Effects of fish oil supplementation in rheumatoid arthritis. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Long-term moderate intervention with n-3 long-chain PUFA-supplemented dairy products: effects on pathophysiological biomarkers in patients with rheumatoid arthritis. Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. Effect of six months of fish oil supplementation in stable rheumatoid arthritis. A double-blind, controlled study. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study. Effect of n-3 polyunsaturated fatty acid supplementation in patients with rheumatoid arthritis: a 16-week randomized, double-blind, placebo-controlled, parallel-design multicenter study in Korea. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. EFFECTS OF MANIPULATION OF DIETARY FATTY ACIDS ON CLINICAL MANIFESTATIONS OF RHEUMATOID ARTHRITIS Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study.
Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids . A r and omised , double blind , placebo controlled crossover design with 12 week treatment periods was used . Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study . Placebo consisted of fractionated coconut oil . The following results favoured fish oil rather than placebo :  joint swelling index and duration of early morning stiffness . Other clinical indices improved but did not reach statistical significance . During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased , mainly at the expense of the omega-6 fatty acids . The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation . Leucotriene B5 production , which could not be detected either in the control or in the placebo period , rose to substantial quantities during fish oil treatment . This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis OBJECTIVES Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA . The n-3 essential fatty acids ( EFAs ) have previously demonstrated some anti-inflammatory and NSAID-sparing properties . The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA . METHODS Dual-centre , double-blind placebo-controlled r and omized study of 9 months ' duration . Ninety-seven patients with RA were r and omized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or air-filled identical placebo capsules . Documentation of NSAID daily requirement , clinical and laboratory parameters of RA disease activity and safety checks were done at 0 , 4 , 12 , 24 and 36 weeks . At 12 weeks , patients were instructed to gradually reduce , and if possible , stop their NSAID intake . Relative reduction of daily NSAID requirement by > 30 % after 9 months was the primary outcome measure . RESULTS Fifty-eight patients ( 60 % ) completed the study . Out of 49 patients 19 ( 39 % ) in the cod liver oil group and out of 48 patients 5 ( 10 % ) in the placebo group were able to reduce their daily NSAID requirement by > 30 % ( P = 0.002 , chi-squared test ) . No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed . CONCLUSIONS This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients 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 r and omly 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 sample s 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 In a controlled , double blind , clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo , respectively , in 67 patients with active rheumatoid arthritis . The patients were r and omized into 3 groups that received the following treatment : Group 1 , corn oil ( " placebo omega-3 fatty acids " ) , 7 g/day for 16 weeks , and naproxen , 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks ; Group 2 , omega-3 fatty acids , 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid , and naproxen , 750 mg/day for 16 weeks ; and Group 3 , omega-3 fatty acids as Group 2 and naproxen as Group 1 . At the end of the trial , patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient . In Groups 1 and 3 there was a significant deterioration for most of the variables measured . However , for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1 . These effects might be ascribed to the dietary omega-3 fatty acid supplementation Therapeutic effects of fish oil ( 10 g/day ) in rheumatoid arthritis were investigated in a r and omized , controlled , double-blind study . Forty-three patients completing the study were evaluated at 0 , 3 and 6 months . The nutrient intake in the fish oil group and in the control group was essentially similar . In the fish oil group , the percentage of n-3 fatty acids in serum phosphatidylcholine increased by 9.6 ( range 2.6 - 16.1 ) . Patients in the fish oil group reported a significantly decreased consumption of NSAID at 3 and 6 months , and the status of global arthritic activity improved at 3 months in physician 's assessment . Control patients reported an increased global arthritic activity at 6 months . No change was found in patient assessment of pain , duration of morning stiffness or functional capacity . Essentially no change occurred in biochemical markers of inflammation . We conclude that fish oil has small anti-inflammatory effects with at most a NSAID-saving potential . The value of prolonged supplementation remains to be evaluated OBJECTIVE This study evaluated whether supplementation with olive oil could improve clinical and laboratory parameters of disease activity in patients who had rheumatoid arthritis and were using fish oil supplements .  METHODS Forty-three patients ( 34 female , 9 male ; mean age = 49 + /- 19y ) were investigated in a parallel r and omized design . Patients were assigned to one of three groups . In addition to their usual medication , the first group ( G1 ) received placebo ( soy oil ) , the second group ( G2 ) received fish oil omega-3 fatty acids ( 3 g/d ) , and the third group ( G3 ) received fish oil omega-3 fatty acids ( 3 g/d ) and 9.6 mL of olive oil .  Disease activity was measured by clinical and laboratory indicators at the beginning of the study and after 12 and 24 wk . Patients ' satisfaction in activities of daily living was also measured . RESULTS There was a statistically significant improvement ( P < 0.05 ) in G2 and G3 in relation to G1 with respect to joint pain intensity , right and left h and grip strength after 12 and 24 wk , duration of morning stiffness , onset of fatigue , Ritchie 's articular index for pain joints after 24 wk , ability to bend down to pick up clothing from the floor , and getting in and out of a car after 24 wk . G3 , but not G2 , in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 wk , patient global assessment after 12 and 24 wk , ability to turn faucets on and off after 24 wk , and rheumatoid factor after 24 wk . In addition , G3 showed a significant improvement in patient global assessment in relation to G2 after 12 wk . CONCLUSIONS Ingestion of fish oil omega-3 fatty acids relieved several clinical parameters used in the present study . However , patients showed a more precocious and accentuated improvement when fish oil supplements were used in combination with olive oil OBJECTIVE To determine the efficacy of fish oil derived ( n-3 ) fatty acid supplementation ( 3 - 6 capsules/day ) in subjects with rheumatoid arthritis ( RA ) whose ( n-6 ) fatty acid intake in the background diet was < 10 g/day , compared to olive/corn oil capsule supplement over a 15 week period . METHODS A placebo controlled , double blind , r and omized 15 week study to determine the effect of supplementation on clinical variables in 50 subjects with RA whose background diet was naturally low in ( n-6 ) fatty acids .  Fish oil containing 60 % ( n-3 ) fatty acids was supplemented at a rate of 40 mg/kg body weight . RESULTS Analysis of 9 clinical variables indicated there was a significant difference ( p < 0.02 ) between control and treatment groups . Five subjects in the treatment group and 3 in the control group met the American College of Rheumatology 20 % improvement criteria . Dietary supplementation result ed in a significant increase in eicosapentaenoic acid in plasma and monocyte lipids in the supplemented group . CONCLUSION The findings suggest that fish oil supplementation that delivers ( n-3 ) fatty acids at a dose of 40 mg/kg body weight/day , with dietary ( n-6 ) fatty acid intake < 10 g/day in the background diet , results in substantial cellular incorporation of ( n-3 ) fatty acids and improvements in clinical status in patients with RA 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 prostagl and ins ( ' 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 review ed 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 N-3 polyunsaturated fatty acids ( PUFA ) have anti-inflammatory effects and may be useful for the treatment of inflammatory diseases such as rheumatoid arthritis (RA).We examined the efficacy of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) supplementation on RA on top of st and ard anti-inflammatory treatment . Patients with RA were r and omized into two groups in a double-blind , placebo-controlled , parallel- design multicenter study . One hundred nine patients received five capsules of either n-3 PUFA ( 2.090 g of EPA and 1.165 g of DHA ) or high-oleic-acid sunflower oil for 16 weeks . Eighty-one patients completed the study , and no adverse effects were reported . Dietary intake did not change significantly during the study . There were significant increases in n-3 PUFA and EPA levels in erythrocytes in the n-3 PUFA group versus the placebo group , but decreases in n-6 PUFA , 18:2n6 , 20:4n6 and 18:1n9 levels in the n-3 PUFA group versus the placebo group . N-3 PUFA supplementation had no significant effects on nonsteroidal anti-inflammatory drug ( NSAID ) requirements , clinical symptoms of RA or the concentration of cytokines , eicosanoids and bone turnover markers . However , n-3 PUFA supplementation significantly decreased NSAID requirements and leukotriene B4 levels in patients who weighed more than 55 kg . Our results suggest that n-3 PUFA supplementation has no significant effect on RA but may decrease the requirement for NSAIDs in Korean patients with RA who weigh more than 55 kg OBJECTIVE To determine the following : 1 ) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs ( NSAIDs ) in patients with rheumatoid arthritis ( RA ) ; 2 ) the clinical efficacy of high-dose dietary omega 3 fatty acid fish oil supplementation in RA patients ; and 3 ) the effect of fish oil supplements on the production of multiple cytokines in this population . METHODS Sixty-six RA patients entered a double-blind , placebo-controlled , prospect i ve study of fish oil supplementation while taking diclofenac ( 75 mg twice a day ) . Patients took either 130 mg/kg/day of omega 3 fatty acids or 9 capsules/day of corn oil . Placebo diclofenac was substituted at week 18 or 22 , and fish oil supplements were continued for 8 weeks ( to week 26 or 30 ) . Serum levels of interleukin-1 beta ( IL-1 beta ) , IL-2 , IL-6 , and IL-8 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay at baseline and during the study . RESULTS In the group taking fish oil , there were significant decreases from baseline in the mean ( + /- SEM ) number of tender joints ( 5.3 + /- 0.835 ; P < 0.0001 ) , duration of morning stiffness ( -67.7 + /- 23.3 minutes ; P = 0.008 ) , physician 's and patient 's evaluation of global arthritis activity ( -0.33 + /- 0.13 ; P = 0.017 and -0.38 + /- 0.17 ; P = 0.036 , respectively ) , and physician 's evaluation of pain ( -0.38 + /- 0.12 ; P = 0.004 ) . In patients taking corn oil , no clinical parameters improved from baseline . The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil ( -7.8 + /- 2.6 ; P = 0.011 ) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil ( P = 0.043 ) . IL-1 beta decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil ( -7.7 + /- 3.1 ; P = 0.026 ) . CONCLUSION Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline , including the number of tender joints , and these improvements are associated with significant decreases in levels of IL-1 beta from baseline . Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare Background . Patients with rheumatoid arthritis ( RA ) improve on a vegetarian diet or supplementation with fish oil . We investigated the effects of both dietary measures , alone and in combination , on inflammation , fatty acid composition of erythrocyte lipids , eicosanoids , and cytokine bio synthesis in patients with RA . Methods . Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each . One group was observed for 8 months on a normal western diet ( WD ) and the other on an anti-inflammatory diet ( AID ) providing an arachidonic acid intake of less than 90 mg/day . Patients in both groups were allocated to receive placebo or fish oil capsules ( 30 mg/kg body weight ) for 3 months in a double-blind crossover study with a 2-month washout period between treatments . Clinical examination and routine laboratory findings were evaluated every month , and erythrocyte fatty acids , eicosanoids , and cytokines were evaluated before and after each 3-month experimental period . Results . Sixty patients completed the study . In AID patients , but not in WD patients , the numbers of tender and swollen joints decreased by 14 % during placebo treatment . In AID patients , as compared to WD patients , fish oil led to a significant reduction in the numbers of tender ( 28 % vs 11 % ) and swollen ( 34 % vs 22 % ) joints ( P<0.01 ) . Compared to baseline levels , higher enrichment of eicosapentaenoic acid in erythrocyte lipids ( 244 % vs 217 % ) and lower formation of leukotriene B4 ( 34 % vs 8 % , P>0.01 ) , 11-dehydro-thromboxane B2 ( 15 % vs 10 % , P<0.05 ) , and prostagl and in metabolites ( 21 % vs 16 % , P<0.003 ) were found in AID patients , especially when fish oil was given during months 6–8 of the experiment . Conclusion . A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation 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 , r and omized 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 STUDY OBJECTIVE To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids ( n-3 PUFA ) on disease variables in patients with rheumatoid arthritis . DESIGN Multicenter , r and omized , placebo controlled , double blind . SETTING Three Danish hospital Departments of Rheumatology . PATIENTS Fifty-one patients with active rheumatoid arthritis . INTERVENTION R and om allocation to 12 weeks of treatment with either six n-3 PUFA capsules ( 3.6 g ) or six capsules with fat composition as the average Danish diet . MAIN RESULTS Significant improvement of morning stiffness and joint tenderness . No significant effect on the four other assessed clinical parameters . No serious side effects . CONCLUSIONS Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters . Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis The effects of manipulation of dietary fatty acids in patients with rheumatoid arthritis were investigated in a 12-week , prospect i ve , 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 The primary objective of this study was to determine whether it is the fish oil itself or the alpha-tocopherol that is added to the fish oil preparations ( to prevent peroxidation ) that is responsible for the beneficial effects of dietary supplementation with fish oil in patients with rheumatoid arthritis ( RA ) . One group of RA patients took fish oil supplements and another group took alpha-tocopherol-enriched coconut oil supplements ( placebo controls ) , both for 3 months . Clinical and laboratory indices of RA activity in relation to cellular and plasma vitamin E levels were assessed at the beginning and the end of the trial . The results of the study provide evidence that the beneficial effects of fish oil supplementation can not be ascribed to the antioxidizing properties of the alpha-tocopherol per se In a double blind noncrossover study , dietary supplementation with fish oil ( 18 g/day ) , was compared with an olive oil supplement over a 12-week period in patients with rheumatoid arthritis receiving established conventional therapies . An improvement in tender joint score and grip strength was seen at 12 weeks in the fish oil treated group but not in the olive oil treated group . The more subjective measures of mean duration of morning stiffness and analogue pain score improved to a similar extent in both groups , although statistical significance was only achieved in paired analyses in the olive oil treated group . Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30 % in the fish oil treated group and unchanged in the olive oil treated group STUDY OBJECTIVE to determine the efficacy of fish-oil dietary supplements in active rheumatoid arthritis and their effect on neutrophil leukotriene levels . DESIGN nonr and omized , double-blinded , placebo-controlled , crossover trial with 14-week treatment periods and 4-week washout periods . SETTING academic medical center , referral-based rheumatology clinic . PATIENTS forty volunteers with active , definite , or classical rheumatoid arthritis . Five patients dropped out , and two were removed for noncompliance . INTERVENTIONS treatment with nonsteroidal anti-inflammatory drugs , slow-acting antirheumatic drugs , and prednisone was continued . Twenty-one patients began with a daily dosage of 2.7 g of eicosapaentanic acid and 1.8 g of docosahexenoic acid given in 15 MAX-EPA capsules ( R.P. Scherer , Clearwater , Florida ) , and 19 began with identical-appearing placebos . The background diet was unchanged . MEASUREMENTS AND MAIN RESULTS the following results favored fish oil placebo after 14 weeks : mean time to onset of fatigue improved by 156 minutes ( 95 % confidence interval , 1.2 to 311.0 minutes ) , and number of tender joints decreased by 3.5 ( 95 % Cl , -6.0 to -1.0 ) . Other clinical measures favored fish oil as well but did reach statistical significance . Neutrophil leukotriene B4 production was correlated with the decrease in number of tender joints ( Spearman rank correlation r=0.53 ; p less than 0.05 ) . There were no statistically significant differences in hemoglobin level , sedimentation rate , or presence of rheumatoid factor or in patient-reported adverse effects . An effect from the fish oil persisted beyond the 4-week washout period . CONCLUSIONS fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production . Further studies are needed to eluci date mechanisms of action and optimal dose and duration of fish-oil supplementation
OBJECTIVES Pain is a significant problem in rheumatoid arthritis ( RA ) and is associated with prostagl and ins derived from the ω-6 polyunsaturated fatty acid ( PUFA ) arachidonic acid .
The ω-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid have been shown to reduce inflammation , with some studies showing clinical improvements in RA .
The aim of this systematic review was to investigate the effect of ω-3 PUFAs on arthritic pain .