8-11-14-eicosatrienoic-acid and Dermatitis--Atopic

Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; Aged; Analysis of Variance; Biomarkers; Dermatitis, Atopic; Double-Blind Method; Female; gamma-Linolenic Acid; Humans; Male; Middle Aged; Plant Oils; Triglycerides

Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis-5, 8, 11-eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B

Topics: 8,11,14-Eicosatrienoic Acid; Actins; Animals; Biomarkers; Capillary Permeability; Chemotaxis; Coconut Oil; Dermatitis, Atopic; Dermatitis, Contact; Dietary Fats, Unsaturated; Disease Models, Animal; Female; Immunohistochemistry; Immunophenotyping; Leukotriene B4; Lipid Metabolism; Mice; Neutrophils; Skin

Atopic dermatitis (AD) is a chronic and relapsing skin disorder with pruritic skin symptoms. We previously reported that dihomo-γ-linolenic acid (DGLA) prevented the development of AD in NC/Tnd mice, though the mechanism remained unclear.. We attempted to investigate the mechanism of preventive effect of DGLA on AD development in NC/Tnd mice.. The clinical outcomes of NC/Tnd mice that were given diets containing DGLA, arachidonic acid, or eicosapentaenoic acid were compared. Lipid mediator contents in the skin in each group were also quantified. In addition, release of lipid mediators from RBL-2H3 mast cells treated with either DGLA or prostaglandin D1 (PGD1) was measured. Furthermore, effect of PGD1 on gene expression of thymic stromal lymphopoietin (TSLP) in PAM212 keratinocyte cells was determined.. Only DGLA containing diet suppressed the development of dermatitis in vivo. By quantifying the 20-carbon fatty acid-derived eicosanoids in the skin, the application of DGLA was found to upregulate PGD1, which correlated with a better outcome in NC/Tnd mice. Moreover, we confirmed that mast cells produced PGD1 after DGLA exposure, thereby exerting a suppressive effect on immunoglobulin E-mediated degranulation. PGD1 also suppressed gene expression of TSLP in keratinocytes.. These results suggest that oral administration of DGLA causes preventive effects on AD development in NC/Tnd mice by regulating the PGD1 supply.

Topics: 8,11,14-Eicosatrienoic Acid; Administration, Cutaneous; Animals; Arachidonic Acid; Cell Degranulation; Cytokines; Dermatitis, Atopic; Dietary Supplements; Eicosapentaenoic Acid; Gene Expression; Mast Cells; Mice; Prostaglandin D2; Prostaglandins D; RNA, Messenger; Thymic Stromal Lymphopoietin; Up-Regulation

Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index.. The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography.. A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008).. The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; Child; Child, Preschool; Cohort Studies; Dermatitis, Atopic; Dermatologic Agents; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Plant Oils; Prospective Studies; Treatment Outcome; Young Adult

Administration of dihomo-gamma-linolenic acid is useful for atopic dermatitis and atherosclerosis in mice; however, the metabolites of dihomo-gamma-linolenic acid have been little studied. We employed a method which enabled simultaneous analysis of nine prostaglandins using liquid chromatography-tandem mass spectrometry, and determined the concentrations of prostaglandins in the supernatants of cultures of mouse peritoneal macrophages stimulated with lipopolysaccharide after pre-incubation with dihomo-gamma-linolenic acid, arachidonic acid, or eicosapentaenoic acid. Accumulated prostaglandin concentrations from mouse macrophages with dihomo-gamma-linolenic acid uptake increased in a dihomo-gamma-linolenic acid concentration-dependent fashion. These increases were mainly due to prostaglandin D(1) and prostaglandin E(1). The order of accumulated prostaglandin concentrations was dihomo-gamma-linolenic acid>arachidonic acid>eicosapentaenoic acid in supernatants with the same concentration of polyunsaturated fatty acid. Since mouse macrophages can clearly produce series-1 prostaglandins, they must be formed in vivo. These findings suggest that the effects of dihomo-gamma-linolenic acid on diseases may be due to series-1 prostaglandins.

Topics: 8,11,14-Eicosatrienoic Acid; Alprostadil; Animals; Arachidonic Acid; Dermatitis, Atopic; Dose-Response Relationship, Drug; Eicosanoic Acids; Humans; Lipopolysaccharides; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Prostaglandins D

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Dermatitis, Atopic; Dog Diseases; Dogs; gamma-Linolenic Acid; Linoleic Acids, Conjugated; Linolenic Acids; Plant Oils

Disorders of the metabolism of essential fatty acids (EFAs) are related to atopic dermatitis (AD). Concentrations of dihomo-gamma-linolenic acid (DGLA), an EFA, in the serum of AD patients are lower than those in healthy volunteers. Recently we developed a fermented DGLA oil, and examined whether oral administration of DGLA prevents development of dermatitis in NC/Nga mice, which spontaneously develop human AD-like skin lesions. NC/Nga mice were fed a diet either containing or not containing DGLA for 8 weeks under in air-uncontrolled conventional circumstances. Clinical skin severity scores were significantly lower in mice fed DGLA than in mice not fed it. Scratching behavior and plasma total IgE levels were also reduced in the DGLA group, in association with histological improvement. DGLA suppressed clinical severity of skin lesions dose-dependently, with an increase in DGLA contents in phospholipids of skin, spleen, and plasma. Discontinuation of DGLA administration resulted in the onset of dermatitis and a decrease in DGLA contents in skin, spleen, and plasma. These findings indicate that oral administration of DGLA effectively prevents the development of AD in NC/Nga mice, and that DGLA in phospholipids is a compound of key importance in the development and prevention of dermatitis.

Topics: 8,11,14-Eicosatrienoic Acid; Administration, Oral; Animals; Dermatitis, Atopic; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Immunoglobulin E; Male; Mice; Mice, Inbred Strains; Severity of Illness Index; Skin; Skin Tests

It has been suggested that atopic dermatitis (AD) is associated with impaired delta-6 desaturase activity and the subsequent altered composition of n-6 essential fatty acids (EFAs).. To investigate whether n-6 EFA deficiency accounts for AD by affecting transepidermal water loss or the immune response.. Serum levels of n-6 EFAs were measured using gas chromatography-mass spectrometry in a well-defined group of 35 children with AD (IgE level >150 U/mL); 35 age-matched children with allergic rhinitis, asthma, or both (IgE level >150 U/mL); and 31 nonatopic controls (IgE level <100 U/mL). Skin barrier function was evaluated by measuring transepidermal water loss and severity of AD by computing the Scoring Atopic Dermatitis (SCORAD) index.. Atopic children had higher levels of linoleic acid (LA) and lower levels of its metabolites. Furthermore, gamma-linolenic acid to LA and dihommo-gamma-linolenic acid to LA ratios were significantly reduced in atopic patients. Transepidermal water loss and the SCORAD index were negatively correlated with serum levels of LA metabolites. There was no correlation between the SCORAD index and IgE level (P = .51) or between n-6 EFA concentrations and IgE level (P > .10).. Deficits in n-6 EFAs were correlated with the severity of AD by affecting skin barrier function and cutaneous inflammation. The link between impaired n-6 EFA metabolism and IgE level could not be defined.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Arachidonic Acid; Asthma; Child; Child, Preschool; Dermatitis, Atopic; Epidermis; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Immunoglobulin E; Linoleic Acid; Lipids; Male; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Water; Water Loss, Insensible

We compared the dietary effects of dihomo-gamma-linolenic acid (DGLA) contained in the DGLA oil produced by a fungus with gamma-linolenic acid (GLA) on the fatty acid composition. Wistar rats were fed with three kinds of oil for two weeks as follows: (i) control group: corn oil; (ii) GLA group: borage oil; (iii) DGLA group: DGLA oil/safflower oil = 55:45. The DGLA concentrations in the liver, serum, and brain of the DGLA group were higher than those of the GLA oil group. We also examined the dose effect of DGLA. The DGLA levels in the liver, serum, and brain significantly increased with increasing dosage of DGLA in the diet. DGLA administration significantly increased the ratio of PGE1/PGE2 in the rat plasma. The mechanism for GLA administration to improve atopic eczema is thought to involve an increase in the concentration of DGLA metabolized from GLA, so these results suggest that the dietary effect of DGLA would be more dominant than GLA.

Topics: 8,11,14-Eicosatrienoic Acid; Administration, Oral; Alprostadil; Animals; Brain; Delta-5 Fatty Acid Desaturase; Dermatitis, Atopic; Dinoprostone; Fatty Acid Desaturases; gamma-Linolenic Acid; Linoleoyl-CoA Desaturase; Liver; Male; PPAR alpha; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sterol Regulatory Element Binding Proteins

It has been demonstrated that patients with atopic disease have anomalies of fatty acid composition, as a result of altered metabolism or abnormal incorporation of fatty acids into the tissues. In the present study, in 57 newborns 'at risk' for atopic disease, the polyunsaturated fatty acid (PUFA) levels were found to be lower in cord blood in infants who subsequently developed atopic disease than in non-atopics. In all babies, levels of arachidonic acid and dihomo-gamma-linolenic acid in sera at 1 and 3 months of age were lower than those in cord blood. These changes were more marked in children who subsequently developed atopic disease, and in those who, independently of signs and/or symptoms of atopic disease, were formula-fed. A comparison between IgE and PUFA levels revealed no significant differences at any tested time interval. In conclusion, our data suggest that in children 'at risk' for atopy, PUFA levels may be predictive of atopic disease.

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Asthma; Biomarkers; Breast Feeding; Dermatitis, Atopic; Fatty Acids, Unsaturated; Female; Fetal Blood; Follow-Up Studies; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Infant, Newborn; Male; Neonatal Screening