gamma-linolenic-acid and Arthritis--Rheumatoid

The etiology of diet-related disorders is closely associated with dietary factors. A special role is attributed to intake of fat and fatty acid profile, both quantitative and qualitative. For prevention and treatment of the abovementioned diseases a proper supply of unsaturated fatty acids plays a significant role, because of their particular importance to health. γ-Linolenic acid (GLA), with three double bonds in the carbon chain, also known as all-cis 6,9,12-octadecatrienoic acid, belongs to the n-6 family of fatty acids. It plays biologically important functions in the human body, such as being a substrate for eicosanoids synthesis, involvement in the transport and oxidation of cholesterol, and being one of the components of lipid membrane. Its inadequate dietary intake or impaired formation is the cause of many inflammatory and degenerative diseases. A rich source of this fatty acid is vegetable oils, until recently used mainly in folk medicine. Nowadays, studies conducted both in animal models and in humans suggest its health-promoting properties in the prevention and treatment of atopic dermatitis, cardiovascular diseases, diabetes, cancers and rheumatoid arthritis.

Topics: Animals; Antineoplastic Agents; Arthritis, Rheumatoid; Cardiovascular Diseases; Dermatitis, Atopic; Dry Eye Syndromes; gamma-Linolenic Acid; Humans; Metabolic Diseases; Neoplasms

Herbal medicine interventions have been identified as having potential benefit in the treatment of rheumatoid arthritis (RA).. To update an existing systematic (Cochrane) review of herbal therapies in RA.. We searched electronic databases Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, AMED, CINAHL, Web of Science, Dissertation Abstracts (1996 to 2009), unrestricted by language, and the WHO International Clinical Trials Registry Platform in October 2010.. Randomised controlled trials of herbal interventions compared with placebo or active controls in RA.. Two authors selected trials for inclusion, assessed risk of bias and extracted data. . Twelve new studies were added to the update, a total of 22 studies were included.Evidence from seven studies indicate potential benefits of gamma linolenic acid (GLA) from evening primrose oil, borage seed oil, or blackcurrent seed oil, in terms of reduced pain intensity (mean difference (MD) -32.83 points, 95% confidence interval (CI) -56.25 to -9.42,100 point pain scale); improved disability (MD -15.75% 95% CI -27.06 to -4.44%); and an increase in adverse events (GLA 20% versus placebo 3%), that was not statistically different (relative risk 4.24, 95% CI 0.78 to 22.99).Three studies compared Tripterygium wilfordii (thunder god vine) to placebo and one to sulfasalazine and indicated improvements in some outcomes, but data could not be pooled due to differing interventions, comparisons and outcomes. One study reported serious side effects with oral Tripterygium wilfordii Hook F. In the follow-up studies, all side effects were mild to moderate and resolved after the intervention ceased. Two studies compared Phytodolor(®) N to placebo but poor reporting limited data extraction. The remaining studies each considered differing herbal interventions.. Several herbal interventions are inadequately justified by single studies or non-comparable studies in the treatment of rheumatoid arthritis. There is moderate evidence that oils containing GLA (evening primrose, borage, or blackcurrant seed oil) afford some benefit in relieving symptoms for RA, while evidence for Phytodolor® N is less convincing.Tripterygium wilfordii products may reduce some RA symptoms, however, oral use may be associated with several side effects. Many trials of herbal therapies are hampered by research design flaws and inadequate reporting. Further investigation of each herbal therapy is warranted, particularly via well designed, fully powered, confirmatory clinical trials that use American College of Rheumatology improvement criteria to measure outcomes and report results according to CONSORT guidelines.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; gamma-Linolenic Acid; Humans; Phytotherapy; Placebo Effect; Plant Oils; Primula; Randomized Controlled Trials as Topic; Tripterygium

To critically evaluate the evidence regarding complementary and alternative medicine (CAM) taken orally or applied topically (excluding fish oil) in the treatment of RA.. Randomized controlled trials (RCTs) of RA using CAMs, in comparison with other treatments or placebo, published in English up to August 2010, were eligible for inclusion. They were identified using systematic searches of bibliographic databases and manual searching of reference lists. Information was extracted on outcomes and statistical significance, in comparison with alternative treatments, and reported side effects. The methodological quality of the primary studies was determined using the Jadad scoring system.. Reported RCTs were available for 18 CAMs in the management of RA. There was no consistent evidence available for any of the reviewed substances to suggest that they were efficacious as complementary medicines to standard treatment. Nevertheless, the studies conducted on borage seed oil (n = 2) and thunder god vine (n = 3) have been positive and may warrant further investigation. Not all CAM compounds studied were free of major adverse effects.. The major limitation in reviewing the evidence for CAMs is the paucity of RCTs in the area. The available evidence does not support their current use in the management of RA.

Topics: Administration, Oral; Administration, Topical; Arthritis, Rheumatoid; Complementary Therapies; gamma-Linolenic Acid; Humans; Plant Oils; Randomized Controlled Trials as Topic; Treatment Outcome; Tripterygium

Herbal medicinal products (HMPs) that interact with the mediators of inflammation are used in the treatment of rheumatoid arthritis (RA). The aim of this study was to update a previous systematic review published in 2000. We searched electronic databases (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007, unrestricted by date or language, and included randomized controlled trials that compared HMPs with inert (placebo) or active controls in patients with rheumatoid arthritis. Five reviewers contributed to data extraction. Disagreements were discussed and resolved by consensus with reference to Cochrane guidelines and advice from the Cochrane Collaboration. Twenty studies (10 identified for this review update, and 10 of the 11 studies of the original review) investigating 14 HMPs were included. Meta-analysis was restricted to data from previous seven studies with oils from borage, blackcurrant and evening primrose containing gamma linolenic acid (GLA). GLA doses equal or higher than 1400 mg/day showed benefit in the alleviation of rheumatic complaints whereas lower doses ( approximately 500 mg) were ineffective. Three studies compared products from Tripterygium wilfordii (thunder god vine) to placebos and returned favorable results but data could not be pooled because the interventions and measures differed. Serious adverse effects occurred in one study. In a follow-up study all side effects were mild to moderate and resolved after the intervention ceased, but time to resolution was variable. Two studies comparing Phytodolor NR to placebo were of limited use because some measures were poorly defined. The remaining studies, each considering differing HMPs, were assessed individually. For most HMPs used in the treatment of RA, the evidence of effectiveness was insufficient to either recommend or discourage their use. Interventions with HMPs containing GLA or Tripterygium wilfordii extract appear to produce therapeutic effects but further investigations are warranted to prove their effectiveness and safety.

Topics: Arthritis, Rheumatoid; gamma-Linolenic Acid; Herbal Medicine; Humans; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Tripterygium

The essential fatty acid deficiency (EFA) gives rise to many pathologic states and may predispose for certain disease development. One of the most frequently deficient EFA is gamma-linolenic acid. The gamma-linolenic acid supplementation brings some hopeful effects in treatment of diabetic neuropathy, eczema, cyclic mastalgia, rheumatoid arthritis, osteoporosis and ADHD. Many double blind trials have been performed for defective assessment of GLA efficiency. Some of them have proved statistically significant efficacy, the others have led to some doubts. There is a necessity to perform more trials. The gamma-linolenic acid is completely safe, non-toxic, and non-cancerogenic substance. It can be an interesting alternative for supporting treatment.

Topics: Arthritis, Rheumatoid; Attention Deficit Disorder with Hyperactivity; Diabetic Neuropathies; Dietary Supplements; Eczema; gamma-Linolenic Acid; Humans; Osteoporosis; Treatment Outcome

Conclusions based on systematic reviews of randomized controlled trials are considered to provide the highest level of evidence about the effectiveness of an intervention. This overview summarizes the available evidence from systematic reviews on the effects of nonpharmacological and nonsurgical interventions for rheumatoid arthritis (RA). Systematic reviews of studies of patients with RA (aged >18 years) published between 2000 and 2007 were identified by comprehensive literature searches. Methodological quality was independently assessed by 2 authors, and the quality of evidence was summarized by explicit methods. Pain, function, and patient global assessment were considered primary outcomes of interest. Twenty-eight systematic reviews were included in this overview. High-quality evidence was found for beneficial effects of joint protection and patient education, moderate-quality evidence was found for beneficial effects of herbal therapy (gamma-linolenic acid) and low-level laser therapy, and low-quality evidence was found for the effectiveness of the other interventions. The quality of evidence for the effectiveness of most nonpharmacological and nonsurgical interventions in RA is moderate to low.

Topics: Adult; Arthritis, Rheumatoid; Disability Evaluation; gamma-Linolenic Acid; Humans; Low-Level Light Therapy; Orthotic Devices; Pain Measurement; Patient Education as Topic; Randomized Controlled Trials as Topic; Recovery of Function

With the growing interest in herbal therapies among persons with rheumatoid arthritis, there exists a need for investigation into their safety and efficacy. The purpose of this study was to conduct a systematic review to examine the evidence for the use of herbal medicines for RA based on randomized clinical trials (RCTs).. A computerized search of eight electronic databases and the bibliographies of identified articles resulted in 14 studies meeting the inclusion criteria. Two raters independently extracted data and rated the trials for quality.. There is moderate support for gamma-linolenic acid (GLA), which is found in some herbal medicines, for reducing pain, tender joint count and stiffness. For other herbal medicines there was only a single RCT available, resulting in weak evidence. In general, herbal preparations were relatively safe to use.. Given the number of herbal medicines promoted for RA, further research is needed to examine their efficacy, safety and potential drug interactions.

Topics: Arthritis, Rheumatoid; gamma-Linolenic Acid; Humans; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic

Patients with rheumatic diseases frequently ask the physician for diet recommendations. Although much has been written about this subject, scientifically validated studies investigating the impact of certain diets on rheumatoid arthritis are scant and often inconclusive. Elimination diets or total fasting is believed to eliminate food ingredients that cause or aggravate arthritis. In contrast, supplementation with fish oil, gamma-linoleic acid or vitamin E is directed at anti-oxidative and anti-inflammatory effects of these food compounds. So far, both approaches have failed to reveal a significant benefit with respect to objective signs of inflammation. Supplementation with other vitamins such as vitamin A and C, or with trace elements like selenium and zinc are of no proven influence on the disease activity as well. There is a higher request for calcium and vitamin D in patients with active RA under steroid treatment to prevent osteoporosis. In addition, patients with active RA have a slightly increased risk for cardiovascular events. Therefore, cholesterol-lowering diets and drugs should be applied early.

Topics: Antioxidants; Arthritis, Rheumatoid; Diet, Vegetarian; Fasting; Fatty Acids, Omega-3; Food, Formulated; gamma-Linolenic Acid; Humans; Treatment Outcome; Vitamins

The increasing popularity of the use of complementary and alternative interventions or treatments appears to be particularly evident amongst people with chronic disease. In the treatment of rheumatoid arthritis, one therapy that has been identified as having potential benefit, is herbal medicine (phytotherapy).. To assess the effectiveness of herbal therapies in the treatment of rheumatoid arthritis.. We developed a search strategy using terms to include all forms of arthritis combined with herbal medicine. We searched the following electronic databases from 1966 to 2000: MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane Controlled Trials Register (CCTR), Cochrane Musculoskeletal specialized register, Dissertation Abstracts, BIDS ISI and the Cochrane Complementary Medicine Fields Specialized Register. This was supplemented by searching the reference lists from retrieved trials.. All randomized trials of herbal interventions in rheumatoid arthritis, compared to placebo. Two reviewers independently read and selected each potential study according to the criteria published in an a priori protocol. Papers of any language were included.. Data were extracted independently by the same two reviewers and an assessment of methodological quality was conducted.. Eleven studies met the inclusion criteria. Seven of the studies compared gamma-linolenic acid (GLA) to placebo although three of these were not suitable for data pooling. The remaining studies considered four different herbal interventions and were assessed individually. All of the GLA studies found some improvement in clinical outcomes but methodology and study quality was variable, making it difficult to draw conclusive results. However, the better quality studies suggest potential relief of pain, morning stiffness and joint tenderness. With the exception of one intervention (Tripterygium wilfordii hook F), no serious side effects were reported.. There appears to be some potential benefit for the use of GLA in rheumatoid arthritis although further studies are required to establish optimum dosage and duration of treatment. The single studies are inconclusive.

Topics: Arthritis, Rheumatoid; gamma-Linolenic Acid; Humans; Phytotherapy; Placebo Effect; Randomized Controlled Trials as Topic

Recent double blind studies have shown some benefit of borage oil in treatment of rheumatoid arthritis. Tumor necrosis factor-alpha has been shown to be a central mediator of inflammatory and joint destructive processes in rheumatoid arthritis. In this paper, evidence from published research is reviewed that indicates gamma linolenic acid component of borage oil increases prostaglandin E levels that increase cAMP levels that in turn suppress tumor necrosis factor-alpha synthesis. If this biochemical path of borage oil is correct then (1) concomitant non-steroidal anti-inflammatory drug use would tend to undermine borage oil effects, and (2) borage oil would be contraindicated in pregnancy given the teratogenic and labor inducing effects of prostaglandin E agonists.

Topics: Abortion, Spontaneous; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Borago; Contraindications; Cyclic AMP; Dinoprostone; Double-Blind Method; Drug Interactions; Female; gamma-Linolenic Acid; Humans; Phytotherapy; Plant Oils; Pregnancy; Randomized Controlled Trials as Topic; Second Messenger Systems; Tumor Necrosis Factor-alpha

Diets rich in arachidonic acid (20:4n-6) lead to the formation of 2-series prostaglandins (PGs) and 4-series leukotrienes (LTs), with proinflammatory effects. Nonsteroidal antiinflammatory drugs are used in rheumatoid arthritis to inhibit cyclooxygenase (prostaglandin-endoperoxide synthase), thereby decreasing production of 2-series PGs. Lipoxygenase activity remains intact, however, allowing LT production (eg, synthesis of LTB(4), a potent inflammatory mediator) to continue. Altering the essential fatty acid (EFA) content of the diet can modify some of these effects. Ingestion of a diet rich in evening primrose oil elevates concentrations of dihomo-gamma-linolenic acid (DGLA; 20:3n-6), which results in the production of 1-series PGs, eg, PGE(1). DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and thus suppress inflammation. The results of in vitro and animal work evaluating EFAs in inflammatory situations are encouraging, which has stimulated clinical workers to evaluate these compounds in rheumatoid arthritis. Several well-controlled, randomized clinical studies have now been completed in which various EFAs were evaluated as treatments. The results of most of these studies suggest some clinical benefit to these treatments; these data are reviewed here.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Psoriatic; Arthritis, Rheumatoid; Dietary Fats, Unsaturated; Dietary Supplements; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Leukotrienes; Linoleic Acids; Oenothera biennis; Plant Oils; Prostaglandins; Raynaud Disease; Sjogren's Syndrome

This review discusses the rationale and experimental data that led to clinical trials of certain botanical lipids, mainly gammalinolenic acid (GLA), for the treatment of rheumatoid arthritis (RA).. Pertinent articles and reviews, and a bibliographic database in English using the following indexing terms: rheumatoid arthritis, fatty acids, gammalinolenic acid, lymphocytes, and monocytes, were used.. All clinical trials in which GLA was used to treat arthritis are included in this review. Data from appropriately peer reviewed in vitro and animal experiments evaluating the effects of botanical lipids as regulators of cell activation and immune responses are also reviewed.. GLA treatment is associated with clinical improvement in patients with RA, as evaluated by duration of morning stiffness, joint pain and swelling, and ability to reduce other medications. However, studies vary in terms of duration, GLA dose, whether or not they were placebo controlled, and, if so, what placebo was used, criteria for evaluation, and use of concomitant medication. Studies done in vitro generally indicated that GLA reduces lymphocyte activation and production of mediators of inflammation.. A small number of studies suggest that GLA is effective treatment for RA patients. Further controlled studies of its use in RA seem warranted.

Topics: Animals; Arthritis, Rheumatoid; Blood Platelets; Clinical Trials as Topic; Eicosanoids; Fatty Acids; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Immune System; Inflammation; Lymphocytes; Phagocytes

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Bivalvia; Clinical Trials as Topic; Dietary Fats, Unsaturated; Fatty Acids, Essential; Fish Oils; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Plant Oils; Randomized Controlled Trials as Topic; Selenium; Tissue Extracts

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Oenothera biennis; Plant Oils

Topics: Animals; Arthritis, Rheumatoid; Cod Liver Oil; Dietary Fats; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Plant Oils; Rats

Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been reported to reduce platelet aggregation. Our aim was to prospectively assess the potential influence of different supplementation omega-3 PUFA on the antiplatelet effects in rheumatoid arthritis (RA) patients.. The study included 60 patients with RA at the Department of Rheumatology, Clinical Center Kragujevac. Patients were divided into three groups depending on who used concentrated fish oil only or concentrated fish oil in combination with evening primrose oil or control group without supplementation in a period of 3 months. Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test, aranchidonic acid-induced aggregation (ASPI) test, thrombin receptor-activating peptide (TRAP) test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP representing the degree of inhibition of platelet aggregation compared to the basal value. The platelet function analysis in whole blood was performed 18-24 h before starting supplementation and after 90 days. Considerations were taken in the representation of demographic, clinical characteristics, and laboratory parameters between the groups.. Patients who used concentrated fish oil only had a significantly lower value of the ratio of ADP/TRAP (0.68 ± 0.20) compared to patients without supplementation (0.83 ± 0.12; p = 0.008), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups.. Co-administration of supplementation-concentrated fish oil may reduce platelet aggregation in adults with RA.. • Omega-3 PUFAs are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases.. • In this paper, we report on anti-aggregation effects n-3 PUFAs and ɤ-linolenic acid in RA. • The risk of cardiovascular morbidity and mortality is increased in RA, and dietary supplementation of n-3 PUFA may have preventive potential for the cardiovascular management in rheumatoid arthritis.

Topics: Aged; Arthritis, Rheumatoid; Dietary Supplements; Female; Fish Oils; gamma-Linolenic Acid; Humans; Linoleic Acids; Middle Aged; Oenothera biennis; Plant Oils; Platelet Aggregation; Platelet Function Tests

Marine n-3 fatty acids and γ-linolenic acid both have anti-inflammatory effects and may be useful to help treat inflammatory diseases. The effects of these alone or combined were examined in patients with arthritis in a randomized controlled trial.. Patients with rheumatoid arthritis or psoriatic arthritis were randomized into four groups in a double-blind, placebo-controlled parallel designed study. Patients received the respective capsules (1: 3.0 g n-3 LC-PUFA/d; 2: 3.2 g γ-linolenic acid/d; 3: 1.6 g n-3 LC-PUFA + 1.8 g γ-linolenic acid/d; 4: 3.0 g olive oil) for a twelve week period. Clinical status was evaluated and blood samples were taken at the beginning and at the end of the period. Differences before and after intervention were tested with paired t-test or with Wilcoxon test for non-normal data distribution.. 60 patients (54 rheumatoid arthritis, 6 psoriatic arthritis) were randomised, 47 finished per protocol. In group 1, the ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA) decreased from 6.5 ± 3.7 to 2.7 ± 2.1 in plasma lipids and from 25.1 ± 10.1 to 7.2 ± 4.7 in erythrocyte membranes (p ≤ 0.001). There was no significant influence on AA/EPA ratio due to interventions in group 2-4. In group 2, the intake of γ-linolenic acid resulted in a strong rise of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte membranes. The combination of n-3 LC-PUFA and γ-linolenic acid (group 3) led to an increase of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte mem-branes. This increase was only half of that in group 2.. Incorporation of eicosanoid precursor FAs was influenced by an intake of n-3 LC-PUFA and γ-linolenic acid suggesting a possible benefit for therapy of chronic inflammatory diseases.. ClinicalTrials NCT01179971.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Aged; Aged, 80 and over; Arachidonic Acid; Arthritis, Psoriatic; Arthritis, Rheumatoid; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids, Omega-3; Female; gamma-Linolenic Acid; Humans; Lipid Metabolism; Male; Membrane Lipids; Middle Aged

Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX) and suppressor of leukotriene B4 (LTB4), can attenuate the clinical course of rheumatoid arthritics, with negligible side effects. Since Zileuton, also an inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we investigated whether dietary GLA would suppress biosynthesis of PMN-LTB4 isolated from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma patients (16-75 years) were randomized to receive either 2.0 g daily GLA (borage oil) or corn oil (placebo) for 12 months. Blood drawn at 3 months intervals was used to prepare sera for fatty acid analysis, PMNs for determining phospholipid fatty acids and for LTB4 generation. Patients were monitored by daily asthma scores, pulmonary function, and exhaled NO. Ingestion of daily GLA (i) increased DGLA (GLA metabolite) in PMN-phospholipids; (ii) increased generation of PMN-15-HETrE (5-LOX metabolite of DGLA). Increased PMN-DGLA/15-HETrE paralleled the decreased PMN generation of proinflammatory LTB4. However, the suppression of PMN-LTB4 did not reveal statistically significant suppression of the asthma scores evaluated. Nonetheless, the study demonstrated dietary fatty acid modulation of endogenous inflammatory mediators without side effects and thus warrant further explorations into the roles of GLA at higher doses, leukotrienes and asthma.

Topics: Adult; Aged; Arthritis, Rheumatoid; Asthma; Dietary Supplements; Double-Blind Method; Fatty Acids; Female; gamma-Linolenic Acid; Humans; Hydroxyurea; Leukotriene B4; Lipoxygenase Inhibitors; Male; Middle Aged; Neutrophils; Plant Oils; Prospective Studies

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).. RA patients were randomized 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.. Outpatient university clinic.. 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).. 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.

Topics: Antioxidants; Arthritis, Rheumatoid; Ascorbic Acid; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Hand Strength; Humans; Male; Micronutrients; Middle Aged; Pain; Treatment Outcome; Vitamin E

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).. Fifty-six patients with active RA were randomized 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.. Treatment with GLA for 6 months resulted in statistically significant and clinically 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Blood Platelets; Fatty Acids; Female; gamma-Linolenic Acid; Humans; Lipids; Male; Middle Aged; Placebos

The objective of this study was to assess the clinical efficacy and side effects of blackcurrant seed oil (BCSO), in a randomized, 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 resulted 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.

Topics: Adult; Aged; Arthritis, Rheumatoid; Double-Blind Method; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Humans; Male; Middle Aged; Plant Oils; Prospective Studies; Severity of Illness Index; Treatment Outcome

To assess the clinical efficacy and side effects of gammalinolenic acid, a plant-seed-derived essential fatty acid that suppresses inflammation and joint tissue injury in animal models.. A randomized, double-blind, placebo-controlled, 24-week trial.. Rheumatology clinic of a university hospital.. Thirty-seven patients with rheumatoid arthritis and active synovitis.. Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo).. Physicians' and patients' global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities.. Treatment with gammalinolenic acid resulted in clinically important reduction in the signs and symptoms of disease activity in patients with rheumatoid arthritis (P < 0.05). In contrast, patients given a placebo showed no change or showed worsening of disease. Gammalinolenic acid reduced the number of tender joints by 36%, the tender joint score by 45%, swollen joint count by 28%, and the swollen joint score by 41%, whereas the placebo group did not show significant improvement in any measure. Overall clinical responses (significant change in four measures) were also better in the treatment group (P < 0.05). No patients withdrew from gammalinolenic acid treatment because of adverse reactions.. Gammalinolenic acid in doses used in this study is a well-tolerated and effective treatment for active rheumatoid arthritis. Gammalinolenic acid is available worldwide as a component of evening primrose and borage seed oils. It is usually taken in far lower doses than 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 use in rheumatoid arthritis are warranted.

Topics: Adult; Aged; Arthritis, Rheumatoid; Chi-Square Distribution; Double-Blind Method; Female; gamma-Linolenic Acid; Humans; Male; Middle Aged; Synovitis

Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 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.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Gastritis; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Olive Oil; Peptic Ulcer; Plant Oils; Prospective Studies

The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Dietary Fats, Unsaturated; Double-Blind Method; Fatty Acids; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acids; Lipids; Middle Aged; Oenothera biennis; Olive Oil; Plant Oils; Random Allocation

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Plant Oils

In rheumatoid arthritis (RA) benefit from non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through inhibition of the cyclo-oxygenase enzyme, thereby decreasing production of the 2 series prostaglandins (PGs). The lipoxygenase enzyme is intact, however, allowing leucotriene (LT) production, e.g., LTB4 (an inflammatory mediator). Treatment with evening primrose oil (EPO) which contains gamma-linolenic acid (GLA) leads to production of the 1 series PGs, e.g., PGE1, which has less inflammatory effects. Also LT production is inhibited. Eicosapentaenoic acid (EPA, fish oil) treatment provides a substrate for PGs and LTs, which are also less inflammatory. In this study 16 patients with RA were given 540 mg GLA/day (EPO), 15 patients 240 mg EPA and 450 mg GLA/day (EPO/fish oil), and 18 patients an inert oil (placebo). The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA. The initial 12 month treatment period was followed by three months of placebo for all groups. Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo. In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs. After 3 months of placebo those receiving active treatment had relapsed. Despite the decrease in NSAIDs, measures of disease activity did not worsen. It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs. There is, however, no evidence that they act as disease modifying agents.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Eicosapentaenoic Acid; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Plant Oils; Random Allocation

Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.

Topics: Administration, Oral; Angiopoietin-1; Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Arthritis, Rheumatoid; Aspirin; Celecoxib; Disease Progression; Drug Therapy, Combination; gamma-Linolenic Acid; Inflammation; Linoleic Acids; Lipid Peroxidation; Male; Neovascularization, Pathologic; Oenothera biennis; Oxidative Stress; Plant Oils; Pyrazoles; Rats; Rats, Wistar; Sulfonamides; Tumor Necrosis Factor-alpha

Administration of gammalinolenic acid (GLA), an unsaturated fatty acid, reduces joint inflammation in patients with rheumatoid arthritis. Addition of GLA in vitro suppresses release of interleukin-1beta (IL-1beta) from human monocytes stimulated with lipopolysaccharide (LPS). LPS-induced IL-1beta release is followed by IL-1-induced IL-1beta release, an amplification process termed "autoinduction." We show here, using IL-1alpha stimulation to simulate autoinduction, that administration of GLA to healthy volunteers and to patients with inflammatory arthritis reduces LPS-induced IL-1beta secretion mainly by reducing autoinduction of IL-1beta. GLA reduces LPS-induced pro-IL-1beta mRNA modestly and IL-la-induced pro-IL-1beta gene expression markedly. In addition to reducing amplification of IL-1beta, GLA increases the amount of IL-1 receptor antagonist (IL-1Ra) secreted from stimulated cells, thereby facilitating an increase in the secreted IL-1Ra/IL-1beta ratio. IL-1beta is important to host defense, but the amplification mechanism may be excessive in genetically predisposed individuals. Thus, reduction of IL-1beta autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Psoriatic; Arthritis, Rheumatoid; Cells, Cultured; Female; gamma-Linolenic Acid; Granulomatosis with Polyangiitis; Humans; In Vitro Techniques; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Male; Middle Aged; Monocytes; Sialoglycoproteins; Sjogren's Syndrome

Administration of gammalinolenic acid (GLA), an unsaturated fatty acid, reduces joint inflammation in patients with rheumatoid arthritis. Addition of GLA in vitro suppresses release of IL-1beta from human monocytes stimulated with LPS. LPS-induced IL-1beta release is followed by IL-1-induced IL-1beta release, an amplification process termed autoinduction. We show here with peripheral blood monocytes from normal volunteers and from patients with rheumatoid arthritis by using IL-1R antagonist to block autoinduction and IL-1alpha stimulation to simulate autoinduction that approximately 40% of IL-1beta released from LPS-stimulated cells is attributable to autoinduction and that GLA reduces autoinduction of IL-1beta while leaving the initial IL-1beta response to LPS intact. Experiments with cells in which transcription and protein synthesis were blocked suggest that GLA induces a protein that reduces pro-IL-1beta mRNA stability. IL-1beta is important to host defense, but the amplification mechanism may be excessive in genetically predisposed patients. Thus, reduction of IL-1beta autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cell Separation; Cells, Cultured; Dose-Response Relationship, Drug; Dose-Response Relationship, Immunologic; Female; gamma-Linolenic Acid; Gene Expression Regulation; Humans; Interleukin-1; Lipopolysaccharides; Macrophage Activation; Middle Aged; Monocytes; Protein Precursors; RNA, Messenger

The Cochrane collaboration has recently published a systematic review of placebo controlled randomized trials of herbal therapies for rheumatoid arthritis. An extensive search including all languages screened 2500 hits, identified 47 trials and accepted 11 as meeting set quality criteria. Modest efficacy of gamma linolenic acid containing products was supported by 7 trials, 4 trials dealt with 4 different products, and no conclusions could be derived from these. Although it was stated in the review that safety was probably good, this is not apparent from the presented material.

Topics: Arthritis, Rheumatoid; gamma-Linolenic Acid; Humans; Meta-Analysis as Topic; Plant Extracts; Randomized Controlled Trials as Topic

Oils enriched in gammalinolenic acid, an unsaturated fatty acid, reduce joint pain and swelling in patients with rheumatoid arthritis. The cytokines interleukin-1 beta and tumor necrosis factor-alpha appear to contribute directly to joint tissue damage in patients with rheumatoid arthritis. Agents designed to interfere with the actions of interleukin-1 beta and tumor necrosis factor-alpha are being used to treat rheumatoid arthritis.. We examined the influence of gammalinolenic acid added to cells in vitro and administered orally in vivo on interleukin-1 beta and tumor necrosis factor-alpha secretion from activated human peripheral blood monocytes. Secretion of both cytokines was reduced by gammalinolenic acid. Administration of safflower oil as a polyunsaturated fatty acid control devoid of gammalinolenic acid did not change secretion of either cytokine.. Suppression of IL-beta and TNF-alpha secretion by activated cells may be one mechanism whereby gammalinolenic acid suppresses synovitis in patients with rheumatoid arthritis.

Topics: Administration, Oral; Arthritis, Rheumatoid; gamma-Linolenic Acid; Humans; In Vitro Techniques; Inflammation Mediators; Interleukin-1; Monocytes; Synovitis; Tumor Necrosis Factor-alpha

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Cross-Over Studies; Dermatitis, Atopic; Dermatologic Agents; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Hypolipidemic Agents; Linoleic Acids; Oenothera biennis; Plant Oils; Premenstrual Syndrome

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.

Topics: 8,11,14-Eicosatrienoic Acid; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acids; Arthritis, Rheumatoid; Dietary Fats, Unsaturated; Fatty Acids, Unsaturated; Fish Oils; gamma-Linolenic Acid; Humans; Linolenic Acids; Phospholipids

Topics: Arthritis, Rheumatoid; Fatty Acids, Essential; Fatty Acids, Unsaturated; Fish Oils; gamma-Linolenic Acid; Humans; In Vitro Techniques; Interleukin-1; Linoleic Acids; Lipopolysaccharides; Monocytes; Oenothera biennis; Plant Oils

The effects of 10 ml of evening primrose oil or olive oil, administered twice daily for 12 weeks, on clinical and laboratory signs and on plasma prostaglandins were studied in 18 patients with rheumatoid arthritis. The plasma concentration of PGE2 decreased and that of TxB2 increased in both treatment groups, but no significant improvement could be seen in either group.

Topics: Adult; Arthritis, Rheumatoid; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Olive Oil; Osmolar Concentration; Pain; Plant Oils; Prostaglandins

20 patients with active rheumatoid arthritis were treated for 12 weeks with the prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid in the form of primrose evening oil (Efamol) and the co-factors zinc, ascorbic acid, niacin, and pyridoxin (Efavit). There was a slight fall in skin reactivity to UV light during the treatment, but no effect on plasma or urine concentrations of PGE1, cAMP or cGMP. There was no effect of the treatment on ESR, P-fibrinogen, number of tender joints, number of swollen joints, the duration of morning stiffness, or on the patient's estimation of pain.

Topics: Adult; Aged; Arthritis, Rheumatoid; Ascorbic Acid; Cyclic AMP; Cyclic GMP; Drug Combinations; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Niacin; Oenothera biennis; Plant Oils; Prostaglandins E; Pyridoxine; Radioimmunoassay; Skin; Ultraviolet Rays; Zinc; Zinc Compounds