflammatory joint disease: efficacy and utility.

Proudman SM, Cleland LG, James MJ.

Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.

There is high level evidence (meta-analysis of randomized, controlled trials) for symptomatic benefits from fish oil use in rheumatoid arthritis, and there is biologic plausibility for its clinical effects. Fish oil also has safety advantages in reducing cardiovascular risk via direct cardiovascular effects and via nonsteroidal anti-inflammatory drug-sparing. This is an important aspect of fish oil use, given the increased cardiovascular risk in rheumatoid arthritis. Perceived barriers to clinical use are readily addressed.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18638687&dopt=ExternalLink

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PMID: 18638687 [PubMed - indexed for MEDLINE]

15: Rev Med Brux. 2006 Sep;27(4):S355-60.

[Omega-3 and health]

[Article in French]

Herbaut C.

Service de Medecine Interne/Endocrino-Diabetologie, C.H.U. Brugmann, Bruxelles.

N-3 PUFA (omega-3), and the n-6 PUFA (omega-6) are essential fatty acids. They must be absorbed by alimentation and play a very important role in the coagulation (inhibition of platelets aggregation) and in the inflammatory reaction (anti-inflammatory effects). Their effects have been studied in different sicknesses. In cardiovascular diseases, particularly in coronary diseases, studies demonstrated a decreased mortality in populations who eat an omega-3 rich diet or who take an omega-3 supplement. Among others, sudden death after myocardial infarction is decreased. In inflammatory diseases an effect seem to be found in some studies. In rheumatoid arthritis a decrease of different biological markers of inflammation and in some case a clinical improvement has been noticed. It may be the same in COPD. On the other hand, they seem not to give any protection against cancer in general. At this moment the recommendations for healthy people are to eat twice a week fat fish and to take omega-3 rich oils. For pathological cases, recommendations exist only for coronary disease: 1 g of fish oils : mixture of eicosapentaenoic and docosahexaenoic acids (EPA/DHA) should be given after a myocardial infarction.

Publication Types: English Abstract

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17091903&dopt=ExternalLink

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PMID: 17091903 [PubMed - indexed for MEDLINE]

16: Scand J Rheumatol. 2006 Sep-Oct;35(5):359-62.

Supplementation of omega-3 fatty acids in patients with ankylosing spondylitis.

Sundstrom B, Stalnacke K, Hagfors L, Johansson G.

Department of Medical Rehabilitation, Gallivare Hospital, Sweden. bjorn.sundstrom@nll.se

OBJECTIVE: To study the effect of supplementation with omega-3 fatty acids on disease variables and drug consumption in patients with ankylosing spondylitis (AS). METHODS: Twenty-four patients were randomized to either a low-dose (1.95 g omega-3/day) or a high-dose (4.55 g omega-3/day) supplement. Disease activity, functional impairment, erythrocyte sedimentation rate (ESR), and drug consumption were assessed during visits at baseline and at weeks 7, 14, and 21. RESULTS: Eighteen patients completed the study, nine patients from each group. The patients in the high-dose group exhibited a significant decrease in disease activity according to the Bath Ankylosing Disease Activity Index (BASDAI; p = 0.038), which was not seen in the low-dose group. Significant differences were not found on drug consumption or in functional capacity in either of the groups. No significant differences were found when comparing the results between the high- and low-dose groups. CONCLUSION: Omega-3 fatty acids in adequate doses may have the capacity to decrease the disease activity of AS. However, larger and better controlled studies are needed before any further conclusions can be made on the extent of this capacity.

Publication Types: Randomized Controlled Trial

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17062435&dopt=ExternalLink

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PMID: 17062435 [PubMed - indexed for MEDLINE]

17: Nutr Clin Pract. 2006 Aug;21(4):323-41.

Current clinical applications of omega-6 and omega-3 fatty acids.

Lee S, Gura KM, Kim S, Arsenault DA, Bistrian BR, Puder M.

Children's Hospital Boston, 300 Longwood Ave., MA 02115, USA.

BACKGROUND: Recent years have brought a resurgence of research interest in fatty acids, with studied fields running the gamut of human disease. This movement has run in parallel with an increased interest in using nutrition modalities as therapeutic measures, as opposed to their conventional role as energy sources. The aim of this manuscript is to provide a basic review of current clinical applications of omega-6 and omega-3 fatty acids, with a particular focus on the latter. METHODS: A selective review of the voluminous literature, including randomized controlled trials, meta-analyses, population studies, and case reports, was used to compile data and identify trends in pertinent clinical applications of fatty acid therapy. CONCLUSIONS: There are a myriad of disorders and maladies that seem to benefit from fatty acid supplementation, specifically omega-3 fatty acids. It has clearly been shown that omega-3 fatty acid supplementation provides a protective benefit in heart disease, and in particular sudden cardiac death. Rheumatoid arthritis (RA) is another disease entity that has been proven to benefit from this nutrition intervention, with improvement in symptoms and diminished nonsteroidal antiinflammatory drug (NSAID) usage. In addition, many psychiatric disorders, particularly schizophrenia and major depressive disorder (MDD), have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. The remainder of clinical applications for omega-3 fatty acids requires further investigation. Specifically, according to preliminary clinical evidence, parenteral administration of fatty acids warrants further study.

Publication Types: Meta-Analysis Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=16870801&dopt=ExternalLink

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PMID: 16870801 [PubMed - indexed for MEDLINE]

18: Lipids. 2006 Jan;41(1):29-34.

Intravenous application of omega-3 fatty acids in patients with active rheumatoid arthritis. The ORA-1 trial. An open pilot study.

Leeb BF, Sautner J, Andel I, Rintelen B.

Second Department of Medicine, Lower Austrian Center for Rheumatology, Humanisklinikum Lower Austria, Stockerau, Austria. leeb.humanis@kav-kost.at

The objective of this work was to assess the therapeutic efficacy and tolerability of intravenously applied n-3-PUFA in patients with active rheumatoid arthritis (RA). Thirty-four patients with active RA [identified as having a DAS28 (disease activity score including a 28 joint count) > 4.0] were enrolled into this 5-wk open pilot study (one group design). From the time of screening (visit 0, or V0), background therapy had to remain unchanged. Patients received 2 mL/kg (= 0.1-0.2 g fish oil/kg) fish oil emulsion intravenously on 7 consecutive days (Visit 1-Visit 2, or V1-V2) in addition to their background therapy. A decrease of the DAS28 > 0.6 at day 8 (Visit 2) was the primary efficacy measure. Moreover, the DAS28 at day 35 (Visit 3, or V3), the modified Health Assessment Questionnaire, the American College of Rheumatology (ACR) response criteria (V2, V3) and the Short Form-36 (V3) were assessed. Thirty-three patients completed the trial. The mean DAS28 at V1 was 5.45;at V2, 4.51 (P < .001 V1-V2) and at V3, 4.73 (P < .001 V1-V3; V2-V3, not significantly different). Of the 34 patients, 56% achieved a reduction of the DAS28 > 0.6 at V2 (mean 1.52); 27% > 1.2. At V3, 41% of the patients showed a DAS28 reduction > 0.6 (mean 1.06), and 36% > 1.2. ACR 20 and 50% responses at V2 were seen in 29 and 12% of patients, respectively; at V3, the comparable values were 18 and 9%, respectively. Overall tolerability was excellent. Intravenous application of n-3-PUFA (as an add-on therapy) was considerably well tolerated and led to improvement of the disease activity status in a reasonable number of RA patients. Future trials are warranted to answer whether the intravenous application of n-3-PUFA constitutes a therapeutic option in RA patients.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=16555468&dopt=ExternalLink

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PMID: 16555468 [PubMed - indexed for MEDLINE]

19: J Am Coll Nutr. 2005 Jun;24(3):200-9.

Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids.

Bhattacharya A, Rahman M, Banu J, Lawrence RA, McGuff HS, Garrett IR, Fischbach M, Fernandes G.

Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/lpr mice model of arthritis and in humans. METHODS: In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints. RESULTS: At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice. CONCLUSIONS: These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.

Publication Types: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=15930486&dopt=ExternalLink

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PMID: 15930486 [PubMed - indexed for MEDLINE]

20: Adv Ther. 2004 May-Jun;21(3):197-201.

Efficacy and tolerability of a combination of Lyprinol and high concentrations of EPA and DHA in inflammatory rheumatoid disorders.

Gruenwald J, Graubaum HJ, Hansen K, Grube B.

PhytoPharm Consulting, Institute for Phytopharmaceuticals, Berlin, Germany.

This 12-week drug-monitoring study was conducted to evaluate the efficacy of Sanhelios Mussel Lyprinol Lipid Complex on 50 adult men and women with inflammatory rheumatoid arthritis. A total of 34 patients required drug therapy before and during the study. By the end of the study, 21 (62%) patients were able to reduce their dosage and 13 were able to terminate drug therapy. At the end of the treatment period, 38% were regarded symptom free, and the number of patients with severe pain decreased significantly from 60% at baseline to 25% at the completion of the trial. A significant effect was observed for each investigated parameter. The special combination of Lyprinol and omega-3 fatty acids was generally very well tolerated, with only one, nonserious adverse event (mild nausea) reported. This dietary supplement may therefore be considered an effective and well-tolerated component of treatment regimens for inflammatory rheumatoid arthritis.

Publication Types: Comparative Study Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=15509136&dopt=ExternalLink

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PMID: 15509136 [PubMed - indexed for MEDLINE]

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