gamma-linolenic-acid and Sjogren-s-Syndrome

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 focus on the double-blind clinical investigations in patients with Sjögren's syndrome and describe the historical developments. It is divided into two passages--systemic and topically treatment.

Topics: Bromhexine; Clinical Trials as Topic; Double-Blind Method; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Ophthalmic Solutions; Plant Oils; Sjogren's Syndrome

Evidence from biochemical studies and from experimental animals indicates that abnormalities of essential fatty acid (EFA) and eicosanoid metabolism could lead to salivary and lacrimal gland atrophy and to immunological and cardio-vascular defects. Measurements of EFA levels in erythrocytes from patients with primary Sjögren's syndrome have shown that abnormalities are indeed present. Controlled clinical trials of supplementation with gamma-linolenic acid (GLA) as evening primrose oil (Efamol) in both primary Sjögren's syndrome and systemic sclerosis have given positive results. There are strong arguments to indicate that sophisticated manipulation of EFA metabolism may have a role to play, not only in Sjögren's syndrome but also in other rheumatological disorders.

Topics: Erythrocyte Membrane; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Plant Oils; Prostaglandins; Scleroderma, Systemic; Sjogren's Syndrome

To determine the effect of oral omega-6 essential fatty acids on PGE(1) tear content and signs and symptoms of ocular discomfort in patients with Sjögren's syndrome (SS).. This randomized, double-masked, controlled, clinical trial involved 40 patients with primary SS, divided into two groups: group 1: 20 patients (18 women, 2 men; mean age, 36.9 +/- 7.9 years [SD]) treated for 1 month with linoleic acid (LA; 112 mg), and gamma-linolenic acid (GLA; 15 mg) administered twice daily; group 2: 20 patients (19 women, 1 man; mean age, 36.3 +/- 5.5 years) treated twice daily with placebo. Patients underwent three examinations: at baseline (T0), after 1 month of treatment (T1), and 15 days after suspension of treatment (T2). At each examination, the following tests were performed: tear sampling (2 microL) from the inferior meniscus, tear break-up time (BUT), fluorescein stain of the ocular surface, and tear basal secretion. A symptom score was also obtained at each examination. PGE1 was evaluated by enzyme immunoassay. The primary efficacy variable was PGE1 content of tears.. The tear PGE1 levels were significantly increased in group 1 at T1 versus T0 (PGE1 level: T0, 44 +/- 5.4 ng/mL; T1, 58.3 +/- 5.5 ng/mL; P < 0.01 versus T0 and group 2 at T1). At examination T2, a statistically significant reduction of PGE1 levels toward baseline was observed (45.7 +/- 5.2 ng/mL; P < 0.01 versus T1). A statistically significant reduction of symptom score was observed in group 1 at examination T1 (P < 0.01 versus T0 and group 2 score). At examination T2, the symptom score was significantly higher than T1 but remained lower than T0. The corneal fluorescein stain in group 1 showed a statistically significant improvement at examination T1 versus T0 and group 2 (P < 0.01). This improvement was also present at T2 (P < 0.02). No statistically significant differences were found for the other tests. No statistically significant changes were observed in the patients in group 2 at all examination time points.. Omega-6 administration increases the PGE1 levels in tears of patients with SS and improves ocular surface signs and symptoms of ocular discomfort.

Topics: Administration, Oral; Adult; Alprostadil; Cornea; Double-Blind Method; Female; Fluorescein; Fluorophotometry; gamma-Linolenic Acid; Humans; Immunoenzyme Techniques; Linoleic Acid; Male; Sjogren's Syndrome; Tears

To evaluate the efficacy of the essential omega-6 fatty acid Gammalinolenic acid (GLA) on fatigue associated with primary Sjögren's syndrome.. Ninety patients with primary Sjögren's syndrome (with or without signs of autoimmunity) entered a 6-month double blind placebo-controlled randomised trial with high dose GLA (extracted from Evening Primrose Oil) or corn oil. The primary outcome parameter was fatigue; secondary endpoints were eye dryness, mouth dryness, muscle and joint pain.. No statistically significant improvement was found in fatigue assessed by Visual Analogue Scale (VAS) or in the time needed for sleeping/resting during a 24-hour period. No differences were found between the treatment and placebo group. The same applies to the secondary endpoints: no differences in VAS for eye and mouth dryness or pain, no significant changes in Schirmer-1-test, van Bijsterveld score, unstimulated whole sialometry (UWS), or use of artificial tears or analgesics. Only mild side effects were observed.. According to our study results GLA (Evening Primrose oil) treatment for fatigue in primary Sjögren's syndrome is ineffective.

Topics: Aged; Dermatologic Agents; Double-Blind Method; Fatigue; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Patient Compliance; Plant Oils; Sjogren's Syndrome; Treatment Outcome

This review focus on the double-blind clinical investigations in patients with Sjögren's syndrome and describe the historical developments. It is divided into two passages--systemic and topically treatment.

Topics: Bromhexine; Clinical Trials as Topic; Double-Blind Method; Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Ophthalmic Solutions; Plant Oils; Sjogren's Syndrome

Twenty-four female and 4 male patients, all fulfilling the Copenhagen criteria for primary Sjögren's syndrome (primary SS), were treated for 8 weeks with evening primrose oil (Efamol). Efamol is a seed oil which consists primarily of the n-6 essential fatty acids (EFA): cis-linoleic acid and gammalinolenic acid (GLA). The investigation was carried out as a randomized, double-blind, placebo-controlled, cross-over trial in order to determine whether long-term treatment of patients with primary SS with Efamol would improve the ocular and oral clinical status, and whether the levels of EFA in plasma and erythrocytes increase during Efamol treatment. The objective ocular status, evaluated by a combined ocular score, including the results from Schirmer-I test, break-up time and van Bijsterveld score, improved significantly during Efamol treatment when compared with Efamol start-values (p less than 0.05), but not when compared with placebo values (p less than 0.2). The GLA metabolite and prostaglandin-E1 (PGE1) precursor dihomogammalinolenic acid (20: 3n6, DGLA) increased both in plasma (p less than 0.001) and in erythrocytes (p less than 0.001) during treatment with Efamol. No correlations between objective ocular and oral status and DGLA values in plasma or erythrocytes were found.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Eye; Fatty Acids; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Immunosuppressive Agents; Linoleic Acids; Lip; Male; Middle Aged; Oenothera biennis; Phospholipids; Plant Oils; Random Allocation; Sjogren's Syndrome; Xerostomia

Topics: Fatty Acids, Essential; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Plant Oils; Research Design; Sjogren's Syndrome

Thirty-six patients with primary Sjögren's syndrome participated in a randomised double-blind, cross-over, 3-week, study to compare the effect of Efamol (1500 mg X 2) with that of placebo. Efamol contains 9% of the prostaglandin-E1 precursor gamma-linolenic acid, which is presumed to occur in reduced levels in Sjögren's syndrome. Efamol treatment improved the Schirmer-I-test (P less than 0.03) while values of break-up time,-van Bijsterveld score, corneasensitivity, tear-lysozyme and nuclear chromatin in conjunctival epithelial cells did not reach the statistical 0.05 level.

Topics: Adult; Aged; Ascorbic Acid; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Flushing; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Niacin; Oenothera biennis; Plant Oils; Pyridoxine; Sjogren's Syndrome; Zinc; Zinc Compounds

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

Drugs which modify the conversion of essential fatty acids to prostaglandins and leukotrienes are the mainstays of treatment in rheumatology. Yet these drugs have little or no action in scleroderma or Sjogren's syndrome and under some circumstances may have adverse effects. Patients with scleroderma have been shown to have very high levels of circulating prostaglandins, coupled with depletion of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. Levels of the metabolites of arachidonic acid, 22:4n-6 and 22:5n-6, which have major roles in maintaining normal cell membrane characteristics were exceptionally low in both plasma and red cell membranes. Others have observed that various functions are highly resistant to normal actions of PGs in scleroderma. This raises the possibility that the high rate of PG formation in scleroderma may be beneficial, in compensation, and that clinical symptoms develop when PG precursors begin to be depleted. Red cell membrane fatty acids patterns in Sjogren's syndrome are almost identical to those in scleroderma. Placebo-controlled trials of supplementation with essential fatty acids have been found to be beneficial in both scleroderma and Sjogren's syndrome.

Topics: Animals; Ascorbic Acid Deficiency; Connective Tissue Diseases; Cyclic AMP; Diabetes Mellitus; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linolenic Acids; Prostaglandins; Scleroderma, Systemic; Sjogren's Syndrome