Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs. 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. Interpreting estimates of treatment effects: implications for managed care. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed 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. A randomized, double-blinded, placebo-controlled study of the effect of a combination of lemon verbena extract and fish oil omega-3 fatty acid on joint management. 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. Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans. Treatment of rheumatoid arthritis with blackcurrant seed oil. 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. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: A randomized trial Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Nutritional status of Danish rheumatoid arthritis patients and effects of a diet adjusted in energy intake, fish-meal, and antioxidants. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects Effect of omega-3 fatty acids on intensity of primary dysmenorrhea. The nuts and bolts of PROSPERO: an international prospective register of systematic reviews Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea. 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. Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis EFFECTS OF MANIPULATION OF DIETARY FATTY ACIDS ON CLINICAL MANIFESTATIONS OF RHEUMATOID ARTHRITIS Vitamin E and evening primrose oil for management of cyclical mastalgia: a randomized pilot study. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. Treatment of Rheumatoid Arthritis with Gammalinolenic Acid Diet therapy for rheumatoid arthritis. A controlled double-blind study of two different dietary regimens. Effects of n-3 fatty acids on serum interleukin-6, tumour necrosis factor-alpha and soluble tumour necrosis factor receptor p55 in active rheumatoid arthritis. Effect of Clupeonella grimmi (anchovy/kilka) fish oil on dysmenorrhoea. gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. A randomized multicenter study of gamolenic acid (Efamast) with and without antioxidant vitamins and minerals in the management of mastalgia. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study. Evaluation of the effect of omega-3 fatty acids in the treatment of premenstrual syndrome: "a pilot trial".
Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospect i ve 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day . Nineteen patients received active therapy ( as evening primrose oil 6 g/day ) and 21 received placebo ( olive oil 6 g/day ) . No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose . Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil . Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis , olive oil may itself have hitherto unrecognized benefits 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 How should health care professionals choose among the many therapies cl aim ed to be efficacious for treating specific disorders ? The practice of evidence -based medicine provides an answer . Advocates of this approach urge health care professionals to base treatment choices on the best evidence from systematic research on both the efficacy and adverse effects of various therapeutic alternatives . Ideally , health care professionals would compare different treatments by referring to r and omized , double-blind , head-to-head trials that compared the treatment options . Although individual medications are typically well research ed when these placebo-controlled studies are performed , studies that directly compare treatments are rare . In the absence of direct head-to-head trials , other evidence comes from indirect comparisons of two or more therapies by examining individual studies involving each treatment . This article provides an introductory review of methods of such indirect comparisons of therapies across studies , provides examples of how these methods can be used to make treatment decisions , and presents a general overview of relevant issues and statistics for readers interested in underst and ing these methods more thoroughly Forty-nine patients with active rheumatoid arthritis completed a 24-week , prospect i ve , double-blind , r and omized 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 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 In rheumatoid arthris s various pro-inflammatory metabolites of arachidonic acid ( AA ) , such as leukotriene B4 ( LTB4 ) and prostagl and in E2 ( PGE2 ) , contribute to tissue destruction and pain . In contrast to AA , which is an omega-6 fatty acid , the omega-3 fatty acids , after having been liberated from the cell membrane phospholipids , are further converted into the non-or anti-inflammatory eicosanoids LTB5 and PGI3 . AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens . Dietary supplementation with eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects . EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid ( alpha-LNA ) found in flaxseed oil . We , therefore , performed a placebocontrolled trial with alpha-LNA in 22 patients with rheumatoid arthritis , using a linoleic acid preparation as a placebo . After a 3-month follow-up , the treatment group showed an increased bleeding time , but the clinical , subjective ( global assessment , classification of functional status , joint score index , visual analogue scale , pain tendereness score ) and laboratory parameters ( haemoglobin , erythrocyte sedimentation rate , C-reactive protein ) did not show any statistical alterations . AA , EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group . Thus , 3-month 's supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis 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 OBJECTIVES The aim of this study was to test the efficacy of an antioxidant/anti-inflammatory supplement containing st and ardized lemon verbena ( Aloysia triphylla , Lippia citriodora ) extract and fish oil omega-3 fatty acid in a human pilot trial as an alternative treatment for joint management . METHODS AND DESIGN First , antioxidant activity of the supplement was determined through an oxygen radical absorbance capacity ( ORAC ) assay . In a r and omized , double-blinded placebo-controlled trial , 45 subjects with pain discomfort received the nutritional supplement or placebo for 9 weeks . Western Ontario MacMaster ( WOMAC ) and Lequesne 's question naires , which are disease-specific measurements vali date d to measure joint dysfunction and pain , were administered and evaluated once per week in the placebo and intervention groups . OUTCOME MEASURES Pain and stiffness symptoms , and joint function were determined once per week through recording their respective WOMAC and Lequesne 's scores in the placebo and intervention groups . Statistically significant differences were determined at every measurement point between the two groups . RESULTS Lemon verbena extract showed strong antioxidant properties as measured by the ORAC assay . The nutritional supplement containing st and ardized lemon verbena extract ( 14 % verbascoside , w/w ) and fish oil omega-3 fatty acid reduced symptoms of pain and stiffness significantly , and improved physical function as shown by WOMAC and Lequesne 's scores after 9 weeks of treatment . WOMAC and Lequesne 's total scores decreased 53 % and 78 % , respectively , at the end of the study compared to initial conditions . Onset of the effect was observed at the third and fourth weeks , when statistically significant differences were detected , compared to placebo . CONCLUSIONS This pilot study reveals that supplementation with lemon verbena combined with omega-3 fatty acids may be considered for further investigation as a complementary and alternative treatment for improving joint status in subjects with joint discomfort 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 The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil , bilberry extract , and lutein on subjective symptoms of asthenopia in humans by a double- blind , r and omized , parallel-group , and placebo-controlled trial . In the Active group , eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil ( docosahexaenoic acid 783 mg/day , eicosapentaenoic acid 162 mg/day ) , bilberry extract ( anthocyanidin 59 mg/day ) , and lutein ( 17.5 mg/day ) in soft gel capsule form , every day for 4 weeks . In the Placebo group , nine subjects ingested placebo capsules . Before and after supplementation , subjects completed a question naire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale ( VAS ) test . Asthenopia symptoms such as " stiff shoulder , low back pain " , " frustration " , " dry-eye " , and " stuffy head " were improved in the Active group . Furthermore , a score of mental fatigue was improved after 4 weeks of supplementation , and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group . These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil , bilberry extract , and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans The objective of this study was to assess the clinical efficacy and side effects of blackcurrant seed oil ( BCSO ) , in a r and omized , double-blind , placebo controlled , 24-week trial in patients with RA and active synovitis .  BCSO is rich in gammalinolenic acid ( GLA ) and alphalinolenic acid ( ALA ) . Both GLA and eicosapentaenoic acid which derives from ALA suppress inflammation and joint tissue injury in animal models . Treatment with BCSO result ed in reduction in signs and symptoms of disease activity in patients with RA ( P < 0.05 ) . In contrast , patients given a  placebo  showed no change in disease . Overall clinical responses ( significant change in four measures ) were no better in the treatment group than in the placebo group . No patients withdrew from BCSO treatment because of adverse reactions . However , many patients withdrew because BCSO and its placebo had to be administered in 15 large capsules daily . Nonetheless , the study indicates that BCSO is a potentially effective treatment for active RA . However , means must be found to reduce the size and number of capsules taken , so that larger studies of longer duration in RA patients can be done 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 Summary A dietary intervention increasing n‐3 and reducing n‐6 fatty acids reduced headache pain , altered antinociceptive lipid mediators , and improved quality of life in a chronic headache population . Abstract Omega‐3 and n‐6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties . We conducted a r and omized , single‐blinded , parallel‐group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n‐3 and n‐6 fatty acids for treatment of chronic headaches . After a 4‐week preintervention phase , ambulatory patients with chronic daily headache undergoing usual care were r and omized to 1 of 2 intensive , food‐based 12‐week dietary interventions : a high n‐3 plus low n‐6 ( H3‐L6 ) intervention , or a low n‐6 ( L6 ) intervention . Clinical outcomes included the Headache Impact Test ( HIT‐6 , primary clinical outcome ) , Headache Days per month , and Headache Hours per day . Biochemical outcomes included the erythrocyte n‐6 in highly unsaturated fatty acids ( HUFA ) score ( primary biochemical outcome ) and bioactive n‐3 and n‐6 derivatives . Fifty‐six of 67 patients completed the intervention . Both groups achieved targeted intakes of n‐3 and n‐6 fatty acids . In intention‐to‐treat analysis , the H3‐L6 intervention produced significantly greater improvement in the HIT‐6 score ( −7.5 vs −2.1 ; P < 0.001 ) and the number of Headache Days per month ( −8.8 vs −4.0 ; P = 0.02 ) , compared to the L6 group . The H3‐L6 intervention also produced significantly greater reductions in Headache Hours per day ( −4.6 vs −1.2 ; P = 0.01 ) and the n‐6 in HUFA score ( −21.0 vs −4.0 % ; P < 0.001 ) , and greater increases in antinociceptive n‐3 pathway markers 18‐hydroxy‐eicosapentaenoic acid ( + 118.4 vs + 61.1 % ; P < 0.001 ) and 17‐hydroxy‐docosahexaenoic acid ( + 170.2 vs + 27.2 ; P < 0.001 ) . A dietary intervention increasing n‐3 and reducing n‐6 fatty acids  reduced headache pain , altered antinociceptive lipid mediators , and improved quality ‐of‐life in this population 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 This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation . In a prospect i ve , single-blinded study of 6 months duration , 109 patients with active RA were r and omly assigned to either treatment with or without a specialized diet . The energy consumption was adjusted to normal st and ards of body weights and the intake of fish meals and antioxidants were increased . A daily food diary was completed by the patients , and the total intake of 47 different food-elements was calculated . Nutritional status together with disease activity parameters were recorded . At baseline , the Danish RA- patients had neglected food habits with a significant reduction in intake of total energy , of D-vitamin  and of E-vitamin .  A very low intake of n-3 fatty acids was also found . During the study , 28 of the 109 patients dropped out , introducing a confounding effect on the overall result . In the remaining 81 , those following the diet demonstrated a significant improvement in the duration of morning stiffness , number of swollen joints , pain status , and reduced cost of medicine , while doctors global assessment , laboratory data , X-ray , and daily activities were unaltered . In conclusion , dietary analysis and appropriate , corrective advice should be offered to Danish RA patients OBJECTIVES The hypothesis tested was that menstrual discomfort , e.g. dysmenorrhoea , known to be prostagl and in-mediated , can be influenced by the dietary ratio of n-3 and n-6 polyunsaturated fatty acids . The prostagl and ins derived from marine n-3 fatty acids are normally less aggressive and therefore expected to be associated with milder symptoms . DESIGN The question was surveyed in an epidemiological study based upon self-administered question naires concerning menstrual history , present symptoms , general health , socioeconomic factors , and general dietary habits . Two ( prospect i ve ) 4-day dietary records were used to estimate average daily nutrient intake . SUBJECTS The subjects were recruited by advertising ( about 220 volunteered ) ; 181 healthy Danish women were selected , aged 20 - 45 years ; they were not pregnant and did not use oral contraceptives . RESULTS No correlations were found between socioeconomic or anthropometric data and menstrual problems . On the contrary certain dietary habits , e.g. low intake of animal and fish products , and intakes of specific nutrients , were correlated with menstrual pain . The average dietary n-3/n-6 ratio of women with menstrual pain was 0.24 . It was significantly higher among those with low intake of B12 coincident with low intake of n-3 ( 0.42 , P < 0.001 ) ( chi-square ) , with low n-3 intake coincident with low n-3/n-6 ratio ( 0.42 , P < 0.005 ) , and finally with low intake of B12 coincident with low n-3/n-6 ratio ( 0.47 , P < 0.001 ) . CONCLUSION The results were highly significant and mutually consistent and supported the hypothesis that a higher intake of marine n-3 fatty acids correlates with milder menstrual symptoms Objective : To investigate in a double-blind placebo-controlled , parallel group study , the effects of a nutrient supplement , containing , among other ingredients , the omega-3 fatty acids eicosapentaenoic acid ( 1.4 g EPA ) , docosahexaenoic acid ( 0.211 g DHA ) , omega-6 fatty acid gamma-linolenic acid ( 0.5 g GLA ) and micronutrients in patients with active rheumatoid arthritis ( RA ) . Design , subjects and intervention : RA patients were r and omized to receive either daily liquid nutrient supplementation or placebo for 4 months . The primary end point was the change in tender joint count at 2 and 4 months . Other clinical variables included swollen joint count , visual analogue scales for pain and disease activity , grip strength , functionality score and morning stiffness . Biochemical parameters included plasma concentrations of PUFA and vitamins C and E. Setting : Outpatient university clinic . Results : In all , 66 patients enrolled , 55 completed the study . No significant change from baseline in tender joint count or any of the other clinical parameters was detected in either group . Patients receiving nutrient supplementation , but not those receiving placebo , had significant increases in plasma concentrations of vitamin E ( P=0.015 ) , and EPA , DHA and docosapentaenoic acid concomitant with decreases of arachidonic acid ( P=0.01 ) . Intergroup differences for PUFA and vitamin E were significantly different ( P=0.01 and 0.03 , respectively ) . Conclusions : This double-blind , placebo-controlled study in RA patients did not show superior clinical benefit of daily nutrient supplementation with EPA , GLA and micronutrients at the doses tested as compared to placebo . The study adds information regarding doses of omega-3 fatty acids , below which anti-inflammatory effects in RA are not seen OBJECTIVE To examine whether dietary supplementation with omega-3 fatty acids relieved symptoms of primary dysmenorrhea . METHODS Women aged 18 - 22 years with primary dysmenorrhea were enrolled in a double-blind crossover study . Women assigned to group 1 ( n=47 ) received 1 omega-3 capsule daily for 3 months , followed by placebo for 3 months . Women in group 2 ( n=48 ) received placebo for 3 months , followed by omega-3 for 3 months . A washout period was performed in both groups . Participants used 400 mg of ibuprofen as a rescue dose if severe menstrual pains were experienced . RESULTS A marked reduction in pain intensity was observed after 3 months of treatment with omega-3 fatty acids ( P<0.05 ) . Women who received omega-3 fatty acids required fewer rescue doses than women who received placebo ( P<0.05 ) . The mean numbers of ibuprofen tablets used after 3 months with omega-3 fatty acids were 4.3±2.1 ( group 1 ) and 3.2±2.5 ( group 2 ) ; the mean numbers of tablets used after 3 months of placebo were 5.3±2.2 ( group 1 ) and 6.0±2.6 ( group 2 ) ( P=0.001 for both ) . CONCLUSION Supplementation with omega-3 fatty acids reduced the symptom intensity of primary dysmenorrhea . Supplementation efficacy was sufficient to decrease the ibuprofen rescue dose Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions 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 A double blind , placebo controlled trial was carried out to assess the efficacy of cod liver oil as an adjunct treatment to non-steroidal anti-inflammatory drugs ( NSAIDs ) in the management of  osteoarthritis  in general practice . Eighty six patients were given 10 ml of either cod liver oil or olive oil placebo daily as a supplement to their regular NSAID treatment for 24 weeks . Patients were assessed by their general practitioner at four week intervals for joint pain/inflammation , overall interference with activities , and unwanted effects of treatment . Patients recorded on visual analogue scales their daily pain and the extent to which arthritis interfered with everyday activities . There was no significant benefit for the patients taking cod liver oil compared with those taking placebo PRIMARY OBJECTIVE To evaluate the effectiveness of Neptune Krill Oil ( NKO ) for the management of  premenstrual syndrome and dysmenorrhea .  SECONDARY OBJECTIVE To compare the effectiveness of NKO for the management of premenstrual syndrome and dysmenorrhea with that of omega-3 fish oil . METHODS / DESIGN Double-blind , r and omized clinical trial . SETTING Outpatient clinic . PARTICIPANTS Seventy patients of reproductive age diagnosed with premenstrual syndrome according to the Diagnostic and Statistical Manual of Mental Disorders , Third Edition , Revised ( DSM-III-R ) . INTERVENTIONS Treatment period of three months with either NKO or omega-3 fish oil . OUTCOME MEASURES Self- Assessment Question naire based on the American College of Obstetricians and Gynecologists ( ACOG ) diagnostic criteria for premenstrual syndrome and dysmenorrhea and number of analgesics used for dysmenorrhea . RESULTS In 70 patients with complete data , a statistically significant improvement was demonstrated among baseline , interim , and final evaluations in the self assessment question naire ( P < 0.001 ) within the NKO group as well as between-group comparison to fish oil , after three cycles or 45 and 90 days of treatment . Data analysis showed a significant reduction of the number of analgesics used for dysmenorrhea within the NKO group ( comparing baseline vs. 45- vs. 90-day visit ) . The between-groups analysis illustrated that women taking NKO consumed significantly fewer analgesics during the 10-day treatment period than women receiving omega-3 fish oil ( P < 0.03 ) . CONCLUSION Neptune Krill Oil can significantly reduce dysmenorrhea and the emotional symptoms of premenstrual syndrome and is shown to be significantly more effective for the complete management of premenstrual symptoms compared to omega-3 fish oil 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 PURPOSE To examine whether dietary supplementation with fish oil rich in very long-chain n-3 polyunsaturated fatty acids might reduce frequency and severity of migraines in adolescents . METHODS Twenty-seven adolescents suffering from frequent migraines for at least 1 year ( mean 4 + /- 1 years since migraine onset ) participated in a r and omized , double-blind , cross-over study consisting of 2 months of fish oil , 1-month washout period , and 2 months of placebo ( olive oil ) . Participants self-assessed severity and duration of headache episodes ( 7-point faces and 10-point visual analog pain scales , 5-point frequency and severity rating scale ) throughout the study . At the end of every 2-month treatment period , participants rated the effectiveness of treatment on a 7-point Likert scale ( 1,"not effective , not worthwhile " ; 4,"moderately effective , moderately worthwhile " ; 7 , " totally effective , totally worthwhile " ) . A score of > or = 4 on the Likert scale was considered as improvement . RESULTS Twenty-three adolescents ( 16 girls , 7 boys , 18 Whites , 3 Hispanics , 1 African-American , 1 Cape Verdean , mean age 15 + /- 1 years ) completed the study . Compared with frequency of headaches before the study ( 31 + /- 4 episodes/2 months ) , there was a significant ( p < .0001 ) reduction in headache frequency during fish oil treatment ( 4 + /- 1 episodes/2 months ) and during placebo ( olive oil ) treatment ( 4 + /- 1 episodes/2 months ) but no significant ( NS ) difference between treatments . Likewise , self- assessment on a 7-point faces pain scale revealed a significant reduction in headache severity during fish oil treatment ( 2.9 + /- 0.5 , p = .01 ) and during placebo ( olive oil ) treatment ( 3.5 + /- 0.4 , < p = .03 ) , compared with headache severity before study ( 5.0 + /- 0.3 ) and no significant difference between treatments . Patients ' ratings of treatments revealed that 87 % experienced reduction in headache frequency , 74 % experienced reduction in headache duration , and 83 % experienced reduction in headache severity during treatment with fish oil , compared with 78 % who experienced reduction in headache frequency , 70 % who experienced reduction in headache duration , and 65 % who experienced reduction in headache severity during treatment with placebo ( olive oil , NS ) . About 91 % stated that they would recommend fish oil to friends or relatives with headaches vs. 91 % who would recommend placebo ( olive oil , NS ) . CONCLUSIONS Patients experienced a similar reduction in frequency , duration , and severity of headaches during treatment with fish oil and during treatment with olive oil . Although there was no significant difference between treatments , the marked improvement from baseline experienced by the patients suggests that the effect should not be dismissed as simply a placebo effect . In fact , results of this preliminary study suggest that both fish oil and olive oil may be beneficial in the treatment of recurrent migraines in adolescents . Further studies are warranted to compare each of these treatments with other interventions 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 , r and omized , 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 ≥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 ≥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 ( ≥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 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 OBJECTIVE To evaluate the effectiveness of vitamin E , evening primrose oil ( EPO ) , and the combination of vitamin E and EPO for pain control in women with cyclical mastalgia . PROCEDURE A double-blind , r and omized , placebo-controlled trial was conducted at two U.S. academic medical centers . Eighty-five women with premenstrual cyclical breast discomfort were enrolled . Participants were r and omly assigned to one of four six-month oral treatments : vitamin E ( 1,200 IU per day ) , EPO ( 3,000 mg per day ) , vitamin E ( 1,200 IU per day ) plus EPO ( 3,000 mg per day ) , or double placebo . The primary outcome measure was change in breast pain , measured by the modified McGill Pain Question naire at enrollment and at six months . RESULTS Forty-one patients completed the study . Intent-to-treat analysis ( pretesting and post testing ) showed a difference in worst-pain improvement with the treatments EPO ( p=0.005 ) , vitamin E ( p=0.04 ) , and EPO plus vitamin E ( p=0.05 ) , but no difference with placebo ( p=0.93 ) . Results from two- sample t-test showed a nonsignificant decrease in cyclical mastalgia individually for the three treatment groups compared with the placebo group ( EPO , p=0.18 ; vitamin E , p=0.10 ; and EPO plus vitamin E , p=0.16 ) . The data were also analyzed with the separation test by Aickin , which showed a trend toward a reduction of cyclical mastalgia with vitamin E and EPO individually and in combination . CONCLUSION Daily doses of 1,200 IU vitamin E , 3,000 mg EPO , or vitamin E and EPO in combination at these same dosages taken for six months may decrease the severity of cyclical mastalgia 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 Improvements have been made in the management of patients with rheumatoid arthritis , mainly through development of many anti-inflammatory drugs , advances in the surgical repair and replacement of damaged joints , and more informed use of corticosteroids and second-line drugs such as methotrexate . Many of these interventions are associated with adverse effects , however , that can often be as difficult to manage as the disease itself . A need exists for new ways to treat these patients . Particular fatty acids may be effective anti-inflammatory and immunomodulating agents . For example , certain plant seed oils , notably those extracted from the seeds of Oenothera biennis ( evening primrose ) and Borago officinalis ( borage ) , contain relatively large amounts of gammalinolenic acid . Gammalinolenic acid is converted rapidly to dihomogammalinolenic acid ( Figure 1 ) , the immediate precursor of prostagl and in E1 , an eicosanoid with known anti-inflammatory and immunoregulating properties [ 1 - 4 ] . Figure 1 . Metabolic pathway of omega-6 ( n-6 ) fatty acids . In addition to their role as precursors of prostagl and in and leukotriene ( eicosanoids ) , essential fatty acids are important for the maintenance of cell-membrane structure and function . Our previous studies [ 5 , 6 ] suggest that dihomogammalinolenic acid can modulate immune responses , in a prostagl and in-independent manner , by acting directly on T cells .  Gammalinolenic acid also suppresses acute and chronic inflammation , including arthritis , in several animal models [ 7 , 8 ] . Moreover , in a study design ed to determine biochemical responses to gammalinolenic acid [ 9 ] , administration of the fatty acid for 12 weeks ( 1.1 g/d in borage seed oil ) in an open uncontrolled manner appeared to reduce synovitis in six of seven patients with rheumatoid arthritis . Taken together , these observations suggest that enrichment of cells with dihomogammalinolenic acid by administration of gammalinolenic acid may be a worthwhile strategy for the control of inflammation . We therefore did a trial of gammalinolenic acid treatment in patients with rheumatoid arthritis and active synovitis to assess the clinical efficacy and tolerability of gammalinolenic acid . Methods Our study was a 24-week , r and omized , double-blind comparison of gammalinolenic acid to placebo in patients with rheumatoid arthritis and with active synovitis . The protocol was review ed and approved by the Committee on Human Experimentation at the University of Pennsylvania and at the University of Massachusetts and by the Food and Drug Administration . Written , informed consent was obtained from each patient . Patients were eligible to participate in the study if they had rheumatoid arthritis according to the revised criteria of the American Rheumatism Association [ 10 ] , were between the ages of 18 and 80 years , had functional class I , II , or III disease [ 11 ] , and were treated with only aspirin or other nonsteroidal anti-inflammatory drugs or corticosteroids ( not to exceed 10 mg/d of prednisone or an equivalent ) or both . This represented approximately 10 % of patients with rheumatoid arthritis followed at a university hospital rheumatology clinic . Most patients ( about 90 % ) seen had been referred to the clinic , mainly by primary care physicians , orthopedic surgeons , and rheumatologists .  Nonsteroidal anti-inflammatory drugs and corticosteroids were maintained at a stable dose for at least 1 month before entry into the study . Patients who had previously received therapy with either gold salts ( oral or parenteral ) , penicillamine , hydroxychloroquine , methotrexate , sulfasalazine , or other second-line agents were eligible only if they had discontinued the medications at least 3 months before entering the study . All patients had disease activity as defined by the presence of at least three of the following four criteria : six or more painful or tender joints ; three or more swollen joints ; morning stiffness of at least 45 minutes ' duration , and a Westergren erythrocyte sedimentation rate of at least 28 mm/h . Patients were instructed to maintain their pre-entry doses of nonsteroidal anti-inflammatory drugs or corticosteroids or both during the study . Medications required for coexisting medical conditions were permitted ; these conditions were mild and well controlled . Patients were instructed to maintain their typical diet . Patients were ineligible for entry if they had been treated with any investigational drug within 1 month of entry , had treatment with commercially available fish or plant seed oil products within 3 months of entry , or had intra-articular injection of corticosteroids within 1 month of entry . Patients were r and omized to receive either gammalinolenic acid or placebo capsules . Each capsule contained 0.6 mL of oil , 13.6 International Units of vitamin E , and provided 5.4 Kcal daily . Gammalinolenic acid was administered as borage seed oil in capsules ( Boracelle Capsules with oil of borage , Bio Oil Research Ltd. , Nantwich , Cheshire , Engl and ) . The approximate composition of the borage seed oil was 23 % gammalinolenic acid , 62 % cis-linoleic acid , 8 % oleic acid , and 7 % other fatty acids . The total daily dose ( four capsules three times daily after meals ) provided 1.4 g of gammalinolenic acid . Placebo capsules , identical in appearance and taken according to the same schedule , contained cottonseed oil ( Bio Oil Research Ltd. ) , which was 54 % linoleic acid , 18 % oleic acid , 24 % palmitic acid , and 4 % other fatty acids . Capsules were counted at each visit to monitor compliance . Fatty acid analysis of plasma or circulating cells was not used as a measure of compliance because the amount of gammalinolenic acid present would not necessarily reflect the number of capsules ingested . Gammalinolenic acid was administered under an Investigational New Drug approval ( # 28 867 ) issued to one of the investigators . Disease activity , clinical ly assessed at baseline and at 6-week intervals , included 1 ) the physician 's global assessment of disease activity rated as 0 ( none ) , 1 ( mild ) , 2 ( moderate ) , 3 ( severe ) , or 4 [ very severe ] ; 2 ) the patient 's global assessment of disease activity and pain assessment using the same scale plus a 100-mm visual analog scale for each ; 3 ) the number of joints with tenderness or pain on pressure or passive motion or both [ of a total of 68 diarthrodial joints ] ; 4 ) the number of joints with swelling [ of a total of 66 diarthrodial joints ] ; 5 ) joint pain or tenderness score in which each joint was grade d on a scale of 0 ( none ) , 1 ( mild ) , 2 ( moderate ) , or 3 [ severe ] ; 6 ) the joint swelling score , using the same scale ; 7 ) the duration of morning stiffness [ min ] ; 8) the ability to do vocational activity and household chores rated as 0 ( without difficulty ) , 1 ( with minimal difficulty ) , 2 ( with difficulty ) , 3 [ with great difficulty ] ; 9 ) the grip strength ( mm Hg ) in each h and using a sphygmomanometer inflated initially to 20 mm Hg . A complete blood cell count ( including differential cell count and platelet count ) , blood chemistry profile , urinalysis , and rheumatoid factor were measured at baseline and at week 24 . The erythrocyte sedimentation rate was determined at baseline and at weeks 12 and 24 . Radiographs were not used to assess disease progression because it is unlikely that changes would be detected during the relatively short ( 24 weeks ) period of the study . Patients were asked about adverse experiences at each visit . Criteria for patient withdrawal from the study included 1 ) adverse drug reaction that required missed doses for more than 7 days ; 2 ) violation of study protocol ; 3 ) the patient 's desire to withdraw from the study ; or 4 ) onset of a serious medical condition . Categories of Response The following definitions were used to characterize changes for several clinical measures . Important improvement in any measure was defined as at least a 25 % improvement in continuous variables or an improvement of two levels or from a baseline value of 1 to a value of 0 in the scaled variables . Important worsening in any measure was defined as at least a 30 % worsening in continuous variables or a worsening of two levels or from a baseline of 3 to 4 in the scaled variables . Patients completing the study were classified into one of four overall response categories as described by several investigators [ 12 - 15 ] : remission , meaningful improvement , no meaningful change , or deterioration . A patient was considered in remission if global assessment s by physician and patient were 0 , no joints were tender or swollen , and the erythrocyte sedimentation rate was less than 20 mm/h for at least 2 consecutive months . Overall meaningful improvement ( or deterioration ) occurred if the patient had important improvement ( or important worsening ) in at least four of the following measures : joint tenderness count or score , joint swelling count or score , global assessment by physician , global assessment by patient , morning stiffness , and erythrocyte sedimentation rate . Statistical Analysis Statistical analysis was done using chi-square testing ( with Yates correction for continuity when appropriate ) , Mann-Whitney U-test for comparisons between groups , and the Wilcoxon signed-rank test for within-group comparisons of final visit to baseline data . Nonparametric tests were used because most variables were not normally distributed . Data were analyzed for both the entire group of patients enrolled in the study and for patients who completed the study . Results are expressed as means st and ard deviation . Statistical significance was defined as P < 0.05 , measured in a two-tailed manner . We used SPS + software ( SPS , Inc. , Chicago , Illinois ) for the analysis . Overall responses were compared using the Fisher exact test . Results Of 37 patients enrolled in the study , 19 received gammalinolenic acid  and 18 received  placebo .  Demographic and clinical characteristics , laboratory data , and treatment at entry were similar for the two groups ( Table 1 ) . Although more patients in the placebo group had previously OBJECTIVE To evaluate the effects of a diet therapy in patients with rheumatoid arthritis ( RA ) . METHODS Fifty RA patients entered a 24-week double-blind , r and omised , controlled- study of two different dietary regimens ( an experimental diet high in unsaturated fats , low in saturated fats with hypoallergenic foods vs. a control well-balanced diet ) . The primary end points of the study were 20 % and 50 % improvement in disease activity according to composite symptoms ( Paulus index ) of arthritis . Other end points were the other measures of disease activity at 12 and 24 weeks of diet treatment . RESULTS The 2 groups were comparable at inclusion . Diet treatment was well tolerated and the rate of drop-outs was low . Percentage of patients with global 20 or 50 % response did n't differ between experimental and control group after the 24-week of diet treatment . The experimental diet group did better for all the variables considered but only four variables ( Ritchie 's index , tender and swollen joints , and ESR ) reached a statistical difference by multivariate analysis . Adjusting these data for weight variations , the number of tender joints ( p=0.014 ) and ESR ( p=0.025 ) were still statistically significant . CONCLUSIONS Dietary manipulation , either by modifying food supplements or by reducing weight , may give some clinical benefit although no significant improvement can be observed assessing the results with a composite index We investigated the effects of a low n-6 fatty acid ( FA ) diet supplemented with fish oil on serum pro-inflammatory cytokine concentrations and clinical variables in patients with active rheumatoid arthritis ( RA ) . Sixty patients were r and omly assigned to receive a diet low in n-6 FAs and n-3 FAs supplement ( fish oil group ) , a diet low in n-6 FAs and placebo ( placebo group ) , or no special diet or intervention ( control group ) . Serum cytokines and clinical and biochemical variables were evaluated at baseline and various timepoints . At week 18 the fish oil group had significant reductions in linoleic acid , C-reactive protein ( CRP ) and soluble tumour necrosis factor receptor p55 ( sTNF-R p55 ) , and significant elevations in eicosapentaenoic acid and docosahexaenoic acid compared with baseline . There were no significant differences in the clinical variables between the three groups . At week 24 there were significant reductions in interleukin-6 and TNF-alpha in the fish oil and placebo groups . Supplementation with n-3 FA and a low n-6 FA intake decreased serum sTNF-R p55 and CRP levels in patients with RA To examine whether dietary supplementation with omega-3 fatty acids from Clupeonella grimmi can relieve symptoms of  dysmenorrhoea  , we carried out a cross-over clinical trial on 36 girls aged 18 - 22 years . They were r and omly allocated into 2 groups of 18 . Group A received 15 mL fish oil daily ( 550 mg eicosapentaenoic acid ; 205 mg decosahexaenoic acid ) while Group B received placebo . After 3 months , the treatment regimens were swapped . The treatment groups reported a significant difference after 3 months of supplementation with fish oil ( visual analogue scale score 20.9 compared with 61.8 for the placebo ( P= 0.001 ) . There was also a marked reduction in low back pain and abdominal pain ( P < 0.05 ) , and participants needed significantly fewer rescue doses of ibuprofen while using fish oil OBJECTIVE To assess the clinical efficacy and adverse effects of gamma-linolenic acid ( GLA ) , a plant seed oil-derived unsaturated fatty acid that suppresses inflammation and joint tissue injury in animal models , in the treatment of active rheumatoid arthritis ( RA ) . METHODS Fifty-six patients with active RA were r and omized to treatment groups in a 6-month , double-blind trial of GLA versus placebo . This was followed by a 6-month , single-blind trial during which all patients received GLA . Patients were treated with 2.8 gm/day of GLA as the free fatty acid or with sunflower seed oil ( placebo ) administered in identical capsules . RESULTS Treatment with GLA for 6 months result ed in statistically significant and clinical ly relevant reductions in the signs and symptoms of disease activity in patients with RA . Overall meaningful responses ( at least 25 % improvement in 4 measures ) were also better in the GLA treatment group ( 14 of 22 patients versus 4 of 19 in the placebo group ; P = 0.015 ) . During the second 6 months , both groups exhibited improvement in disease activity . Thus , patients taking GLA during the entire study showed progressive improvement during the second 6 months . In this group , 16 of 21 patients showed meaningful improvement at 12 months compared with study entry . CONCLUSION GLA at doses used in this study is a well-tolerated and effective treatment for active RA . GLA is available as a component of several plant seed oils and is usually taken in far lower doses than were used in this trial . It is not approved in the United States for the treatment of any condition , and should not be viewed as therapy for any disease . Further controlled studies of its in RA are warranted In a double-blind , placebo-controlled , parallel group , multicenter study , 555 women with moderate to severe mastalgia were r and omized to one of the four treatment groups to receive ( a ) gamolenic acid ( GLA ) and antioxidants , ( b ) placebo fatty acids and antioxidants , ( c ) GLA and placebo antioxidants , or ( d ) placebo fatty acids and placebo antioxidants , for four menstrual cycles . This was followed by a further eight menstrual cycles of open treatment in which all patients received GLA , but continued to be r and omized to active or placebo antioxidants as in the preceding parallel phase . Diary pain cards and linear analog charts were used for assessment of response . A reduction in breast pain was seen in all four treatment groups during the blinded treatment phase . There was a substantial improvement in the placebo fatty acids groups ( response rate of 40 % ) , and there were no significant differences among the four treatment groups . During the open treatment phase , a further reduction in breast pain was seen in all groups , with no statistically significant differences between groups . This study showed that GLA ( Efamast ) efficacy did not differ from that of placebo fatty acids , regardless of whether or not antioxidant vitamins were present OBJECTIVES The purpose of the study was to examine whether dietary supplementation with omega-3 fatty acids can relieve symptoms of dysmenorrhea in adolescents . STUDY DESIGN Forty-two adolescents with dysmenorrhea were r and omly allocated to two groups . In the first group 21 girls received fish oil ( 1080 mg icosapentaenoic acid , 720 mg docosahexaenoic acid , and 1.5 mg vitamin E ) daily for 2 months followed by a placebo for an additional 2 months . In the second group 21 girls received placebo for the first 2 months , followed by fish oil for 2 more months . The Cox Menstrual Symptom Scale was used to assess response to treatment . RESULTS There were no significant differences in the Cox Menstrual Symptom Scale between the two groups at baseline after 2 months of placebo administration . After 2 months of treatment with fish oil there was a marked reduction in the Cox Menstrual Symptom Scale from a baseline mean value of 69.9 to 44.0 ( p < 0.0004 ) . CONCLUSIONS This study suggests that dietary supplementation with omega-3 fatty acids has a beneficial effect on symptoms of dysmenorrhea in adolescents 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 INTRODUCTION Premenstrual syndrome ( PMS ) refers to a cyclic appearance of somatic and psychiatric symptoms that affect some women . Finding an effective and safe method for the treatment of PMS has always been a serious concern , because approximately 40 % of women report PMS , and in 2 - 10 % of cases it is severe enough to affect their life style and job . OBJECTIVE The purpose of the present study is to evaluate the effect of omega-3 fatty acids on the treatment of PMS . METHOD A r and omized double blind controlled trial was performed on 184 eligible women . The eligible women were r and omly assigned into two groups . The number of women who have finalized the study with us was 124 . In the case group ( omega-3 group = group A , n = 70 ) , omega-3 in an amount of 2 g was prescribed for a one per day basis on a single dosage ( two 1 g pearls ) , and in the control group ( placebo group = group B , n = 69 ) 2 placebo soft gel , which were completely similar to omega-3 soft gels , were prescribed . The severity and duration of each of the symptoms were compared in both groups 1.5 and 3 months after the beginning of treatment . RESULTS There were no significant differences between the two groups according to age , BMI , level of education , and the severity and duration of primary symptoms . After 45 days from starting omega-3 , the mean severity of depression ( P = 0.03 ) , anxiety ( P = 0.02 ) , lack of concentration ( P = 0.03 ) and bloating ( P = 0.02 ) in the case group , were all significantly lower than in the control group . The duration of depression ( P = 0.04 ) and bloating ( P = 0.031 ) in the case group were less than in the control group . After 90 days from starting the treatment , the mean severity of depression ( P = 0.007 ) , anxiety ( P = 0.004 ) , lack of concentration ( P = 0.009 ) , bloating ( P = 0.004 ) , nervousness ( P = 0.01 ) and the duration of depression ( P = 0.01 ) , nervousness ( P = 0.02 ) , anxiety ( P = 0.03 ) , lack of concentration ( P = 0.02 ) , bloating ( P = 0.004 ) , headache ( P = 0.04 ) and breast tenderness ( P = 0.02 ) were all lower in the case group . CONCLUSION It appears that omega-3 fatty acids may reduce the psychiatric symptoms of PMS including depression , nervousness , anxiety , and lack of concentration and may also reduce the somatic symptoms of PMS including bloating , headache and breast tenderness . These effects increased by longer duration of treatment
BACKGROUND Chronic pain is one of the most frequent disease symptoms and represents a global health problem with a considerable economic burden .
The role of polyunsaturated fatty acids ( PUFA ) in chronic pain conditions was debated during the last decade with conflicting results .
OBJECTIVE To assess whether polyunsaturated fatty acids intake is useful as a preventive or curative tool in chronic pain .