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January 2011

The impact of a medical food containing gammalinolenic and eicosapentaenoic acids on asthma management and the quality of life of adult asthma patients.

BACKGROUND: 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. OBJECTIVE: To evaluate asthma management and the QOL of asthmatic adult subjects consuming a medical food emulsion containing GLA and EPA. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSION: The inclusion of the medical food EFF1009 in asthma management regimens can improve patient quality of life and decrease reliance on rescue medication.

Curr Med Res Opin. 2008 Feb;24(2):559-67

Treatment of rheumatoid arthritis with gammalinolenic acid.

OBJECTIVE: 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. DESIGN: A randomized, double-blind, placebo-controlled, 24-week trial. SETTING: Rheumatology clinic of a university hospital. PATIENTS: Thirty-seven patients with rheumatoid arthritis and active synovitis. INTERVENTION: Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo). MEASUREMENTS: Physicians’ and patients’ global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities. RESULTS: 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. CONCLUSION: 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.

Ann Intern Med. 1993 Nov 1;119(9):867-73

Effects of gammalinolenic acid on plasma lipoproteins and apolipoproteins.

Nineteen hypercholesterolemic patients (10 without and 9 with hypertriglyceridemia) were given evening primrose oil rich in gammalinolenic acid (GLA, 18: 3n - 6), in a placebo controlled cross-over design, over 16 weeks (8 + 8 weeks), with safflower oil as the placebo. During supplementation with evening primrose oil, dihomogammalinolenic acid (20: 3n - 6) increased in plasma lipids and red blood cells, and in subjects without hypertriglyceridemia there was a significant decrease in low density lipoprotein-cholesterol and plasma apolipoprotein B compared with the levels observed during safflower oil administration. Our results confirmed that evening primrose oil is effective in lowering low density lipoprotein in hypercholesterolemic patients.

Atherosclerosis. 1989 Feb;75(2-3):95-104

Gamma-linolenate reduces weight regain in formerly obese humans.

The purpose of this study was to determine whether gamma-linolenate (GLA) supplementation would suppress weight regain following major weight loss. Fifty formerly obese humans were randomized into a double-blind study and given either 890 mg/d of GLA (5 g/d borage oil) or 5 g/d olive oil (controls) for 1 y. Body weight and composition and adipose fatty acids of fasting subjects were assessed at 0, 3, 12, and 33 mo. After 12 subjects in each group had completed 1 y of supplementation, weight regain differed between the GLA (2.17 +/- 1.78 kg) and control (8.78 +/- 2.78 kg) groups (P < 0.03). The initial study was terminated, and all remaining subjects were assessed over a 6-wk period. Unblinding revealed weight regains of 1.8 +/- 1.6 kg in the GLA group and 7.6 +/- 2.1 kg in controls for the 13 and 17 subjects, respectively, who completed a minimum of 50 wk in the study. Weight regain did not differ in the remaining 10 GLA and 5 control subjects who completed <50 wk in the study. In a follow-up study, a subgroup from both the original GLA (GLA-GLA, n = 9) and the original control (Control-GLA, n = 14) populations either continued or crossed over to GLA supplementation for an additional 21 mo. Interim weight regains between 15 and 33 mo were 6.48 +/- 1.79 kg and 6.04 +/- 2.52 kg for the GLA-GLA and Control-GLA groups, respectively. Adipose triglyceride GLA levels increased 152% (P < 0.0001) in the GLA group at 12 mo, but did not increase further after 33 mo of GLA administration. In conclusion, GLA reduced weight regain in humans following major weight loss, suggesting a role for essential fatty acids in fuel partitioning in humans prone to obesity.

J Nutr. 2007 Jun;137(6):1430-5

An open-label phase I/II dose escalation study of the treatment of pancreatic cancer using lithium gammalinolenate.

There are currently no satisfactory treatments for inoperable pancreatic cancer. Median survivals for untreated patients are of the order of 100 days and, with one exception, no chemotherapy or radiotherapy regime has been found to produce a worthwhile extension of life with reasonably tolerable side effects. Gamma-linolenic acid (GLA) has been found to kill about 40 different human cancer cell lines in vitro without harming normal cells. The lithium salt of GLA (LiGLA) can be administered intravenously and a dose escalation study of a 10 day infusion followed by oral therapy in patients with inoperable pancreatic cancer was carried out in 48 patients in two centres. Peripheral venous infusion caused thrombophlebitis but this could be avoided by infusing via a central vein with appropriate heparinisation. Too rapid infusion caused haemolysis which could be avoided by slow dose escalation in the first few days and maintenance of plasma lithium below 0.8 mmol/l. Doses ranged from 7 to 77g/patient cumulatively delivered over 2-12 days. Other than the above described events there were no important side effects and patients felt well during the infusions. A Kaplan-Meier analysis showed that survival was not significantly influenced by which centre the patients were treated in, the sex of the patients or the presence or absence of histological confirmation. The presence or absence of liver metastases, the patients’ Karnofsky scores and the-dose of LiGLA had significant effects on survival from treatment. A Cox proportional hazards model revealed similar results: in both centres, in both sexes, and in patients with and without liver metastases according to the model the highest doses of LiGLA were associated with longer survival times as compared with the lowest doses. LiGLA deserves investigation in a randomised prospective study.

Anticancer Res. 1996 Mar-Apr;16(2):867-74

Gamma linolenic acid: an antiinflammatory omega-6 fatty acid.

Inflammation plays an important role in health and disease. Most of the chronic diseases of modern society, including cancer, diabetes, heart disease, arthritis, Alzheimer’s disease, etc. have inflammatory component. At the same time, the link between diet and disease is also being recognized. Amongst dietary constituents, fat has gained most recognition in affecting health. Saturated and trans fatty acids have been implicated in obesity, heart disease, diabetes and cancer while polyunsaturated fatty acids (PUFAs) generally have a positive effect on health. The PUFAs of omega-3 and omega-6 series play a significant role in health and disease by generating potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins) and affecting the gene expression of various bioactive molecules. Gamma linolenic acid (GLA, all cis 6, 9, 12-Octadecatrienoic acid, C18:3, n-6), is produced in the body from linoleic acid (all cis 6,9-octadecadienoic acid), an essential fatty acid of omega-6 series by the enzyme delta-6-desaturase. Preformed GLA is present in trace amounts in green leafy vegetables and in nuts. The most significant source of GLA for infants is breast milk. GLA is further metabolized to dihomogamma linlenic acid (DGLA) which undergoes oxidative metabolism by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 and leukotrienes of series 3). GLA and its metabolites also affect expression of various genes where by regulating the levels of gene products including matrix proteins. These gene products play a significant role in immune functions and also in cell death (apoptosis). The present review will emphasize the role of GLA in modulating inflammatory response, and hence its potential applications as an anti-inflammatory nutrient or adjuvant.

Curr Pharm Biotechnol. 2006 Dec;7(6):531-4

The metabolism of dihomo-gamma-linolenic acid in man.

Orally administered dihomo-gamma-linolenic acid (DHLA) is well absorbed in man; it appears in blood after ca. 4 hr first as triglyceride ester and later as phospholipid. After sustained-dosing, DHLA penetrated membrane pools and all phospholipid components but, depending on the dosage, reached a metabolic equilibrium in 4-16 days. Intact platelets do not accumulate arachidonate following DHLA administration, and species differences occur in the capacity of animals to metabolize DHLA to arachidonic acid (AA). The rat appears to be unusual in having a very active hepatic delta5-desaturase enzyme system. Potentially antithrombotic changes in platelet function which followed the administration of DHLA to man were accompanied by a significant increase in the capacity of platelets to synthesize PGE1. Concomitant increases in PGE2 synthesis do not apparently result from an increased production of AA and suggest that DHLA, or a DHLA metabolite, interferes with the metabolism of AA. Effects on thromboxane and prostacyclin synthesis are being studied.

Lipids. 1979 Feb;14(2):174-80

Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans.

To understand the in vivo metabolism of dietary gamma-linolenic acid (GLA), we supplemented the diets of 29 volunteers with GLA in doses of 1.5-6.0 g/d. Twenty-four subjects ate controlled eucaloric diets consisting of 25% fat; the remaining subjects maintained their typical Western diets. GLA and dihomo-gamma-linolenic acid (DGLA) increased in serum lipids of subjects supplemented with 3.0 and 6.0 g/d; serum arachidonic acid increased in all subjects. GLA supplementation with 3.0 and 6.0 g/d also resulted in an enrichment of DGLA in neutrophil phospholipids but no change in GLA or AA levels. Before supplementation, DGLA was associated primarily with phosphatidylethanolamine (PE) of neutrophil glycerolipids, and DGLA increased significantly in PE and neutral lipids after GLA supplementation. Extending the supplementation to 12 wk did not consistently change the magnitude of increase in either serum or neutrophil lipids in subjects receiving 3.0 g/d. After GLA supplementation, A23187-stimulated neutrophils released significantly more DGLA, but AA release did not change. Neutrophils obtained from subjects after 3 wk of supplementation with 3.0 g/d GLA synthesized less leukotriene B4 (P < 0.05) and platelet-activating factor. Together, these data reveal that DGLA, the elongase product of GLA, but not AA accumulates in neutrophil glycerolipids after GLA supplementation. The increase in DGLA relative to AA within inflammatory cells such as the neutrophil may attenuate the biosynthesis of AA metabolites and may represent a mechanism by which dietary GLA exerts an anti-inflammatory effect.

J Nutr. 1997 Aug;127(8):1435-44

Clinical and experimental study on the long-term effect of dietary gamma-linolenic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production.

Effects of a dietary intake of the polyunsaturated omega-6 essential fatty acids (EFAs) linoleic and gamma-linolenic acids (GLA) on blood lipids, platelet function, and vascular prostacyclin production were studied 12 hyperlipidemic patients (doses of 3 g/day) and 12 male Wistar rats (doses of 3 mg/kg/day) for 4 months. In humans, GLA supplementation decreased plasma triglyceride (TG) levels by 48% (p < 0.001) and increased HDL-cholesterol concentration by 22% (p < 0.01). Total cholesterol and LDL-cholesterol levels were significantly decreased by omega-6 EFAs. Platelet aggregation induced by low concentrations of adenosine diphosphate (ADP) and epinephrine, and serum thromboxane B2 decreased by 45% both in humans and animals after GLA supplementation. Bleeding time increased 40% (p , 0.01). In rats, vascular prostacyclin production measured by radioimmunoassay of 6-keto-PGF1 alpha was enhanced by GLA intake. These effects of omega-6 EFAs may contribute to cardiovascular protection and prevention of the atherosclerotic disease.

Prostaglandins Leukot Essent Fatty Acids. 1994 Nov;51(5):311-6