gamma-linolenic-acid and Asthma

Changes in diet over the past century have markedly altered the consumption of fatty acids. The dramatic increase in the ingestion of saturated and n-6 fatty acids and concomitant decrease in n-3 fatty acids are thought to be a major driver of the increase in the incidence of inflammatory diseases such as asthma, allergy, and atherosclerosis. The central objective of the Center for Botanical Lipids at Wake Forest University School of Medicine and the Brigham and Women's Hospital is to delineate the mechanisms by which fatty acid-based dietary supplements inhibit inflammation leading to chronic human diseases such as cardiovascular disease and asthma. The key question that this center addresses is whether botanical n-6 and n-3 fatty acids directly block recognized biochemical pathways or the expression of critical genes that lead to asthma and atherosclerosis. Dietary supplementation with flaxseed oil, borage oil, and echium oil affects the biochemistry of fatty acid metabolism and thus the balance of proinflammatory mediators and atherogenic lipids. Supplementation studies have begun to identify key molecular and genetic mechanisms that regulate the production of lipid mediators involved in inflammatory and hyperlipidemic diseases. Echium oil and other oils containing stearidonic acid as well as botanical oil combinations (such as echium and borage oils) hold great promise for modulating inflammatory diseases.

Topics: Animals; Asthma; Atherosclerosis; Cholesterol; Chronic Disease; Dietary Fats; Dietary Fats, Unsaturated; Dietary Supplements; Echium; Fatty Acids, Omega-3; Fatty Acids, Omega-6; gamma-Linolenic Acid; Humans; Hyperlipidemias; Inflammation; Linseed Oil; Plant Oils; Signal Transduction; Triglycerides

This article discusses the role of diet in the management of asthma. Readers will gain an understanding of how evolution of the western diet has contributed to increased asthma prevalence and how dietary modification that includes management of dietary lipids may reduce symptoms of asthma.. Relevant studies published in English were reviewed.. Medline search to identify peer-reviewed abstracts and journal articles.. Asthma and obesity, which often occur together, have increased in prevalence in recent years. Studies suggest adaption of a western diet has not only contributed to obesity, but that increased intake of specific nutrients can cause changes in the frequency and severity of asthma. Increased asthma prevalence has also been proposed to arise from increased exposure to diesel particles or lack of exposure to infectious agents or endotoxins during childhood, generating a biased Th2 immune response, and increased cytokine and leukotriene production. Antagonists directed against these pro-inflammatory mediators include anticytokines and antileukotrienes. A reduction in the levels of inflammatory mediators associated with asthma has also been seen with dietary interventions, such as the administration of oils containing gamma-linolenic acid and eicosapentaenoic acid.. Evidence suggests elevated body mass index and dietary patterns, especially intake of dietary lipids, contribute to symptoms of asthma. Dietary modification may help patients manage their asthma as well as contribute to their overall health.

Topics: Adolescent; Adult; Arachidonic Acids; Asthma; Body Mass Index; Child; Comorbidity; Dietary Fats; Fatty Acids, Essential; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Fish Oils; gamma-Linolenic Acid; Humans; Hypersensitivity, Immediate; Inflammation Mediators; Leukotrienes; Male; Membrane Lipids; Obesity; Prevalence; Tumor Necrosis Factor-alpha

DF Horrobin hypothesized that the low prevalence of lung disease among Eskimos is the result of their diet, which is high in n-3 fatty acids. The n-3 and n-6 fatty acids shunt eicosanoid production away from the arachidonic acid pathway, and hence decrease the production of bronchoconstrictive leukotrienes. Animal studies showed that eicosapentaenoic acid or gamma-linolenic acid supplementation of animals exposed to endotoxins results in decreased effects on thromboxane B(2) and pulmonary vascular resistance. Small human trials confirmed that supplementation with eicosapentaenoic acid results in increased eicosapentaenoic acid in phospholipids and decreased generation of leukotrienes by neutrophils. Hence, a protective effect of such fatty acids in lung disease is biologically plausible. The results of human intervention studies looking at respiratory outcomes have been mixed, but they do suggest a possible difference between long-term and short-term effects. Epidemiologic studies showed possible protective effects against asthma in children, but weak to no evidence of such effects in adults. Results for bronchitis are more positive, although intervention trials are lacking. Recently, a cross-sectional analysis of data from the first National Health and Nutrition Examination Survey reported an approximately 80-mL difference in forced expiratory volume at 1 s between adults with high compared with low fish consumption. This response was not limited to asthmatic subjects. Others found that both fish consumption and n-3 fatty acid consumption (as estimated from food-frequency questionnaires) were protective against physician-diagnosed emphysema and chronic bronchitis and low spirometry values. Only smokers were included in this analysis. These results suggest that dietary fatty acids may play a role in lung disease; further work is needed to elucidate that role.

Topics: Adult; Animals; Asthma; Bronchitis; Child; Cystic Fibrosis; Dietary Fats, Unsaturated; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Lung Diseases; Lung Diseases, Obstructive; Rabbits; Respiratory Function Tests; Swine

Asthma can have a negative impact on quality of life although this is not well correlated with objective evaluations of pulmonary function. A medical food, EFF1009, containing the fatty acids gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) decreases leukotriene B(4) synthesis in patients with asthma. Two previous clinical studies with EFF1009 provided preliminary evidence that the medical food improves asthma-related quality of life (ARQOL) and asthma management.. To evaluate the impact on ARQOL of EFF1009 in adults with asthma.. The study was a randomized, prospective, double-blind, placebo-controlled, parallel group study in twenty-one (N = 21 evaluable) subjects with mild to moderate persistent asthma who consumed the medical food emulsion or placebo emulsion daily for 28 days. All participants continued their asthma medications throughout the study. ARQOL, including asthma signs and symptoms, and asthma control were measured using the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) and the Asthma Control Questionnaire (ACQ), administered at baseline, Day 14 and Day 28. Safety and tolerability parameters, including adverse events, were monitored.. Baseline ARQOL scores, forced expiratory volume in one second (FEV(1)) and other characteristics were balanced between both groups. Mean (standard error) total MiniAQLQ scores changed by 0.73 (0.38) and -0.22 (0.36) in the EFF1009 and placebo groups, respectively, (p < 0.05). The MiniAQLQ symptom domain score was improved in the EFF1009 group (p < 0.05). Total scores for the ACQ were not significantly improved in either group. Levels of the fatty acid EPA in plasma increased in the EFF1009 group but not the placebo group (p < 0.03). The medical food was well tolerated and no safety concerns were identified.. The dietary addition of the medical food EFF1009 to asthma management regimens can improve patient perceived, ARQOL and can also improve asthma management as evidenced by reduced asthma symptoms. An additional study of the medical food, with larger subject population and longer treatment duration, is warranted to confirm these findings.

Topics: Adult; Asthma; Double-Blind Method; Eicosapentaenoic Acid; Emulsions; Female; Food, Fortified; gamma-Linolenic Acid; Humans; Leukotriene B4; Male; Placebos; Plant Oils; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

Leukotriene synthesis inhibitors and receptor antagonists are efficacious for the treatment of asthma. Diets containing the fatty acids gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) decrease leukotriene synthesis; however, their impact on asthma management and quality of life (QOL) has not been evaluated in asthmatic subjects.. To evaluate asthma management and the QOL of asthmatic adult subjects consuming a medical food emulsion containing GLA and EPA.. Trial 1 was a randomized, prospective, double-blind, placebo-controlled, parallel group trial in atopic subjects with mild-to-moderate asthma (n = 35 evaluable) consuming a low dose (0.75 g GLA + 0.5 g EPA), high dose (1.13 g GLA + 0.75 g EPA) or placebo emulsion daily. Subjects were questioned about their asthma management using a non-validated questionnaire after 2 and 4 weeks. Blood leukotrienes were measured at baseline and after 4 weeks. Trial 2 was an open-label study (n = 65 evaluable) where subjects consumed the low-dose medical food emulsion, EFF1009, daily. QOL and asthma management were measured using the validated Mini Asthma Quality of Life (MiniAQLQ) and the Asthma Control (ACQ) questionnaires, respectively, administered at baseline and after 4 weeks.. In Trial 1, leukotriene biosynthesis decreased (p < 0.05). Self-reported asthma status and bronchodilator use improved in subjects consuming low- and high-dose emulsion between week 2 and week 4 (p < 0.01), but not compared to placebo (p > 0.1). In Trial 2, mean +/- standard error total MiniAQLQ and ACQ scores improved by 1.5 +/- 0.2 and 1.0 +/- 0.1, respectively (p < 0.001). Subdomain scores from MiniAQLQ improved and rescue bronchodilator use decreased (p < 0.001).. The inclusion of the medical food EFF1009 in asthma management regimens can improve patient quality of life and decrease reliance on rescue medication.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Eicosapentaenoic Acid; Female; Food, Fortified; gamma-Linolenic Acid; Humans; Leukotriene Antagonists; Leukotrienes; Male; Nutritional Status; Quality of Life; Respiratory Function Tests; Sickness Impact Profile; Surveys and Questionnaires; Treatment Outcome

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

Leukotriene inhibitors and leukotriene-receptor antagonists are effective in the treatment of inflammatory diseases such as asthma. A search of the entirety of MEDLINE using the terms diet plus leukotrienes identified numerous studies that have explored dietary-management strategies to reduce leukotriene levels through supplementation with polyunsaturated fatty acids such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA). However, the search found no studies on the use of combinations of these fatty acids in patients with asthma.. The goal of this study was to determine the effect of daily intake of an emulsion (PLT 3514) containing dietary GLA and EPA on ex vivo stimulated whole blood leukotriene biosynthesis in patients with atopic asthma.. This was a randomized, double-blind, placebo-controlled, parallel-group, prospective trial in patients with mild to moderate atopic asthma. Patients consumed 10 g PLT 3514 emulsion (containing 0.75 g GLA + 0.5 g EPA), 15 g PLT 3514 emulsion (containing 1.13 g GLA + 0.75 g EPA), or placebo (olive oil) emulsion daily for 4 weeks. Plasma fatty acids were measured by gas chromatography, and stimulated whole blood leukotrienes were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection using a diode array detector.. Forty-three patients (33 women, 10 men) participated in the study. Leukotriene biosynthesis was significantly decreased in patients consuming 10 or 15 g PLT 3514 compared with placebo (P < 0.05, analysis of covariance). No clinically significant changes in vital signs were observed throughout the study, and there were no significant between-group differences in treatment-emergent adverse events or mean clinical laboratory values.. Daily consumption of dietary GLA and EPA in a novel emulsion formulation inhibited leukotriene biosynthesis in this population of patients with atopic asthma and was well tolerated.

Topics: Adult; Asthma; Double-Blind Method; Eicosapentaenoic Acid; Emulsions; Fatty Acids; Fatty Acids, Unsaturated; Female; Food, Formulated; gamma-Linolenic Acid; Humans; Leukotriene A4; Male; Prospective Studies

Essential fatty acids are claimed to have positive effects in atopic diseases. In a double blind, placebo controlled, parallel group study 58 out of 60 children, with atopic dermatitis and the need for regular treatment with topical skin steroids, completed a 16 weeks' treatment period with either Epogam evening primrose oil or placebo capsules. Twenty two of these subjects also had asthma. The parents used diaries to record symptom scores and concomitant medication. Peak expiratory flow was measured and disease activity was monitored by the clinician every four weeks. The plasma concentrations of essential fatty acids increased significantly in the group treated with Epogam capsules. The study demonstrated significant improvements of the eczema symptoms but no significant difference was found between the placebo and the Epogam groups. No therapeutic effect was shown on asthma symptoms or fidget.

Topics: Administration, Topical; Adolescent; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Drug Administration Schedule; Fatty Acids, Essential; gamma-Linolenic Acid; Glucocorticoids; Humans; Infant; Linoleic Acids; Oenothera biennis; Plant Oils; Severity of Illness Index

It has shown recently that Evening Primrose Oil (Efamol) produces a significant clinical improvement in atopic eczema. Efamol contains gamma-linolenic acid which is a precursor to PGE1 a more consistent bronchodilator than PGE2. We have conducted a double blind placebo controlled study in atopic asthmatics given Efamol for an eight week period looking at the control of asthma, including histamine challenge tests. We have found no effect on the asthma or challenge tests although Efamol produced an alteration in fatty acid profile. The patients showed an abnormal fatty acid profile. We speculate that such fatty acid abnormalities could be important in the aetiology of asthma.

Topics: Adult; Asthma; Double-Blind Method; Fatty Acids; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Phospholipids; Plant Oils; Random Allocation; Respiratory Function Tests

The effect of daily dietary supplementation with 15 to 20 mL of evening primrose seed oil or fish oil was assessed by comparison with olive oil as placebo in a cross-over study in 29 asthmatics. During 10 weeks of each regimen, the patients kept record of symptoms, peak expiratory flow rates and medication. Plasma and urine TxB2, PGE2, PGF2 alpha and 6 keto-PGF1 alpha and plasma fatty acid composition of plasma cholesterol esters were measured at the end of each treatment period. There were no differences between regimes with regard to peak flow rates, symptoms, or drug consumption. Plasma PGE2 levels increased during the fish oil treatment but there were no changes in other prostanoids in plasma or urine. The fatty acid pattern of plasma cholesterol esters showed significant differences between the supplementation periods. We conclude that moderate doses of evening primrose oil or fish oil are ineffective as a supplementary treatment of bronchial asthma.

Topics: Adult; Aged; Asthma; Fatty Acids, Essential; Female; Fish Oils; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Middle Aged; Oenothera biennis; Plant Oils; Prostaglandins E; Prostaglandins F; Thromboxanes

Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders.. The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes.. Supplementation with several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%.. This study shows that dietary supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; alpha-Linolenic Acid; Asthma; Cells, Cultured; Dietary Supplements; Echium; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Inflammation; Leukocytes, Mononuclear; Leukotrienes; Male; Middle Aged; Plant Oils; Seeds

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

It has been suggested that atopy is associated with an impairment in the delta 6-desaturation of (n-6)-polyunsaturated fatty acids and subsequently low levels of eicosanoid precursors. To evaluate this hypothesis we analyzed the fatty acid composition of plasma phospholipids and plasma cholesterol esters in a well-defined group of children with atopic bronchial asthma (n = 17) and age-matched healthy controls (n = 10). Atopic children showed significantly higher levels of linoleic acid and lower proportions of arachidonic acid in plasma lipids. No differences were observed with respect to gamma-linolenic acid (GLA) and dihomo-gamma-linolenic acid (DHLA). It is concluded that there is no biochemical evidence for a delta 6-desaturation defect in atopic children and therefore no justification for the supplementation of GLA and DHLA; e.g., by the use of evening primrose oil preparations.

Topics: 8,11,14-Eicosatrienoic Acid; Asthma; Child; Cholesterol Esters; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Hypersensitivity, Immediate; Lipids; Male; Phospholipids

Topics: Albuterol; Asthma; Bacterial Infections; Breast Diseases; Carboprost; Cefixime; Cefotaxime; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Oenothera biennis; Pain; Plant Oils; Postpartum Hemorrhage; Pregnancy; Salmeterol Xinafoate