Levels Of Gamma-linolenic Acid Research Articles

263 Selected Seed Treatments to Enhance Germination of Oil-bearing Oenothera Species

The oil extracted from seed of selected accessions of Oenothera, also known as the wildflower evening primrose, has documented medical applications. Evening primrose oil contains from 0.0 to 12.0% gamma-linolenic acid (GLA) (C 18:3, delta 6, 9, 12). This unique fatty acid, which occurs in only a few plant species, can correct deficiencies in the delta 6 desaturase enzyme. Low levels of this enzyme prevent formation of the long chain fatty acids responsible for the production of prostaglandins and thromboxanes. Supplementation of the diet with evening primrose oil rich in GLA ensures adequate levels of these essential products. Inconsistent seed germination, poor emergence, and small seed size of accessions containing higher levels of GLA have limited commercial production of this crop. Currently, most producers establish their field through transplants. In this project, methods of improving seed germination have been explored. Seed coatings using diatomaceous earth were shown to facilitate handling and improve germination in the laboratory. Osmotic priming and red light exposure were also evaluated as means of improving germination.

Requirements for long-chain polyunsaturated fatty acids in the preterm infant.

Dietary long-chain polyunsaturated fatty acids have demonstrable beneficial effects on early development. The effects on neural development are of particular interest. Human milk is the best and only time-proven source of fat and essential fatty acids in the infant diet. Technologic procedures based on chemical and physical separation of the unsaturated fatty acids have permitted the isolation of concentrated sources of docosahexaenoic acid and arachidonic acid for clinical use. Virtually all infant formulas in developed countries have increased the levels of gamma-linolenic acid, and several manufacturers in Europe and in Japan have added docosahexaenoic acid, or docosahexaenoic acid plus arachidonic acid, or have also included gamma-linolenic acid in formulas for preterm and term infants. The efficacy of this practice for preterm infants seems fairly well established. The use of stable isotope methods to evaluate biosynthesis of long-chain polyunsaturated fatty acids from dietary precursors may help to better define optimal amounts and relationships of fatty acids in infant formula.

Cytokine levels affected by gamma-linolenic acid

This study was undertaken to assess whether gamma-linolenic acid (GLA) in the form of evening primrose oil (EPO) could affect rat serum cytokines, interferon-γ (IFN-γ), monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor-α (TNF-α). The following diets were administered: control, glucan, Freund's adjuvant and glucan plus Freund's adjuvant with and without GLA. In the presence of GLA, the IFN-γ and MCP-1 levels were significantly decreased in contrast to the control group of TNF-α, which was significantly stimulated. On account of interaction between diets and GLA, the remaining diet groups of TNF-α were either not affected or were inhibited in the presence of GLA. The observations indicate that GLA may modulate the level of serum IFN-γ, MCP-1 and TNF-α, which may be a worthwhile line of treatment in certain human diseases.

Dietary borage oil alters plasma, hepatic and vascular tissue fatty acid composition in spontaneously hypertensive rats

Dietary borage oil rich in gamma-linolenic acid (GLA) has been shown to lower blood pressure in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). A potential mechanism for this effect may be attributed to changes in metabolism of GLA to dihomogamma-linolenic (DGLA) and arachidonic acids (AA). We investigated the effects of dietary borage oil on fatty acid composition in the plasma, liver and vascular tissue in WKY and SHR. The diet significantly increased the levels of omega-6 polyunsaturated fatty acids. GLA and DGLA levels in the plasma, liver, aorta and renal artery tissues increased in SHR ( P < 0.001) and WKY ( P < 0.001). AA levels were also increased in both plasma and liver of SHR ( P < 0.05) and WKY ( P < 0.05) fed the borage oil enriched diet. The results demonstrate that dietary borage oil produces marked changes in the metabolism of GLA which may contribute to its blood pressure lowering effect in WKY and SHR.

Gamma-linolenic Acid Levels of Native Species of Evening Primrose (Oenothera)

Gamma-linolenic acid (GLA) is an essential fatty acid that serves as a precursor for prostaglandin biosynthesis in humans. GLA was first extracted from the seed oils of evening primrose, and currently Oenothera biennis is the major commercial source of evening primrose oil. In this study, native species of the Onagraceae family occurring in semiarid regions of Texas were surveyed. Seeds from these native populations were collected and oil extracted for analyzation of fatty acid composition. Gamma-linolenic acid levels ranged from less than 1% to 8% and was species specific. GLA levels from field-grown plants from native seed were compared with GLA levels from corresponding native populations. Two species of native Oenothera were evaluated for relative levels of GLA over several harvest dates.

Effects of Seed Treatments on Germination of Seed Collected from Native Populations of Oenothera

Oenothera biennis, common evening primrose, is grown commercially for its seed, which contains high levels of gamma-linolenic acid (GLA), a fatty acid with pharmaceutical and dietary importance. Other native species of Oenothera are being evaluated for the presence of GLA in their seed and their potential as a commercial source of GLA. Native evening primrose species have shown slow emergence and low germination percentages. Studies were conducted to determine the effects of chilling, scarification, and priming on germination of seed for six species of native evening primrose. Overall, seed germination was improved by seed treatments. However, responses to the various treatments differed among species.

Effect of high‐fat cholesterol enriched diets on hypolipemic action of Oenothera paradoxa oil in rats. Part 2. Blood serum and liver fatty acids

The effect of Oenothera paradoxa oil on blood serum and liver fatty acids composition in rats was studied. Rats were fed high-fat diets containing 15% of lard or sunflower oil with or without 0.5% of cholesterol. Soybean protein isolate (27%) was the source of proteins. Intake of Oe. paradoxa oil resulted in increase of levels of gamma-linolenic acid (GLA) and linoleic acid (LA) in blood serum and liver of experimental animals. The effect of Oe. paradoxa oil on blood serum and liver fatty acids composition depended mainly on the type and to the lower degree on the amount of fat in a diet. The addition of cholesterol did not change the influence of examined oil on the composition of fatty acids.

The induction of apoptosis in human cervical carcinoma (HeLa) cells by gamma-linolenic acid

A high concentration (50 μg/ml) of gamma-linolenic acid (GLA) induced morphological lesions typical of apoptosis, as well as DNA fragmentation, in HeLa cells. A lower concentration of GLA (20 μg/ml), caused an increased proliferating cell nuclear antigen (PCNA) labelling, with 92.7% cells positive, compared to 27.7% at a concentration of 50 μg/ml GLA. In correlation with these results, the number of cells with degraded DNA below the G 0 G 1 peak increased significantly in the 50 μg/ml GLA-treated cells, but increased only slightly in cells exposed to the lower level of GLA. The high levels of PCNA induced by 20 μg/ml GLA, in both G 1 and S phases, may indicate a state of DNA repair synthesis, whilst at the higher concentration of GLA, most of the cells became apoptotic. Since apoptosis is associated with the deregulation of c-Myc expression, and as the Raf-1-MAP kinase cascade activates the expression of c-Myc and c-Jun, we investigated the effects of 20 and 50 μg/ml GLA on the Raf-1, c-Myc and c-Jun levels, and on the activity of MAP kinase. The results showed that 50 μg/ml GLA lowered the activity of MAP kinase. As expected with the decreased MAP kinase activity in the cells exposed to the higher level GLA, the c-Jun levels were also lowered. The levels of c-Myc, however, were increased. It is therefore possible that the deregulated expression of c-Myc in the HeLa cells exposed to the high level of GLA (50 μg/ml) may contribute to the induction of apoptosis in HeLa cells.

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.

Effects of dietary gamma-linolenic acid on the tissue phospholipid fatty acid composition and the synthesis of eicosanoids in rats.

The purpose of this study was to evaluate the effects of different doses of dietary gamma-linolenic acid (GLA) on the tissue phospholipid fatty acid composition and the synthesis of eicosanoids in growing rats. The supplementation with different oils rich in GLA (borage oil, evening primrose oil, or Spirulina oil) and poor in n-3 polyunsaturated fatty acids or biomass of Spirulina results in a significant dose-related increase of GLA and dihomo-GLA in liver, erythrocyte, and aorta phospholipids in rats fed during 6 weeks different levels of GLA. The arachidonic acid (AA)/dihomo-GLA ratios decreased with increasing intake of dietary GLA, but the AA proportions remained stable. The dietary administration of GLA increased the in vitro production by the aorta of prostaglandin E1 derived from dihomo-GLA, but did not significantly influence the production of prostaglandin E2 derived from AA by the aorta and the thromboxane B2 level in serum.

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.

Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer.

1. The effects of essential fatty acids (gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines--interleukin (interleukin-1 beta, 2, 4 and 6), tumour necrosis factor-alpha and interferon-gamma--were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: tricylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1 beta levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-alpha by 73% (P = 0.040) and interferon-gamma by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.

Potential Link Between Dietary Intake of Fatty Acids and Behavior: Pilot Exploration of Serum Lipids in Attention-Deficit Hyperactivity Disorder

Essential fatty acids are structural components of all biological membranes and form the environment for membrane receptors, ion channels, and enzymes. Dietary linoleic acid is metabolized by delta-6-desaturase to gamma-linolenic acid (GLA). Through several further metabolic steps, GLA is eventually converted to series-1 prostaglandins, thromboxanes, and other molecules involved in regulating the moment-to-moment function of various physiological processes. For example, prostaglandins interact with dopamine neurotransmission. The biochemistry and physiology of essential fatty acids are reviewed, with attention to possible implications for behavior. Delta-6-desaturase deficiency has been hypothesized to be one cause of attention-deficit hyperactivity disorder (ADHD). To explore this possibility, we examined the correlations of serum lipids and behavior in a double-blind crossover comparison of GLA, d-amphetamine, and placebo in 16 boys (ages 6-12) with ADHD. Looking at the fatty-acid components of serum triglycerides across treatment conditions, we found that higher scores for behavior problems correlated with lower levels of GLA (for each of four behavioral ratings, p < 0.015) but not with its precursor, linoleic acid. This is compatible with a metabolic bottleneck at delta-6-desaturase being related to some ADHD symptoms. These preliminary findings are consistent with the possibility that fatty-acid intake or metabolism may influence behavior, at least in children with ADHD, and could conceivably modulate the effects of psychopharmacological treatment. This study must be considered exploratory and heuristic, and more definitive studies are needed to examine the possible relevance of fatty-acid metabolism to psychiatric disorders.

Borage or primrose oil added to standardized diets are equivalent sources for gamma-linolenic acid in rats.

The aim of this study was to evaluate the effect of different doses and sources of dietary gamma-linolenic acid (GLA) on the tissue phospholipid fatty acid composition. Rats fed four different levels of GLA (2.3, 4.6, 6.4 and 16.2 g of GLA/kg diet) in the form of either borage oil or evening primrose oil during 6 wk were compared with animals fed corn oil. The levels of dihomo-gamma-linolenic acid (DHLA) and GLA showed a significant dose-related increase in liver, erythrocyte and aorta phospholipids. Moreover, the arachidonic acid/DHLA ratios in tissues decreased with increasing intake of dietary GLA. There was no significant difference in tissue GLA and DHLA levels within groups given equal amounts of dietary GLA either as borage oil or evening primrose oil. The amount of dietary GLA administered did not significantly influence prostaglandin E2 production in stimulated aortic rings and thromboxane B2 levels in serum; however, an increase in prostaglandin E1 derived from DHLA was observed in the supernatants of stimulated aorta.

Dietary intake of concentrated gamma-linolenic acid (GLA)-enriched oil suppresses cutaneous level of dihomo-gamma-linolenic acid (DGLA): Possible in vivo inhibition of microsomal elongation of GLA to DGLA

The dietary supplementation of normal guinea-pig diet with moderate levels of vegetable oils containing gamma-linolenic acid (GLA) is associated with elevation of epidermal levels of dihomo-gamma-linolenic acid (DGLA) and 15-hydroxyeicosatrienoic acid (15-lipoxygenase product of DGLA). However, supplementation of diet with higher level (70%) of GLA (GLA-70) resulted in marked decrease of epidermal level of DGLA. This nutritional observation prompted us to investigate in vitro the effects of varying concentrations of polyunsaturated fatty acids (PUFAs) on rat liver microsomal chain elongation of GLA into DGLA. Our data revealed that low concentrations of GLA (< 100 μM) are stimulatory on the chain elongation while higher concentrations (> 100 μM) are inhibitory. The 18-carbon linoleic acid (precursor of GLA) was also markedly inhibitory at high concentrations. Interestingly, the longer chain 20-carbon n-3 PUFAs: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exerted negligible effect. The results suggest that increased systemic presence of free PUFAs, such as may occur in vivo after dietary intake of high n-6 PUFA-containing vegetable oils, may explain the decreased level of DGLA in the epidermal tissue.

Antihypertensive effect of gamma-linolenic acid in spontaneously hypertensive rats.

The effects of chronic treatments of adult (aged 16-17 weeks) spontaneously hypertensive rats (SHRs) with different doses of gamma-linolenic acid (GLA) on blood pressure, heart rate, and body weight were studied. Twice-daily injection of SHRs with GLA lowered systolic blood pressure from 175 +/- 4 to 145 +/- 4 mm Hg within 1 week; systolic blood pressure in all three treated groups became stabilized in the normotensive range after 2 weeks of treatment. Control SHRs injected with olive oil showed only a transient decrease in systolic blood pressure on the third day. Heart rate and body weight were not affected by GLA treatment. Withdrawal of GLA treatment resulted in a rapid rise in systolic blood pressure within 1 day from 140 +/- 3 to 165 +/- 3 mm Hg, and it stabilized after 1 week at 191 +/- 5 mm Hg in the three experimental groups. A rapid increase in systolic blood pressure from 175 +/- 5 to 203 +/- 5 mm Hg was also observed in the control group treated with olive oil 1 day after the withdrawal of the treatment. Addition of aspirin (3 mg/kg) with the GLA treatment in olive oil abolished the antihypertensive effect of GLA. In contrast, once-daily treatment with GLA also lowered systolic blood pressure of the SHR, but blood pressure was still in the hypertensive range (170 +/- 6 mm Hg). Systolic blood pressure of control SHRs treated with olive oil was not affected. Plasma from untreated SHRs contained a small amount of GLA. One hour after the injection, the plasma level of GLA increased. We conclude that GLA when given twice daily is an effective antihypertensive agent in the SHR.

Δ6 Desaturase Inhibition

The herbicide Norflurazone was shown to be an inhibitor of fatty acid of the Delta6 desaturation system. Treating cultures of the microalgae Spirulina platensis or Monodus subterraneus with this herbicide brought about a reduction in the level of gamma-linolenic acid and in an increase in the level of linoleic acid. In Monodus, the increase in linoleic acid made it more available for omega3 desaturation, resulting in an increase in the proportion of eicosapentaenoic acid. The proportion of arachidonic acid did not decrease albeit the drastic decrease in its precursor gamma-linolenic acid.

Eicosanoid synthesis in 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats fed primrose oil, menhaden oil or corn oil diet.

The comparative effects of high-fat diets (20%, w/w) on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats were studied using diets containing 20% primrose oil (PO), 20% menhaden oil (MO) or 20% corn oil (CO). Sprague-Dawley rats fed the PO or MO diet had 21% of 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically (i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid (GLA). Arachidonic acid (AA) levels were significantly higher (p less than 0.05) in PO-fed than in CO- or MO-fed rats. MO-fed rats had significantly higher levels of plasma palmitic acid, while palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were detected only in MO-fed rats. As expected, linoleic acid (LA) and AA levels were lower (p less than 0.05) in the MO-fed rats than in PO- or CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2-10 times higher than in mammary fat pads of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The P/S ratio of dietary fats and lipid metabolism in rats: Gamma-linolenic acid as a source of polyunsaturated fatty acid.

The effects of different dietary levels of gamma-linolenic acid (GLA) on lipid metabolism was studied in rats using a combination of evening primrose oil (EPO) and palm oil (PLO). EPO compared to PLO significantly reduced liver cholesterol and triglyceride after 4 weeks of feeding, and the effect remained even when EPO was mixed with PLO at the same weight basis. The serum triglyceride level also tended to be low on feeding EPO. Neither liver Δ6-desaturase and phospholipase A2 activities nor aortic production of prostacyclin and thromboxane A2 production by platelets were influenced significantly by the fat type, suggesting a peculiar effect of PLO. The percentage of arachidonic acid in liver, serum, and aortic phosphatidylcholine depended on the dietary level of GLA. A more distinct increase in arachidonic acid was observed in tissue triglycerides of rats fed EPO. GLA appears to exert favorable effects on lipid metabolism even when the P/S ratio was lowered from 13.7 of EPO to 1.8 of the 1:1 mixture of E...

Fatty acid composition of liver lipids in rats fed brominated fatty acids.

Feeding rats diets containing brominated corn oil or di- or tetrabromostearate as the monoglyceride produced changes in fatty acid composition of liver lipids. Those changes associated with the feeding of brominated corn oil or tetrabromostearate could be explained by the accumulation of triglyceride, and the changes associated with the feeding of dibromostearate could result from the proliferation of a membrane system. A unique response to the feeding of diets containing brominated corn oil is an increase in the level of gamma-linolenic acid.