Gamma-linolenic Acid Supplementation Research Articles

68 Titration of GLA supplementation is linearly related to incorporation of DGLA into equine red blood cells

The omega-6 fatty acid gamma-linolenic acid (GLA) has received considerable research attention in other species for its anti-inflammatory properties, largely attributed to the conversion of dietary GLA to dihomo-gamma-linolenic acid (DGLA). However, there is little to no published research on supplementing GLA to horses. The objective of this study was to determine how varied levels of supplemental GLA influence the equine blood fatty acid profile. Twenty Thoroughbred horses (9.9 ± 3.7 yr; 605 ± 58 kg BW; mean ± SD) were used in a longitudinal design for 6 mo including 3 mo of supplementation and 3 mo post-supplementation. Horses were stratified into 5 groups balanced primarily for age, BW, and initial grain intake and randomly assigned to one of 5 GLA oil treatments (n = 4): 0 (control), 1.9, 3.7, 7.3, or 9.7 g/d GLA top-dressed on similar low-starch commercial concentrates (1 to 5 kg/d). Fatty acid composition of plasma and red blood cells (RBCs) was measured every 28 d using gas chromatography at a commercial laboratory. Data were analyzed using linear regression and repeated measures ANOVA (GraphPad Prism). There was a strong positive linear relationship (R2 = 0.87; [% DGLA in RBC = 0.053(g/d of GLA intake) + 0.243]) between GLA intake and RBC DGLA incorporationafter 3 mo of supplementation, indicating horses can effectively convert GLA to DGLA in a dose-responsive manner. As GLA intake increased, more DGLA was incorporated into RBCs at a faster rate. Between baseline and 3 mo of supplementation, RBC DGLA did not change at 0 g/d GLA (0.26 to 0.23; P = 0.41) but increased 164% (0.28 to 0.74; P < 0.01) at 9.7 g/d GLA. At 1.9 g/d GLA, RBC DGLA did not differ (P > 0.05) from baseline until 3 mo of supplementation and returned after one month of washout. At 7.3 and 9.7 g/d GLA, RBC DGLA was different (P < 0.05) from baseline within one month of supplementation and remained elevated after 3 mo of washout. Results indicate that higher levels of supplementation respond faster, but take longer to peak and more time to wash out. More research is needed to determine if there is an upper limit to the dose response of GLA. Although an optimal equine blood fatty acid profile has not been delineated, these results provide novel data on the impact GLA supplementation has on the equine blood fatty acid profile.

Is there a beneficial effect of gamma-linolenic acid supplementation on body fat in postmenopausal hypertensive women? A prospective randomized double-blind placebo-controlled trial.

Systemic arterial hypertension and obesity are major public health problems that increase risks of serious cardiovascular diseases and kidney failure as well as increase mortality. Substances that can alleviate these problems are desirable. We evaluated the beneficial effects of nutritional supplementation with gamma-linolenic acid in postmenopausal hypertensive women. This was a prospective, double-blind, placebo-controlled, randomized study involving 96 postmenopausal women. Participants were divided into two groups either receiving 1,000 mg of borage oil rich in gamma-linolenic acid + vitamin E (drug) or only vitamin E (placebo) capsules for 6 months. They were followed up monthly to assess the impact on systemic blood pressure and body composition. To verify group homogeneity, Fisher's exact and Student t tests were performed. To evaluate differences in various parameters between the two groups and at various times, repeated measures analysis of variance was performed, with Bonferroni correction. The power of the test was calculated based on the difference in the mean systolic blood pressure between baseline and after 6 months of treatment in the placebo group and in the drug group. A 92.9% test power was found with a 95% confidence interval. There was a significant reduction in the systolic and diastolic pressure as well as a significant change in waist-hip ratio (P < 0.01) in the drug group as compared with the placebo group. Supplementation with borage oil rich in gamma-linolenic acid had significant beneficial short-term effects without showing any adverse effect. There remains a need for further studies to evaluate long-term benefits.

A Randomized, Placebo-Controlled Trial of Gamma Linolenic Acid as an Add-on Therapy to Minocycline for the Treatment of Rosacea.

BackgroundA recent study suggested a possible role of skin barrier dysfunction in the pathogenesis of rosacea, which leads to irritation symptoms. Gamma linolenic acid (GLA) is an essential omega-6 fatty acid that is known to restore defective epidermal skin barrier. GLA supplementation has not previously been performed in rosacea patients.ObjectiveTo investigate the efficacy and safety of adding GLA to minocycline compared to minocycline alone in rosacea patients.MethodsThis prospective, double-blind, randomized, placebo-controlled trial enrolled 31 rosacea patients. They were randomly assigned to receive 320 mg/day of GLA (Evoprim®) (n=16) or placebo (n=15) in addition to 100 mg/day of minocycline for 8 weeks. Investigator's global assessment (IGA) and patient's global assessment (PGA) were used to assess clinical severity at weeks 0, 4, 8, and 12. Biophysical parameters including melanin index, erythema index, transepidermal water loss (TEWL), lipid concentration, and stratum corneum hydration were measured.ResultsIn the GLA group, a higher proportion of patients achieved treatment success (IGA≤1) at week 8 (68.75% vs. 33.33%) and patient satisfaction (PGA≥3) at weeks 8 (75.0% vs. 40.0%) and 12 (81.3% vs. 46.6%). Both groups, throughout 12 weeks of treatment, revealed a trend toward improvement in erythema index, melanin index, TEWL, and stratum corneum hydration. Particularly, there was a significant difference in TEWL and stratum corneum hydration over time between the two groups (p=0.033, p=0.003, respectively). No serious adverse event was observed in both groups.ConclusionGLA is beneficial as an additional therapeutic option for rosacea patients treated with minocycline.

GLA supplementation regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DMBA induced mammary gland carcinoma.

The aim of the present study is to evaluate the effect of gamma linolenic acid (GLA) on mitochondrial mediated death apoptosis, hypoxic microenvironment and cholinergic anti-inflammatory pathway against 7, 12-dimethylbenz (a) anthracene (DMBA) induced mammary gland carcinoma. The effects of GLA were evaluated morphologically and biochemically against DMBA induced mammary gland carcinoma. The metabolic study was done for evaluation of biomarkers using 1H NMR. The present study was also verified through immunoblotting and qRT-PCR studies for the evaluation of various pathways. GLA treatment has a delineate implementation upon morphology of the tissues when evaluated through carmine staining, hematoxyline and eosin staining and scanning electron microscopy. GLA also demarked a commendatory proclamation of the fifteen key serum metabolites analogous with amino acid metabolism and fatty acid metabolism when recognized through1H NMR studies. The immunoblotting and qRT-PCR studies accomplished that GLA mediated mitochondrial death apoptosis, curtail hypoxic microenvironment along with hindrance of de novo fatty acid synthesis and also mediate the cholinergic anti-inflammatory pathway to proclaim its anticancer effects.

Dietary Supplementation of Gamma-Linolenic Acid Improves Skin Parameters in Subjects with Dry Skin and Mild Atopic Dermatitis

Disruption of the skin barrier function caused by epidermal hyper-proliferation, results in the skin becoming dry and showing high transepidermal water loss (TEWL). Gamma linolenic acid (GLA) is reportedly efficacious for treating TEWL and epidermal hyper-proliferation. In this study, to elucidate the effect of GLA-rich oil on skin function, GLA-containing food was given to adults with dry skin or mild atopic dermatitis and skin parameters were evaluated. In the results, we recognized beneficial effects on the TEWL index. The efficacy of GLA was also demonstrated to be statistically significant especially in subjects with pro-inflammatory features. The results suggest that the mechanism of improvement of skin barrier has been associated with possible generation of anti-inflammatory metabolites from GLA. The clinical physician also confirmed that none of the subjects showed any noteworthy side effects. GLA-enriched food appears to be safe and to improve skin barrier function in subjects with dry skin conditions and mild atopic dermatitis.

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

The Effect of Isoflavone and Gamma-linolenic Acid Supplementation on Serum Lipids and Menopausal Symptoms in Postmenopausal Women

This study was performed to examine the combined effects of gamma linolenic acid and isoflavone supplementation on menopausal symptoms and serum lipids in 73 postmenopausal women. A total subjects were randomly assigned to isoflavone (30 ㎎) + gamma-linolenic acid (110 ㎎) group or placebo group. We measured menopausal symptoms by modified Kupperman Index (KI) and oxidized LDL, lipid peroxides, blood components and anthropometric parameters before and after the 12 week intervention period. After the 12 weeks of supplementation, supplement group and placebo group showed a significant reduction of modified kupperman index (p < 0.001). Isoflavone (30 ㎎) + gamma-linolenic acid (110 ㎎) supplement group showed a significant reduction of oxidized LDL cholesterol concentration (p = 0.006) whereas placebo group did not show significant change. Isoflavone and gamma-linolenic acid consumption did not significantly affect plasma concentrations of total, LDL, HDL cholesterol, triglyceride, apo A1, B and blood components. The result of present study demonstrated the supplementation of 30 ㎎ isoflavone and 110 ㎎ gamma-linolenic acid per day for 12 weeks may protect LDL cholesterol from oxidative stress.

Gamma-Linolenic Acid Inhibits Inflammatory Responses by Regulating NF-κB and AP-1 Activation in Lipopolysaccharide-Induced RAW 264.7 Macrophages

Gamma linolenic acid (GLA) is a member of the n-6 family of polyunsaturated fatty acids and can be synthesized from linoleic acid (LA) by the enzyme delta-6-desaturase. The therapeutic values of GLA supplementation have been documented, but the molecular mechanism behind the action of GLA in health benefits is not clear. In this study, we assessed the effect of GLA with that of LA on lipopolysaccharide (LPS)-induced inflammatory responses and further explored the molecular mechanism underlying the pharmacological properties of GLA in mouse RAW 264.7 macrophages. GLA significantly inhibited LPS-induced protein expression of inducible nitric oxide synthase, pro-interleukin-1beta, and cyclooxygenase-2 as well as nitric oxide production and the intracellular glutathione level. LA was less potent than GLA in inhibiting LPS-induced inflammatory mediators. Both GLA and LA treatments dramatically inhibited LPS-induced IkappaB-alpha degradation, IkappaB-alpha phosphorylation, and nuclear p65 protein expression. Moreover, LPS-induced nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) nuclear protein-DNA binding affinity and reporter gene activity were significantly decreased by LA and GLA. Exogenous addition of GLA but not LA significantly reduced LPS-induced expression of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK)-1. Our data suggest that GLA inhibits inflammatory responses through inactivation of NF-kappaB and AP-1 by suppressed oxidative stress and signal transduction pathway of ERK and JNK in LPS-induced RAW 264.7 macrophages.

Dietary Effect of .GAMMA.-Linolenic Acid on the Lipid Profile of Rat Fed Erucic Acid Rich Oil

This study evaluated the effects of dietary supplementation of gamma-Linolenic acid (18:3n-6, GLA) on the lipid profile of serum and other tissues of rats fed erucic acid (C22:1) rich oil like mustard oil. The rats were fed diet containing 20% mustard oil as erucic acid rich oil and 20% groundnut oil as dietary fat. These groups were kept as reference groups. Another group fed diet containing 20% fat to which evening primrose oil as a source of GLA was blended with mustard oil and groundnut oil at 5% level. The feeding experiment was done for 4 weeks. In another set mustard oil fed group was kept as control while the experimental group was fed evening primrose oil as a source of GLA blended with mustard oil at 2.5% level. The feeding experiment was carried out for 12 weeks. The other dietary components remained same for all the groups. After the scheduled feeding period, it was found that there was no significant change in weight gain, food intake and food efficiency ratio. It was found that dietary GLA resulted in significant decrease in serum triglyceride (TG) and very low density lipoprotein (VLDL) cholesterol and significant increase in high density lipoprotein (HDL) cholesterol in serum in the experimental group. In liver total cholesterol (TC) is significantly higher and in heart and liver TG is significantly lower in GLA fed group.

Therapeutic Effect of Topical Gamma-Linolenic Acid on Refractory Uremic Pruritus

Pruritus is a bothersome symptom affecting up to 80% of dialysis patients. Lymphocyte and cytokine interaction has an important role in the pathogenesis of uremic pruritus. Gamma-linolenic acid (GLA) is associated with immune modulation of T lymphocytes and lymphokines. The aim of this study is to determine whether topical GLA can attenuate uremic pruritus. Seventeen dialysis patients with refractory uremic pruritus who passed the screening criteria entered a prospective, randomized, double-blind, placebo-controlled, crossover study. They stopped all antipruritic therapy at least 2 weeks before the study and were randomly assigned to treatment with either GLA 2.2% cream or placebo-based cream applied to the entire body after taking a bath once a day and to pruritic sites 3 times a day for 2 weeks, and then the reverse treatment after a 2-week washout period. Severity of pruritus was evaluated by using a traditional visual analogue scale (VAS) and a modified questionnaire method (pruritus score [PS]). Hemogram, aspartate and alanine aminotransferases, bilirubin, albumin, blood urea nitrogen, creatinine, calcium, phosphate, and intact parathyroid hormone were measured. Sixteen patients completed the study; 1 patient was withdrawn because of an allergic skin reaction. There were no significant differences between groups except for sex distribution. Median VAS and PS values between groups did not differ significantly at baseline. There is a greater antipruritic effect of GLA based on evaluation with both the VAS and PS. There is persistence of a residual effect into the second treatment period after GLA treatment. GLA-rich cream is better than placebo-based cream for alleviating uremic pruritus. It is a useful adjuvant in the management of refractory uremic pruritus.

Oral essential fatty acid supplementation in atopic dermatitis-a meta-analysis of placebo-controlled trials.

Essential fatty acids are components of cell membranes and precursors of immunomodulating factors that may play a role in the inflammatory and immunological pathogenesis of atopic dermatitis. Trials of supplementation with essential fatty acids (EFA) to alleviate atopic dermatitis (AD) have given inconsistent results. To summarize and quantify the results of placebo-controlled trials with EFA for AD. Publications of clinical trials were searched in a systematic way and the study characteristics assessed independently by three assessors. Trials were selected for inclusion in the meta-analysis when they had included a placebo group and when the outcome measure included the severity of AD. The pooled effect sizes of improvement of the overall severity of AD were calculated by random effects meta-analysis. The dependence of the results on study characteristics was studied using meta-regression analysis. We identified 34 publications of controlled trials in AD up to April 2002. Nineteen trials of gamma-linolenic acid (GLA) and five trials of fish oil matched our inclusion criterion of placebo-controlled trial. The effect size of GLA supplementation on the improvement of the overall severity of AD could be calculated from 11 of these trials. The pooled effect size was 0.15 [95% confidence limits (CL) - 0.02, 0.32]. The effect size of fish oil supplementation, calculated from three trials was - 0.01 (95% CL - 0.37, 0.30). For component subscales such as itch, scaling and lichenification, EFA supplementation showed no benefit. The study characteristics showed no detectable influence on the overall result. Supplementation with EFA has no clinically relevant effect on the severity of AD.

Effects of supplementation with fish oil–derived n−3 fatty acids and γ-linolenic acid on circulating plasma lipids and fatty acid profiles in women

Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and gamma-linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The effects of supplement mixtures of these fatty acids on plasma lipids and the fatty acid compositions of serum phospholipids have received little attention. The objective was to determine the effects of different levels of GLA supplementation together with a constant intake of EPA plus DHA on the triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid patterns (eicosanoid precursors) of serum phospholipids. Thirty-one women were assigned to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum phospholipids were measured on days 0 and 28. Plasma triacylglycerol concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1, and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2 group. Dihomo-gamma-linolenic acid increased significantly in serum phospholipids only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4 groups. A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women. On the basis of calculated PROCAM values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of myocardial infarction.

γ-Linolenic Acid Restores Renal Medullary Thick Ascending Limb Na+,K+-ATPase Activity in Diabetic Rats

In diabetes, the activity of Delta-6 desaturase, which converts linoleic acid (LA) into gamma-linolenic acid (GLA), the first step of arachidonic acid (AA) synthesis, is decreased, leading to alterations in membrane phospholipid composition. On the other hand, 12 wk after the onset of diabetes, Na(+),K(+)-ATPase activity is reduced in many organs, including the kidney. The medullary thick ascending limb (MTAL) reduced Na(+),K(+)-ATPase activity, whereas the sodium load secondary to glomerular hyperfiltration was increased. The aim of our study was to examine whether the changes in membrane fatty acid composition resulting from the inhibition of Delta-6 desaturase may be involved in the decreased Na(+),K(+)-ATPase activity observed in the outer MTAL after 12 wk of diabetes. GLA is a fatty acid that by-passes the Delta-6 desaturase step. We measured the membrane fatty acid composition and the Na(+),K(+)-ATPase activity in the renal outer medulla of control and streptozotocin (STZ)-induced diabetic rats 12 wk after the induction of diabetes. Measurements were performed after supplementation of control rats with sunflower oil (SO) or GLA for 12 wk, and supplementation of 12 wk diabetic rats with SO for 12 wk or with GLA for 6 or 12 wk. Supplementation with GLA not only prevented the decrease in Na(+),K(+)-ATPase activity observed after 12 wk of diabetes but also time dependently stimulated Na(+),K(+)-ATPase activity in the outer medulla. The changes in Na(+),K(+)-ATPase activity were related to parallel changes in the amount of Na(+),K(+)-ATPase alpha(1) subunit protein. In addition, in diabetic rats only, Na(+),K(+)-ATPase activity was positively correlated with the amount of AA present in cell membranes (r = 0.92, P < 0.05). Our results indicate that nutritional GLA supplementation increases Na(+),K(+)-ATPase activity and expression in diabetic rats. In addition, the positive correlation between AA content and Na(+),K(+)-ATPase activity suggests that in diabetic rats, alterations in membrane fatty acid composition contribute to the decreased Na(+),K(+)-ATPase activity in outer medulla.

Role of polyunsaturated fatty acids in lung disease

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.

Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P < 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Na+, K+ ATPase activity in the preventive treatment group (P < 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.

Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes.

This study compares the effect of gamma-linolenic acid (GLA) and its precursor linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes. By contrast, LA supplementation did not affect the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36B10 cells and astrocytes. GLA and LA supplementation increased the total polyunsaturated fatty acid (PUFA) content of the cells indicating increased oxidative potential. However, elevated levels of 8-isoprostane, an indicator of increased oxidative stress, were only observed in the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did not affect the radiation response of either cell type. While cyclo-oxygenase inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma cells but not to normal astrocytes.

γ-Linolenic Acid Supplementation Can Affect Cancer Cell Proliferation via Modification of Fatty Acid Composition

We examined the effect of gamma-linolenic acid (GLA) supplementation on the growth and fatty acid composition of three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), in order to evaluate the relationship between GLA-induced tumor cell death and the distribution of fatty acids in tumor cells. At the highest GLA concentrations (10 and 20 μg/ml), the DNA synthesis was completely abolished; at 5 μg/ml GLA only SW-620 cells did not proliferate, while CHP-212 and TG cells showed a residual [3H]-thymidine incorporation. GLA levels were very low in cells grown in control medium; GLA supplementation caused a significant incorporation of GLA itself in all the cell lines at each concentration. In TG and CHP-212 cells, GLA was metabolized, although to a different extent, to dihomo-gamma linolenic acid and arachidonic acid. SW-620 cells neither elongated nor desaturated the incorporated GLA. The highest cytostatic effect was reached when GLA was not transformed into its metabolites, suggesting that the GLA toxicity to tumor cells is not dependent on metabolites but is due to GLA itself.

Metabolism of linoleic and alpha-linolenic acids in cultured cardiomyocytes: effect of different N-6 and N-3 fatty acid supplementation.

The metabolites of linoleic (LA) and alpha-linolenic (ALA) acids are involved in coronary heart disease. Both n-6 and n-3 essential fatty acids (EFAs) are likely to be important in prevention of atherosclerosis since the common risk factors are associated with their reduced 6-desaturation. We previously demonstrated the ability of heart tissue to desaturate LA. In this study we examined the ability of cultured cardiomyocytes to metabolize both LA and ALA in vivo, in the absence and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) alone or combined together. In control conditions, about 25% or LA and about 90% of ALA were converted in PUFAs. GLA supplementation had no influence on LA conversion to more unsaturated fatty acids, while the addition of n-3 fatty acids, alone or combined together, significantly decreased the formation of interconversion products from LA. Using the combination of n-6 and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of EPA and DHA on LA desaturation/elongation. The conversion of ALA to more unsaturated metabolites was greatly affected by GLA supplementation. Each supplemented fatty acid was incorporated to a significant extent into cardiomyocyte lipids, as revealed by gas chromatographic analysis. The n-6/n-3 fatty acid ratio was greatly influenced by the different supplementations; the ratio in GLA+EPA+DHA supplemented cardiomyocytes was the most similar to that recorded in control cardiomyocytes. Since important risk factors for coronary disease may be associated with reduced 6-desaturation of the parent EFAs, administration of n-6 or n-3 EFA metabolites alone could cause undesirable effects. Since they appear to have different and synergistic roles, only combined treatment with both n-6 and n-3 metabolites is likely to achieve optimum results.

(n-6)-Fatty acids in plasma lipids of children with atopic bronchial asthma.

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.

Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease

Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alapha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin E 1, (PGE 1), prostacyclin (PGI 2), and PGI 3, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians. Since insulin resistance and hyperinsulinemia and features of obesity, NIDDM, HTN and CHD, diseases that are common in Indians, and as decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids (PUFAs) in skeletal muscle phospholipids and, possibly, in the plasma, the possibility is raised that changes in the metabolism of EFAs may have a fundamental role in the pathobiology of these conditions. If this is true, this suggests that supplementation of GLA, DGLA, AA, EPA and/or DHA may be indicated to prevent CHD, HTN and NIDDM in Indians.